Datasets:

allenai

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mslr2022

like 8

[ "17608870", "15332470", "11036893", "1737710" ]

[ "Increased satisfaction with care and lower costs: results of a randomized trial of in-home palliative care.", "Caregiver bereavement outcome: relationship with hospice at home, satisfaction with care, and home death.", "A palliative-care intervention and death at home: a cluster randomised trial.", "A randomized trial of the cost effectiveness of VA hospital-based home care for the terminally ill." ]

[ "To determine whether an in-home palliative care intervention for terminally ill patients can improve patient satisfaction, reduce medical care costs, and increase the proportion of patients dying at home.\n A randomized, controlled trial.\n Two health maintenance organizations in two states.\n Homebound, terminally ill patients (N=298) with a prognosis of approximately 1 year or less to live plus one or more hospital or emergency department visits in the previous 12 months.\n Usual versus in-home palliative care plus usual care delivered by an interdisciplinary team providing pain and symptom relief, patient and family education and training, and an array of medical and social support services.\n Measured outcomes were satisfaction with care, use of medical services, site of death, and costs of care.\n Patients randomized to in-home palliative care reported greater improvement in satisfaction with care at 30 and 90 days after enrollment (P<.05) and were more likely to die at home than those receiving usual care (P<.001). In addition, in-home palliative care subjects were less likely to visit the emergency department (P=.01) or be admitted to the hospital than those receiving usual care (P<.001), resulting in significantly lower costs of care for intervention patients (P=.03).\n In-home palliative care significantly increased patient satisfaction while reducing use of medical services and costs of medical care at the end of life. This study, although modest in scope, presents strong evidence for reforming end-of-life care.", "This study used a randomized controlled trial design to investigate the impact of hospice at home (HAH) on caregiver bereavement outcome. Secondary analyses considered the association between bereavement, place of death, and carers' assessment of support. Ninety-six informal carers of patients referred to HAH were surveyed six weeks post-bereavement about the quality of terminal care. Carers next completed measures of their own bereavement response and general health six months post-bereavement. There was no evidence that HAH had an impact on bereavement outcome. In contrast, perceptions of inadequate terminal support and high symptom severity were associated with worse carer bereavement response. However, it remains unclear whether carers' retrospective ratings constitute an accurate account of symptoms and care. Home deaths were associated with both better bereavement response and better physical health post-bereavement than were inpatient deaths. Further research is needed to investigate the implications of death at home for the carer.", "The Palliative Medicine Unit at University Hospital of Trondheim, Norway, started an intervention programme that aims to enable patients to spend more time at home and die there if they prefer. Close cooperation was needed with the community health-care professionals, who acted as the principal formal caregivers, and a multidisciplinary consultant team coordinated the care. We did a cluster randomised trial to assess the intervention's effectiveness compared with conventional care\n Community health-care districts in and around Trondheim, Norway, were defined as the clusters to be randomised. We enrolled 434 patients (235 assigned intervention and 199 conventional care [controls]) in these districts who had incurable malignant disease and an expected survival of 2-9 months. Main outcomes were place of death and time spent in institutions in the last month of life.\n 395 patients died. Of these, more intervention patients than controls died at home (54 [25%] vs 26 [15%], p<0.05). The time spent at home was not significantly increased, although intervention patients spent a smaller proportion of time in nursing homes in the last month of life than did controls (7.2 vs 14.6%, p<0.05). Hospital use was similar in the two groups.\n The palliative-care intervention enabled more patients to die at home. More resources for care in the home (palliative care training and staff) and an increased focus on use of nursing homes would be necessary, however, to increase time at home and reduce hospital admissions.", "All admissions to a 1,100-bed Department of Veterans Affairs (VA) hospital were screened to identify 171 terminally ill patients with informal caregivers who were then randomly assigned to VA hospital-based team home care (HBHC, N = 85) or customary care (N = 86). Patient functioning, and patient and caregiver morale and satisfaction with care were measured at baseline, one month, and six months. Health services utilization was monitored over the six-month study period and converted to cost. Findings included no differences in patient survival, activities of daily living (ADL), cognitive functioning, or morale, but a significant increase in patient (p = .02) and caregiver (p = .005) satisfaction with care at one month. A substitution effect of HBHC was seen. Those in the experimental group used 5.9 fewer VA hospital days (p = .03), resulting in a $1,639 or 47 percent per capita saving in VA hospital costs (p = .02). As a result, total per capita health care costs, including HBHC, were $769 or 18 percent (n.s.) lower in the HBHC sample, indicating that expansion of VA HBHC to serve terminally ill veterans would increase satisfaction with care at no additional cost." ]

[ "3632987", "4708113", "4414728" ]

[ "Social dramatics: social skills development for the chronically mentally ill.", "The use of modeling and role playing to increase social interaction among asocial psychiatric patients.", "Movement and drama therapy with long-stay schizophrenics." ]

[ "The purpose of this study was to investigate the use of social dramatics as a clinical tool for teaching social skills to the chronically mentally ill on adult inpatient units of a state hospital. The research tested the hypothesis that patients exposed to social dramatics with videotape feedback would demonstrate greater ability to perform social skills as measured by the Nurses' Observation Scale for Inpatient Evaluation (NOSIE-30). Fifteen schizophrenic adults of both sexes meeting specific criteria were randomly assigned to experimental and control groups. Subjects were exposed over an 8-week period to randomly introduced social dramatic scenarios. The Wilcoxin test for two independent samples was used for testing differences between experimental and control groups. The research findings supported the hypothesis for one positive factor, social competence. The findings did not support any treatment effect on either social interest and personal neatness or irritability, manifest psychosis, and psychotic depression. There were no significant differences on the total score NOSIE-30. Recommendations for psychiatric nursing are made. Limitations of research methodologies and sample size were addressed.", "nan", "nan" ]

[ "8098293", "6846433" ]

[ "Nutritional factors and rest reduce pregnancy-induced hypertension and pre-eclampsia in positive roll-over test primigravidas.", "Effective prevention of gestational hypertension in nulliparous women at high risk as identified by the rollover test." ]

[ "The possibility of reducing pregnancy-induced hypertension and preeclampsia in primigravidas with low doses of nutritional factors and relative rest in the left lateral position was investigated in a randomized controlled, double-blind trial.\n Seventy-four normotensive women at 28-29 weeks' gestation, judged to be at risk of PIH or pre-eclampsia because they presented with a mean blood pressure of 80 mmHg or higher and a positive roll-over test, were studied. The treatment protocol was received by 37 women and the other 37 women received standard antenatal control until delivery.\n Twenty-nine (78.3%) women in the control group developed PIH and/or pre-eclampsia, as opposed to only 4 (10.8%) cases in the treatment group (P < 0.001). There were no adverse effects of treatment in mothers or in infants.\n This protocol reduces PIH and pre-eclampsia in primigravidas judged to be at risk of hypertension. Further studies are required to evaluate prostacyclin and prostaglandin E2 changes.", "The supine pressor (rollover) test was performed on a population of nulliparous patients between 28 and 32 weeks' gestation. Sixteen patients with abnormal test results were treated with increased rest in the left lateral recumbent position. Only one of this group developed gestational hypertension at term (6%), the rest remaining normotensive through delivery. A control group of 16 patients with abnormal test results were left untreated. Three patients of this group (19%) remained normotensive while 13 patients developed hypertensive complications (81%). Of the 13 patients who had hypertensive problems, nine developed preeclampsia and the remaining four had pregnancy-induced hypertension. A significant decrease was noted in the incidence of hypertensive complications in the patients treated with increased rest in the left lateral recumbent position when compared with the incidence in the control group and a composite of untreated patients in other studies. This treatment plan affords an economical approach for treatment of those at high risk for developing gestational hypertension and/or preeclampsia." ]

[ "10812143", "12814712", "12722044", "7991041", "15754269", "10617243", "8442035", "8633373", "11389707", "8396749", "11209008", "11959339", "11267254", "11703619", "11477342" ]

[ "Comparison of the effects of simvastatin and pravastatin on acute rejection episodes in renal transplant patients.", "Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial.", "Effect of a 3-year therapy with the 3-hydroxy-3-methylglutaryl coenzyme a reductase-inhibitor fluvastatin on endothelial function and distensibility of large arteries in hypercholesterolemic renal transplant recipient.", "Low-dose simvastatin is a well-tolerated and efficacious cholesterol-lowering agent in ciclosporin-treated kidney transplant recipients: double-blind, randomized, placebo-controlled study in 40 patients.", "First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease.", "A double-blind placebo controlled trial of simvastatin for the treatment of dyslipidaemia in renal allograft recipients.", "HMGCoA reductase inhibitors lovastatin and simvastatin in the treatment of hypercholesterolemia after renal transplantation.", "The effect of pravastatin on acute rejection after kidney transplantation--a pilot study.", "Effect of lovastatin, an HMG CoA reductase inhibitor, on acute renal allograft rejection.", "Low-dose simvastatin is safe in hyperlipidaemic renal transplant patients.", "Efficacy and drug interactions of the new HMG-CoA reductase inhibitors cerivastatin and atorvastatin in CsA-treated renal transplant recipients.", "Pravastatin improves low-density lipoprotein oxidation in renal transplantation.", "Safety and efficacy of simvastatin for hyperlipidemia in renal transplant recipients: a double-blind, randomized, placebo-controlled study.", "Effect of fluvastatin on acute renal allograft rejection: a randomized multicenter trial.", "The effects of lipid-lowering agents on acute renal allograft rejection." ]

[ "nan", "Renal transplant recipients are at increased risk of premature cardiovascular disease. Although statins reduce cardiovascular risk in the general population, their efficacy and safety in renal transplant recipients have not been established. We investigated the effects of fluvastatin on cardiac and renal endpoints in this population.\n We did a multicentre, randomised, double-blind, placebo-controlled trial in 2102 renal transplant recipients with total cholesterol 4.0-9.0 mmol/L. We randomly assigned patients fluvastatin (n=1050) or placebo (n=1052) and follow up was for 5-6 years. The primary endpoint was the occurrence of a major adverse cardiac event, defined as cardiac death, non-fatal myocardial infarction (MI), or coronary intervention procedure. Secondary endpoints were individual cardiac events, combined cardiac death or non-fatal MI, cerebrovascular events, non-cardiovascular death, all-cause mortality, and graft loss or doubling of serum creatinine. Analysis was by intention to treat.\n After a mean follow-up of 5.1 years, fluvastatin lowered LDL cholesterol concentrations by 32%. Risk reduction with fluvastatin for the primary endpoint (risk ratio 0.83 [95% CI 0.64-1.06], p=0.139) was not significant, although there were fewer cardiac deaths or non-fatal MI (70 vs 104, 0.65 [0.48-0.88] p=0.005) in the fluvastatin group than in the placebo group. Coronary intervention procedures and other secondary endpoints did not differ significantly between groups.\n Although cardiac deaths and non-fatal MI seemed to be reduced, fluvastatin did not generally reduce rates of coronary intervention procedures or mortality. Overall effects of fluvastatin were similar to those of statins in other populations.", "In patients after renal transplantation functional arterial vessel wall properties are impaired. Whether 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have a sustained effect on endothelial function and arterial distensibility in patients after renal transplantation is not clear. The authors studied the effects of a long-term therapy with fluvastatin on large artery distensibility and flow-mediated vasodilation (FMD) in hypercholesterolemic patients after renal transplantation in a prospective, blinded, and randomized trial.\n Twenty-six patients who had undergone renal transplantation were assigned randomly to either fluvastatin, 40 mg/d (n = 13) or placebo (n = 13) and underwent follow-up for 3 years. At baseline and after 6, 12, and 36 months of treatment, carotid and brachial artery distensibility, endothelium-dependent FMD, and nitroglycerine-induced vasodilation (NMD) of the brachial artery were measured by a echo-tracking device.\n A significant decrease in total and low-density cholesterol was observed after 6, 12, and 36 months in patients treated with fluvastatin but not in the placebo group. FMD increased with fluvastatin from 4.6 +/- 2% to 12.4 +/- 2% after 12 months; this improvement was sustained with 13.4 +/- 3% after 36 months (P < 0.05). However, placebo did not alter FMD (P < 0.001 for trend difference between groups by analysis of covariance). Endothelium-independent NMD was similar in both groups at baseline and during therapy. Neither carotid nor brachial artery distensibility coefficients were altered by either treatment.\n HMG-CoA reductase inhibitor therapy over 3 years results in a significant and sustained improvement of endothelial function in hypercholesterolemic patients after renal transplantation. However, this is not accompanied by a beneficial effect on impaired large artery distensibility even after long-term therapy with fluvastatin.", "The high prevalence of hypercholesterolemia in kidney transplant recipients probably contributes to the high cardiovascular mortality in these patients. Except for diet, there is no generally recommended cholesterol-lowering treatment. We conducted a double-blind, randomized, placebo-controlled study with low-dose simvastatin in 40 ciclosporin (CS)-treated kidney transplant recipients during 16 weeks, focusing on side effects and dose finding. In the simvastatin group, the mean serum total and LDL cholesterol concentrations decreased by 23 and 33%, respectively, and the mean serum HDL cholesterol concentration increased by 12%, after 4 weeks of treatment with simvastatin 10 mg daily. Increasing the dose to 20 mg daily in a few patients only resulted in marginal further reductions of the serum cholesterol concentrations at the expense of doubling the plasma simvastatin 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity concentrations. The differences between the changes in the serum cholesterol concentrations in the simvastatin group and the negligible changes in the placebo group were statistically significant. There was no case of proximal myopathy and the serum creatine kinase concentrations did not differ between treatment groups. In conclusion, low-dose simvastatin appears to be a well tolerated and efficacious cholesterol-lowering treatment in CS-treated kidney transplant recipients. Simvastatin 10 mg daily seems to be the most suitable dose for the majority of these patients.", "Patients with chronic kidney disease are at increased risk for cardiovascular disease, but the efficacy and safety of simvastatin and aspirin are unknown in this patient group.\n Patients were randomly assigned in a 2 x 2 factorial design to the administration of: (1) 20 mg of simvastatin daily versus matching placebo, and (2) 100 mg of modified-release aspirin daily versus matching placebo.\n Overall, 448 patients with chronic kidney disease were randomly assigned (242 predialysis patients with a creatinine level > or = 1.7 mg/dL [> or =150 micromol/L], 73 patients on dialysis therapy, and 133 patients with a functioning transplant). Compliance with study treatments was 80% at 12 months. Allocation to treatment with 100 mg of aspirin daily was not associated with an excess of major bleeds (aspirin, 4 of 225 patients [2%] versus placebo, 6 of 223 patients [3%]; P = not significant [NS]), although there was a 3-fold excess of minor bleeds (34 of 225 [15%] versus 12 of 223 patients [5%]; P = 0.001). Among those with predialysis renal failure or a functioning transplant at baseline, aspirin did not increase the number of patients who progressed to dialysis therapy (7 of 187 [4%] versus 6 of 188 patients [3%]; P = NS) or experienced a greater than 20% increase in creatinine level (63 of 187 patients [34%] versus 56 of 188 patients [30%]; P = NS). After 12 months of follow-up, allocation to 20 mg of simvastatin daily reduced nonfasting total cholesterol levels by 18% (simvastatin, 163 mg/dL [4.22 mmol/L] versus placebo, 196 mg/dL [5.08 mmol/L]; P < 0.0001), directly measured low-density lipoprotein cholesterol levels by 24% (89 mg/dL [2.31 mmol/L] versus 114 mg/dL [2.96 mmol/L]; P < 0.0001), and triglyceride levels by 13% (166 mg/dL [1.87 mmol/L] versus 186 mg/dL [2.10 mmol/L]; P < 0.01), but there was no significant effect on high-density lipoprotein cholesterol levels (2% increase; P = NS). Allocation to simvastatin therapy was not associated with excess risk for abnormal liver function test results or elevated creatine kinase levels.\n During a 1-year treatment period, simvastatin, 20 mg/d, produced a sustained reduction of approximately one quarter in low-density lipoprotein cholesterol levels, with no evidence of toxicity, and aspirin, 100 mg/d, did not substantially increase the risk for a major bleeding episode. Much larger trials are now needed to assess whether these treatments can prevent vascular events.", "With current techniques, renal failure patients are now able to regain near-normal health following renal transplantation. However, the development of premature cardiovascular disease is a major problem. Dyslipidaemia may be an important contributor to this. The use of lipid lowering agents in renal allograft recipients has been limited by potential interaction of these agents with the now widely used immunosuppressive agent, cyclosporine.\n This study was designed to investigate efficacy and safety of simvastatin in subjects taking either cyclosporine or azothioprine post renal transplantation.\n Fifty-one subjects (32 females, 19 males -- mean age 51 +/- 12.5 yr) who were at least 1 yr post transplant, had creatinine < or = 2.5 mmol/L and a total cholesterol > or = 6 mmol/L were enrolled in a prospective, double-blind, placebo-controlled study. After an initial 10-wk dietary period, the last 4 wk on placebo, subjects were randomised to receive either 5 mg simvastatin/d for 6 wk followed by 10 mg simvastatin/d for 6 wk, or matching placebo. After this 12-wk double-blind phase, there was an open-label phase when all subjects were treated with 10 mg simvastatin/d for a period of 36 wk.\n Compared to placebo, 5 mg simvastatin/d significantly decreased total cholesterol by 20% (p < 0.01), low-density lipoprotein cholesterol (LDL cholesterol) by 29% (p < 0.01), and Apolipoprotein B (ApoB) by 26% (p < 0.01). Increasing simvastatin to 10 mg/d did not lead to further significant changes. But high-density lipoprotein cholesterol (HDL cholesterol) increased by 9% (p < 0.01) and Apolipoprotein A1 (ApoA1) by 7% (p < 0.01) only on 10 mg simvastatin/d. During the open-label phase, subjects previously randomised to placebo achieved similar significant changes to their lipoprotein profile. The benefits achieved from simvastatin were maintained to the end of the study. There were three withdrawals from the study, all from the simvastatin/ cyclosporine group. Two subjects had musculoskeletal pain and 1 had abdominal pain. Minor adverse events were similar in both the simvastatin- and placebo-treated groups.\n Low-dose simvastatin is an effective and well-tolerated agent in the treatment of dyslipidaemia in renal allograft recipients.", "nan", "Hyperlipidemia is an important complication of kidney transplantation affecting up to 74% of recipients. HMG-CoA reductase inhibitors are reported to provide safe and effective treatment for this problem. A recent study suggests that pravastatin, an HMG-CoA reductase inhibitor, also decreases the incidence of both clinically severe acute rejection episodes and natural killer cell cytotoxicity after orthotopic heart transplantation. We have performed a prospective randomized pilot study of the effect of pravastatin on these same parameters after cadaveric kidney transplantation. Graft recipients were randomized to receive pravastatin after transplantation or no pravastatin (24 patients in each group) in addition to routine cyclosporine and prednisone immunosuppression. Lipid levels, acute rejection episodes and serial natural killer cell cytotoxicities were followed for 4 months after the transplant. At the end of the study period, pravastatin had successfully controlled mean total cholesterol levels (202.6 +/- 9.3 vs. 236.5 +/- 11.9 mg/dl, P < 0.02), LDL levels (107.9 +/- 6.6 vs.149.6 +/- 10.7 mg/dl, P < 0.002), and triglyceride levels (118.8 +/- 14.2 vs. 157.2 +/- 13.8 mg/dl, P < 0.05). In addition, the pravastatin-treated group experienced a reduction in the incidence of biopsy-proven acute rejection episodes (25% vs. 58%, P = 0.01), the incidence of multiple rejections episodes (P < 0.05), and the use of both pulse methylprednisolone (P = 0.01) and OKT3 (P = 0.02). Mean natural killer cell cytotoxicity was similarly reduced (11.3 +/- 1.6 vs. 20.0 +/- 2.0% lysis of K562 target cells, P < 0.002). These data suggest that pravastatin exerts an additional immunosuppressive effect in kidney transplant recipients treated with cyclosporine-based immunosuppression.", "3-Hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitors are established anti-lipidemic agents. They also exert immunomodulatory effects. Two recent reports suggest that pravastatin may be useful in decreasing the incidence and severity of acute rejections (ARs) in heart and kidney transplant recipients. We undertook this prospective, randomized, placebo-controlled, double blind trial to investigate the effect of lovastatin on acute renal allograft rejection. Sixty-five consecutive, one-haplotype-matched, living related first renal transplant recipients were randomized to receive either lovastatin 20 mg/d or placebo for 3 months, in addition to cyclosporine, azathioprine, and steroids. Lipid levels, AR episodes, and liver and muscle enzymes were followed for 3 months post-transplant. At the end of the study period, lovastatin had successfully controlled lipid levels. However, there was no effect on AR episodes (15.15% in the treatment group vs. 18.75% in the placebo group).", "Hyperlipidaemia is common after renal transplantation, and because of its association with atherosclerosis, interest has increased in the use of lipid-lowering drugs in transplant patients. Dietary approaches have not been consistently successful, and multiple pharmacotherapy and drug interactions have led to difficulties in establishing lipid-lowering drug regimes. The statins reduce plasma cholesterol by inhibiting the rate-limiting step in cholesterol synthesis, and although some side-effects have been reported in their use after transplantation, the efficacy and safety of low doses has not been formally established. A randomized single-blind placebo crossover study designed to determine the safety and effectiveness of simvastatin in a single daily 5-mg evening dose was therefore conducted in 26 stable renal transplant patients, 14 of whom were receiving cyclosporin A. The results demonstrated no difference between total cholesterol levels in the baseline simvastatin and placebo periods: 7.97 +/- 1.2 and 7.59 +/- 1.5 mmol/l respectively. After 8 weeks of simvastatin, the total cholesterol declined significantly to 6.72 +/- 0.87 mmol/l (P < 0.001). A significant difference was found when the placebo and simvastatin cholesterol levels were compared at 4 and 8 weeks (P < 0.01). LDL cholesterol decreased from 4.74 +/- 0.87 to 3.78 +/- 0.78 mmol/l after 8 weeks on simvastatin (P < 0.001), and apo B fell from 142 +/- 31 to 112 +/- 22 mg/dl (P < 0.001). The difference in LDL cholesterol and apo B after 8 weeks of simvastatin when compared with the corresponding values on placebo was also significant (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "Hyperlipidaemia is an important risk factor for cardiovascular disease in renal transplant recipients. The aim of this study was to test the efficacy and possible drug-drug interactions of the new HMG-CoA reductase inhibitors (statins) atorvastatin and cerivastatin in cyclosporin A (CsA)-treated renal transplant patients. Subjects and methods. Thirty patients with stable graft function and LDL cholesterol of 130 mg/dl were randomly assigned to active treatment groups (10 mg atorvastatin or 0.2 mg cerivastatin), or a control group. CsA blood trough levels were controlled on a weekly basis and adapted if they changed more than 25% from baseline values (100-150 ng/ml). Lipid levels and routine laboratory parameters before and after a treatment period of 3 months were compared.\n In the group treated with cerivastatin no significant changes in CsA blood trough levels occurred (CsA 116+/-21 ng/ml vs 110+/-20 ng/ml). In contrast, in the group treated with atorvastatin, four of 10 patients had a rise in CsA blood trough levels of more than 25% within 7-14 days of starting therapy. In the remaining patients no significant changes in CsA drug levels occurred. After therapy with atorvastatin or cerivastatin, total cholesterol, LDL cholesterol, and triglycerides were significantly lower compared with baseline conditions. No changes of CsA or lipoprotein levels were present in the control group.\n In our study population both statins were very effective in lowering elevated LDL cholesterol levels. Cerivastatin did not influence CsA blood trough levels, whereas atorvastatin increased CsA levels in four of 10 patients. Further research in a larger study is necessary in order to confirm these results and to investigate the possible reasons for this drug interaction.", "nan", "nan", "Statin therapy has been reported to reduce the acute rejection rate following renal transplantation in a pilot study. The present study is the first randomized, double-blind and adequately powered study to examine the effect of statins on acute rejection of renal allografts.\n A total of 364 patients were randomly assigned to receive either fluvastatin 40 mg or placebo in combination with conventional cyclosporine-based immunosuppressive therapy. The primary end point was treated first acute rejection. Secondary end points included biopsy-proven rejection, histological severity of rejection, occurrence of steroid-resistant rejection, and serum creatinine at three months following transplantation.\n Fluvastatin was well tolerated; no patients developed myositis or rhabdomyolysis. There was no difference in the acute rejection rate [86 (47.3%) fluvastatin vs. 87 (47.8%) placebo] and no significant difference in the severity of rejection, steroid resistant rejection or mean serum creatinine at three months (160 micromol/L vs. 160 micromol/L). Total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglyceride levels increased following renal transplantation. With the exception of the increase in HDL-C, which was augmented, the increases in lipid parameters were significantly reduced by fluvastatin (total cholesterol +17.5% vs. 35.7%; LDL-C +6.3% vs. 46.7%; HDL-C +43.3% vs. 38.1%; triglyceride +52.2% vs 77.6%).\n Contrary to the reported effects of statins, fluvastatin had no effect on the incidence or severity of acute rejection following renal transplantation. There were no increases in adverse events. A significant and potentially beneficial alteration in the lipid profile was observed in the early post transplant period. We conclude that fluvastatin may be used safely to correct dyslipidemia in patients with end-stage renal failure through the peri-transplant period.", "Preliminary results from clinical trials suggest that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors may help prevent acute renal allograft rejection. However, the mechanism for this putative effect of 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors, and whether it is independent of lipid-lowering per SE are unknown.\n Immediately after renal transplantation we randomly allocated (proportioned 2:1:2) patients to: 1) simvastatin (10 mg/day, n=53), 2) simvastatin placebo plus gemfibrozil (dose adjusted for renal function, n=36), and 3) simvastatin placebo (n=52).\n Simvastatin, but not gemfibrozil, reduced total and low density lipoprotein cholesterol during the first 90 days posttransplant. There were no major adverse effects of therapy. However, there were no effects of treatment on acute rejection. Indeed, survival free of acute rejection at 90 days was 72% in the simvastatin group, 72% in the gemfibrozil group, and 77% in the placebo control group (P=0.771). A post hoc power analysis suggested that there was only a 7.5% chance that a true effect of simvastatin on acute rejection (versus placebo) was not detected, and a 2.5% chance that an effect of gemfibrozil on acute rejection (versus placebo) was not detected in this study.\n Lipid-lowering agents may not reduce the incidence of acute renal allograft rejection. However, additional studies are needed to confirm this observation. In the mean time, many if not most renal transplant recipients should be treated with HMG-CoA reductase inhibitors starting early posttransplant to prevent cardiovascular disease complications. The results of this study suggest that starting lipid-lowering therapy immediately after renal transplantation is both safe and effective in lowering total and low density lipoprotein cholesterol." ]

[ "9321530", "11677200", "11313302", "9048788" ]

[ "A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group.", "Etanercept for active Crohn's disease: a randomized, double-blind, placebo-controlled trial.", "An engineered human antibody to TNF (CDP571) for active Crohn's disease: a randomized double-blind placebo-controlled trial.", "Randomised controlled trial of CDP571 antibody to tumour necrosis factor-alpha in Crohn's disease." ]

[ "Studies in animals and an open-label trial have suggested a role for antibodies to tumor necrosis factor alpha, specifically chimeric monoclonal antibody cA2, in the treatment of Crohn's disease.\n We conducted a 12-week multicenter, double-blind, placebo-controlled trial of cA2 in 108 patients with moderate-to-severe Crohn's disease that was resistant to treatment. All had scores on the Crohn's Disease Activity Index between 220 and 400 (scores can range from 0 to about 600, with higher scores indicating more severe illness). Patients were randomly assigned to receive a single two-hour intravenous infusion of either placebo or cA2 in a dose of 5 mg per kilogram of body weight, 10 mg per kilogram, or 20 mg per kilogram. Clinical response, the primary end point, was defined as a reduction of 70 or more points in the score on the Crohn's Disease Activity Index at four weeks that was not accompanied by a change in any concomitant medications.\n At four weeks, 81 percent of the patients given 5 mg of cA2 per kilogram (22 of 27 patients), 50 percent of those given 10 mg of cA2 per kilogram (14 of 28), and 64 percent of those given 20 mg of cA2 per kilogram (18 of 28) had had a clinical response, as compared with 17 percent of patients in the placebo group (4 of 24) (p<0.001 for the comparison of the cA2 group as a whole with placebo). Thirty-three percent of the patients given cA2 went into remission (defined as a score below 150 on the Crohn's Disease Activity Index), as compared with 4 percent of the patients given placebo (P=0.005). At 12 weeks, 41 percent of the cA2-treated patients (34 of 83) had had a clinical response, as compared with 12 percent of the patients in the placebo group (3 of 25) (P=0.008). The rates of adverse effects were similar in the groups.\n A single infusion of cA2 was an effective short-term treatment in many patients with moderate-to-severe, treatment-resistant Crohn's disease.", "We evaluated etanercept, a human soluble tumor necrosis factor receptor: Fc fusion protein, for the treatment of active Crohn's disease.\n Forty-three patients with moderate to severe Crohn's disease were enrolled in an 8-week placebo-controlled trial. Patients were randomized to subcutaneous etanercept 25 mg or placebo twice weekly. The primary outcome measure was clinical response at week 4, defined as a decrease in the baseline Crohn's Disease Activity Index score > or =70 points or a Crohn's Disease Activity Index score <150 points.\n At week 4, 39% of etanercept-treated patients had clinical response as compared with 45% of placebo-treated patients (P = 0.763). The frequency of common adverse events including headache, new injection site reaction, asthenia, abdominal pain, Crohn's disease-related anemia, and skin disorders was similar in both groups. Likewise, the frequency of severe or serious adverse events was similar in both groups.\n Subcutaneous etanercept at a dose of 25 mg twice weekly is safe, but not effective, for the treatment of patients with moderate to severe Crohn's disease. The dose of etanercept administered in this study is that approved for rheumatoid arthritis. Higher doses or more frequent dosing may be required to attain a response in patients with active Crohn's disease.", "We evaluated CDP571, a humanized antibody to tumor necrosis factor, for the treatment of active Crohn's disease.\n One hundred sixty-nine patients with moderate-to-severe Crohn's disease were enrolled in a 24-week placebo-controlled trial. Patients were initially randomized to a single dose of 10 or 20 mg/kg CDP571 or placebo to assess dose response. Patients were then retreated with 10 mg/kg CDP571 or placebo every 8 or 12 weeks to assess subsequent dosing intervals. The primary endpoint was clinical response at week 2, defined as a decrease in the Crohn's Disease Activity Index score > or = 70 points.\n At week 2, clinical response occurred in 45% of CDP571-treated patients compared with 27% of patients in the placebo group (P = 0.023). Patients appeared to benefit from retreatment with CDP571 over 24 weeks, but not all of the results for secondary endpoints were statistically significant. The frequency of severe or serious adverse events was similar among all groups.\n CDP571 at an initial dose of 10 or 20 mg/kg is safe and effective for treatment of patients with moderate-to-severe Crohn's disease. Preliminary evidence suggests that retreatment with 10 mg/kg CDP571 at dose intervals of 8 or 12 weeks may also be beneficial, but additional studies are needed.", "Tumour necrosis factor-alpha (TNF alpha) is thought to have a central role in the pathogenesis of Crohn's disease. We tested the hypothesis that CDP571, a genetically engineered human antibody to TNF alpha, is effective in modifying disease activity in patients with moderately active Crohn's disease.\n In this double-blind, placebo-controlled study, 31 patients were randomly assigned to CDP571 (n = 21) or placebo (n = 10). The primary endpoint was change in Crohn's disease activity index 2 weeks after a single infusion of CDP571 (5 mg/kg), or human albumin as placebo. One patient who attended no follow-up assessments was excluded from the analyses (CDP571 group).\n The median Crohn's disease activity index fell from 263 (IQR 186.5-323.5) at baseline to 167 (137.5-294.0) at 2 weeks in the CDP571-treated patients (p = 0.0003); the change in the placebo group (253 [240-334] to 247 [183-256]) was not significant. In the treated group, there were also significant differences between baseline and 2 weeks in Harvey-Bradshaw score (p = 0.0005), key symptom score (p = 0.049), alpha 1-glycoprotein concentration (p = 0.012), and erythrocyte sedimentation rate (p = 0.01); concentrations of C-reactive protein fell, but not significantly (p = 0.067). Six patients achieved remission (Crohn's disease activity index < or = 150) and three others had activity indices of 156 or lower. There were no significant changes in the placebo group.\n A single 5 mg/kg infusion of CDP571 reduced disease activity in Crohn's disease at 2 weeks. These data suggest that antibody neutralisation of TNF alpha is a potentially effective strategy in the management of Crohn's disease. The use of CDP571 in Crohn's disease requires further study." ]

[ "3308737", "1375082", "7631676", "7282298" ]

[ "Calcium and magnesium status in pregnant women. A comparison between treatment with calcium and vitamin C in pregnant women with leg cramps.", "Effects of a multivitamin mineral supplement on zinc and copper status during pregnancy.", "The effect of oral magnesium substitution on pregnancy-induced leg cramps.", "Calcium treatment of leg cramps in pregnancy. Effect on clinical symptoms and total serum and ionized serum calcium concentrations." ]

[ "60 pregnant women underwent a double blind trial with calcium or ascorbic acid (1 g twice daily) as treatment for leg cramps. There was no significant difference between the two treatment groups with respect to clinical improvement. In 14 out of 60 patients the symptoms were totally abolished and in another 27 patients the symptoms were significantly decreased by the treatment (irrespective of drug used). In 17 patients the symptoms were unaffected while only two patients experienced an increase in frequency of their leg cramps during therapy. Serum total and ionized calcium concentrations, serum total magnesium and albumin concentrations were determined and were not significantly changed throughout therapy in any of the groups. No biochemical differences were found between the different treatment regimens or between those patients relieved or not relieved of their symptoms. Serum magnesium concentrations were at or just below the lower normal limit (for non pregnant women) in treated women and pregnant controls.", "The effect of a multivitamin-mineral supplement was investigated during pregnancy according to a double-blind protocol by determining zinc and copper in maternal plasma, mononuclear and polynuclear zinc and copper at the third, sixth, eighth, and ninth months of gestation. The subjects were supplemented from the first trimester until delivery. A significant decrease was observed in plasma zinc that varied from 11.5 mumol/L to 10.8 mumol/L in the supplemented group (n = 29) and from 11 mumol/L to 10 mumol/L in the placebo group (n = 33) at 3 and 9 mo of gestation, respectively. In contrast, plasma copper levels increased in a way depending upon the stage of gestation in both groups: from 24.7 to 28.2 mumol/L in the treated group and from 24.9 to 30.9 mumol/L in the placebo group at 3 and 9 mo of gestation, respectively, but the difference was only significant in the placebo group. No difference between groups was observed in mononuclear and polynuclear zinc or copper levels. These trace elements were also determined in cord blood at delivery. There were no statistically significant differences in zinc and copper concentration found in placebo group and supplemented group. Finally, the beneficial effect of supplementation on muscular cramps and appearance of vergetures was noted.", "Our purpose was to determine whether women with pregnancy-related leg cramps would benefit from oral magnesium supplementation.\n Seventy-three women with pregnancy-related leg cramps were interviewed about their symptoms in a prospective, double-blind, randomized trial. Initial serum magnesium levels and diurnal magnesium excretion was determined in 50% of the patients. Oral magnesium or placebo was given for 3 weeks, after which new interviews and laboratory analyses were performed.\n Serum magnesium levels in these patients were at or below the lower reference limit, as is also often the case in healthy pregnant patients. Oral magnesium substitution decreased leg cramp distress (p < 0.05 compared with the placebo group, p < 0.001 compared with initial complaints), but did not significantly increase serum magnesium levels, excess magnesium being excreted as measured by an increase in urinary magnesium levels (p < 0.002).\n Oral magnesium supplementation seems to be a valuable therapeutic tool in the treatment of pregnancy-related leg cramps.", "Up to 30 per cent of pregnant women suffer from leg cramps. The cause of these cramps is not known, but changes in calcium concentration have been suggested. Therefore 42 pregnant women with leg cramps were studied. No differences in total serum or ionized serum calcium concentrations were found as compared with a control group of pregnant women without leg cramps. Twenty-one patients were treated with 1 g calcium orally twice daily for 2 weeks and in this group good clinical improvement was achieved (p less than 0.001). The treatment increased the total serum calcium concentration from 2.25 mmol/l to 2.30 mmol/l but did not alter the ionized serum calcium concentration. Twenty-one untreated patients had the same frequency of cramps and showed no change in serum calcium concentrations throughout the investigation." ]

[ "2494620", "3520319" ]

[ "Prevention of neonatal group B streptococcal disease: intrapartum detection and chemoprophylaxis of heavily colonized parturients.", "Prevention of early-onset neonatal group B streptococcal disease with selective intrapartum chemoprophylaxis." ]

[ "Parturients with heavy vaginal colonization of group B streptococci were selected randomly to receive either penicillin or no antibiotic. A simple and fast latex agglutination test, applied in 8977 consecutive parturients, detected 412 women with heavy colonization with group B streptococcus, 199 of whom were eligible for the study. The offspring of penicillin-treated women had a lower incidence of early-onset group B streptococcal disease (1.1%; 95% confidence interval 0-3.4%) than the controls (9.0%; 95% confidence interval 3.6--14.4%) (P less than .01). Among the offspring of streptolatex-negative parturients, the incidence of streptococcal disease was very low (0.07%). Thus, antibiotic prophylaxis of latex agglutination test-positive parturients would reduce the total incidence of group B streptococcal disease in the newborn by 25-80%.", "Most cases of neonatal group B streptococcal disease with early onset have an intrapartum pathogenesis. Attack rates are increased substantially in infants born to mothers with prenatal group B streptococcal colonization and various perinatal risk factors (premature labor, prolonged membrane rupture, or intrapartum fever). In a randomized controlled trial, we studied the effect of selective intrapartum prophylaxis with ampicillin in 160 such high-risk women. In infants born to mothers who received intravenous ampicillin during labor, as compared with controls who received no treatment, neonatal colonization with group B streptococci was present in 8 of 85 (9 percent) versus 40 of 79 (51 percent; P less than 0.001), colonization at multiple (greater than or equal to 3) sites was observed in 3 of 85 (4 percent) versus 24 of 79 (30 percent; P less than 0.001), and bacteremia occurred in none of 85 versus 5 of 79 (6 percent; P = 0.024). The side effects of ampicillin were limited to a single episode of urticaria in a mother who had no history of penicillin allergy. We conclude that intrapartum ampicillin prophylaxis in women with positive prenatal cultures for group B streptococci who have certain perinatal risk factors can prevent early-onset neonatal group B streptococcal disease." ]

[ "1699337", "10408487", "9068812", "9068813", "9692130", "10753731", "12383985" ]

[ "An investigation of patients with pulmonary tuberculosis in Kuwait in preparation for studies of immunotherapy with Mycobacterium vaccae.", "Immunotherapy with Mycobacterium vaccae in patients with newly diagnosed pulmonary tuberculosis: a randomised controlled trial. Durban Immunotherapy Trial Group.", "Immunotherapy with Mycobacterium vaccae in the treatment of tuberculosis in Romania. 1. Newly-diagnosed pulmonary disease.", "Immunotherapy with Mycobacterium vaccae in the treatment of tuberculosis in Romania. 2. Chronic or relapsed disease.", "Mycobacterium vaccae: a study of safety and outcome measures.", "Randomized controlled trial of Mycobacterium vaccae immunotherapy in non-human immunodeficiency virus-infected ugandan adults with newly diagnosed pulmonary tuberculosis. The Uganda-Case Western Reserve University Research Collaboration.", "Mycobacterium vaccae (SRL172) immunotherapy as an adjunct to standard antituberculosis treatment in HIV-infected adults with pulmonary tuberculosis: a randomised placebo-controlled trial." ]

[ "Sixty-five patients, many of them immigrant to Kuwait, with bacteriologically proven, adult type, pulmonary tuberculosis were studied by many parameters over the 4 months following diagnosis. Twelve were infected with tubercle bacilli resistant to at least one anti-tuberculosis drug. Preliminary evidence suggested that this was frequently primary resistance in patients infected in their countries of origin. The Kuwaiti environment results in very high skin test and lymphocyte proliferative responses (LTT) to shared and species specific antigens of mycobacteria in healthy persons. In comparison, patients with tuberculosis lacked cellular responses to group i and group ii antigens, but had increased IgG and IgA binding to mycobacterial antigens in general. LTT responses to added interleukin 2, and production of alpha interferon, were normal in our patients, but induction of gamma interferon in response to phytohaemagglutinin was reduced initially, rising towards normal during treatment. Biochemical and haematological abnormalities present at the time of diagnosis rapidly corrected. The disease differed from that reported in most previous studies in that fever was uncommon, the disease was never fatal, and most tuberculin tests were not necrotising. This implied that a detrimental immunopathological component is less pronounced in those exposed to the Kuwaiti environment, and a hypothesis is put forward to explain this.", "Mycobacterium vaccae, an environmental saprophyte, has immunogenic properties that enhance the host immune response. Immunotherapy with M. vaccae has been suggested to shorten short-course antituberculosis chemotherapy. We tested the hypothesis that the addition of M. vaccae to standard short-course antituberculosis chemotherapy would decrease the time to achieve a negative sputum culture.\n Patients with newly diagnosed tuberculosis were randomly assigned an injection of saline (placebo) or M. vaccae on day 8. All patients received antituberculosis chemotherapy with rifampicin, isoniazid, pyrazinamide, and ethambutol. Sputum samples were checked by microscopy and culture every week for the first 8 weeks and monthly until the end of chemotherapy at 6 months. The primary outcome was the time to a negative sputum culture in the first 8 weeks. Intention-to-treat analysis was used and time to sputum clearance was assessed by log-rank test and Cox's proportional-hazards regression.\n 172 patients received M. vaccae and 175 patients received placebo. At 8 weeks, 70 patients in the M. vaccae group and 65 patients in the placebo group had a negative culture; there was no difference between groups in the time to a negative culture (p=0.83). There was no interaction between HIV status and treatment.\n M. vaccae immunotherapy has no benefit when added to standard antituberculosis chemotherapy.", "In this study, 206 previously untreated patients with sputum culture positive pulmonary tuberculosis were randomized to receive an injection of killed Mycobacterium vaccae as immunotherapy, or of saline as placebo, after 1 month of a 6-month chemotherapeutic regime. Not surprisingly in a disease for which there is good chemotherapy, the difference in numbers which were culture negative at the end of treatment was small, and the final outcome at the latest post-treatment follow-up did not reach statistical significance between the two arms of the study. Nonetheless, those receiving immunotherapy showed better progression in every parameter measured, suggesting faster and more complete cure. Whereas seven of 97 patients receiving immunotherapy required a course of re-treatment and five still had active disease after a mean follow-up of 2 yr, 13 of 109 placebo recipients required re-treatment and nine still had active disease at the end of the study. Only one patient receiving M. vaccae plus chemotherapy died of tuberculosis, compared with four of those receiving chemotherapy alone. A degree of drug resistance was shown by the bacilli cultured from 25 of 175 (14%) patients, and seven of them (4.0%) were multi-drug resistant. Fourteen patients received immunotherapy of whom 13 were cured, including all three of those showing multi-drug resistance. Of the 11 patients with drug resistance in the control group, eight were cured, and one patient with multi-drug-resistant disease died of tuberculosis during re-treatment.", "In this study of 102 patients with culture-positive chronic treatment failure or repeatedly relapsed pulmonary tuberculosis receiving chemotherapy, 56 received an injection of killed Mycobacterium vaccae as immunotherapy after 1 month of treatment. At the start of treatment, there was little difference between those receiving immunotherapy and the 46 patients in the control group receiving chemotherapy alone. Thereafter, the two groups diverged so that 1 yr later, 43 of 56 (77%) patients receiving M. vaccae had a successful outcome, in comparison with 24 of 46 (52%) patients receiving chemotherapy alone (P < 0.02). Successful results were obtained from patients infected with drug-resistant bacilli, 20 of 32 (63%) patients compared with 11 of 25 (44%) patients, respectively, as well as from fully drug-sensitive cases (23 of 24 compared with 12 of 21 patients; P = 0.004). At the final follow-up after 22 months, 13 of 56 patients receiving immunotherapy had an unfavourable outcome compared with 26 of 46 members of the control group (P = 0.0006). During the study, 16 patients died of tuberculosis (six after immunotherapy), and 12 were lost to follow-up. Not only was bacteriological success improved by immunotherapy, chest X-ray showed markedly better resolution of cavities and other radiological lesions, recovery of body weight was improved, and the mean erythrocyte sedimentation rate returned almost to normal (P < 0.001) in comparison with those receiving chemotherapy alone. These changes were seen even in those failing bacteriological cure, suggesting that the immunotherapy had been effective, but that bacilli were replicating in an extracellular situation, protecting them from its effects.", "nan", "Adjunctive immunotherapy with heat-killed Mycobacterium vaccae was studied in a randomized, placebo-controlled trial of 120 non-human immunodeficiency virus-infected adults with newly diagnosed pulmonary tuberculosis. Patients were randomized to a single dose of M. vaccae or placebo 1 week after beginning chemotherapy and were followed up for 1 year. M. vaccae was safe and well tolerated. The rate of sputum culture conversion after 1 month of tuberculosis treatment was 35% in the M. vaccae group and only 14% in the placebo group (P=.01) but was comparable at 2 months and thereafter. Patients receiving M. vaccae had greater improvement on chest radiography at 6 months (91% vs. 77% for placebo recipients; P=.04) and 12 months (94% vs. 80%; P=.04) after initiation of tuberculosis treatment. These data provide evidence of an early increase in sputum culture conversion and greater radiographic improvement among patients who received M. vaccae. Further studies are warranted.", "Mortality rates of HIV-infected patients treated for tuberculosis remain high. This study aimed to assess the effect on mortality of immunotherapy with single-dose SRL172 added to standard antituberculosis chemotherapy in such patients.\n The double-blind trial enrolled 1229 patients aged 18-60 years, who had never received antiretroviral treatment and who presented with newly diagnosed, sputum-smear-positive pulmonary tuberculosis to referral centres in Lusaka, Zambia, and Karonga, Malawi. Both HIV-positive and HIV-negative patients were enrolled, to avoid stigmatisation. Participants were randomly assigned a single injection of SRL172 or matching placebo within 2 weeks of starting 8 months of antituberculosis chemotherapy and followed up for at least 12 months. The primary endpoint was time to death in the HIV-infected population. Analyses were based on 760 HIV-positive patients after exclusion of 84 patients with errors in storage of the injection, no bacteriological confirmation, or no HIV result.\n Of 760 HIV-infected patients, 374 received SRL172 and 386 received placebo. SRL172 did not cause any serious adverse events. The follow-up rate was 88% at 12 months in both groups. Of the HIV-positive patients, 109 (19.5 per 100 person-years) of 372 assigned SRL172 and 107 (19.3 per 100 person-years) of 386 assigned placebo died. In the Cox's regression analysis, stratified by centre, the hazard ratio of deaths (SRL172/placebo) was 1.03 (95% CI 0.79-1.35). There was no evidence of benefit to the group assigned SRL172.\n Immunotherapy with single-dose SRL172 as an adjunct to standard antituberculosis treatment in HIV-positive adults with pulmonary tuberculosis had no significant effect on survival or bacteriological outcome, though the treatment was safe and well tolerated." ]

[ "18046062", "3897335", "20605648", "16996783", "11230889", "19386439", "15520052", "12040756" ]

[ "Does hyperbaric oxygen administration decrease side effect and improve quality of life after pelvic radiation?", "Prevention of osteoradionecrosis: a randomized prospective clinical trial of hyperbaric oxygen versus penicillin.", "Randomised phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema after radiotherapy for cancer.", "Rehabilitation of oral function in head and neck cancer patients after radiotherapy with implant-retained dentures: effects of hyperbaric oxygen therapy.", "Double-blind randomized phase II study of hyperbaric oxygen in patients with radiation-induced brachial plexopathy.", "Early hyperbaric oxygen therapy for reducing radiotherapy side effects: early results of a randomized trial in oropharyngeal and nasopharyngeal cancer.", "Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double-blind trial from the ORN96 study group.", "Hyperbaric oxygen therapy for cognitive disorders after irradiation of the brain." ]

[ "to evaluate the influence of HBOT to the side effect and quality of life after pelvic radiation.\n this is an open randomized, parallel, prospective study conducted in Department of Obstetrics and Gynecology, Oncology Division and Department of Radiotherapy. Endoscopy procedure was performed in Department of Internal Medicine and tissue biopsy in Department of Pathology Anatomy. The hyperbaric oxygen therapy (HBOT) was done in Dr. Mintohardjo, Navy Seal Hospital Jakarta. The side effect was measured using LENT SOMA scale ratio, the quality of life used the Karnofsky score. The difference of two mean was analyzed using student t test.\n of 32 patients undergoing HBOT and 33 patients as control, the ratio of ASE of control group was 44.1+/-28.2%, HBOT group was 0.7+/-30.1%; p<0.001; the LSE of control group was 33.6+/-57.6%, HBOT group was -19.6+/-69.4%; p=0.008. Quality of life of control group after intervention was 4.5+/-10.7%; HBOT group was 19.7+/-9.6%; p <0.001. After 6 months of intervention the quality of life was 2.5+/-16.1% in the control group, and HBOT group was 15.2+/-14.7%; p =0.007.\n the study showed that HBOT decreased acute and late side effect, also improved the quality of life of patients with proctitis radiation.", "A prospective randomized trial comparing hyperbaric oxygen and systemic antibiotics in the prevention of osteoradionecrosis was presented. The results indicated, in a high-risk population who required tooth removal in irradiated mandibles, that up-front hyperbaric oxygen produced an incidence of osteoradionecrosis of 5.4% as compared with the antibiotic group of 29.9% (P = .005). Hyperbaric oxygen should be considered a prophylactic measure when post-irradiation dental care involving trauma to tissue is necessary.", "A non-randomised phase II study suggested a therapeutic effect of hyperbaric oxygen (HBO) therapy on arm lymphoedema following adjuvant radiotherapy for early breast cancer, justifying further investigation in a randomised trial.\n Fifty-eight patients with ≥ 15% increase in arm volume after supraclavicular ± axillary radiotherapy (axillary surgery in 52/58 patients) were randomised in a 2:1 ratio to HBO (n=38) or to best standard care (n=20). The HBO group breathed 100% oxygen at 2.4 atmospheres absolute for 100 min on 30 occasions over 6 weeks. Primary endpoint was ipsilateral limb volume expressed as a percentage of contralateral limb volume. Secondary endpoints included fractional removal rate of radioisotopic tracer from the arm, extracellular water content, patient self-assessments and UK SF-36 Health Survey Questionnaire.\n Of 53/58 (91.4%) patients with baseline assessments, 46 had 12-month assessments (86.8%). Median volume of ipsilateral limb (relative to contralateral) at baseline was 133.5% (IQR 126.0-152.3%) in the control group, and 135.5% (IQR 126.5-146.0%) in the treatment group. Twelve months after baseline the median (IQR) volume of the ipsilateral limb was 131.2% (IQR 122.7-151.5%) in the control group and 133.5% (IQR 122.3-144.9%) in the treatment group. Results for the secondary endpoints were similar between randomised groups.\n No evidence has been found of a beneficial effect of HBO in the treatment of arm lymphoedema following primary surgery and adjuvant radiotherapy for early breast cancer.\n Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.", "Surgical treatment of malignancies in the oral cavity and subsequent radiotherapy often result in an anatomic and physiological oral condition unfavorable for prosthodontic rehabilitation. The objective of this prospective study was to assess the effect of hyperbaric oxygen therapy on treatment outcome (condition of peri-implant tissues, implant survival, oral functioning and quality of life) of prosthodontic rehabilitation with implant-retained lower dentures in radiated head and neck cancer patients 6 weeks and 1 year after placing the new dentures. The treatment outcome was assessed in a group of 26 head neck cancer patients who were subjected to radiotherapy after tumour surgery. Standardized questionnaires were completed and clinical and radiographic assessments were performed. After randomization, endosseous Brånemark implants were placed in the anterior part of the mandible either under antibiotic prophylaxis (13 patients) or under antibiotic prophylaxis combined with pre and postsurgery hyperbaric oxygen (HBO) treatment (13 patients). In the HBO and non-HBO group eight implants (implant survival 85.2%) and three implants (implant survival 93.9%) were lost, respectively. Peri-implant tissues had a healthy appearance in both groups. Osteoradionecrosis developed in one patient in the HBO group. All patients functioned well with their implant-retained lower denture. The quality of life related to oral functioning and denture satisfaction were improved to a comparable extent in the HBO and non-HBO group. Implant-retained lower dentures can improve the quality of life related to oral functioning and denture satisfaction in head and neck cancer patients. Adjuvant hyperbaric oxygen therapy could not be shown to enhance implant survival in radiated mandibular jaw bone.", "Radiation-induced brachial plexopathy (RIBP) is an untreatable complication of curative radiotherapy for early breast cancer, characterized by chronic neuropathic pain and limb paralysis. Hyperbaric oxygen (HBO2) therapy is known to promote healing of tissue rendered ischaemic by radiotherapy, but is untested in RIBP.\n Thirty four eligible research volunteers suffering from RIBP were randomized to HBO2 or control group. The HBO2 group breathed 100% oxygen for 100 min in a multiplace hyperbaric chamber on 30 occasions over a period of 6 weeks. The control group accompanied the HBO2 group and breathed a gas mixture equivalent to breathing 100% oxygen at surface pressure. All volunteers and investigators, except the operators of the hyperbaric chamber and the trial statistician, were blind to treatment assignments. The warm sensory threshold, which measures the function of small sensory fibres, was selected as the primary endpoint.\n Pre-treatment neurophysiological tests were grossly abnormal in the affected hand compared to the unaffected hand in both HBO2 and control groups, as expected, but no statistically significant differences were noted in either group at any time up to 12 months post-treatment. However, normalization of the warm sensory threshold in two of the HBO2 group was reliably recorded. Two cases with marked chronic arm lymphoedema reported major and persistent improvements in arm volume for at least 12 months after treatment with HBO2. IINTERPRETATION: There is no reliable evidence to support the hypothesis that HBO2 therapy slows or reverses RIBP in a substantial proportion of affected individuals, although improvements in warm sensory threshold offer some suggestion of therapeutic effect. Improvement in long-standing arm lymphoedema was not anticipated, and justifies further investigation.", "Comparison of quality of life (QoL) and side effects in a randomized trial for early hyperbaric oxygen therapy (HBOT) after radiotherapy (RT).\n From 2006, 19 patients with tumor originating from the tonsillar fossa and/or soft palate (15), base of tongue (1), and nasopharynx (3) were randomized to receive HBOT or not. HBOT consisted of 30 sessions at 2.5 ATA (15 msw) with oxygen breathing for 90 min daily, 5 days per week, applied shortly after the RT treatment was completed. As of 2005, all patients received validated questionnaires (i.e., the European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30, EORTC QLQ Head and Neck Cancer Module (H&N35), Performance Status Scale): before treatment; at the start of RT treatment; after 46 Gy; at the end of RT treatment; and 2, 4, and 6 weeks and 3, 6, 12, and 18 months after follow-up.\n On all QoL items, better scores were obtained in patients treated with hyperbaric oxygen. The difference between HBOT vs. non-HBOT was significant for all parameters: EORTC H&N35 Swallowing (p = 0.011), EORTC H&N35 Dry Mouth (p = 0.009), EORTC H&N35, Sticky Saliva (p = 0.01), PSS Eating in Public (p = 0.027), and Pain in Mouth (visual analogue scale; p < 0.0001).\n Patients randomized for receiving hyperbaric oxygen after the RT had better QoL scores for swallowing, sticky saliva, xerostomia, and pain in mouth.", "To determine the efficacy and safety of hyperbaric oxygen therapy (HBO) for overt mandibular osteoradionecrosis.\n This prospective, multicenter, randomized, double-blind, placebo-controlled trial was conducted at 12 university hospitals. Ambulatory adults with overt osteoradionecrosis of the mandible were assigned to receive 30 HBO exposures preoperatively at 2.4 absolute atmosphere for 90 minutes or a placebo, and 10 additional HBO dives postoperatively or a placebo. The main outcome measure was 1-year recovery rate from osteoradionecrosis. Secondary end points included time to treatment failure, time to pain relief, 1-year mortality rate, and treatment safety.\n At the time of the second interim analysis, based on the triangular test, the study was stopped for potentially worse outcomes in the HBO arm. A total of 68 patients were enrolled and analyzed. At 1 year, six (19%) of 31 patients had recovered in the HBO arm and 12 (32%) of 37 in the placebo arm (relative risk = 0.60; 95% CI, 0.25 to 1.41; P = .23). Time to treatment failure (hazard ratio = 1.33; 95% CI, 0.68 to 2.60; P = .41) and time to pain relief (hazard ratio = 1.00; 95% CI, 0.52 to 1.89; P = .99) were similar between the two treatment arms.\n Patients with overt mandibular osteoradionecrosis did not benefit from hyperbaric oxygenation.", "Analysis of the feasibility and effect of hyperbaric oxygen treatment (HBO) on cognitive functioning in patients with cognitive disorders after irradiation of the brain.\n Seven patients with cognitive impairment after brain irradiation, with an interval of at least 1.5 years after treatment, were treated with 30 sessions of HBO in a phase I-II study. A comprehensive neuropsychological test battery was performed before treatment, at 3 and 6 months thereafter. Patients were randomized into an immediate treatment group and a delayed treatment group. The delayed group had a second neuropsychological test at 3 months without treatment in that period and started HBO thereafter.\n All eligible patients completed the HBO treatment and the extensive neuropsychological testing. One out of seven patients had a meaningful improvement in neuropsychological functioning. At 3 months there was a small, but not significant benefit in neuropsychological performance for the group with HBO compared to the group without HBO treatment. Six out of seven patients eventually showed improvement after HBO in one to nine (median 2.5) of the 31 tests, although without statistical significance.\n HBO treatment was feasible and resulted in a meaningful improvement of cognitive functioning in one out of seven patients. Overall there was a small but not significant improvement." ]

[ "12074791", "17203353", "12887481", "15928959", "18082217", "11744467", "9340898", "16618015", "8876706", "1702340", "2418902", "6207850", "2413558", "21954478", "12189745", "12092634", "16467543", "10751856" ]

[ "Comparison of a phytotherapeutic agent (Permixon) with an alpha-blocker (Tamsulosin) in the treatment of benign prostatic hyperplasia: a 1-year randomized international study.", "A prospective study of the efficacy of Serenoa repens, tamsulosin, and Serenoa repens plus tamsulosin treatment for patients with benign prostate hyperplasia.", "Serenoa repens extract for benign prostate hyperplasia: a randomized controlled trial.", "Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms--a placebo-controlled, double-blind, multicenter trial.", "Effect of saw palmetto soft gel capsule on lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized trial in Shanghai, China.", "Randomized, double-blind, placebo-controlled trial of saw palmetto in men with lower urinary tract symptoms.", "[Combination of Sabal and Urtica extract vs. finasteride in benign prostatic hyperplasia (Aiken stages I to II). Comparison of therapeutic effectiveness in a one year double-blind study].", "Efficacy and safety of a combination of sabal and urtica extract in lower urinary tract symptoms. A randomized, double-blind study versus tamsulosin.", "Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients.", "Treatment of benign prostatic hyperplasia with phytosterols.", "The value of permixon in benign prostatic hypertrophy.", "A double-blind trial of an extract of the plant Serenoa repens in benign prostatic hyperplasia.", "[Treatment of obstructive symptomatology caused by prostatic adenoma with an extract of Serenoa repens. Double-blind clinical study vs. placebo].", "Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial.", "[Tamsulosin with or without Serenoa repens in benign prostatic hyperplasia: the OCOS trial].", "Randomized trial of a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) on symptoms of benign prostatic hyperplasia (BPH).", "Saw palmetto for benign prostatic hyperplasia.", "Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia." ]

[ "While the lipido-sterolic extract of Serenoa repens (LSESr)-Permixon((R))-has been shown to have an equivalent efficacy to finasteride in patients with benign prostatic hyperplasia (BPH), to date, there has been no valid comparison of phytotherapy with alpha-blockers. The aim of this study was to assess the equivalent efficacy of Permixon and tamsulosin.\n Eight hundred and eleven men with symptomatic BPH (I-PSS> or =10) were recruited in 11 European countries for a 12-month, double-blind randomized trial. After a 4-week run-in period, 704 patients were randomly assigned to either tamsulosin 0.4mg/day (N=354) or Permixon 320mg/day (N=350). I-PSS, QoL and Q(max) were evaluated at baseline and periodically for 1 year. Prostate volume and serum prostate-specific antigen (PSA) were measured at selection and at endpoint. The endpoint analysis was performed on the per-protocol population of 542 patients (tamsulosin: N=273; Permixon: N=269).\n At 12 months, I-PSS decreased by 4.4in each group and no differences were observed in either irritative or obstructive symptom improvements. The increase in Q(max) was similar in both treatment groups (1.8ml/s Permixon, 1.9ml/s tamsulosin). PSA remained stable while prostate volume decreased slightly in the Permixon-treated patients. The two compounds were well tolerated, however, ejaculation disorders occurred more frequently in the tamsulosin group.\n This study demonstrates that Permixon and tamsulosin are equivalent in the medical treatment of lower urinary tract symptoms in men with BPH, during and up to 12 months of therapy.", "Increasing attention has been focused on the use of phytotherapeutic agents to alleviate the symptoms of benign prostatic hyperplasia (BPH) in recent times. The best described and studied phytotherapeutic agent is Serenoa repens (SR).\n This prospective study was designed to have 3 arms including SR 320 mg per day (N = 20), Tamsulosin (TAM) 0.4 mg per day (N = 20) and SR + TAM (N = 20) to reveal the superiority or equivalence between these treatment regimens in BPH.\n The groups were not statistically different with regard to increase in maximal urinary flow rate (Q (max)) and decrease in International Prostate Symptom Score (I-PSS) (P > 0.05). No adverse effect was detected in SR therapy group.\n Treatment of BPH by both SR and TAM seems to be effective alone. None of them had superiority to another and additionally, combined therapy (SR + TAM) does not provide extra benefits. Furthermore SR is a well-tolerated agent that can be used alternatively in the treatment of LUTS due to BPH.", "To compare the effect of a Serenoa repens extract with placebo for symptoms of benign prostatic hyperplasia (BPH).\n In a double-blind placebo-controlled randomized trial between January 1999 and March 2000, 100 men with symptoms of BPH, aged < 80 years, with a maximum urinary flow rate of 5-15 mL/s for a voiding volume of 150 mL, were randomly and equally allocated to 320 mg S. repens extract or placebo (paraffin oil). The main outcome measures were the International Prostate Symptom Score (IPSS), peak urinary flow rate, and the Rosen International Index of Erectile Function (IIEF) questionnaire.\n There was no significant difference between the treatments over the 12 weeks of the study in the IPSS, peak urinary flow rate or for the IIEF questionnaire.\n During the trial all participants had some improvement in their symptoms of BPH but there was no significant beneficial effect of this S. repens extract over placebo in this 12-week trial.", "The efficacy and tolerability of a fixed combination of 160 mg sabal fruit extract WS 1473 and 120 mg urtica root extract WS 1031 per capsule (PRO 160/120) was investigated in elderly, male patients suffering from lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia in a prospective multicenter trial. A total of 257 patients (129 and 128, respectively) were randomized to treatment with PRO 160/120 or placebo (127 and 126 were evaluable for efficacy). Following a single-blind placebo run-in phase of 2 weeks, the patients received 2 x 1 capsule/day of the study medication under double-blind conditions over a period of 24 weeks. Double-blind treatment was followed by an open control period of 24 weeks during which all patients were administered PRO 160/120. Outcome measures for treatment efficacy included the assessment of the patients' LUTS by means of the I-PSS self-rating questionnaire and a quality of life index as well as uroflow and sonographic parameters. Using the International Prostate Symptom Score (I-PSS), patients treated with PRO 160/120 exhibited a substantially higher total score reduction after 24 weeks of double-blind treatment than patients of the placebo group (6 points vs 4 points; P=0.003, one tailed) with a tendency in the same direction after 16 weeks. This applied to obstructive as well as to irritative symptoms, and to patients with moderate or severe symptoms at baseline. Patients randomized to placebo showed a marked improvement in LUTS (as measured by the I-PSS) after being switched to PRO 160/120 during the control period (P=0.01, one tailed, in comparison to those who had been treated with PRO 160/120 in the double-blind phase). The tolerability of PRO 160/120 was comparable to the placebo. In conclusion, PRO 160/120 was clearly superior to the placebo for the amelioration of LUTS as measured by the I-PSS. PRO 160/120 is advantageous in obstructive and irritative urinary symptoms and in patients with moderate and severe symptoms. The tolerability of the herbal extract was excellent.", "We determined the effect of Prostataplex in men with lower urinary tract symptoms associated with benign prostatic hyperplasia.\n A total of 92 Chinese men between 49 and 75 years old with lower urinary tract symptoms were randomly assigned in this double-blind, placebo controlled trial. The 46 patients in the intervention group were given 2 Prostataplex soft gels daily for 12 weeks, while the 46 in the control group were given 2 placebo soft gels for the same time.\n The treated and control groups appeared to have more than a 95% compliance rate, as judged by counting the remaining pills in the bottle collected at the end of trial months 1 to 3. After 12 weeks of intervention the mean +/- SD maximum urinary flow rate was significantly higher in the treatment group than in the control group (14.07 +/- 2.56 vs 11.74 +/- 1.23 ml per second, p <0.001), while relative urinary resistance was significantly lower in the treatment group than in the control group (2.35 +/- 0.83 vs 3.02 +/- 1.18, p = 0.002). While there was no significant difference in mean prostate volume or International Prostate Symptom Score between the 2 groups, 18 of 46 patients (39.1%) in the treatment group showed an International Prostate Symptom Score improvement (decrease of 3 or greater) after intervention, whereas only 1 of 46 (2.2%) in the control group showed an International Prostate Symptom Score improvement (chi-square test p <0.001).\n Prostataplex may have short-term effects in improving symptoms and objective measures in Chinese men with lower urinary tract symptoms associated with benign prostatic hyperplasia.", "To assess the effects of saw palmetto on urinary symptoms, sexual function, and urinary flow rate in men with lower urinary tract symptoms using a double-blind, randomized, placebo-controlled trial.\n The eligible patients were 45 years of age or older and had an International Prostate Symptom Score of 8 or greater. After a 1-month placebo run-in period, 85 men were randomized to receive saw palmetto or placebo for 6 months. Patients were evaluated using the International Prostate Symptom Score, a sexual function questionnaire, and by measurement of the urinary flow rate.\n The mean symptom score decreased from 16.7 to 12.3 in the saw palmetto group compared with 15.8 to 13.6 in the placebo group (P = 0.038). The quality-of-life score improved to a greater degree in the saw palmetto group, but this difference was not statistically significant. No change occurred in the sexual function questionnaire results in either group. The peak flow rate increased by 1.0 mL/s and 1.4 mL/s in the saw palmetto and placebo groups, respectively (P = 0.73).\n Saw palmetto led to a statistically significant improvement in urinary symptoms in men with lower urinary tract symptoms compared with placebo. Saw palmetto had no measurable effect on the urinary flow rates. The mechanism by which saw palmetto improves urinary symptoms remains unknown.", "Therapeutic equivalence should be demonstrated in a randomised, reference-controlled multicentric double blind clinical trial with PRO 160/120, a combination of Sabal- and Urtica-Extract, and Finasteride, respectively, in patients suffering from benign prostatic hyperplasia (BPH, Stage I to II according to Aiken). The study involved 543 patients, who were treated for 48 weeks with two capsules of PRO 160/120 or one capsule of Finasteride per day, in a double dummy design. Primary variable was the change of the maximum urinary flow after 24 weeks of therapy in comparison to therapy start. As secondary variables urodynamic parameters such as average urinary flow, miction volume and miction time were monitored. Urinary symptoms were recorded by the International-Prostate-Symptom-Score (I-PSS, Paris 1993). Additionally, the impacts of the symptoms on quality of life had been assessed by a quality of life questionnaire according to The American Urological Association Measurement Committee (1991). An increase of the urinary flow rate could be observed in both treatment groups (1.9 ml/s with PRO 160/ 120; 2.4 ml/s with Finasteride). During the trial, the average urinary flow increased, whereas the miction time decreased in both groups in a similar extent. The miction volume did not show any relevant differences after treatment with either PRO 160/120 or Finasteride. The I-PSS decreased from 11.3 at the therapy start to 8.2 after 24 weeks and 6.5 (week 48) under PRO 160/120 and from 11.8 to 8.0 and 6.2, under Finasteride, respectively. Accordingly, life quality improved between therapy start and therapy end from 7.5 to 4.3 with PRO 160/120 and from 7.7 to 4.1 with Finasteride. In terms of safety aspects less adverse events occurred with the Sabal/Urtica-Extract as with Finasteride. Especially less cases of diminished ejaculation volume, erectile dysfunction and headache have been reported.", "The aim of this prospective, randomized, double-blind, double-dummy, multicenter clinical trial was to investigate the efficacy and safety of PRO 160/120 (Prostagutt forte), a fixed combination preparation of 160 mg Sabal fruit extract WS 1473 and 120 mg Urtica root extract WS 1031 per capsule, in comparison to the alpha1-adrenoceptor antagonist tamsulosin (CAS 106463-17-6) in lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). 140 elderly out-patients suffering from LUTS caused by BPH, with an initial score > or = 13 points in the International Prostate Symptom Score (I-PSS), received 2 x 1 capsule/d PRO 160/120 or 1 x 0.4 mg/d tamsulosin and were treated for 60 weeks with interim visits at weeks 8, 16, 24, 36, and 48. The primary outcome measure for efficacy was the change in I-PSS total score, the percentage of patients with an I-PSS score < or = 7 points at endpoint ('responders') was analyzed as well. During 60 weeks of randomized treatment the I-PSS total score was reduced by a median of 9 points in both groups. In total, 32.4 % of the patients in the PRO 160/120 group and 27.9% in the tamsulosin group were responders (test for non-inferiority of PRO 160/120: p = 0.034; non-inferiority margin 10%). Both drugs were well tolerated, with one adverse event in 1514 treatment days for PRO 160/120 and one event in 1164 days for tamsulosin. The study supports non-inferiority of PRO 160/120 in comparison to tamsulosin in the treatment of LUTS caused by BPH.", "Controversy regarding the relative efficacy of treatments for the relief of the symptoms of benign prostatic hyperplasia (BPH).\n This was a 6-month double-blind randomized equivalence study that compared the effects of a plant extract (320 mg Permixon) with those of a 5 alpha-reductase inhibitor (5 mg finasteride) in 1,098 men with moderate BPH using the International Prostate Symptom Score (IPSS) as the primary end-point.\n Both Permixon and finasteride decreased the IPSS (-37% and -39%, respectively), improved quality of life (by 38 and 41%), and increased peak urinary flow rate (+25% and +30%, P = 0.035), with no statistical difference in the percent of responders with a 3 ml/sec improvement. Finasteride markedly decreased prostate volume (-18%) and serum PSA levels (-41%); Permixon improved symptoms with little effect on volume (-6%) and no change in PSA levels. Permixon fared better than finasteride in a sexual function questionnaire and gave rise to less complaints of decreased libido and impotence.\n Both treatments relieve the symptoms of BPH in about two-thirds of patients but, unlike finasteride, Permixon has little effect on so-called androgen-dependent parameters. This suggests that other pathways might also be involved in the symptomatology of BPH.", "In a randomised, double-blind study, the preparation Curbicin, obtained from pumpkin seeds and dwarf palm plants (Cucurbita pepo L. and Sabal serrulata), was compared with a placebo in the treatment of symptoms caused by prostatic hyperplasia; 53 patients took part in the study, which was carried out over a 3-month period. Urinary flow, micturition time, residual urine, frequency of micturition and a subjective assessment of the effect of treatment were all significantly improved in the treatment group. No untoward side effects were noted.", "A double-blind trial comparing the effect of Permixon (160 mg bd) against placebo in the treatment of benign prostatic hypertrophy is described. In both groups a significant improvement in flow rate and subjective assessment of symptoms was seen. There was no significant difference between the results of treatment in either group.", "nan", "nan", "Saw palmetto fruit extracts are widely used for treating lower urinary tract symptoms attributed to benign prostatic hyperplasia (BPH); however, recent clinical trials have questioned their efficacy, at least at standard doses (320 mg/d).\n To determine the effect of saw palmetto extract (Serenoa repens, from saw palmetto berries) at up to 3 times the standard dose on lower urinary tract symptoms attributed to BPH.\n A double-blind, multicenter, placebo-controlled randomized trial at 11 North American clinical sites conducted between June 5, 2008, and October 10, 2010, of 369 men aged 45 years or older, with a peak urinary flow rate of at least 4 mL/s, an American Urological Association Symptom Index (AUASI) score of between 8 and 24 at 2 screening visits, and no exclusions.\n One, 2, and then 3 doses (320 mg/d) of saw palmetto extract or placebo, with dose increases at 24 and 48 weeks.\n Difference in AUASI score between baseline and 72 weeks. Secondary outcomes included measures of urinary bother, nocturia, peak uroflow, postvoid residual volume, prostate-specific antigen level, participants' global assessments, and indices of sexual function, continence, sleep quality, and prostatitis symptoms.\n Between baseline and 72 weeks, mean AUASI scores decreased from 14.42 to 12.22 points (-2.20 points; 95% CI, -3.04 to -0.36) with saw palmetto extract and from 14.69 to 11.70 points (-2.99 points; 95% CI, -3.81 to -2.17) with placebo. The group mean difference in AUASI score change from baseline to 72 weeks between the saw palmetto extract and placebo groups was 0.79 points favoring placebo (upper bound of the 1-sided 95% CI most favorable to saw palmetto extract was 1.77 points, 1-sided P = .91). Saw palmetto extract was no more effective than placebo for any secondary outcome. No clearly attributable adverse effects were identified.\n Increasing doses of a saw palmetto fruit extract did not reduce lower urinary tract symptoms more than placebo.\n clinicaltrials.gov Identifier: NCT00603304.", "In the treatment of the symptoms of benign prostatic hyperplasia (BPH), a French guideline opposes the use of drugs in conjunction, in the absence of proven utility. The OCOS trial therefore compared one of the possible drug combinations (tamsulosin and Serenoa repens) with tamsulosin alone, to see if there was any difference in effectiveness and to evaluate the clinical tolerance of each in patients with symptoms of BPH.\n In this double-blind, randomised trial, patients had to have an IPSS (International Prostate Symptom Score) > or = 13 and a Qmax between 7 and 15 mL/s. Tamsulosin (0.4 mg) was to be administered once a day for 52 weeks, with, twice daily, a placebo (TAM) or Serenoa repens 160 mg (TAM + SR).\n 352 patients were recruited by 47 centres; 329 (average age 65) were randomised: 161 into the TAM group and 168 into the TAM + SR group. No statistically significant difference was found between the two groups, neither for the major end-point [change in total IPSS between the baseline value and the final evaluation (TAM: -5.2; TAM + SR: -6.0; p = 0.286)], nor for the secondary end-points [changes in the voiding scores (p = 0.239) and in filling scores (p = 0.475) of the IPSS, Qmax (p = 0.564), percentage of respondents according to the IPSS (p = 0.361), improvement in quality of life (IPSS-QoL: p = 0.091; UROLIFE BPH QoL: p = 0.442), safety].\n The addition of Serenoa repens to tamsulosin did not provide any significant benefit to the patients: the OCOS trial does not cast doubt on the guideline applicable to the treatment of BPH.", "Because benign prostatic hyperplasia (BPH) is relatively common, it is important to discover safe and effective means to treat this often debilitating perturbation. Accordingly, we examined the effectiveness of a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) in treating symptoms of BPH. We undertook a randomized, placebo-controlled, double-blind study. Patients were enrolled from 3 urological practices in the USA. 144 subjects were randomized for study. 17 subjects eventually withdrew, leaving 70 patients in the test group and 57 in the placebo group to complete the study. Inclusion criteria consisted of a diagnosis of BPH, no evidence of cancer, and a maximal urinary flow rate between 5 and 15 ml/second. Patients received either placebo or the combined natural products for 3 months. Evaluations were performed via the American Urological Association (AUA) Symptom Index score, urinary flow rate, PSA measurement, and residual bladder volume. Nocturia showed a markedly significant decrease in severity in patients receiving the combined natural products compared to those taking placebo (p < 0.001). Daytime frequency was also lessened significantly (p < 0.04). When the average individual total AUA Symptom Index score in the test group was compared to that in the placebo group at the end of the study, the difference proved highly significant (p < 0.014). PSA measurements, maximal and average urinary flow rates, and residual volumes showed no statistically significant differences. When taken for 3 months, a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) compared to placebo can significantly lessen nocturia and frequency and diminish overall symptomatology of BPH as indicated by an improvement in the total AUA Symptom Index score. The combination of natural products caused no significant adverse side effects.", "Saw palmetto is used by over 2 million men in the United States for the treatment of benign prostatic hyperplasia and is commonly recommended as an alternative to drugs approved by the Food and Drug Administration.\n In this double-blind trial, we randomly assigned 225 men over the age of 49 years who had moderate-to-severe symptoms of benign prostatic hyperplasia to one year of treatment with saw palmetto extract (160 mg twice a day) or placebo. The primary outcome measures were changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values, and the rate of reported adverse effects.\n There was no significant difference between the saw palmetto and placebo groups in the change in AUASI scores (mean difference, 0.04 point; 95 percent confidence interval, -0.93 to 1.01), maximal urinary flow rate (mean difference, 0.43 ml per minute; 95 percent confidence interval, -0.52 to 1.38), prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen levels during the one-year study. The incidence of side effects was similar in the two groups.\n In this study, saw palmetto did not improve symptoms or objective measures of benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00037154.).\n Copyright 2006 Massachusetts Medical Society.", "We tested the effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia (BPH) via a randomized, placebo controlled trial.\n We randomized 44 men 45 to 80 years old with symptomatic BPH into a trial of a saw palmetto herbal blend versus placebo. End points included routine clinical measures (symptom score, uroflowmetry and post-void residual urine volume), blood chemistry studies (prostate specific antigen, sex hormones and multiphasic analysis), prostate volumetrics by magnetic resonance imaging, and prostate biopsy for zonal tissue morphometry and semiquantitative histology studies.\n Saw palmetto herbal blend and placebo groups had improved clinical parameters with a slight advantage in the saw palmetto group (not statistically significant). Neither prostate specific antigen nor prostate volume changed from baseline. Prostate epithelial contraction was noted, especially in the transition zone, where percent epithelium decreased from 17.8% at baseline to 10.7% after 6 months of saw palmetto herbal blend (p <0.01). Histological studies showed that the percent of atrophic glands increased from 25. 2% to 40.9% after treatment with saw palmetto herbal blend (p <0.01). The mechanism of action appeared to be nonhormonal but it was not identified by tissue studies of apoptosis, cellular proliferation, angiogenesis, growth factors or androgen receptor expression. We noted no adverse effects of saw palmetto herbal blend. When the study was no longer blinded, 41 men elected to continue therapy in an open label extension.\n Saw palmetto herbal blend appears to be a safe, highly desirable option for men with moderately symptomatic BPH. The secondary outcome measures of clinical effect in our study were only slightly better for saw palmetto herbal blend than placebo (not statistically significant). However, saw palmetto herbal blend therapy was associated with epithelial contraction, especially in the transition zone (p <0.01), indicating a possible mechanism of action underlying the clinical significance detected in other studies." ]

[ "2670950", "7327728" ]

[ "Operative or conservative treatment for trochanteric fractures of the femur. A randomised epidemiological trial in elderly patients.", "The treatment of unstable intertrochanteric fractures of the hip: a prospective trial of 150 cases." ]

[ "All elderly patients with extracapsular hip fractures seen in hospitals in Newcastle upon Tyne over a 12-month period were studied and followed up for six months. At one of the hospitals, patients were randomised to treatment by AO dynamic hip-screw or by traction. Complications specific to the two treatments were low, and general complications, six-month mortality and prevalence of pain, leg swelling and unhealed sores, showed no difference between the two modes of treatment. Operative treatment gave better anatomical results and a shorter hospital stay, but significantly more of the patients treated by traction showed loss of independence six months after injury.", "We report a prospective clinical trial of 150 cases for the treatment of unstable intertrochanteric fracture of the neck of the femur. Three methods were tested in our series--skeletal traction with a tibial pin, medial displacement osteotomy and valgus osteotomy--with 50 patients in each group. Our results showed no significant difference between those treated with the Dimon and Hughston osteotomy and those treated by the Sarmiento osteotomy. Conservative treatment of skeletal traction for unstable fracture was found to be well tolerated by the Chinese patient. A low mortality and morbidity rate was found in this series with an overall infection rate of 4 per cent." ]

[ "7465140", "6363696", "6374539", "2563695", "3996091", "4688806", "6373481", "360120", "7041652", "6386593", "11245321", "3929609", "3885107", "6361251", "3046651", "1906042", "4032389", "7015540", "2126657", "7085368", "351488", "164642", "1673937", "4997830", "1303479", "6336898", "7086761", "7270617", "6828277", "2406439", "6337491", "4580966", "6353923", "3486596", "15512174", "10968046", "15806236", "6760969", "2694741", "7222872", "2880755", "7807484", "4016830", "6380723", "8051377", "7043345", "7001295", "10802077", "2147500", "3748494", "2738328", "11236113", "6344283", "7315901", "7447362", "9246960", "4550682", "333603", "7100224", "2315771", "6344970", "3046399", "7045356" ]

[ "Bacteriologic effects of antibiotic prophylaxis in high-risk cesarean section.", "Perioperative use of cefoxitin in primary cesarean section.", "Comparison of irrigation and intravenous antibiotic prophylaxis at cesarean section.", "Prophylactic short course rectal metronidazole for cesarean section. A double-blind controlled trial of a simple low cost regimen.", "Prophylaxis and treatment of anaerobic infections following caesarean section with tinidazole.", "The use of prophylactic antibiotics in patients undergoing cesarean section.", "[Advantages and hazards of preventing infection following cesarean section--clinical and bacteriologic results of a high-dosage treatment with mezlocillin and oxacillin short-term preventive following clamping of the umbilical cord].", "Perioperative antibiotic prophylaxis is cesarean section.", "Randomized clinical trial of perioperative cefoxitin in preventing maternal infection after primary cesarean section.", "[Perioperative short-term prevention of puerperal infections following cesarean section with metronidazole].", "Randomized trial of cefotiam prophylaxis in the prevention of postoperative infectious morbidity after elective cesarean section.", "Antibiotic irrigation prophylaxis in the high-risk cesarean section patient.", "Single-dose antibiotic prophylaxis in high-risk patients undergoing cesarean section.", "Effects of antibiotic prophylaxis on women undergoing nonelective cesarean section in a community hospital.", "A double-blind randomized controlled trial on the use of prophylactic antibiotics in patients undergoing elective caesarean section.", "[Prophylactic use of antibiotics in cesarean section].", "Effect of intrauterine antibiotic lavage after cesarean birth on postoperative morbidity.", "Prophylactic and antimicrobial therapy using lincomycin in patients undergoing emergency caesarean section.", "Single-dose cefuroxime prophylaxis in non-elective cesarean section.", "The efficacy of prophylactic antibiotics in high-risk patients undergoing cesarean section.", "Prophylactic use of cefazolin in monitored obstetric patients undergoing cesarean section.", "Prophylactic antibiotics in cesarean section.", "Prevention of postcesarean infectious morbidity with a single dose of intravenous metronidazole.", "Prophylactic antibiotics in cesarean section.", "The role of prophylactic antibiotics in caesarean section--a randomised trial.", "Multicenter comparison of cefoxitin versus cefazolin for prevention of infectious morbidity after nonelective cesarean section.", "Antibiotic prophylaxis in low-risk cesarean section.", "Febrile morbidity following cefamandole nafate intrauterine irrigation during cesarean section.", "Single-dose ampicillin for cesarean section prophylaxis.", "Selective effect of cefoxitin prophylaxis on post-cesarean-section microbial flora.", "Short-term antibiotic prophylaxis in high-risk patients following cesarean section.", "A follow-up study on prophylactic antibiotics in cesarean section.", "Reduction of post-cesarean section infectious morbidity by means of antibiotic irrigation.", "Single-dose trimethoprim-sulfamethoxazole prophylaxis for cesarean section.", "Comparison of four different antibiotics as prophylaxis in caesarean section.", "Single-dose antibiotic prophylaxis in women undergoing elective caesarean section.", "Randomized trial of ceftriaxone prophylaxis in elective cesarean section.", "Short-term versus long-term cefuroxime prophylaxis in patients undergoing emergency cesarean section.", "Reduced rate of postoperative infections in emergency cesarean section after two doses of cefuroxim perioperatively. A placebo-controlled study.", "[Perioperative metronidazole-prophylaxis for cesarian section (author's transl].", "Prevention of postoperative infection in cesarean section after rupture of the membranes.", "Post-cesarean section febrile morbidity. Antibiotic prophylaxis in low-risk patients.", "Single-dose mezlocillin prophylaxis in emergency cesarean section.", "Perioperative mezlocillin prophylaxis in cesarean section.", "[Antibiotic prophylaxis in a priori cesarean sections without a high risk of infection. Experiences of a Tunisian maternity department].", "Prophylactic antibiotics for cesarean section: comparison of high- and low-risk patients for endomyometritis.", "The prophylactic use of metronidazole in caesarean section.", "The routine use of cefazolin in cesarean section.", "[Antibiotic prophylaxis in cesarean sections without high risk of infection. Therapeutic trial of cefotetan versus placebo].", "Randomized comparison of five irrigation solutions at cesarean section.", "[Prevention of infectious complications after cesarean section by the use of cefotetan].", "A randomised controlled trial of antibiotic prophylaxis in elective caesarean delivery.", "Prophylactic cefoxitin in cesarean section.", "Selection of patients for antibiotic prophylaxis in cesarean sections.", "Prophylactic antibiotics in Caesarean section: effect of a short preoperative course of benzyl penicillin or clindamycin plus gentamicin on postoperative infectious morbidity.", "A study on prophylactic antibiotics in cesarean sections--is it worthwhile?", "Use of a prophylactic antibiotic in elective major gynecologic operations.", "Role of preventive antibiotics in patients undergoing cesarean section.", "Cefuroxime prophylaxis in caesarean section.", "Antibiotic prophylactic uterine lavage in cesarean section: a double-blind comparison of saline, ticarcillin, and cefoxitin irrigation in indigent patients.", "[Use of cephalosporins as antibiotic prophylaxis in cesarean section].", "[Comparative double-blind study of intravenous metronidazole versus placebo in preventing infection after cesarean section].", "Low-dose cephradine prophylaxis in obstetric and gynecologic surgery." ]

[ "A double-blind placebo-controlled experiment was performed in 100 patients in labor with membrane rupture to determine the bacteriologic effects of antibiotic prophylaxis. Each subject received either 2.0 g cefamandole or placebo after cord clamping and 4 and 8 hours later. The cefamandole group had significantly less endometritis, but did not have significantly fewer major complications. Amniotic fluid cultures of the 2 groups were similar, but uterine lavage cultures of the cefamandole group showed significant increases in enterococci and gram-negative aerobes and decreases in gram-positive anerobes and low virulence organisms (Staphylococcus epidermidis, lactobacilli, and diphtheroids). Although clinical problems did not regularly accompany these changes, it would be foolhardy to ignore them. Thus, when patients develop infection after antibiotic prophylaxis, the physician should check for infection with resistant organisms.", "We performed a randomized, double-blind trial on a relatively low-risk population comparing the use of three doses of cefoxitin vs. placebo in the prevention of infection following primary cesarean section. Major site-related morbidity (endometritis, wound infection and septicemia) was significantly reduced in the cefoxitin group (8.9% vs. 27.8%; p = 0.017). Febrile morbidity alone tended to occur in the cefoxitin group (15.6% vs. 3.7%; p = 0.091), and all five urinary tract infections occurred in the cefoxitin group as well. Total morbidity was therefore not significantly different (cefoxitin, 35.6%; placebo, 31.5% [not significant]). Duration of hospitalization (mean, 6.0 days) and need for further postoperative antibiotic therapy were similar in the two groups. Our study demonstrated a modest benefit from the perioperative use of antibiotics in relatively low-risk patients undergoing primary cesarean section. Issues that need further study include definition of the optimal prophylactic regimen and of high-risk populations for whom prophylaxis would be most helpful.", "Despite recent enthusiasm for antibiotic prophylaxis by uterine irrigation at the time of cesarean section, no data exists comparing the efficacy of this technique with standard intravenous antibiotic administration. Therefore, 124 patients about to undergo cesarean section were entered into a prospective, randomized, double-blind evaluation of uterine irrigation versus intravenous administration of either normal saline or cefoxitin. All women were considered to be at increased risk for postoperative infection because of the presence of labor or ruptured membranes. The incidence of endometritis and the fever index in patients receiving intravenous cefoxitin (3.2%, 4.6 degree hours) was significantly less than in patients receiving intravenous normal saline (21.2%, 22.3 degree hours). There was no significant difference between the use of intravenous normal saline and uterine irrigation with either cefoxitin (18.9%, 16.6 degree hours) or normal saline (17.4%, 24.6 degree hours). These results suggest that intravenous infusion is the most effective means of administering cefoxitin as a prophylactic antibiotic.", "One hundred and eighty two patients undergoing elective and emergency cesarean section were entered in a randomized double-blind placebo controlled trial of short course metronidazole rectal suppositories. There was a significant reduction in wound infection, febrile morbidity and postoperative hospitalization in the treated group. The reduction was greatest for serious wound infection. The simplicity and low cost of the regimen make it suitable for hospitals in developing countries.", "The purpose of this prospective, double-blind, placebo-controlled study was to clarify the effect of a single intravenous infusion of 500 mg of tinidazole on infections that followed a caesarean section. 80 consecutive caesarean-section patients and thereafter 72 women undergoing non-elective caesarean section were randomly assigned to two groups, each receiving intravenous infusions at cord clamping. In the entire sample the incidence of endometritis/wound infection in the placebo group was 27.3% (21/77) versus 10.7% (8/75) in the tinidazole group (p less than 0.01). In the non-elective caesarean-section group the incidence of endometritis/wound infection was 39.6% (21/53) in the placebo group versus 14.3% (7/49) in the tinidazole group (p less than 0.01). 27 positive bacterial cultures yielded a pure anaerobic growth in 59% (16/27) of cases, of which 87.5% (14/16) were treated successfully with oral tinidazole.", "nan", "Between August 1980 and August 1981 a prospective randomised study was conducted at the Krankenhaus Nordwest , Dept. of OBGYN , Frankfurt, to investigate the efficacy of a short term prophylaxis using mezlocillin and oxacillin ( Optocillin ) in reducing infections after Caesarean section (6 gs Optocillin after clamping the umbilical cord and after 8 and 16 hours, respectively). Both the study group (sg) and the control group (cg) consisted of 50 patients each. Both groups were statistically homogeneous . Infections were significantly reduced by the prophylaxis: sg 26%/cg 64% - p less than 0,001, febrile morbidity: sg 10%/cg 38% - p less than 0,001, endometritis: sg 6%/cg 20% - p less than 0,08, UTI: sg 18%/cg 36% - p less than 0,05, wound infections: sg 2%/cg 18% - p less than 0,02. Severe infections, however, were seen in neither group. The duration of infections was shorter in the sg. The various postoperative infections were associated with different risk factors (rf) - endometritis: green amniotic fluid, operating time greater than 75 min; cervical dilatation less than 2 cm, UTI: PROM (greater than 6 hs), operating time less than 75 min, internal monitoring, cervical dilatation greater than 2 cm, wound infections: green amniotic fluid, internal monitoring, frequent vaginal examinations (greater than 6), cervical dilatation greater than 2 cm and operating time greater than 75 min. The prophylaxis was especially effective in the presence of the following rfs: green amniotic fluid, internal monitoring, frequent vaginal examinations (6), operating time greater than 75 min and when associated with combined rfs. The reduction of wound infections following the prophylaxis can be ascribed to the elimination of organisms (Staph. spec., enterococci,) at the site of operation.(ABSTRACT TRUNCATED AT 250 WORDS)", "The effect of an 8-hour, 3-dose perioperative regimen of cefazolin or placebo was evaluated in 97 patients. Postoperative morbidity occurred in 13 patients (27.1%) in the cefazolin group and in 17 patients (34.7%) who received placebo. The clinical sites of infection were similar in both groups except that wound infections (2) and sepsis (2) were found only in patients receiving placebo. Aerobic organisms diminished and anaerobes increased in patients who received antibiotics. Aerobic isolates were essentially unchanged and fewer anaerobes were recovered from patients given placebo. Antibiotic levels observed at cesarean section were in the therapeutic range. The only risk factor which correlated with morbidity was the presence of ruptured membranes. This short course, single drug regimen did not significantly reduce morbidity although it was bacteriologically effective.", "To determine the efficacy of perioperative cefoxitin in preventing infections after primary cesarean section, a randomized placebo-controlled, double-blind clinical trial was performed. Among 266 participants, those who received three perioperative 2 gm doses of cefoxitin (138) had significantly fewer serious infections (19.5% vs. 4.3%), fewer urinary tract infections (10.7% vs. 4.4%), less standard febrile morbidity (9.4% vs. 3.6%), and fewer courses of antibiotics postoperatively (23.4% vs. 11.6%). There was no reduction in the length of hospitalization. Use of perioperative cefoxitin umbilical cord is clamped are safe and efficacious in preventing infection after primary cesarean section.", "A prospective randomised placebo-controlled clinical study showed that it was not possible to reduce the infectious morbidity following Caesarean section by one perioperative intravenous infusion of 500 mg metronidazole. Of all the 219 patients the endometritis rate was 6%, the wound infection rate 6% and the puerperal sepsis rate 2%.", "A prospective, randomized study was performed in order to evaluate the effect of cefotiam in the prevention of postoperative infectious morbidity in patients undergoing low-risk elective cesarean section. A total of 146 patients were randomly assigned to receive either intraoperative single-shot prophylaxis with 2 g cefotiam (study group, n =76) or no prophylaxis (control group, n=70). Due to a higher rate of urinary tract infections, the incidence of infectious morbidity after cefotiam prophylaxis was higher in the study group than in the control group (16% vs. 9%, P=0.1). Postoperative infectious morbidity following low-risk elective cesarean section cannot be reduced by intraoperative cefotiam prophylaxis.", "Two hundred twenty-three women who underwent cesarean section delivery were studied to assess the effectiveness of operative antibiotic irrigation in preventing postoperative uterine infection. Patients were prospectively randomized into high-risk and low-risk groups according to length of labor, and received irrigation with either a 2 gm solution of cefamandole or normal saline solution, or no irrigation. Infection rates of 48.6% and 54.8% were observed in high-risk patients given either saline solution or no irrigation, respectively. Three of 27 high-risk patients (11.1%) given antibiotic irrigation developed metritis. The authors find this method of preventing infection to be advantageous in terms of both efficacy and minimization of antibiotic exposure.", "A prospective, double-blind, placebo-controlled study was performed to determine the effectiveness of single-dose antibiotic prophylaxis in decreasing infectious complications after primary cesarean section. One hundred women at high risk for postoperative infectious morbidity were randomly assigned to receive either placebo or one 2-g dose of ceftizoxime at cord clamping. The incidence of endometritis in the antibiotic group was 6.0 versus 24.5% in the placebo group (P less than .05). The incidence of febrile morbidity in the group receiving one dose of ceftizoxime was 14.0 versus 32.7% in the placebo group (P less than .05). Single-dose ceftizoxime prophylaxis significantly reduced the incidence of endometritis and febrile morbidity in high-risk patients undergoing cesarean section.", "A randomized, double-blind, placebo-controlled study was done of a short course of cefamandole administered intravenously after cord clamping as prophylaxis in women undergoing primary nonelective cesarean section in a community hospital. Duration of labor equal to or more than 14 hours was the only significant risk factor between patients who had postoperative infectious morbidity and those who had none. Four of 43 patients (9.3%) who received cefamandole, as opposed to 13 of 47 (27.7%) who received the placebo, developed infections (p less than 0.05). This difference was reflected totally in the difference in endomyometritis development between the groups. The use of intraoperative culturing predicted infection in 4 of 13 patients in the placebo group who developed infections postoperatively. No adverse side effects were noted, and there were no cases of delayed serious infection.", "In a double-blind randomized controlled study 232 patients undergoing elective lower segment caesarean section were randomly allocated to receive a pre-operative prophylactic dose of a combination of crystalline penicillin and chloramphenicol or a placebo. The two groups were comparable in terms of patient characteristics and operation variables. The group receiving antibiotics had significantly fewer febrile and infectious morbid events and thus spent fewer days in hospital than the group receiving the placebo.", "The objective of this investigation was to determine the effectiveness of ampicillin administration as a prophylactic regime in patients undergoing cesarean section. A double blind randomized study compared a long course of ampicillin (7 days) to a short course of ampicillin (three doses) to placebo. Thirty one patients were included in the placebo group and sixty patients in the drug groups. Only one patient in the placebo group and one in the drug group developed infectious morbidity. There was no significant difference (p less than 0.001) between the placebo and ampicillin groups.", "Intrauterine lavage using broad-spectrum antibiotics after cesarean section has been reported to reduce maternal morbidity, but many such patients are not at high risk for postoperative infection. This study tested intrauterine antibiotic lavage in patients at risk for infectious morbidity. The patients were randomly assigned to one of three groups based on the last digit of the hospital admission number. Group I received no lavage, group II received lavage with 800 ml of saline plus 2 gm of cefamandole nafate in the intrauterine incision, bladder flap and peritoneal cavity, and group III received a similar lavage using 800 ml of saline alone. There was a significant decrease in maternal hyperpyrexia (simple morbidity) as well as serious infection in both lavage groups as compared to the control group (p less than 0.01 and 0.05, respectively). Also, there was significantly reduced morbidity when the antibiotic lavage was compared to the saline technique (p less than 0.001). The use of intrauterine lavage with saline, with or without antibiotics, appears helpful in reducing postoperative morbidity in patients at high risk for infectious morbidity after cesarean section.", "The influence of prophylactic antimicrobial therapy with lincomycin and metronidazole on the vaginal carriage rates of anaerobes and the development of postoperative infection was studied in 60 women who underwent emergency surgery. Lincomycin prophylaxis in 20 patients led to a decrease in the vaginal carriage rate from 85% pre-operatively to 20% on both the 3rd and the 5th postoperative day. Metronidazole prophylaxis resulted in a similar decrease. In the placebo group of 20 patients no significant decrease in anaerobic yield was noted, the corresponding figures being 100%, 75% and 80% respectively. Furthermore, 6 of the placebo group had wound infections, compared with one each in the lincomycin and metronidazole groups.", "A prospective randomized study was undertaken to evaluate the efficacy of a single dose of cefuroxime in alleviating infectious complications following non-elective cesarean section. One hundred and two women were allocated to receive 750 mg of cefuroxime after cord clamping and 99 were allocated to a control group not receiving any antibiotic prophylaxis. The incidence of febrile morbidity was 2.0% in the cefuroxime group and 19.2% in the control group (p less than 0.001). The incidence of endometritis in the two groups was 1.0% and 6.1%, respectively, the incidence of fever of unknown origin was 1.0% and 9.1%, respectively. Single-dose cefuroxime prophylaxis significantly reduced the incidence of febrile morbidity in patients undergoing non-elective cesarean section, without producing any side effects.", "nan", "Prophylactic cefazolin was evaluated in high-risk obstetric patients who had invasive fetal monitoring and subsequent cesarean section. A three-dose regimen of either cefazolin or placebo was administered randomly in a double-blind manner to 93 patients, 48 receiving cefazolin and 45 placebo, with the first dose given when the cord was clamped. In the placebo group, 51% of the patients were treated for endomyometritis compared to 29% in the cefazolin group. The incidence of urinary tract and wound infections was similar in the 2 groups. One patient in the active drug group was diagnosed as having septic pelvic thrombophlebitis and received multiple antibiotics and heparin before she recovered. One patient in the placebo group required triple antibiotic therapy. Operation to control infection was not required in any patients and there were no maternal deaths. The cefazolin patients had fewer degree-hours of morbidity as calculated by the quantitative fever index (P less than 0.002). The perioperative use of cefazolin was efficacious in reducing the incidence of endomyometritis, but did not prevent serious postoperative pelvic infection.", "Using a random selection procedure, 100 patients were evaluated in order to determine the value of prophylactic antibiotics in cesarean section. All patients were evaluated for febrile morbidity, and specific infection sites were recorded. Significant differences were found between the treated and control groups and between cesarean sections performed prior to the onset of labor and after the onset of labor.", "The efficacy of intravenous metronidazole for the prevention of postcesarean section infectious morbidity was studied in 100 healthy women, randomly given either the drug or a placebo. The metronidazole group received 1.0 g intravenously, immediately after cord clamping. Among the 50 patients who received metronidazole, endometritis developed in 7 (14%) as it did in 15 (30%) of the placebo group (P less than 0.01); wound infection was found in 1 (2%) and 4 (8%), respectively (P less than 0.01). If both infectious complications are compared together, the difference (16% versus 38%) is more significant (P less than 0.001). Metronidazole was well tolerated by the mother and with this type of administration regimen, the fetus is not exposed to the drug. It is concluded that metronidazole, used as here reported, is effective in reducing the frequency of postcesarean section endometritis and wound infection with the consequent clinical and economic impacts.", "nan", "A prospective randomised controlled study was conducted over a 6 month period on the value of administering prophylactic antibiotics in patients undergoing emergency caesarean section at the Ipoh General Hospital. A total of 222 patients were randomised to receive 24 hours of ampicillin (500 mg per dose), cefoperazone (1 gm per dose) or no antibiotics. In all parameters of patient morbidity, the group receiving cefoperazone showed significantly better results as compared to the group not receiving antibiotics. The ampicillin group also had favourable results but generally not achieving statistical significance. Prophylactic antibiotics appear to be beneficial and consideration should be given to make it a routine in all emergency caesarean sections.", "A randomized double-blind placebo-controlled comparison of prophylactic cefoxitin, an antibiotic with good activity against anaerobic bacteria, with cefazolin, an agent effective predominantly against aerobes, was undertaken in 354 women who underwent nonelective cesarean section (124 receiving cefoxitin, 119 cefazolin, and 111 placebo). Among the placebo group, 24.3% developed genital tract-related infection, in comparison to 5.6% of the cefoxitin patients and 6.7% of the cefazolin patients (P less than 0.001). Standard febrile morbidity, fever index, and duration of postoperative hospital stay were also significantly less in the antibiotic prophylactic groups. For patients with febrile morbidity, the mean fever index was less in the cefoxitin group (24.8 degree-hours) than that in the cefazolin group (42.7 degree-hours), and this difference approached statistical significance (P less than 0.1, greater than 0.05). Postoperative hospital stay longer than 1 week for infectious morbidity occurred in 26% of cefoxitin patients, a significantly lower incidence compared to the 66% rate for patients who received cefazolin, and the 57% incidence for patients in the placebo group (P less than 0.05).", "This prospective study was undertaken in an effort to evaluate the role of systemic antibiotic prophylaxis in elective abdominal delivery. Eighty-two patients undergoing elective cesarean section who were not in labor and who did not have ruptured membranes were assigned on a randomized, double-blind basis to receive a three-dose perioperative course of either placebo or ampicillin. Postoperatively, patients were evaluated for the development of infection-related complications. Patients in the antibiotic group experienced less febrile morbidity, had lower fever indices and developed fewer operative-site infections than did patients in the control group. No patient in either group, however, developed a potentially life-threatening infection, and all infected patients responded promptly to parenteral antibiotic therapy. Because of the limited morbidity associated with elective cesarean section in this patient population, it is concluded that the theoretical risks of antibiotic prophylaxis outweigh the expected benefits.", "The effectiveness of intrauterine irrigation during cesarean section with a solution of cefamandole nafate in reducing febrile morbidity was studied in a prospective double-blind fashion. Ninety patients who were undergoing cesarean section at Tripler Army Medical Center were randomized into three groups: (1) intrauterine irrigation with cefamandole nafate solution, (2) intrauterine irrigation with normal saline solution, and (3) no irrigation. Febrile morbidity was evaluated by means of a fever index. There was a statistically significant reduction in the fever index in the group that received intrauterine irrigation with cefamandole nafate. The incidences of clinically diagnosed endomyometritis in the three groups were 0%, 26.7%, and 23.3%, respectively. Prophylactic intrauterine irrigation with cefamandole nafate during cesarean section markedly reduces febrile morbidity, primarily by reducing the incidence of endomyometritis.", "A single 2-g dose of ampicillin or a placebo identical in appearance was administered intravenously in a randomized, prospective, double-blind manner to 71 patients undergoing cesarean section. The solutions were given either on call to the operating room or during the intraoperative period. Postoperative morbidity from infection occurred in 59.4% of patients receiving placebo and in 14.7% of those receiving ampicillin (P less than .0001). In those individuals undergoing primary cesarean section the incidence of infection with placebo was 65% and with ampicillin 6.3% (P less than .0004). In patients undergoing repeat cesarean section the incidence was 53% in the placebo group and 22% in the treatment group (P greater than .05). There were no differences in the effectiveness of the drug whether given preoperatively or intraoperatively. Serious infections and wound infections were not encountered in patients receiving ampicillin.", "A double-blind study was done to test the efficacy of cefoxitin in the prevention of post-cesarean-section infection. The antibiotic was given in three 2-g doses; the initial dose was given immediately after the cord was clamped, and subsequent doses were given four and eight hours later. Cefoxitin prophylaxis significantly reduced morbidity serious enough to require therapeutic antibiotics or to prolong the hospital stay and led to an overall reduction in the anaerobic microbial flora of the endocervix. However, the antibiotic was selective for the overgrowth of enterococci, which were present in nearly half the postoperative cultures of patients who had received the drug. Enterococcal sepsis occurred in one patient, and three other patients had significant bacteriuria and/or urinary tract infections from enterococci. No cefoxitin-resistant strains of Enterobacteriaceae, among species normally sensitive to the drug, were isolated from the stool samples after prophylaxis. The risk of enterococcal colonization and superinfection must be weighted against the benefits of reduction of the infection risk when deciding upon routine antibiotic prophylaxis for cesarean section.", "A prospective, blinded, placebo-controlled study was performed to determine the minimum effective duration of short-term antibiotic prophylaxis following cesarean section. Cefoxitin was selected as the study drug, and 189 women at high risk for postoperative infectious morbidity were randomly assigned to three cohorts, each receiving intravenous infusions at cord clamping and at 4 and 8 hours postoperatively. The incidence of endometritis in the placebo group was 29.3% versus 9.4% in patients receiving one dose of cefoxitin (2 gm) at cord clamping and 5.0% in patients receiving three doses of cefoxitin (p less than 0.0001). Cefoxitin prophylaxis significantly reduced the incidence of endometritis in patients with postoperative anemia. There were no serious complications or drug reactions in the treated groups.", "nan", "The effectiveness of antibiotic irrigation in reducing post-cesarean section infectious morbidity was studied in a prospective, randomized, double-blind trial. One hundred twenty-eight patients were divided into three groups and irrigated with either cefoxitin solution, cephapirin solution, or saline. Following delivery of the placenta, the uterine cavity and incision, bladder flap, pelvic gutters, and subcutaneous tissue of the patients were irrigated. There was a significant reduction in total infectious morbidity (p less than 0.02) and wound infection (p less than 0.04) when antibiotic use was compared to the saline control. No statistical difference in the effectiveness of the two antibiotics could be demonstrated. No adverse effects were noted. Antibiotic irrigation is a safe and effective method in reducing infectious morbidity of the parturient patient.", "Single-dose trimethoprim-sulfamethoxazole prophylaxis after clamping of the umbilical cord decreased the rate of endomyometritis in high-risk patients by 50% when compared with placebo. This drug combination may affect the normal flora of the cervix the least so that superinfections should be rare.", "nan", "This prospective, randomised, controlled trial was performed to evaluate the effectiveness of single-dose antibiotic prophylaxis in decreasing the infectious morbidity following elective caesarean section. Two hundred women undergoing elective caesarean section were randomly assigned to receive either 1.2 g of Augmentin intravenously, or no treatment, just before the start of their caesarean section. The two groups of women were comparable in terms of patient characteristics and operation variables. The overall postoperative morbidity rate was 19% in the Augmentin treated group versus 38% in the group that received no prophylaxis (p < 0.01). The incidence of wound sepsis was 3% in the Augmentin group versus 13% in the control group (p < 0.01). The incidence of febrile morbidity with no identifiable cause was 8% in the Augmentin group versus 18% in the control group (p < 0.05). The duration of hospital stay was significantly shorter in the Augmentin group (p < 0.05). A single-dose of prophylactic Augmentin significantly reduced the postoperative morbidity and duration of hospital stay in women who underwent elective caesarean sections.", "nan", "A prospective randomized clinical trial was conducted to test the effectiveness of long-term and short-term prophylaxis with cefuroxime in preventing morbidity after cesarean section. Sixty patients who required emergency cesarean section were randomly assigned to one of three treatment groups: a control group of 20 patients receiving no prophylactic antibiotics; a group of 20 patients receiving 24 hours of cefuroxime prophylaxis (0.75 gm 30 to 60 minutes before surgery and at 8 hours and 16 hours after surgery); and a group of 20 patients receiving five days of cefuroxime prophylaxis (0.75 gm three times a day, the first dose being given postoperatively). The short-term and long-term prophylaxes were equally effective in reducing morbidity, assessed by postoperative temperatures, presence or absence of endometritis, and duration of postoperative hospital stay.", "The rate of postoperative infections after cesarean section was studied in a prospective double-blind randomized study to compare cefuroxim with a placebo. Intravenous bolus injections were given at the beginning of, and 12h after the operation. Eighty patients received cefuroxim and 80 received placebo. Endometritis or wound infection, or both, was diagnosed in 2/80 (2.5%) patients receiving cefuroxim and in 23/80 (29%) patients receiving placebo. No side effects were demonstrated or reported by the patients. Thus, two bolus injections of 1.5 g of cefuroxim given perioperatively significantly reduced postoperative infectious morbidity after emergency cesarean section.", "A prospective, randomized clinical trial was conducted in 103 patients undergoing cesarian section to assess the efficacy of prophylactic, intravenously administered Metronidazole on the infectious morbidity. A group of 53 patients with perioperative Metronidazol-prophylaxis was compared to a similar controll-group without prophylaxis. Bacteriologic swabs were taken from the cervix pre- and postoperatively, using anaerobic transport media. Prophylactic Metronidazole reduced postoperative fever of more than 38 degrees C on two subsequent days from 60% in the controll-group to 30,2% in the Metronidazole-group (p less than 0,01) wound infections were reduced from 18% without to 5,7% with prophylaxis (p less than 0,05) and Endometritis from 30% without to 13,2% with prophylaxis (p less than 0,05). An additional antibiotic therapy was necessary in 44% of the cases in the controllgroup, compared to 24,5% of the cases in the Metronidazolegroup (p less than 0,05). The mean duration of hospitalisation was reduced from 12,1 +/- 3,2 days in the controll-group to 11,2 +/- 2,1 in the Metronidazole-group (p less than 0,01). Anaerobic bacteria were isolated from the servical swabs in 60% preoperatively, with a still increasing incidence to 72% postoperatively, compared to 7% in the Metronidazole-group. Our results suggest, that prophylactic, intravenously administered Metronidazol reduces the infectious morbidity following cesarian section due to the reduction of the anaerobic flora at the female genital-tract.", "Patients having a cesarean section more than 6 h after rupture of the membranes constitute a high risk group for postoperative infections. Two such groups were studied. Patients were given either cefuroxime 1.5 g every 8th hour for 24 h followed by cefadroxil 0.5 g twice daily for 6 days or received no medication. The infection rate was significantly reduced in the treatment group as compared to the control group (15% vs. 48%). Non-infected patients had a significantly shorter stay in hospital (8 days vs. 12 days). Combined use of these drugs for prevention of post-cesarean infection has not previously been reported. No side effects of the antibiotic prophylaxis were reported.", "A study was conducted to assess whether antibiotic prophylaxis in low-risk patients for post-cesarean febrile morbidity was beneficial and cost effective. In a randomized, prospective study, 167 patients received a single, 1-g dose of cefazolin before clamping of the cord, and 140 did not. In the group given prophylaxis the febrile morbidity and postoperative therapeutic antibiotic usage were significantly lower than in the group not given prophylaxis (9% vs. 17.9%, P = .035, and 6.5% vs. 20%, P < .001, respectively). We conclude that single-dose cefazolin prophylaxis is both beneficial and cost effective, even in patients considered to be at low risk of post-cesarean febrile morbidity. Since the value of antibiotic prophylaxis in high-risk patients is accepted, universal antibiotic prophylaxis in every cesarean section case is suggested.", "A single 5-gm dose of mezlocillin or a placebo was administered intravenously 30 minutes before surgery to patients undergoing emergency cesarean section. The assignment of drug or placebo was randomized. Postoperative morbidity occurred in 62.5% of patients receiving placebo and in 18.4% of those receiving mezlocillin (P less than 0.001). The incidences of febrile morbidity, endometritis, and urinary tract infection were significantly lower in the group given mezlocillin. Other benefits of antibiotic prophylaxis included a shorter hospital stay and no serious infections in the group given mezlocillin.", "One hundred thirteen patients were prospectively evaluated to determine the prophylactic effect of mezlocillin in women undergoing cesarean section. Subjects received 2 gm of mezlocillin or placebo intravenously 30 minutes before surgery and four and nine hours after surgery. All patients were evaluated for febrile morbidity and for the development of specific infections. The overall postoperative morbidity was reduced from 51% in the control group to 17% in the mezlocillin group (P less than 0.01). Separate analyses of morbidity in patients undergoing cesarean section after the onset of labor and those having the operation before the onset of labor showed the significant reduction of morbidity by mezlocillin to have occurred only in the former group.", "This study was conducted to evaluate the effect of antibiotic prophylaxy on decreasing the frequency of postoperative infections after cesarean sections performed in cases with no prior indication of a high risk of infection.\n A prospective randomized study included 269 cesarean sections without a high risk of infection performed in the Maternity and Neonatology Ward of the Sousse Hospital from February 1991 to July 1991. The patients were randomly divided into two groups. One group received an antibiotic prophylactic treatment including cephapirine, gentamicin and metronidazole) and the second group was given no treatment.\n Antibiotic prophylactic therapy led to a reduction of infectious morbidity after cesarean section in patients without high risk o infection from 33% to 11%. A 66% rate of efficacy was observed. In addition, antibiotics given in this context led to substantial cost reduction both by reducing the cost of antibiotics prescribed in the postoperative period and by reducing the number of days of hospitalization, and thus total cost.\n This study demonstrated the effectiveness of antibiotic prophylaxy for cesarean sections in patients without a high risk of infection. Nevertheless, a reevaluation of the antibiotic protocols and a rigorous operative procedure are essential.", "The efficacy of ticarcillin in the prevention of post-cesarean section endomyometritis was studied in 259 women randomly given either the antibiotic or a placebo. The ticarcillin group received 6 g intravenously immediately after delivery. Then 22 of those patients were also given a second 3-g dose 6 to 8 hours after delivery. Among the 139 patients who received ticarcillin, endomyometritis developed in 44 (32%), as it did in 66 of 120 patients (55%) in the placebo group. These differences are highly significant (P = .002). Of the 259 patients in the study, 238 could be classified as to risk for endomyometritis developing. Among the 124 high-risk patients, 52 received a placebo and endomyometritis developed in 71%. Only 26 of the 72 high-risk patients who received ticarcillin (36%) were so infected. Among the low-risk patients, endomyometritis developed in 10 of 54 patients (18.5%) who received prophylaxis and in 24 of 60 patients who received placebo (40%). Ticarcillin appears to be effective in reducing the incidence of post-cesarean section endomyometritis in patients at high risk and in those at low risk. The number of pelvic examinations during labor was the most important single factor in the development of endomyometritis.", "A double-blind study of 73 patients was undertaken to evaluate the prophylactic effect of short-term metronidazole in caesarean section. Metronidazole, 500 mg, given intravenously prior to making the incision, followed by 2 g, rectally, on completion of surgery failed to reduce the incidence of infection post-operatively. There was no reduction in the number of patients requiring antibiotics or in the quantity of post-operative pyrexia, as assessed by the fever index. The incidence of post-operative pyrexia was not affected by the duration of ruptured membranes or the use of a fetal scalp electrode.", "To determine the effectiveness and safety of the routine use of antibiotic prophylaxis in women undergoing cesarean section.\n Four hundred and forty-one women undergoing cesarean sections were randomly assigned either to a single dose of 1 g intravenous cefazolin or placebo after clamping of the umbilical cord. The primary outcome was the development of post-operative febrile morbidity and the secondary outcomes were infection-related complications.\n There were 211 emergency and 230 elective cesarean sections. In the emergency cesarean sections, 34 (30.6%) women developed post-operative febrile morbidity in the placebo group compared to 11 (11%) women in the cefazolin group. This was a statistically significant difference (P = 0.001). Similarly, there were statistically significant differences between the two groups in the development of wound infection (P<0.001), use of therapeutic antibiotics (P = 0.001), and post-operative days in hospital (P = 0.003). No statistically significant differences were detected in the development of other infection-related complications. In the elective cesarean sections, no statistically significant differences were found in post-operative febrile morbidity and infection-related complications. There were no serious side effects related to the use of cefazolin.\n The routine use of a single dose of cefazolin is safe and effective in emergency but not elective cesarean section.", "Caesarean sections are performed with an ever increasing frequency, and their morbidity rate due to infection varies between 35 and 40 per cent. The effectiveness of antibiotic prophylaxis has been demonstrated in caesarean sections with a high risk of infection, but few studies have been devoted to caesarean sections without this high risk. The purpose of our study was to evaluate the effectiveness of antibiotic therapy in this second type of caesarean section since its postoperative infection rate is not negligible (about 25 per cent). We therefore set up a two-centre randomized trial comparing two groups of 133 women without any particular risk of infection. At the moment of umbilical cord clamping, one group received cefotetan 1 g intravenously, while the other group received an intravenous injection of a placebo solution. The postoperative infection rate was 12.5 per cent in the treatment group and 26.9 per cent in the control group (P less than 0.05). The relative risk in the placebo-treated women was 2.15 (95 per cent confidence limits, 1.41 to 3.28). Antibiotic prophylaxis prevented 53.5 per cent of postoperative infections (95 per cent confidence limits, 29 to 69.5 per cent). Moreover, in the treatment group infections were less severe, resulting in a significant decrease in hospital stay and a lower overall cost. We conclude that antibiotic prophylaxis with cefotetan is effective in caesarean sections without a high risk of infection, as it significantly reduces the postoperative morbidity due to infection.", "A randomized double-blind study was undertaken to determine which irrigation solution might be best at cesarean section. A saline placebo was compared with ampicillin sodium and one each of three generations of cephalosporins: cephapirin sodium, cefamandole nafate, and moxalactam disodium. A total of 360 cesarean sections were studied, and comparisons made between antibiotic and control groups relative to demographics, possible risk factors, and multiple measures of postoperative morbidity. The total group was further divided into high- and low-risk labor and repeat cesarean groups. Post-cesarean endometritis was diagnosed in the following frequencies for the group as a whole: placebo (24.6%), ampicillin sodium (8.5%), cephapirin sodium (11.4%), cefamandole nafate (4.6%), and moxalactam disodium (16.4%). Cefamandole nafate consistently demonstrated significant decreases in endometritis and other morbidity measures versus placebo both in laboring patients and the group as a whole.", "A prospective, randomised study was carried out on 110 patients to find out the effect of giving Cefotetan prophylactically as against no treatment in the prevention of infections after cesarean sections. The cases were selected before or at the beginning of a trial of labour in 72 cases and after a failure of trial of labour in 38 cases. A single dose of 2 gr of Cefotetan was given during the operation, after the cord had been clamped. It caused a significant drop in infection and in particular the number of cases of endometritis and urinary tract infections, which were twice as common in the non-treated as compared with the treated group.", "To determine whether prophylactic antibiotic administration using cefoxitin at the time of elective caesarean section significantly reduces infectious morbidity.\n A tertiary teaching hospital in a large urban city in South Africa.\n Women undergoing elective caesarean section.\n A prospective, double-blind randomised placebo-controlled trial.\n Four hundred and eighty women undergoing elective caesarean section had cefoxitin or placebo administration after umbilical cord clamping. Postpartum complications including febrile morbidity, wound infection, endometritis, urinary tract infection, pneumonia and transient postpartum fever were recorded, as were the duration of hospital stay and the need for therapeutic antibiotics.\n Wound infection was the most common complication occurring in 13.3% and 12.5% of women in the placebo and cefoxitin groups, respectively. Prophylactic antibiotics did not decrease febrile morbidity, wound infection, endometritis, urinary tract infection and pneumonia. Women who received cefoxitin stayed on average a day less in hospital than those who received placebo (6.9 vs 7.8 days, risk difference 0.94 CI 1.57 - 0.31 days). Eleven women (4.6%) in the placebo group and eight (3.4%) in the cefoxitin group had microbiological evidence of wound infection. Staphylococcus aureus was the most common pathogen (43%) isolated. Similar proportions in both groups (6.3% placebo and 5.1% cefoxitin) required a course of therapeutic antibiotics.\n Antibiotic prophylaxis with cefoxitin in elective caesarean section did not reduce post-operative infectious morbidity in this double-blind randomised placebo controlled trial.", "The effectiveness of prophylactic cefoxitin in preventing postcesarean section infection was studied in a high risk population. One hundred women were evaluated, and on a random double-blind basis 50 received placebo and 50 received cefoxitin. There were three doses of drug given intravenously, either placebo or 1 gram of cefoxitin at the time of cord clamping and again four and eight hours later. Those receiving cefoxitin had significantly less postoperative infections, fewer had bacteremia and there was less postoperative fever as measured by the fever index. The patient with the most protracted infection in this study received cefoxitin. Problems with the use of systemic antibiotic prophylaxis in preventing postcesarean section infection are discussed. Cefoxitin is an effective agent to use in patients undergoing cesarean section who are at high risk for infection.", "We conducted a prospective, double-blind, randomized, placebo-controlled study of cefoxitin perioperative prophylaxis in 386 women having cesarean sections after labor or rupture of membranes. Private patients constituted 70% of subjects. Cefoxitin was chosen for its low toxicity and its broad spectrum against common obstetric pathogens including Bacteroides fragilis. Cefoxitin-treated women received 2 mg of drug intravenously at umbilical cord clamping and at 6 and 12 hours after surgery. Demographic and obstetric variables did not differ between the 190 placebo-treated women and the 196 cefoxitin-treated women. The morbidity rate from infection was significantly reduced by cefoxitin prophylaxis. Seven factors were significantly correlated with increased risk of infection after cesarean section: maternal age, socioeconomic status, race, gestational age, duration of internal fetal monitoring, use of intrauterine pressure catheter, and obesity. Cefoxitin prophylaxis resulted in significant decreases in infection incidence in women with one, two, and three risk factors, respectively, but the reduction was not significant in women with no risk factors. Length of hospital stay was not significantly reduced by cefoxitin prophylaxis but antibiotic use was decreased 24%.", "The efficacy of a narrow-spectrum (benzyl penicillin) versus broad-spectrum (clindamycin + gentamicin) preoperative antimicrobial prophylaxis was studied in a series of 147 consecutive patients undergoing Caesarean section at the State Maternity Hospital, Helsinki, Finland. Both regimens proved effective in reducing postoperative endometritis: from 33% (19/57 cases) to 6.5% (3/46 cases) in the penicillin treated group, and to 9.5% (4/42 cases) in the clindamycin + gentamicin treated group. The reduction in the incidence of endometritis was not reflected in the duration of hospital stay, which was 7.7 days in the untreated group, 7.8 days in the penicillin treated group, and 7.6 days in the clindamycin + gentamicin treated group. No significant differences between the groups were detected in the incidence of wound infections.", "To study the effect of single-dose prophylactic Augmentin on patients undergoing cesarean section.\n Three hundred and twenty women undergoing cesarean section were randomized into two groups in a prospective, double-blind, placebo-controlled study. One hundred and sixty women were allocated to receive a single-dose of 1.2 g Augmentin at induction of anesthesia and 160 were allocated to a control group who received placebo. The following post-cesarean outcome parameters were compared between the two groups: duration of hospital stay, febrile morbidity, urine microscopy, bacteriuria, endometritis, and wound infection.\n There was no significant difference between the two groups with respect to the duration of post-operative hospital stay or the incidence of febrile morbidity, endometritis, and wound infection. However, the study group had fewer post-operative abnormalities in urine microscopy (p < 0.05) and bacteriuria (p < 0.01). The bacterial flora were also different between the two groups.\n Single-dose prophylactic Augmentin did not produce any clinically significant improvement in the post-operative course of patients undergoing cesarean section. If proper surgical techniques are followed in association with closed rectus sheath drainage, it is unlikely that any trial of antibiotics will be able to demonstrate any clinically significant outcome.", "nan", "Eighty patients in labor and requiring cesarean section were selected randomly for a double-blind study using prophylactic cephalosporin and placebo. There were 26 treated patients who had no morbidity versus 13 in the control group. The reduction in endometritis was significant (P = less than .05). The most prevalent organism was Streptococcus viridans, followed by Escherichia coli. Bacterioides organisms were recovered 17 time in 11 patients. Tabulation of the fever index showed significant difference. No major complication occurred in the treatment group. Gastric aspirates from infants showed a good correlation with maternal morbidity and are suggested as a screening procedure.", "A double-blind, randomized prospective study was carried out in 96 women in labour requiring caesarean section to assess the value of antibiotic prophylaxis with cefuroxime compared with placebo. Forty-six patients received 750 mg cefuroxime intravenously before and every 8 hours for the first 72-hours post-operatively; the other 50 women received placebo injections. A significant decrease in post-operative morbidity was observed in the drug-treated group, there were far fewer endometrial, urinary and pulmonary injections, and those who received prophylactic cefuroxime had less days of hospitalization than the placebo-treated group. No serious side-effects were observed.", "The purpose of this present study was to determine whether intraoperative antibiotic uterine irrigation was effective in reducing febrile morbidity (Part 1), and to determine whether ticarcillin disodium (Ticar) or cefoxitin sodium (Mefoxin) was the more effective solution (Part 2). The indications for cesarean section had an effect on febrile morbidity. In patients having nonelective cesarean section, febrile morbidity was high, occurring in 62.7% of the saline control group and 32.9% of those receiving ticarcillin disodium irrigation. In patients having elective cesarean section, febrile morbidity was lower (28% in the saline control group and 8.3% in the ticarcillin group [P less than or equal to .05]). Ticarcillin and cefoxitin were equal in reducing postoperative febrile morbidity. The use of prophylactic antibiotics, therefore, is indicated both in high-risk patients having nonelective cesarean section and in low-risk patients having elective repeat cesarean section.", "Cefoxitin, a second-generation cephalosporin, was compared with cefazolin, a first-generation cephalosporin, and a placebo in a prospective, double-blind study of antibiotic prophylaxis in women undergoing nonelective cesarean section. In the groups that received cefazolin or the placebo there eas no statistically significant change in colonization of the cervix by aerobic bacteria by the fourth day after the operation, but there was a statistically significant increase in colonization by anaerobes. Cefoxitin had the opposite effect. Of the 14 postoperative infections in 11 patients, significantly more were in patients who had received the placebo; the numbers were too small to show a difference in effectiveness between the two antibiotics. Of the microorganisms implicated as the infectious agents, group B Streptococcus was the most frequent aerobe, and Peptostreptococcus and Bacteroides bivius were the most frequent anaerobes. Among the 15 patients for whom at least one perioperative specimen yielded positive culture results, a postoperative infection developed in 5 of the 6 who received the placebo, 2 of the 4 who received cefazolin and 1 of the 5 who received cefoxitin.", "nan", "A short-course, low-dose perioperative prophylactic regimen of cephradine was found to be highly effective in preventing serious postoperative infections (wound, vaginal cuff/pelvic and endometrial) in patients undergoing cesarean sections and vaginal hysterectomies. In patients undergoing abdominal hysterectomy no significant difference was observed in the prevalence of wound and pelvic infections in the antibiotic and placebo-treated groups. In all three operative procedures there was no significant reduction in urinary tract infections. The postoperative length of stay was significantly decreased in cesarean section patients, and a similar trend was observed in vaginal hysterectomy patients. An analysis of risk factors in cesarean section revealed that anemia and labor reduced the effectiveness of prophylaxis. Among vaginal hysterectomy patients those who were anemic and those who were premenopausal were at greater risk of infection. There was a low incidence of adverse drug reactions (less than 0.5%) and no evidence of the promotion of bacterial resistance in cephradine-treated patients." ]

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[ "Ovarian suppression induced with Buserelin or danazol in the management of endometriosis: a randomized, comparative study.", "Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study. Lupron Study Group.", "Clinical experience treating endometriosis with nafarelin.", "[Medical treatment of endometriosis: comparative study of leuprolide acetate and danazol].", "Pain of endometriosis: effects of nafarelin and danazol therapy.", "A comparative treatment trial of endometriosis using the gonadotrophin-releasing hormone agonist, nafarelin, and the synthetic steroid, danazol.", "An open randomized comparative study of the effect of goserelin depot and danazol in the treatment of endometriosis. Zoladex Endometriosis Study Team.", "A randomized, comparative trial of triptorelin depot (D-Trp6-LHRH) and danazol in the treatment of endometriosis.", "Nafarelin versus danazol in the treatment of endometriosis.", "Buserelin versus danazol in the treatment of endometriosis-associated infertility.", "Serum-soluble CD23 in patients with endometriosis and the effect of treatment with danazol and leuprolide acetate depot injection.", "A randomized, parallel, comparative study of the efficacy and safety of nafarelin versus danazol in the treatment of endometriosis in Taiwan.", "Depot leuprolide versus danazol in treatment of women with symptomatic endometriosis. I. Efficacy results.", "Administration of nasal nafarelin as compared with oral danazol for endometriosis. A multicenter double-blind comparative clinical trial.", "Buserelin acetate in the treatment of pelvic pain associated with minimal and mild endometriosis: a controlled study.", "Reversible pituitary ovarian suppression induced by an LHRH agonist in the treatment of endometriosis--comparison of two dose regimens.", "Clinical study on finding optimal dose of a potent LHRH agonist (buserelin) for the treatment of endometriosis--multicenter trial in Japan.", "The levonorgestrel-releasing intrauterine system and endometriosis staging.", "Nafarelin: a new medical therapy for endometriosis.", "A randomized comparative study of the effect of leuprorelin acetate depot and danazol in the treatment of endometriosis.", "Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis.", "Nafarelin in the management of endometriosis: quality of life assessment.", "A randomized, prospective comparison of endocrine changes induced with intranasal leuprolide or danazol for treatment of endometriosis.", "Nafarelin vs. leuprolide acetate depot for endometriosis. Changes in bone mineral density and vasomotor symptoms. Nafarelin Study Group.", "[Influence of GnRH analogue on the intensification of endometriosis symptoms and infertility treatment].", "A double-blind randomized study of the treatment of endometriosis with nafarelin or nafarelin plus norethisterone.", "Effects of the levonorgestrel-releasing intrauterine system on cardiovascular risk markers in patients with endometriosis: a comparative study with the GnRH analogue.", "Zoladex (goserelin acetate implant) in the treatment of endometriosis: a randomized comparison with danazol. The Zoladex Endometriosis Study Group.", "Effects of triptorelin versus placebo on the symptoms of endometriosis." ]

[ "The effectiveness of Buserelin (Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ) (0.2 mg subcutaneously [SC] or 1.2 mg intranasally [IN] per day) and danazol (800 mg per day) in inducing ovarian suppression for the management of endometriosis was compared in a prospective randomized study. During 6 months of treatment, peripheral follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol concentrations were suppressed to a similar degree in both groups. Symptomatic improvement and laparoscopically assessed regression of endometriotic lesions also were comparable. After treatment, 8 of 18 infertile women treated with Buserelin and 5 of 8 treated with danazol conceived. General and hypoestrogenic side effects were similar in both groups, while androgenic and anabolic were more frequent with danazol. High density lipoprotein (HDL)-cholesterol increased in the Buserelin and decreased in the danazol group. The study indicates that at the dose tested, buserelin and danazol induce a similar degree of ovarian suppression resulting in a comparable clinical improvement and regression of endometriotic lesions.", "The safety and efficacy of leuprolide acetate (LA) for depot suspension (Lupron depot; TAP Pharmaceuticals, North Chicago, IL), 3.75 mg versus placebo, in the treatment of pain associated with endometriosis was assessed in a randomized, double-blind, multicenter study involving 52 patients. Dysmenorrhea, pelvic pain, and pelvic tenderness all responded significantly to LA treatment in comparison with placebo. Menses were suppressed in all of the LA patients. Estradiol decreased significantly to menopausal levels in the LA group. There were small to moderate changes in a variety of laboratory parameters, but these were not clinically significant. The most common adverse event was vasodilatation, occurring significantly more frequently in the LA group. Lupron depot was shown to be safe and effective in inducing a hormonal and menstrual suppression in patients with endometriosis, resulting in alleviation of pain symptoms.", "The preliminary results from an ongoing multicenter trial further support the efficacy and excellent tolerability of nafarelin in the management of endometriosis.", "Hypo-oestrogenaemia following surgical oophorectomy leads to a regression of the ectopic endometrial tissue. A medical and transitory oophorectomy can be obtained using leuprolide ac., an analogue of LH-RH. In this study we compare the results of therapy with danazol or leuprolide in the treatment of endometriosis. Fifty patients affected by endometriosis were selected laparoscopically and recorded under the classification of American Fertility Society. 20-40 year old women who were admitted had not received any therapy for endometriosis within the previous 12 months. They were allocated at random to open treatment with intramuscular injection of leuprolide (3.75 mg/monthly) or oral danazol. The dose regimen used for this last drug was 600 mg/daily in the majority of patients. 47 women completed a six months therapy, and 42 underwent to a second laparoscopy to evaluate the effects of the treatment. Both danazol and leuprolide were associated to a decreasing of clinical symptoms and to adverse effects that we described in this paper.", "To compare the efficacy of nafarelin acetate with danazol in the treatment of dysmenorrhea, dyspareunia, and pelvic pain associated with endometriosis.\n Prospective, randomized double-blind controlled study. PATIENTS, SETTING, TREATMENTS: Two hundred thirteen patients aged 18 to 48 with laparoscopically confirmed pelvic endometriosis and dysmenorrhea, dyspareunia or pelvic pain were randomly assigned to 6 months of treatment with either nafarelin acetate 800 micrograms per day or 400 micrograms per day, or danazol 800 micrograms per day.\n The percentage of patients with dysmenorrhea, dyspareunia or pelvic pain before treatment who still had these symptoms after 6 months of treatment and 6 months following completion of treatment. RESULTS [table: see text]\n Nafarelin acetate and danazol both provided significant relief of dysmenorrhea, dyspareunia, and pelvic pain during treatment and for 6 months following treatment in women with endometriosis.", "A randomized and double-blind trial was carried out comparing intranasal nafarelin acetate (400 micrograms daily) and oral danazol (600 mg daily), given over 6 months, in the treatment of 49 patients with laparoscopically proven endometriosis. Both drugs produced a highly significant and similar reduction (of 60 to 70%) in objective American Fertility Society scoring, even in severe disease. No effect was seen on adhesions. Both drugs suppressed oestradiol levels to a similar extent, although nafarelin caused a substantial rise in the first 2 weeks after the initiation of therapy. Nafarelin suppressed LH substantially and FSH, testosterone and prolactin to a small degree, whereas FSH and LH increased slightly during danazol. Pregnancies occurred in 12 of 22 infertile women in the 12 months following nafarelin, and in 6 of 14 in the danazol group. Side-effects were reported at a similar rate with both drugs, but the pattern was different. Hot flushes were the predominant side effect with nafarelin, although oestradiol levels were not suppressed to the extent expected. Small amounts of spotting or light bleeding were experienced with both drugs, but these tended to decrease with time with nafarelin and increase with danazol.", "To compare the efficacy and safety of goserelin depot and danazol for endometriosis.\n Open, randomized comparative trial.\n Multicenter European academic clinical institutions.\n A total of 307 patients with laparoscopically diagnosed endometriosis were randomized to goserelin (n = 204) or danazol (n = 103); 249 patients underwent second look laparoscopy (175 received goserelin and 74 danazol) and were analyzed for efficacy.\n A 3.6-mg depot of goserelin monthly subcutaneously or oral danazol 200 mg three times a day administered for 24 weeks.\n Efficacy assessments were based on changes in visible deposits at laparoscopy before and after treatment and subjective symptom scores at 4-week intervals during treatment and 8-week intervals after treatment for up to 24 weeks. Safety was assessed by adverse event reporting and clinical laboratory measures.\n There were similar proportions of symptomatic (73%) and asymptomatic (but infertile) (27%) and comparable distribution of different severity of endometriosis randomized to each treatment. Significantly fewer patients randomized to goserelin (6.4%) withdrew during treatment compared with 20.4% randomized to danazol (P less than 0.05). There were significantly reduced visible deposits of endometriosis found post-treatment (P less than 0.0001) within each group but no differences between the treatments. The mean total subjective symptoms scores remained significantly less than entry at 24 weeks post-treatment (P less than 0.05). Hypoestrogenic side effects were more common in those receiving goserelin, particularly hot flushes, but anabolic/androgenic side effects of weight gain and muscle cramps were more common in those receiving danazol.\n The monthly administered 3.6-mg depot preparation of goserelin was highly effective at inducing resolution of endometriotic implants and relieving the symptoms of endometriosis with prevention of their return during 24 weeks follow-up in the majority of patients. However, results were not significantly different from those achieved with danazol 600 mg/d.", "To compare treatment efficacy and safety parameters a total of 55 premenopausal women with histologically proven endometriosis (stage II-IV) were randomized to receive the LHRH-analogue depot triptorelin (n = 30) or the steroid danazol (n = 25) for a total of 24 weeks. Immediately after cessation of the endocrine therapy a second-look operation was performed. Four as well as 24 weeks after the end of treatment patients were seen for re-evaluation of clinical symptoms and safety parameters. Estradiol suppression was significantly more pronounced with triptorelin, while the free androgenic index rose with danazol. Both substances were equally effective in reducing endometriotic implants (58% and 51%, respectively). Dysmenorrhea was absent at the end of medical therapy in both treatment groups. Dyspareunia and pelvic pain decreased at least by 50%. Red blood count, thrombocytes, liver enzymes and the atherogenic index rose with danazol, while the urinary calcium/creatinine ratio showed a marked elevation with triptorelin. Adverse effects were mainly due to the hypoestrogenism of the LHRH analogue and the androgenic/anabolic properties of the steroid. Triptorelin and danazol are equally effective in treating endometriosis. Therefore, choice of treatment should be based on the patient's medical history and the pharmacological profile of each substance.", "A double-blind, double-dummy, 6-month multicenter study comparing the effects of nafarelin and danazol in the treatment of endometriosis was completed recently by investigators from 13 institutions in seven European countries. The 194 patients (aged 18 to 45 years) selected for the study were divided into two groups. One group received nafarelin, 200 micrograms twice daily, and placebo capsules identical to danazol, twice daily. The other group received danazol capsules, 200 mg twice daily, and a placebo nasal spray identical to nafarelin, twice daily. A comparison of decreases in both groups of American Fertility Society endometriosis scores and in severity scores developed by the investigators indicates that nafarelin and danazol are equally effective in the treatment of endometriosis.", "A total of 62 infertile women with a laparoscopic diagnosis of endometriosis were allocated randomly to two treatment groups, one of which (32 patients) received oral danazol 600 micrograms/day and the other (30 patients) received intranasal buserelin 1200 micrograms/day for 6 months. Suppression of serum levels of estradiol was greater with the gonadotropin-releasing hormone agonist treatment. Pain symptoms improved markedly during treatment in both groups. At the end of treatment a repeat laparoscopy was performed only in the patients who agreed to it (12 in the buserelin group and 13 in the danazol group), and it did not reveal significant differences in the effects of the two treatments on the endometriotic implants. All of the patients were followed up for at least 12 months, during which pregnancy was attempted. At 18 months the cumulative pregnancy rate was 48% in the patients treated with buserelin and 43% in those treated with danazol. Pain recurrence was observed in about half of the patients in each group 1 year after treatment suspension. The side effects were more frequent and more severe in the danazol-treated patients, whereas those given buserelin generally reported only symptoms of hypoestrogenism. The results of this study suggests that buserelin is at least as effective as danazol in the treatment of endometriosis when the outcome is considered in terms of restored fertility, and its side effects are less severe.", "Activated B cells have recently been shown to produce soluble CD23 from their membranes. The serum-soluble CD23 concentration in 21 patients with pelvic pain diagnosed as having endometriosis and confirmed by histology, and in 18 patients without pelvic pain, who had a normal pelvis during laparoscopic sterilization, was studied by chemiluminescent enzyme-linked immunosorbent assay. The endometriosis patients were randomized to 3 months of either danazol or leuprolide acetate injection. Serum was taken before and after 3 months of therapy. The serum-soluble CD23 concentration was significantly elevated in patients with endometriosis when compared with the controls (P < 0.0001). There was no correlation between soluble CD23 concentrations and the severity of endometriosis (r = 0.48, P > 0.05). The serum concentration of soluble CD23 decreased significantly on treatment with danazol but not leuprolide acetate (P < 0.05). We conclude that the elevation of soluble CD23 in patients with endometriosis suggests that there is activation of B cells, which respond to danazol but not leuprolide acetate injection.", "The purpose of this study was to evaluate the efficacy and safety of nafarelin, a gonadotropin-releasing hormone (GnRH) analogue, versus danazol in the treatment of women with endometriosis in Taiwan.\n Fifty-nine women with laparoscopically and pathologically confirmed endometriosis were randomized to receive nafarelin or danazol for 180 days. Efficacy was assessed from mean changes in laparoscopy score (LS) and total symptom severity score (TSSS). Adverse events (AEs) and laboratory parameters, including hematology, hepatic function, blood pressure, and lipid levels, were monitored for safety evaluations.\n All demographic and baseline factors, except body weight, were comparable between the 2 treatment groups. Both nafarelin and danazol satisfactorily resolved pelvic tenderness, induration, pelvic pain, dysmenorrhea and dyspareunia. No significant differences were noted in efficacy endpoints between nafarelin and danazol regarding LS and TSSS at 90 and 180 days of treatment. No significant difference was observed between the 2 groups regarding the overall incidence of AEs, except for laboratory-related AEs. However, nafarelin tended to have less impact than danazol on aspartate transaminase and alanine transaminase, and nafarelin was better tolerated than danazol regarding changes in lipid profiles. Both treatments had little or no effect on hematologic parameters.\n Nafarelin and danazol demonstrated similar clinical efficacy, but nafarelin was associated with fewer laboratory changes and a stable lipid profile, relative to danazol. Moreover, intranasally administered nafarelin is noninvasive, and may be a more comfortable and safer alternative to slow-release injectable GnRH agonists. Based on this study, we suggest that nafarelin, like other GnRH analogues, may be a treatment of choice for Taiwanese women with endometriosis. However, direct comparative studies of nafarelin with slow-release injectable GnRH agonists are now required.", "We aimed to assess the efficacy of depot leuprolide versus danazol in the treatment of endometriosis.\n A double-blind randomized trial of 270 patients from 22 centers compared the pretreatment and posttreatment laparoscopic extent of endometriosis. Pretreatment and posttreatment endometriosis symptoms and signs were assessed with standardized methods.\n When compared with danazol, leuprolide depot caused a more rapid and profound suppression of estradiol. Leuprolide depot and danazol were similarly efficacious in decreasing the extent of endometriosis, as well as the pain and tenderness associated with endometriosis.\n Depot leuprolide is an effective alternative to danazol in decreasing the extent of endometriosis and endometriosis-related pain.", "Treatment with nafarelin, a gonadotropin-releasing hormone agonist, reversibly inhibits ovarian function and induces hypoestrogenemia. To determine the efficacy of such hormonal manipulation in the treatment of endometriosis, we randomly assigned 213 patients with laparoscopically confirmed endometriosis to receive, for six months, either nafarelin by nasal spray (400 or 800 micrograms per day) or oral danazol (800 mg per day). Placebo nasal spray and placebo tablets were used to double blind the study. Pretreatment and post-treatment laparoscopies were compared by means of the American Fertility Society's scoring system. More than 80 percent of the patients in each treatment group had a reduction in the extent of disease as assessed by laparoscopy. The mean laparoscopic scores decreased from 21.9 to 12.6 with 800 micrograms of nafarelin, from 20.4 to 11.7 with 400 micrograms of nafarelin, and from 18.4 to 10.5 with danazol (P = 0.0001 within each group; there were no statistically significant differences between the groups). The percentage of women with severely painful symptoms of endometriosis decreased from about 40 percent to 5 to 10 percent, whereas the percentage with no or minimal discomfort rose from 25 to 70 percent. Of the 149 patients who tried to become pregnant, 58 (39 percent) succeeded after the completion of treatment; similar rates of pregnancy applied to the three treatment groups. Danazol use decreased high-density lipoprotein levels and increased low-density lipoprotein levels. These changes were not observed in nafarelin users, but a higher percentage of them reported hot flashes and decreased libido. We conclude that nafarelin is an effective agent for treating endometriosis and has few side effects other than hypoestrogenism.", "To evaluate the changes of pain symptoms induced by buserelin acetate, a gonadotropin-releasing hormone agonist, in a group of patients with endometriosis.\n Thirty-five infertile patients with one or more of the following symptoms (dysmenorrhea, pelvic pain, deep dyspareunia, and endometriosis stage I or II) were allocated randomly to treatment with buserelin acetate 1,200 micrograms/d IN for 6 months (n = 19) or expectant management (n = 16). Pain symptoms were recorded by the women themselves using a questionnaire that included two scales for pain evaluation: one analogue and one multidimensional. The treated and untreated patients were followed for a minimum of 18 and 12 months from the time of randomization, respectively.\n Buserelin acetate markedly reduced dysmenorrhea, pelvic pain, and dyspareunia during the treatment and also for the 12 subsequent months. During follow-up of the expectant management group, dysmenorrhea resolved in 19% (3/16) of the cases, and pelvic pain did not recur after diagnostic laparoscopy in one of the three women affected nor did deep dyspareunia in two of the five who reported the symptom before laparoscopy.\n Buserelin acetate induced a significant improvement of pain symptoms that persisted in approximately half of the patients even after withdrawal of the drug. However, symptoms associated with endometriosis showed a spontaneous remission in approximately one fifth of the untreated patients.", "Buserelin [D-Ser(TBU)6-des Gly NH2(10) LHRH ethylamide], an LHRH agonist, was administered intranasally at two dose levels, 200 micrograms t.d.s or 300 micrograms t.d.s., to 20 women with proven endometriosis, many with recurrent disease. Both dose schedules achieved significant suppression of circulating 17 beta-oestradiol levels often to within the postmenopausal range, the larger dose inducing significantly greater suppression (P less than 0.05). Serum FSH values were suppressed below baseline but serum LH remained at pretreatment levels or above, whilst on treatment. Complete resolution of endometriotic deposits was achieved in 68% of cases following 6 months treatment with dramatic and long-standing relief of symptoms with no apparent dose difference. In all other subjects there was significant reduction in the extent of endometriotic deposits and improvement in American Fertility Society classification of disease stage. The most commonly occurring side effect was hot flushes; their intensity and frequency related to the degree of suppression of serum oestradiol and the dose of Buserelin administered.", "nan", "This study aims to determine whether the levonorgestrel-releasing intrauterine system can influence American Society for Reproductive Medicine endometriosis staging scores, as assessed through second-look laparoscopies, and to compare the results with those obtained with a GnRH agonist. Both treatments reduced the extent of pelvic endometriotic lesions in patients with chronic pelvic pain.", "nan", "Administration of superactive agonistic analog of gonadotropin-releasing hormone (GnRH) has shown to induce a paradoxic and reversible suppression of gonadotropins, so that gonadal steroid concentrations are suppressed and hypoestrogenemia is induced. In order to compare the efficacy and safety of leuprorelin acetate depot (LA) and danazol in the treatment of endometriosis, we conducted this study.\n A total of forty-five patients with pelvic endometriosis of different severity at laparoscopy with biopsy of peritoneal implants (n = 33) and surgical procedure (enucleation of ovarian chocolate cysts, cystectomy, or fulguration, n = 12) were included in the study and followed during the 20 weeks of treatment. LA 3.75 mg was injected subcutaneously every 28 days, while the daily oral dose of danazol was 800 mg.\n Both treatments were associated with a lowering of severity score. There was a consistent decrease in women with stage IV disease in the LA group and an increase in patients with stage I disease in the danazol group, but no difference was found between both treatments. Hot flushing was the most common side effect reported in 97% of LA but occurred only in 13% of danazol-treated patients. In contrast, the androgenic, anabolic side effects of weight gain and myalgia were common in those receiving danazol. The CA-125 levels were significantly lower in both treatment groups compared with their pretreatment levels (p < 0.01). During the five months of the LA treatment, biochemical evaluation revealed no pathologic alternation. Only total protein albumin, alkaline phosphatase, total bilirubin, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, uric acid and calcium increased significantly. Danazol was also associated with adverse metabolic effects and significantly increased low-density lipoprotein-cholesterol concentrations (p < 0.05). In the fourth week, serum estradiol (E2) levels decreased to nearly castrated levels (13.87 +/- 1.63 pg/ml) in all patients treated with LA, and remained at this level thereafter. On the contrary, a slight but significant increase of the serum E2 levels was noted during the danazol treatment. After five months of treatment with LA, no significant changes in bone density were observed at the femoral neck or the anteroposterior (AP) view of lumbar spine, but there was a significant loss in bone density at the lateral view of lumbar spine (-7.1%, p < 0.05).\n Both LA and danazol are effective in the treatment of endometriosis. The hypoestrogenic side effects of LA may be better tolerated than the androgenic, anabolic effects of danazol. However, the danazol treatment costs less than LA and has no significant side effect with osteoporosis.", "The objective of this multicentre randomized, controlled clinical trial was to compare the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) and a depot-GnRH-analogue in the control of endometriosis-related pain over a period of six months.\n Eighty-two women, 18 to 40 years of age (mean 30 years), with endometriosis, dysmenorrhoea and/or CPP, were randomized using a computer-generated system of sealed envelopes into either LNG-IUS (n = 39) or GnRH analogue (n = 43) treatment groups at three university centres. Daily scores of endometriosis-associated CPP were evaluated using the Visual Analogue Scale (VAS), daily bleeding score was calculated from bleeding calendars, and improvement in quality of life was evaluated using the Psychological General Well-Being Index Questionnaire (PGWBI). The pain score diary was based on the VAS in which women recorded the occurrence and intensity of pain on a daily basis. A monthly score was calculated from the result of the sum of the daily scores divided by the number of days in each observation period.\n CPP decreased significantly from the first month throughout the six months of therapy with both forms of treatment and there was no difference between the groups (P > 0.999). In both treatment groups, women with stage III and IV endometriosis showed a more rapid improvement in the VAS pain score than women with stage I and II of the disease (P < 0.002). LNG-IUS users had a higher bleeding score than GnRH-analogue users at all time points of observation with 34% and 71% of patients in the LNG-IUS and GnRH-analogue groups, respectively, reporting no bleeding during the first treatment month, and 70% and 98% reporting no bleeding during the sixth month. No difference was observed between groups with reference to improvement in quality of life.\n Both, the LNG-IUS and the GnRH-analogue were effective in the treatment of CPP-associated endometriosis, although no differences were observed between the two treatments. Among the additional advantages of the LNG-IUS is the fact that it does not provoke hypoestrogenism and that it requires only one medical intervention for its introduction every 5 years. This device could therefore become the treatment of choice for CPP-associated endometriosis in women who do not wish to conceive.", "Quality of life is important when comparing the relative advantages of nafarelin versus danazol for the treatment of endometriosis. Recent studies have investigated the potential differences between the safety profiles of nafarelin and danazol and the impact of these profiles on the patient's quality of life. Results show that although these drugs have similar efficacy, they are associated with very different safety profiles. Most notable are the androgenic effects such as weight gain associated with danazol. With nafarelin, hypoestrogenic side effects, such as hot flashes, are more common. More important, these differences in safety profiles may prove to be relevant to patient satisfaction and compliance with therapy.", "A prospective, randomized trial compared hormonal changes induced with intranasal leuprolide 1.6 mg/day to danazol 800 mg/day for treatment of endometriosis. Both regimens induced anovulation and ovarian suppression in all subjects. Mean estradiol (E2) and progesterone (P) levels were suppressed with both regimens, but were lower with leuprolide. There was no difference in cumulative follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, although at times during treatment mean levels of these hormones were lower with leuprolide. Higher P levels in the danazol group, most likely of adrenal origin, indicated a suppressive effect on adrenal steroidogenesis. Symptomatic improvement was significant in both groups. Laparoscopy after treatment also demonstrated a decrease in endometriosis scores in both groups. At 12 months after treatment, cumulative pregnancy and live birth rates were similar in both groups. Leuprolide offers an attractive alternative to danazol for the medical treatment of endometriosis.", "To compare intranasal nafarelin and intramuscular leuprolide acetate (LA) depot in the management of endometriosis.\n A multicenter, prospective, randomized, double-placebo, double-blind study was conducted on subjects who had symptoms and signs of endometriosis and bone mineral density (BMD) within the age-appropriate normal range. For 6 months, 99 subjects received nafarelin, 200 micrograms twice daily, and placebo injections once monthly; 93 subjects received LA depot injections, 3.75 mg once monthly, and placebo nasal spray, twice daily. Subjects were followed throughout treatment and for six months after treatment. The main outcome measures were changes in endometriosis symptoms and signs, BMD measurements, subject-reported and objectively measured hot flushes and circulating estradiol concentrations.\n Nafarelin was as effective as LA depot in alleviating symptoms and signs of endometriosis. LA depot recipients lost significantly more BMD, had more days with subjective hot flushes and more objectively measured hot flushes than did nafarelin recipients. In the nafarelin group, estradiol levels were consistently higher than in the leuprolide depot group, with significant differences by month 3 of dosing.\n Nafarelin and LA depot were equally effective despite higher estradiol levels in nafarelin recipients. Nafarelin-treated subjects lost less BMD, had fewer days with hot flushes and had fewer objectively measured hot flushes.", "The aim of this study was to evaluate the influence of the treatment with oral doses of 50 mg GnRH analogue on the intensification of endometriosis symptoms and infertility amongst women with evident symptoms of endometriosis in comparison with placebo group. A group of 34 women at the age from 18 to 45 were introduced into the study. The inclusion criteria for investigated population contained: endometriosis symptoms, endometriosis diagnosed by laparoscopy, its surgical or pharmacological treatment, negative pregnancy test score and regular menses. The patients were divided into 2 groups: investigated group and control group. Women completed \"Diary\" every day in which they estimated main endometriosis symptoms: dysmenorrhea, dyspareunia, pelvic pain and vaginal bleeding (according to Pain Grading Scale). The intensification of dysmenorrhea and vaginal bleeding was reduced in the investigated group in comparison with control one. These differences were statistically significant. Although the extremity of dyspareunia was decreased in two groups, this correlation was statistically significant only in the investigated group. Pelvic pain evaluation showed that its level was lower in the investigated group (p > 0.05). It was found that 11 women (investigated group) and 5 women (control group) got pregnant after the period of 12-week treatment.\n GnRH analogues have an efficient influence on the reduction of endometriosis symptoms. GnRH analogues could be used in the management of infertility.", "The objective of this study was to compare the efficacy of nafarelin 200 micrograms (Group A), nafarelin 400 micrograms (Group B) and the combination of nafarelin 200 micrograms and norethisterone 1.2 mg (Group C) daily, in treating symptoms of endometriosis, American Fertility Society score and adverse events during 6 months of treatment. A prospective, randomized, double-blind parallel group study was performed in two centers and 49 women with endometriosis diagnosed laparoscopically were included. The patients were seen monthly for physical examination and records were taken for bleeding pattern, symptom score and adverse events. A control laparoscopy was performed at the end of 6 months of treatment. All patients were followed 6 months after treatment. At 3 and 6 months the pelvic examination total score had decreased significantly in all three groups. The total endometriosis score was significantly reduced in Groups B and C. After 2 months the total symptom score showed a significant decrease in Groups B and C. The frequency of hot flushes during the first month of treatment was lowest in Group C, but during the rest of treatment there were no differences between the groups. Best bleeding control was obtained in Group C. We conclude that nafarelin 200 micrograms daily has as good an effect on endometriosis symptoms as nafarelin 400 micrograms daily, and the addition of norethisterone 1.2 mg results in fewer hot flushes and better bleeding control.", "The study was conducted to evaluate the cardiovascular risk markers associated with endometriosis and the influence of the levonorgestrel intrauterine system (LNG-IUS) compared with the GnRH analogue (GnRHa) leuprolide acetate on these risk markers after 6 months of treatment.\n This was a randomized, prospective, open clinical study, with 44 patients with laparoscopically and histologically confirmed endometriosis. Patients were randomized into two groups: the LNG-IUS group, composed of 22 patients who underwent LNG-IUS insertion, and the GnRHa group, composed of 22 patients who received a monthly GnRHa injection for 6 months. Body mass index; systolic and diastolic arterial blood pressure; heart rate; and laboratory cardiovascular risk markers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), homocysteine (HMC), lipid profile, total leukocytes and vascular cell adhesion molecule (VCAM) were measured before and 6 months after treatment.\n After 6 months of treatment, a significant reduction in pain score occurred in both groups with no significant difference in improvement between the two medications evaluated. In the LNG-IUS group, from pretreatment to posttreatment period, there was a significant reduction in the levels (mean+/-SD) of VCAM (92.8+/-4.2 to 91.2+/-2.7 ng/mL, p=.04), CRP (0.38+/-0.30 to 0.28+/-0.21 mg/dL, p=.03), total cholesterol (247.0+/-85.0 to 180.0+/-31.0 mg/dL, p=.0002), triglycerides (118.0+/- 76.0 to 86.5+/-41.5 mg/dL, p=.003), low-density lipoprotein cholesterol (160.5+/-66.0 to 114.5+/-25.5 mg/dL, p=.0005) and high-density lipoprotein cholesterol (63.0+/-20.5 to 48.5+/-10.5 mg/dL, p=.002). The GnRHa group showed an increase in HMC levels (11.5+/-2.9 to 13.0+/-2.7 mumol/L, p=.04) and a reduction in IL-6 levels (4.3+/-3.9 to 2.3+/-0.8 pg/mL, p=.005), VCAM (94.0+/-3.8 to 92.0+/-1.6 ng/mL, p=.03) and total leukocytes (7330+/-2554 to 6350+/-1778, p=.01). In the GnRH group, the remaining variables, including lipid profile, did not show any statistical difference.\n This study shows that some cardiovascular risk markers are influenced by both GnRHa and the LNG-IUS, but the latter had a greater positive impact on the lipid profile, which could lead to a favorable effect during long-term treatment.", "To compare the efficacy, endocrine effects, and safety of Zoladex (goserelin acetate) and danazol in the treatment of premenopausal women with endometriosis in a multicenter, randomized, open study.\n Three hundred fifteen patients with stages I-IV endometriosis (revised American Fertility Society [AFS] classification) were treated with Zoladex, 3.6 mg every 28 days by subcutaneous injection, or danazol, 400 mg orally twice daily for 24 weeks. Efficacy was assessed by determination of pelvic signs and symptoms scores and revised AFS endometriosis scores. Endocrine effects were determined by measurements of hormone levels. Safety was evaluated by physical examination, laboratory indices, occurrence of adverse events, and bone mineral density changes.\n Both treatments significantly (P < .0001) reduced mean subjective signs and symptoms scores both during and after therapy. The mean percent reduction in the revised AFS endometriosis score after 24 weeks of treatment was 53% for Zoladex and 33% for danazol, and reduction in the endometrial implants score was 56% for Zoladex and 46% for danazol. Serum estradiol levels decreased to the postmenopausal range in the Zoladex group and to the early follicular phase range in the danazol group. Hypoestrogenic effects occurred more frequently with Zoladex, whereas androgenic side effects were more common with danazol. There was a higher percentage of withdrawals due to adverse events with danazol than with Zoladex. Mean bone mineral density decreased from baseline by 5.4% in the Zoladex group and increased by 1.0% in the danazol group at the end of treatment.\n Zoladex is as well tolerated and as effective as danazol in the treatment of premenopausal women with endometriosis.", "To compare the effect of a GnRH-agonist, triptorelin, versus placebo on the symptoms of endometriosis.\n A prospective, randomized, double-blind study of 6 months of treatment followed by 12 months of follow-up.\n Departments of Obstetrics and Gynecology at two universities and one general hospital.\n Forty-nine women with symptoms of laparoscopically verified endometriosis.\n Triptorelin depot or placebo was given every 4 weeks. Clinical evaluation, including the Duration Intensity Behavior Scale and Visual Analogue Scale for pain, was performed before the injections and up to 12 months after treatment. A control laparoscopy was performed 4-6 weeks after the last injection.\n Quantitation of pain.\n Twenty-four patients had active treatment and 25 received placebo. Pain symptoms according to both scales were significantly more reduced after 2 months of triptorelin treatment compared to placebo. The extent of endometriotic lesions was reduced 50% during triptorelin treatment and increased 17% during placebo. The average area of endometriotic lesions was reduced 45% during triptorelin treatment but was unchanged during placebo. Side effects, mainly hot flushes, were experienced by 80% of the actively treated group but also by 33% of patients in the placebo group. Because of recurrent symptoms, only five patients could be observed for 12 months after completion of treatment.\n Triptorelin reduces endometriotic lesions and pain to a significantly higher degree than placebo." ]

[ "18700421" ]

[ "Cidofovir efficacy in recurrent respiratory papillomatosis: a randomized, double-blind, placebo-controlled study." ]

[ "We performed a prospective, double-blind, placebo-controlled, longitudinal adjuvant therapy trial to determine the efficacy of cidofovir in the treatment of severe recurrent respiratory papillomatosis (RRP). Although results of case series suggest that cidofovir may decrease the frequency and rapidity of papilloma regrowth, no blinded placebo-controlled studies have demonstrated efficacy.\n Adults and children (n = 19) with aggressive RRP received either active drug (cidofovir) or placebo. When surgical intervention was needed, drug or placebo was injected into affected areas after surgical removal of disease. The following measures were made at baseline and at 2-month intervals for the course of 12 months: Derkay papilloma severity grading scale, Voice Handicap Index, Health-Related Quality of Life, and total number of procedures performed over 12 months.\n At 2- and 12-month follow-ups, there was a significant (p < .05) improvement in the Derkay Severity Score within the cidofovir and placebo groups, but no difference between groups, and no difference between groups in the number of procedures performed. Significant improvement was found in Voice Handicap Index scores in the cidofovir group at the 12-month follow-up. No differences were seen in Health-Related Quality of Life.\n A randomized, blinded, placebo-controlled trial is necessary in the study of RRP, because the natural history of the disease can include remissions and reactivations. We found a significant improvement in the Derkay Severity Score 12 months after the baseline assessment in patients treated with cidofovir. This effect, however, was also seen in the placebo group. Accordingly, we were unable to provide proof of efficacy of cidofovir in the treatment of RRP." ]

[ "12168963", "11504286", "9566570", "8735046" ]

[ "Prospective randomized clinical trial comparing nitrous oxide and carbon dioxide pneumoperitoneum for laparoscopic surgery.", "Metabolic and immunologic consequences of laparoscopy with helium or carbon dioxide insufflation: a randomized clinical study.", "Comparison of N2O and CO2 pneumoperitoneums during laparoscopic cholecystectomy with special reference to postoperative pain.", "Comparative stress hormone changes during helium versus carbon dioxide laparoscopic cholecystectomy." ]

[ "Recent publications demonstrating the safety and advantages of N2O for pneumoperitoneum (PP) prompted us to reconsider N2O as an agent for PP in general surgical laparoscopy. The purpose of this prospective, double-blind, randomized clinical trial was to determine whether N2O PP has any benefits over CO2 PP.\n One hundred three patients received N2O (group I, n = 52) or CO2 (group II, n = 51) PP for elective laparoscopic surgery. Heart rate, mean arterial blood pressure, end-tidal CO2, minute ventilation, and O2 saturation were recorded before PP, during PP, and in the recovery room. Postoperative pain medication use was recorded. Pain was assessed by means of visual analog scale (VAS) at postoperative hours 2 and 4, and on day 1.\n There were no differences between groups I and II in patient age, gender, weight, anesthesia risk (American Society of Anesthesiologists Score > 2), operative time, duration of PP, or length of hospital stay. Mean end-tidal CO2 increase under anesthesia was greater in group II than group I (3.0 versus 0.5 mmHg, p < 0.001) despite a greater mean intraoperative increase in minute ventilation in group II than group I (0.7 versus -0.2 L/min p < 0.001). The patients who had N2O PP had less pain 2 hours postoperatively (VAS: 4.9 versus 5.7, p <0.05), 4 hours postoperatively (VAS: 3.3 versus 5.1, p < 0.01), and 1 day postoperatively (VAS: 1.7 versus 3.5, p < 0.01) than patients who had CO2 PP. Postoperative narcotic or ketorolac use was not statistically different between groups. There were no adverse events related to either N2O or CO2 pneumoperitoneum.\n These results suggest that the use of N2O PP has sufficient advantages over CO2 that it should be considered as the standard agent for therapeutic PP.", "Previous studies using animal models have demonstrated that carbon dioxide (CO2) pneumoperitoneum during laparoscopy is associated with adverse physiological, metabolic, immunological and oncological effects, and many of these problems can be avoided by the use of helium insufflation. The present study was performed in patients to compare the effect of helium and CO2 insufflation on intraperitoneal markers of immunological and metabolic function.\n Eighteen patients undergoing elective upper gastrointestinal laparoscopic surgery were randomized to have insufflation achieved by using either helium (n = 8) or CO2 (n = 10) gas. Intraperitoneal pH was monitored continuously during surgery, and peritoneal macrophage function was determined by harvesting peritoneal macrophages at 5 min and 30 min after commencing laparoscopy, and then assessing their ability to produce tumour necrosis factor-alpha (TNF-alpha), and their phagocytic function.\n Carbon dioxide laparoscopy was associated with a lower intraperitoneal pH at the commencement of laparoscopy, although this difference disappeared as surgery progressed. The production of TNF-alpha was better preserved by CO2 laparoscopy, but the insufflation gas used did not affect macrophage phagocytosis. Patients undergoing helium laparoscopy required less postoperative analgesia.\n The choice of insufflation gas can affect intraperitoneal macrophage function in the clinical setting, and possibly acid-base balance. The present study suggested no immunological advantages for the clinical use of helium as an insufflation gas. The outcomes of the present study, however, are different to those obtained from previous laboratory studies and further research is needed to confirm this outcome.", "To study the possible benefits of N2O pneumoperitoneum, 40 patients scheduled for laparoscopic cholecystectomy for symptomatic cholelithiasis were randomized into either CO2-induced (n = 20) or N2O-induced (n = 20) pneumoperitoneum groups. The intensity of postoperative pain was assessed by the patients themselves using an visual analogue pain score scale. CO2 insufflation caused respiratory acidosis. The total amount of anesthetic enflurane needed was lower in the N2O than in the CO2 group (p < 0.041). The N2O group experienced less pain 1 hour (p < 0.040) and 6 hours (p < 0.017) postoperatively and the next morning. Serum cortisol and plasma adrenaline concentrations in the N2O group did not differ from those in the CO2 group. Patients with N2O pneumoperitoneum seem to have less pain without the side effects caused by CO2. The N2O pneumoperitoneum is a good alternative to the CO2 pneumoperitoneum, especially for prolonged laparoscopic operations in patients with chronic cardiopulmonary diseases.", "Laparoscopic surgery has been termed minimally invasive surgery by advocates of this technology. It has been demonstrated previously that using carbon dioxide for insufflation produces a respiratory acidosis due to transperitoneal absorption of gas. Insufflation with helium does not create this acidosis. We questioned whether laparoscopic surgery would elicit a stress response and whether the absence of acidosis with helium might prevent or reduce the levels of stress hormones. Sixteen female patients undergoing laparoscopic cholecystectomy were randomly assigned to helium (n = 8) or CO2 (n = 8) insufflation. Serum cortisol, epinephrine, and norepinephrine were measured preoperatively, after induction of anesthesia but before insufflation, at 45 min of surgery, and after desufflation. There were increases in epinephrine, norepinephrine, plasma cortisol, and urine cortisol at 45 min and at the conclusion of the procedure over the preoperative value. With ANOVA, each variable showed significant increases from preoperative values, at 45 min, and at the end of the case. Except for the increased epinephrine when helium was used, there were no significant differences in the other variables between helium and CO2. Laparoscopic cholecystectomy produces significant increases in stress hormone levels. Prevention of acidosis with helium insufflation does not appear to protect against increases in stress hormones. Epinephrine levels with helium insufflation are higher than with CO2, and elevations in stress hormones suggest that laparoscopic cholecystectomy is not physiologically minimally invasive." ]

[ "8709374", "3881177" ]

[ "A randomized multicenter trial of adjuvant therapy in superficial bladder cancer: transurethral resection only versus transurethral resection plus mitomycin C versus transurethral resection plus bacillus Calmette-Guerin. Participating Clinics.", "Intravesical administration of bacillus Calmette-Guérin in patients with recurrent superficial carcinoma of the urinary bladder: report of a prospective, randomized trial." ]

[ "A randomized multicenter trial was done to compare transurethral resection only to transurethral resection plus adjuvant mitomycin C and bacillus Calmette Guerin (BCG) instillation for treatment of superficial bladder cancer (stage pTa/1 grades 1 to 3 except primary stage pTa grade 1).\n Included in the study were 337 patients with superficial stage pTa/1 grades 1 to 3 bladder cancer except primary stage pTa grade 1 tumors. One group underwent transurethral resection alone. Mitomycin C (20 mg./50 ml. sodium chloride) was given every 2 weeks during year 1 and once a month during year 2. BCG (120 mg/50 ml. sodium chloride was instilled once a week for 6 weeks and once a month for 4 months.\n At a median followup of 20.2 months, a decrease in recurrence rate was noted for both drug instillations compared to transurethral resection only. The relative risk of recurrence was 0.508 after mitomycin C and 0.618 after BCG instillation compared to transurethral resection alone. There was no significant difference between the mitomycin C and BCG instillations. The progression rate was comparable in all 3 therapy groups, with an estimated common progression rate of 4.22% per year. Side effects occurred most frequently during or after BCG instillation, most often consisting of cystitis. One patient required cystectomy because of ulcerating cystitis and a prostatic abscess subsequent to unsuccessful tuberculostatic therapy. There were no systemic complications.\n Our study showed a positive effect of adjuvant chemotherapy and immunotherapy on decreasing tumor recurrence rate. No influence was observed concerning progression rate, which was low overall.", "In an attempt to prevent, delay, or reduce further tumor occurrence, 88 patients with recurrent, superficial carcinoma of the urinary bladder were randomly assigned to receive either standard therapy (cystoscopy with fulguration) or standard therapy and bacillus Calmette-Guérin (BCG). BCG was administered intravesically and percutaneously once weekly for 6 weeks. No serious toxicity was seen. There were 43 evaluable patients in each of the two groups. Results in the BCG group versus the control group were as follows: reduction in the number of recurrent tumors (43 vs 27 patients [P less than 0.001] ); conversion to negative cytology (11 of 33 vs three of 34 patients [P less than 0.05] ); and tumor progression requiring cystectomy (three vs 15 patients [P less than 0.001] ). Disease-free interval (P less than 0.001), time with negative cytology (P less than 0.001), and time to progression of disease (P less than 0.003) were longer in patients treated with BCG. These results indicate that the combination of standard therapy and BCG is more effective than standard therapy alone in patients with recurrent superficial bladder tumors." ]

[ "21654252", "10378599", "14598248", "23577991", "6525357", "17914654", "12794569", "15467559", "16544149", "18278532", "2209296", "3989196", "15670265", "19966605", "15339325", "20551752", "22013492" ]

[ "Biofeedback for fecal incontinence: a randomized study comparing exercise regimens.", "A prospective, randomized study comparing the effect of augmented biofeedback with sensory biofeedback alone on fecal incontinence after obstetric trauma.", "Randomized controlled trial of biofeedback for fecal incontinence.", "A prospective randomized trial comparing four biofeedback techniques for patients with faecal incontinence.", "A components analysis of biofeedback in the treatment of fecal incontinence.", "Biofeedback vs. electrostimulation in the treatment of postdelivery anal incontinence: a randomized, clinical trial.", "Randomized, controlled trial of biofeedback with anal manometry, transanal ultrasound, or pelvic floor retraining with digital guidance alone in the treatment of mild to moderate fecal incontinence.", "Randomized clinical trial of intra-anal electromyographic biofeedback physiotherapy with intra-anal electromyographic biofeedback augmented with electrical stimulation of the anal sphincter in the early treatment of postpartum fecal incontinence.", "The effects of low-frequency endo-anal electrical stimulation on faecal incontinence: a prospective study.", "Sacral nerve stimulation is more effective than optimal medical therapy for severe fecal incontinence: a randomized, controlled study.", "Investigation of mode of action of biofeedback in treatment of fecal incontinence.", "Biofeedback treatment of fecal incontinence in geriatric patients.", "A randomized-controlled trial comparing an educational intervention alone vs education and biofeedback in the management of faecal incontinence in women.", "Randomized controlled trial shows biofeedback to be superior to pelvic floor exercises for fecal incontinence.", "Adjuvant biofeedback following anal sphincter repair: a randomized study.", "Triple target treatment (3T) is more effective than biofeedback alone for anal incontinence: the 3T-AI study.", "Triple-target treatment versus low-frequency electrostimulation for anal incontinence: a randomized, controlled trial." ]

[ "Fecal incontinence affects up to 11% of Australian community-dwelling adults and 72% of nursing home residents. Biofeedback is a recommended conservative therapy when medication and pelvic floor exercises have failed to improve patient outcomes.\n This study aimed to investigate the impact of a new exercise regimen on the severity of fecal incontinence and the quality of life of participants.\n This was a randomized clinical study.\n This study was conducted at the Anorectal Physiology Clinic, Townsville Hospital, Queensland, Australia.\n Seventy-two participants (19 male), with a mean age of 62.1 years, attended 5 clinic sessions: 4 weekly sessions followed by 4 weeks of home practice and a follow-up assessment session. A postal survey was conducted 2 years later.\n Thirty-seven patients (12 male) were randomly assigned to the standard clinical protocol (sustained submaximal anal and pelvic floor exercises) and 35 patients (7 male) were randomly assigned to the alternative group (rapid squeeze plus sustained submaximal exercises).\n The main outcomes were measured by use of the Cleveland Clinic Florida Fecal Incontinence score and the Fecal Incontinence Quality of Life Scale survey tool.\n No significant differences were found between the 2 exercise groups at the beginning or at the end of the study or as a result of treatment in objective, quality-of-life, or fecal incontinence severity measures. Sixty-nine participants completed treatment. The severity of fecal incontinence decreased significantly (11.5/20 to 5.0/20, P < .001). Eighty-six percent (59/69) of participants reported improved continence. Quality of life significantly improved for all participants (P < .001). Results were sustained 2 years later. Patients who practiced at least the prescribed number of exercises had better outcomes than those who practiced fewer exercises.\n This study was limited because it involved a heterogeneous sample, it was based on subjective reporting of exercise performance, and loss to follow-up occurred because of the highly mobile population.\n Patients attending this biofeedback program attained significant improvement in the severity of their fecal incontinence and in their quality of life. Although introduction of rapid muscle squeezes had little impact on fecal incontinence severity or patient quality of life, patient exercise compliance at prescribed or greater levels did.", "This study was designed to compare prospectively the effects of augmented biofeedback with those of sensory biofeedback alone on fecal incontinence and anorectal manometry after obstetric trauma.\n A consecutive cohort of 40 females with impaired fecal continence after obstetric anal sphincter injury were recruited from a dedicated perineal clinic. Patients were randomly assigned to receive either augmented biofeedback or sensory biofeedback alone. All patients were assessed before and after twelve weeks of biofeedback training, using a fecal continence questionnaire and anorectal manometry.\n Thirty-nine of 40 females recruited completed the study. Continence scores improved in both treatment groups, but the results were better for those who received augmented biofeedback. Anorectal manometry was unchanged by sensory biofeedback, whereas anal resting and squeeze pressures increased with augmented biofeedback. No change in anal vector symmetry was observed in either group.\n Augmented biofeedback training is superior to sensory biofeedback alone in the treatment of impaired fecal continence after obstetric trauma.", "Behavioral treatment (biofeedback) has been reported to improve fecal incontinence but has not been compared with standard care.\n A total of 171 patients with fecal incontinence were randomized to 1 of 4 groups: (1) standard care (advice); (2) advice plus instruction on sphincter exercises; (3) hospital-based computer-assisted sphincter pressure biofeedback; and (4) hospital biofeedback plus the use of a home electromyelogram biofeedback device. Outcome measures included diary, symptom questionnaire, continence score, patient's rating of change, quality of life (short-form 36 and disease specific), psychologic status (Hospital Anxiety and Depression scale), and anal manometry.\n Biofeedback yielded no greater benefit than standard care with advice (53% improved in group 3 vs. 54% in group 1). There was no difference between the groups on any of the following measures: episodes of incontinence decreased from a median of 2 to 0 per week (P < 0.001). Continence score (worst = 20) decreased from a median of 11 to 8 (P < 0.001). Disease-specific quality of life, short-form 36 (vitality, social functioning, and mental health), and Hospital Anxiety and Depression scale all significantly improved. Patients improved resting, squeeze, and sustained squeeze pressures (all P < 0.002). These improvements were largely maintained 1 year after finishing treatment.\n Conservative therapy for fecal incontinence improves continence, quality of life, psychologic well-being, and anal sphincter function. Benefit is maintained in the medium term. Neither pelvic floor exercises nor biofeedback was superior to standard care supplemented by advice and education.", "The aim of this study was to compare four methods of biofeedback therapy for patients with faecal incontinence (FI).\n All patients with FI who were ineligible for surgical management were prospectively randomized using a computer generated randomization method into one of four protocols: 1, out-patient intra-anal electromyographic biofeedback training (EMG); 2, EMG plus intrarectal balloon training (BT); 3, EMG plus a home trainer (HT); and 4, EMG, BT and HT. All patients received weekly, 1 h, out-patient biofeedback training. Success for patients with FI was measured by a reduction in incontinent episodes (days/week). In all instances, patients maintained a daily log in which documentation was recorded regarding each bowel evacuation.\n Forty patients were randomized into one of the four groups. Six patients withdrew after one session and were not included in the analysis. Therefore, 34 patients (23 female and 11 male) with a mean incontinence score of 12 (range 7-14) were randomized to one of the four groups (n=8, 8, 8, and 10, respectively). There was a statistically significant reduction in incontinent episodes for all groups. However, there were no significant differences in treatment outcome found in comparisons among the four groups.\n Biofeedback therapy significantly improves FI. Moreover, EMG training was as effective alone as was the addition of HT, BT or both for the treatment of FI.", "Fecal incontinence is a socially disabling symptom for which rectosphincteric biofeedback has been reported to be dramatically effective. The most commonly employed biofeedback procedure incorporates three separate and potentially effective components: exercise of the external sphincter muscle, training in discrimination of rectal sensations, and training synchrony of the internal and external sphincter responses. This paper reports the results of single case experiments employed with eight incontinent patients to examine the contributions of each of these components. All eight patients improved, but only one required the biofeedback procedure as it was originally described. Three responded to sensory discrimination training, one to exercise training, and one to the training of synchronous sphincteric responses; three recovered independently of the effects of biofeedback. Despite the achievement of continence, the rectosphincteric reflexes following treatment continued to be abnormal in every case. These findings suggest that the character of the external sphincter response to rectal distension is an unreliable index of sphincter function and that exercise and sensory discrimination training procedures are effective for some cases of fecal incontinence.", "This study was designed to evaluate the effect of biofeedback and electrostimulation in a randomized, clinical trial for the treatment of patients with postdelivery anal incontinence.\n Forty-nine females who sustained third-degree or fourth-degree perineal rupture with a mean age of 36 (range, 22-44) years were included in the study. The females were randomized to biofeedback or electrostimulation treatment. Forty females completed the study: 19 in the biofeedback and 21 in the electrostimulation group. Biofeedback or electrostimulation sessions were performed two times daily for eight weeks in each group. Wexner incontinence score, fecal incontinence quality of life scores, and reduced quality of life on visual analog scale were registered before and after treatment. Patients' self-rating of treatment effect also was registered in both groups. The primary outcome measure was the Wexner incontinence score.\n There were no differences in treatment effect between groups. Comparing pretreatment status to posttreatment in each group showed no improvement in Wexner score, reduced quality of life, or any of the fecal incontinence quality of life scores. Patients' self-rating of the treatment effect, however, showed a subjective improvement of symptoms both in the biofeedback and in the electrostimulation group (median, 7 vs. 5.)\n This study shows that there was no difference in effect between biofeedback and electrostimulation. Neither biofeedback nor electrostimulation treatments improved Wexner incontinence score, reduced quality of life, or fecal incontinence quality of life scores. Both treatments resulted in improvement of patients' subjective perception of incontinence control.", "A prospective, three-armed, randomized, controlled trial was performed to assess whether pelvic floor exercises with biofeedback using anal manometry or transanal ultrasound are superior to pelvic floor exercises with feedback from digital examination alone in terms of continence, quality of life, physiologic sphincter strength, and compliance. Its secondary objectives were to assess whether there are any differences in these outcomes between biofeedback with transanal ultrasound vs. anal manometry and to correlate the physiologic measures with clinical outcome.\n One hundred twenty patients with mild to moderate fecal incontinence were randomized into one of three treatment groups: biofeedback with anal manometry, biofeedback with transanal ultrasound, or pelvic floor exercises with feedback from digital examination alone. Commencing one week after an initial 45-minute assessment session, patients attended monthly treatments for a total of five sessions. Each session lasted 30 minutes and involved sphincter exercises with biofeedback that involved instrumentation or digital examination alone, and patients were encouraged to perform identical exercises twice per day between outpatient visits.\n One hundred two patients (85 percent) completed the four-month treatment program. Across all treatment allocations, patients experienced modest but highly significant improvements in all nine outcome measures during treatment, with 70 percent of all patients perceiving improvement in symptom severity and 69 percent of patients reporting improved quality of life. With the possible exception of isotonic fatigue time, there were no significant differences between the three treatment groups in compliance, physiologic sphincter strength, and clinical or quality-of-life measures. Correlations between physiologic measures and clinical outcomes were much stronger with ultrasound-based measures than with manometry.\n Although patients in this study who completed pelvic floor exercises with feedback from digital examination achieved no additional benefit from biofeedback and measurement with transanal ultrasound or manometry, it may be that the guidance received through digital examination alone offered patients in the pelvic floor exercise group an effective biofeedback mechanism. Contrary to our hypothesis, the use of transanal ultrasound offered no benefit over manometry, but the use of ultrasound for isotonic fatigue time and isometric fatigue contractions provided potentially important physiologic measures that require further study. This study has confirmed, through a large sample of patients, that pelvic floor retraining programs are an effective treatment for improving physiologic, clinical, and quality-of-life parameters in the short term.", "The purpose of this study was to compare intra-anal electromyographic biofeedback alone with intra-anal biofeedback that was augmented with electrical stimulation of the anal sphincter in the treatment of postpartum fecal incontinence. A secondary aim was to examine the impact of the treatment on continence-related quality of life.\n Sixty symptomatic women were assigned randomly to receive intra-anal electromyographic biofeedback or electrical stimulation of the anal sphincter once weekly for 12 weeks and to perform daily pelvic floor exercises between treatments. Therapeutic response was evaluated with a symptom questionnaire to determine continence score, anal manometry, and endoanal ultrasound scanning. Quality of life was assessed before and after treatment with a validated questionnaire.\n Fifty-four women completed the treatment; 52 women (96%) had ultrasonic evidence of an external anal sphincter defect. After the treatment, both groups demonstrated significant improvement in continence score (P < .001) and in squeeze anal pressures (P < .04). Resting anal pressures did not alter significantly. Quality of life improved after the completion of physiotherapy, but there were no differences in outcome between intra-anal electromyographic biofeedback and electrical stimulation of the anal sphincter.\n Intra-anal electromyographic biofeedback therapy was associated with improved continence and quality of life in women with altered fecal continence after delivery. The addition of electrical stimulation of the anal sphincter did not enhance symptomatic outcome.", "Faecal incontinence is a distressing problem that is often not amenable to surgical correction. Chronic low-frequency electrical stimulation of damaged axons is thought to reduce synaptic resistance, increase the size of motor units by axonal sprouting and increase the rate of conduction of the pudendal nerve. The aim of this study was to prospectively evaluate the effect of chronic low-frequency endo-anal electrical stimulation on faecal incontinence using a home-based unit and hospital-supervised therapy.\n Forty-eight patients with faecal incontinence completed a prospective randomised trial. Patients were allocated randomly to one of two groups; group 1 was exposed to endo-anal pudendal nerve stimulation daily at home with a portable home unit, group 2 attended the physiotherapy department for endo-anal electrical stimulation under supervision.\n Continence scores improved significantly after treatment in both groups (p<0.001). Both groups showed improved manometric scores, although only group 1 showed significant improvement in both resting and squeeze pressures (mean total resting pressure 184-224 mmHg, p<0.001; mean total squeeze pressure 253-337 mmHg, p<0.001). This was also reflected by an improvement in quality of life in both groups.\n Low-frequency endo-anal electrical stimulation significantly improves continence scores and quality of life in patients with faecal incontinence not amenable to surgical correction. It leads to improved manometric values when carried out on a daily basis with a portable home unit.", "This randomized study was designed to compare the effect of sacral neuromodulation with optimal medical therapy in patients with severe fecal incontinence.\n Patients (aged 39-86 years) with severe fecal incontinence were randomized to have sacral nerve stimulation (SNS group; n = 60) or best supportive therapy (control; n = 60), which consisted of pelvic floor exercises, bulking agent, and dietary manipulation. Full assessment included endoanal ultrasound, anorectal physiology, two-week bowel diary, and fecal incontinence quality of life index. The follow-up duration was 12 months.\n The sacral nerve stimulation group was similar to the control group with regard to gender (F:M = 11:1 vs. 14:1) and age (mean, 63.9 vs. 63 years). The incidence of a defect of < or = 120 degrees of the external anal sphincter and pudendal neuropathy was similar between the groups. Trial screening improved incontinent episodes by more than 50 percent in 54 patients (90 percent). Full-stage sacral nerve stimulation was performed in 53 of these 54 \"successful\" patients. There were no septic complications. With sacral nerve stimulation, mean incontinent episodes per week decreased from 9.5 to 3.1 (P < 0.0001) and mean incontinent days per week from 3.3 to 1 (P < 0.0001). Perfect continence was accomplished in 25 patients (47.2 percent). In the sacral nerve stimulation group, there was a significant (P < 0.0001) improvement in fecal incontinence quality of life index in all four domains. By contrast, there was no significant improvement in fecal continence and the fecal incontinence quality of life scores in the control group.\n Sacral neuromodulation significantly improved the outcome in patients with severe fecal incontinence compared with the control group undergoing optimal medical therapy.", "A study was carried out in 25 incontinent patients to evaluate some of the factors thought to be responsible for the success of retraining for fecal incontinence. Subjects were initially allocated to one of two groups; one group was trained to perceive small rectal volumes (active retraining), the other group carried out the same maneuvers but were not given any information or instruction. Active sensory retraining reduced the sensory threshold from 32 +/- 8 to 7 +/- 2 ml (P less than 0.001), corrected any sensory delay that was present (P less than 0.004), and reduced the frequency of incontinence from 5 +/- 1 to 1 +/- 1 episodes per week (P less than 0.01). Sham retraining caused a modest reduction in the sensory threshold (from 29 +/- 9 to 20 +/- 8; P less than 0.05) but did not significantly reduce the frequency of incontinence. Subsequent strength and coordination training did not significantly improve continence, although at the end of the study, 50% of patients had no incontinent episodes at all and 76% of patients had reduced the frequency of incontinence episodes by more than 75%. This improvement in continence was not associated with any change in sphincter pressures or in the continence to rectally infused saline but was associated with significant improvements in rectal sensation. The functional improvement was sustained over a period of two years in 16 of the 22 patients available for follow-up. In conclusion, the results support the use of retraining in the management of fecal incontinence and suggest that retraining may work by enhancing rectal sensitivity and instilling confidence.", "Eighteen fecally incontinent geriatric patients were first treated for constipation as a possible cause of incontinence, and the 13 who remained incontinent were provided sphincter biofeedback training. Half the patients were instructed to perform 50 sphincter exercises per day for a four-week period prior to the start of biofeedback training to determine whether such exercises would improve bowel control in the absence of biofeedback training. Sphincter exercises alone did not produce clinical improvements and did not significantly increase the strength of sphincter contractions. Biofeedback training did significantly augment sphincter strength and was associated with greater than 75 per cent decreases in incontinence for 10 (77 per cent) of the patients. Improvements were maintained in 60 per cent at six months and in 42 per cent at one year. Thus biofeedback training appears to be of specific value in the treatment of fecal incontinence in geriatric patients.", "Biofeedback (BF) training is an accepted therapy in the treatment of faecal incontinence (FI) despite a paucity of data demonstrating benefit. This study aims to determine whether BF has any specific effect above and beyond an educational intervention. Twenty-three women with regular and frequent idiopathic FI were randomized to education and pelvic exercise vs education and BF therapy. Complete data is available for 18 women. Overall, 61% of participants demonstrated a complete response. There was no difference in response rate between treatment arms. Women with FI demonstrate a good response to treatment with education and exercise and education plus BF thus questioning the specific effect of BF.", "This study aimed to compare manometric biofeedback with pelvic floor exercises for the treatment of fecal incontinence in a randomized controlled trial controlling for nonspecific treatment effects.\n After excluding patients who were adequately treated with medication, education, and behavioral strategies (21%), 108 patients (83 females; average age, 59.6 years) underwent either pelvic floor exercises alone (n = 63) or manometric biofeedback plus pelvic floor exercises (n = 45). Patients in both groups were taught behavioral strategies to avoid incontinence.\n At three-month follow-up, biofeedback patients had significantly greater reductions on the Fecal Incontinence Severity Index (P = 0.01) and fewer days with fecal incontinence (P = 0.083). Biofeedback training increased anal canal squeeze pressure more than pelvic floor exercises did (P = 0.014) and with less abdominal tension during squeeze (P = 0.001). Three months after training 76% of patients treated with biofeedback vs. 41% patients treated with pelvic floor exercises (chi-squared = 12.5, P < 0.001) reported adequate relief. Before treatment, the groups did not differ on demographic, physiologic, or psychologic variables, symptom severity, duration of illness, quality-of-life impact, or expectation of benefit. At 12-month follow-up, biofeedback patients continued to show significantly greater reduction in Fecal Incontinence Severity Index scores (F = 4.83, P = 0.03), and more patients continued to report adequate relief (chi-squared = 3.64, P = 0.056).\n This investigation provides definitive support for the efficacy of biofeedback. Biofeedback training resulted in greater reductions in fecal incontinence severity and days with fecal incontinence. Biofeedback was also more effective than pelvic floor exercises alone in producing adequate relief of fecal incontinence symptoms in patients for whom conservative medical management had failed.", "To evaluate the impact of adjuvant biofeedback following sphincter surgery.\n Thirty-eight patients were randomized into sphincter repair or sphincter repair plus biofeedback groups. Outcome measures included a symptom questionnaire, patient's rating of satisfaction with continence function and improvement, change in continence score, quality of life and anorectal physiology. Endoanal ultrasonography was also performed pre- and post-operatively.\n Immediately following surgery, there was no statistically significant difference in any of the functional or physiological variables between the groups. Continence and patient satisfaction scores improved with a mean difference of -0.48 (95% CI: -3.30-2.33, P = 0.73) and 1.03 (95% CI: -1.40-3.46, P = 0.39), respectively. Only the difference in embarrassment scores reached statistical significance (mean) 0.56 (95% CI: 0.12-0.99, P = 0.014). Resting and squeeze pressures also improved. Thirteen of 14 in the biofeedback and 11 of 17 (control) reported symptomatic improvement. In the biofeedback group, although not statistically significant continence and satisfaction scores improved and were sustained over time. In the control group, continence and satisfaction scores changed little between 3 and 12 months (P = NS). Quality of life measures improved within the biofeedback group but there was no statistical difference between the groups.\n Following surgery continence function improves in all patients but adjuvant biofeedback therapy improves quality of life and maintains symptomatic improvement over time.\n Copyright 2004 Blackwell Publishing Ltd", "The efficacy of EMG-biofeedback and low-frequency electrical stimulation for the treatment of anal incontinence has not been proven. Our purpose was to evaluate a novel therapeutic concept, termed triple target treatment, which combines amplitude-modulated medium-frequency stimulation and EMG-biofeedback.\n Patients with anal incontinence were randomly assigned to the triple target regimen or EMG-biofeedback alone for a 9-month treatment period in a multicenter randomized clinical trial with blinded observers (ClincialTrials.gov registration number NCT00525291). Primary end points were changes in the Cleveland Clinic score and the adapted St. Mark's (Vaizey) score at 9 months compared with baseline. Secondary end points included therapy acceptance and proportion of patients achieving continence or improvement in grade or frequency of incontinence.\n We enrolled 158 patients with anal incontinence. The median decrease in the Cleveland Clinic score from baseline to 9 months was 3 points greater for the triple target regimen than for EMG-biofeedback (95% CI, 1-4; P = .0024). The improvement was 8 points for the triple target regimen (95% CI, 7-9) and 5 points for EMG-biofeedback (95% CI, 4-7). Results were similar for the Vaizey score. Of patients treated for at least 3 months, continence was achieved by 50% of patients with the triple target regimen and 25.8% of those with EMG-biofeedback.\n The combination of amplitude-modulated medium-frequency electrostimulation with EMG-biofeedback in the triple target regimen is superior to EMG-biofeedback alone in the treatment of anal incontinence. Therapy programs for fecal incontinence are most effective if patients participate for longer than 2 to 3 months.", "In the nonsurgical treatment of anal incontinence, the combination of amplitude-modulated medium-frequency stimulation and electromyographic biofeedback (EMG-BF), known as triple-target treatment (3T), is superior to EMG-BF alone. The aim of this trial is to compare 3T with the standard treatment, low-frequency stimulation (LFS).\n 80 patients with anal incontinence of Grade I or higher who presented to physicians or centers specialized in coloproctology were enrolled in this multicenter randomized trial with blinded observer. The trial had an open parallel-group design. Randomization was performed centrally by telephone. The primary endpoint was the Cleveland Clinic Score (CCS) after self-training at home with either 3T or LFS in two 20-minute sessions per day for 6 months. The secondary endpoints included the proportion of patients regaining continence, and the patients' quality of life (QoL). On completion of the trial as planned, the results were evaluated with an intention-to-treat analysis. Study registration: DRKS00000138 (http://register.germanctr.de).\n 39 patients were randomized to 3T, and 41 to LFS. After 6 months of treatment, the CCS (mean ± standard deviation) was 3.1 ± 4.2 in the 3T group and 9.6 ± 3.9 in the LFS group. The median improvement in the CCS at 6 months compared to baseline was 7 points greater in the 3T group than in the LFS group (95% CI: 5-9, p<0.001). Anal continence was regained by 54% of the 3T patients, but none of the LFS patients (95% CI for the difference: 37.18% - 69.91%, p<0.001). QoL scores were higher in all dimensions in the 3T group than in the LFS group. No major adverse effects occurred in either group.\n 3T is superior to LFS in the treatment of anal incontinence. The available evidence suggests that the success of 3T is based on the combined effect of biofeedback and medium-frequency stimulation. LFS of the type applied in this trial has no effect. 3T should be used in routine clinical practice instead of LFS." ]

[ "20670733", "9404675", "17888202", "7888278", "21576533", "19365873", "23028897", "20809267", "1702663", "21990298", "17620655", "19036851" ]

[ "No effect of selenium supplementation on serum glucose levels in men with prostate cancer.", "Supplementary selenium influences the response to fatty acid-induced oxidative stress in humans.", "A short-term intervention trial with selenate, selenium-enriched yeast and selenium-enriched milk: effects on oxidative defence regulation.", "Does dietary arsenic and mercury affect cutaneous bleeding time and blood lipids in humans?", "Effect of supplementation with high-selenium yeast on plasma lipids: a randomized trial.", "Increased consumption of wheat biofortified with selenium does not modify biomarkers of cancer risk, oxidative stress, or immune function in healthy Australian males.", "A randomized trial of selenium supplementation and risk of type-2 diabetes, as assessed by plasma adiponectin.", "Frequent consumption of selenium-enriched chicken meat by adults causes weight loss and maintains their antioxidant status.", "Intervention trial with selenium for the prevention of lung cancer among tin miners in Yunnan, China. A pilot study.", "Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).", "Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial.", "Selenium supplementation does not improve vascular responsiveness in healthy North American men." ]

[ "Literature indicates a relationship between selenium supplementation and risk of diabetes. However, because these data are inconclusive, we investigated the effect of selenium supplementation on serum glucose levels in men with prostate cancer enrolled in a clinical trial testing of the effect of selenium on prostate cancer progression.\n Subjects were randomized to receive placebo (n=46), selenium 200 microg/day (n=47), and selenium 800 microg/day (n=47). Serum glucose levels were obtained every 6 months for up to 5 years. Longitudinal analysis was carried out to assess whether rate of change of serum glucose levels was significantly different in the selenium-supplemented groups as compared with placebo. Sensitivity analyses were performed to assess the robustness of findings.\n Changes in serum glucose levels during the course of the trial were not statistically significantly different as compared with placebo for the selenium 200 microg/day (P=.56) or selenium 800 microg/day (P=.91) treatment groups.\n These results do not support a relationship between selenium supplementation and changes in serum glucose levels. Recommendations about selenium supplementation and risk of diabetes will require more definitive studies.\n Copyright 2010 Elsevier Inc. All rights reserved.", "The mutual influences of wheat selenium (Se) and n-3 polyunsaturated fatty acids (n-3 PUFA) on plasma Se and indicators of increased oxidative stress were investigated in a randomized, double-blind study with 31 women (23.5 +/- 3.4 yr). Groups 1 and 2 ingested 5.4 g n-3 PUFA daily (as ethyl esters), whereas groups 3 and 4 received placebo capsules. Groups 2 and 3 received 3 slices of high-Se bread daily, providing 115 micrograms Se, in addition to the 77 +/- 26 micrograms Se in the diet. Groups 1 and 4 received placebo slices. Blood samples were drawn at baseline and at 3 and 6 wk. Serum Se concentrations increased in both groups given Se-enriched bread, but significantly less in subjects given n-3 PUFA (group 2). There were no changes in the plasma ratio alpha-tocopherol:mg cholesterol or plasma ascorbic acid levels. In group 1, plasma-conjugated dienes and thiobarbituric acid-reactive substances (TBARS) rose by 130% (p < 0.005) and 126% (p < 0.005), respectively. Two-way ANOVA showed significant interaction effects of Se and n-3 PUFA on changes in conjugated dienes (p = 0.03) and TBARS (p = 0.015), Se treatment apparently modifying the peroxidative effects of n-3 PUFA. In subjects receiving n-3 PUFA, changes in conjugated dienes and TBARS were negatively correlated with changes in serum Se. In summary, n-3 PUFA modified the effect of Se supplementation, whereas Se seemed to modify the peroxidative effects of n-3 PUFA.", "Increased Se intakes have been associated with decreased risk of cancer and CVD. Several mechanisms have been proposed, including antioxidant effects through selenoproteins, induction of carcinogen metabolism and effects on the blood lipid profile. In a 4 x 1 week randomised, double-blind cross-over study, healthy young men supplemented their usual diet with selenate, Se-enriched yeast, Se-enriched milk or placebo (Se dose was 300 microg/d for selenate and Se-enriched yeast, and about 480 microg/d for Se-enriched milk) followed by 8-week washout periods. All Se sources increased serum Se levels after supplementation for 1 week. The effect of the organic forms did not differ significantly and both increased serum Se more than selenate. Conversely, thrombocyte glutathione peroxidase (GPX) was increased in the periods where subjects were supplemented with selenate but not in those where they were given Se-enriched yeast or Se-enriched milk. We found no effect on plasma lipid resistance to oxidation, total cholesterol, TAG, HDL- and LDL-cholesterol, GPX, glutathione reductase (GR) and glutathione S-transferase (GST) activities measured in erythrocytes, GPX and GR activities determined in plasma, or GR and GST activities in thrombocytes. Leucocyte expression of genes encoding selenoproteins (GPX1, TrR1 and SelP), and of electrophile response element-regulated genes (GCLC, Fra1 and NQO1) were likewise unaffected at all time points following intervention. We conclude that thrombocyte GPX is specifically increased by short-term selenate supplementation, but not by short-term supplementation with organic Se. Short-term Se supplementation does not seem to affect blood lipid markers or expression and activity of selected enzymes and a transcription factor involved in glutathione-mediated detoxification and antioxidation.", "Fish species may contain considerable amounts of trace elements, such as selenium (Se), arsenic (As), and mercury (Hg). The present study investigated the relationships between dietary intake of these elements and cutaneous bleeding time and blood lipids in 32 healthy volunteers. For 6 wk, one group (n = 11) consumed approx 250 g Se-rich fish daily, providing them with an average Se intake of 115 +/- 31 micrograms Se/d, Hg intake of 18 +/- 8 micrograms/d, and As intake of 806 +/- 405 micrograms/d, all values analyzed in 4-d duplicate food collections. To study the effect of Se alone, one group (n = 11) included Se-rich bread in their normal diet, giving them a Se intake (135 +/- 25 micrograms/d) that was comparable to the fish group. A control group (n = 10) ate their normal diet, providing 77 +/- 25 micrograms Se/d, 3.1 +/- 2.5 micrograms Hg/d, and 101 +/- 33 micrograms As/d. The dietary As load strongly correlated both with bleeding times and changes in bleeding times (r = 0.48, p < 0.01 and r = 0.54, p < 0.002, respectively). Dietary Hg showed a positive correlation with LDL-cholesterol (r = 0.55, p < 0.01), whereas dietary Hg in the fish group showed a strong negative relationship with HDL-cholesterol (r = -0.76, p < 0.01). Selenium seemed to have only a modest effect on bleeding time. Our results suggest that mercury and arsenic from fish may be factors contributing to or modifying some of the known effects of fish ingestion.", "High selenium status has been linked to elevated blood cholesterol levels in cross-sectional studies.\n To investigate the effect of selenium supplementation on plasma lipids.\n Randomized, placebo-controlled, parallel-group study stratified by age and sex. Participants, research nurses, and persons assessing outcomes were blinded to treatment assignment. (International Standard Randomised Controlled Trial Number Register registration number: ISRCTN25193534)\n 4 general practices in the United Kingdom.\n 501 volunteers aged 60 to 74 years.\n Participants received selenium, 100 mcg/d (n = 127), 200 mcg/d (n = 127), or 300 mcg/d (n = 126), as high-selenium yeast or a yeast-based placebo (n = 121) for 6 months.\n Total and high-density lipoprotein (HDL) cholesterol concentrations were measured in nonfasting plasma samples stored from participants in the UK PRECISE (United Kingdom PREvention of Cancer by Intervention with SElenium) Pilot Study at baseline (n = 454) and at 6 months (n = 394). Non-HDL cholesterol levels were calculated.\n Mean plasma selenium concentration was 88.8 ng/g (SD, 19.2) at baseline and increased statistically significantly in the treatment groups. The adjusted difference in change in total cholesterol levels for selenium compared with placebo was -0.22 mmol/L (-8.5 mg/dL) (95% CI, -0.42 to -0.03 mmol/L [-16.2 to -1.2 mg/dL]; P = 0.02) for 100 mcg of selenium per day, -0.25 mmol/L (-9.7 mg/dL) (CI, -0.44 to -0.07 mmol/L [-17.0 to -2.7 mg/dL]; P = 0.008) for 200 mcg of selenium per day, and -0.07 mmol/L (-2.7 mg/dL) (CI, -0.26 to 0.12 mmol/L [-10.1 to 4.6 mg/dL]; P = 0.46) for 300 mcg of selenium per day. Similar reductions were observed for non-HDL cholesterol levels. There was no apparent difference in change in HDL cholesterol levels with 100 and 200 mcg of selenium per day, but the difference was an adjusted 0.06 mmol/L (2.3 mg/dL) (CI, 0.00 to 0.11 mmol/L [0.0 to 4.3 mg/dL]; P = 0.045) with 300 mcg of selenium per day. The total-HDL cholesterol ratio decreased progressively with increasing selenium dose (overall P = 0.01).\n The duration of supplementation was limited, as was the age range of the participants.\n Selenium supplementation seemed to have modestly beneficial effects on plasma lipid levels in this sample of persons with relatively low selenium status. The clinical significance of the findings is unclear and should not be used to justify the use of selenium supplementation as additional or alternative therapy for dyslipidemia. This is particularly true for persons with higher selenium status, given the limitations of the trial and the potential additional risk in other metabolic dimensions.\n The Cancer Research Campaign (now Cancer Research UK) and the University of Surrey.", "Increased intake of selenium (Se) may reduce the risk of degenerative diseases including cancer but excessive intake may be toxic. Wheat is a major source of dietary Se in humans. However, the effect of Se from wheat that is agronomically biofortified with Se on biomarkers of human health status is unknown. This study aimed to investigate whether improving Se status, by increased dietary intake of Se-biofortified wheat, affects biomarkers of cancer risk, cardiovascular disease risk, oxidative stress, and immune function in healthy South Australian men. A 24-week placebo-controlled double-blind intervention was performed in healthy older men (n = 62), with increased dose of Se intake every 8 weeks. Wheat was provided as 1, 2, and 3 puffed wheat biscuits, during weeks 1-8, 9-16, and 17-24, respectively. Blood was collected to measure a wide range of disease risk biomarkers. Consumption of Se-biofortified wheat was found to increase plasma Se concentration from a baseline level of 122 to 192 microg/L following intake of three biscuits/day, which provided 267 microg Se. Platelet glutathione peroxidase, chromosome aberrations, and DNA damage in lymphocytes measured using the cytokinesis-block micronucleus cytome assay and with the Comet assay, plasma F2-isoprostanes, protein carbonyls, plasma C-reactive protein, and leukocyte number were unaffected by the improved Se status. Improvement of Se status by consumption of Se-biofortified wheat did not substantially modify the selected biomarkers of degenerative disease risk and health status in this apparently selenium-replete cohort of healthy older men in South Australia.\n Copyright 2009 Wiley-Liss, Inc.", "Evidence that selenium affects the risk of type-2 diabetes is conflicting, with observational studies and a few randomized trials showing both lower and higher risk linked to the level of selenium intake and status. We investigated the effect of selenium supplementation on the risk of type-2 diabetes in a population of relatively low selenium status as part of the UK PRECISE (PREvention of Cancer by Intervention with SElenium) pilot study. Plasma adiponectin concentration, a recognised independent predictor of type-2 diabetes risk and known to be correlated with circulating selenoprotein P, was the biomarker chosen.\n In a randomized, double-blind, placebo-controlled trial, five hundred and one elderly volunteers were randomly assigned to a six-month intervention with 100, 200 or 300 µg selenium/d as high-selenium or placebo yeast. Adiponectin concentration was measured by ELISA at baseline and after six months of treatment in 473 participants with one or both plasma samples available.\n Mean (SD) plasma selenium concentration was 88.5 ng/g (19.1) at baseline and increased significantly in the selenium-treatment groups. In baseline cross-sectional analyses, the fully adjusted geometric mean of plasma adiponectin was 14% lower (95% CI, 0-27%) in the highest than in the lowest quartile of plasma selenium (P for linear trend = 0.04). In analyses across randomized groups, however, selenium supplementation had no effect on adiponectin levels after six months of treatment (P = 0.96).\n These findings are reassuring as they did not show a diabetogenic effect of a six-month supplementation with selenium in this sample of elderly individuals of relatively low selenium status.", "To assess the effects of a moderately high-protein intake on the body composition, biochemical, and antioxidant status parameters in young adults depending on either selenium- (Se) or non-enriched chicken consumption. The volunteers (n = 24) that completed the 10-week nutritional intervention were distributed in two parallel groups and randomly assigned to follow an isocaloric diet with moderately high content in protein (30% energy), either with the consumption of four 200 g portions/week of Se- or non-enriched chicken breasts. Blood samples were taken at the beginning and at the end of the study and body composition was monitored during the trial. There was a significant reduction in weight, accompanying a decrease on fat mass in both groups, while fat-free mass remained unchanged during the 10 weeks of intervention, without differences between both dietary groups. Selenium blood levels and plasma glutathione peroxidase activity, as well as lipid, glucose, and selected inflammation biomarkers remained stable during the intervention period in both dietary groups. Frequent chicken consumption, within a controlled diet with a moderately high content in protein, produced a slight but statistically significant weight reduction mainly due to the loss of fat mass. An extra Se supplementation (22 μg/day) in the Se-enriched chicken breast did not affect tachyphylactic antioxidant status of the participants neither inflammatory-related markers after weight loss.", "This pilot study evaluated the feasibility and effectiveness of conducting a double-blind clinical trial for the prevention of lung cancer with selenium (Se) in Yunnan Tin Corporation, the People's Republic of China, where the incidence rates of lung cancer are extraordinarily high among the miners. Forty healthy miners were randomized to either 300 micrograms of Se in high Se malt cakes or an identical placebo of malt cakes daily for one year. Subjects consumed their usual daily diet. The low Se concentrations in plasma (0.05 +/- 0.008 microgram/mL) and hair (0.442 +/- 0.085 microgram/g) reflected their low dietary Se intake in the control subjects. In Se-supplemented group, the Se status was increased by 178% for serum and 194.8% for hair. The serum GSHpx activity was increased by 155.7%, whereas the lipid peroxide level was reduced by 74.5% compared to the placebo. The results of UDS assay indicated that the lymphocyte DNA damage induced by ultraviolet irradiation and carcinogen 3,4-benzpyrene could be protected by Se supplementation. Se-supplementation did not affect the liver function test (SGPT), as well as the concentrations of hemoglobin, albumin, and cholesterol. Thus, daily intake of 300 micrograms Se in form of Se-malt as a chemopreventive measure is safe and effective to humans with low Se status.", "The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer.\n To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men.\n A total of 35,533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34,887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011.\n Oral selenium (200 μg/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years.\n Prostate cancer incidence.\n This report includes 54,464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination.\n Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men.\n Clinicaltrials.gov Identifier: NCT00006392.", "Findings from animal models suggest that selenium supplementation improves glucose metabolism.\n To examine the effect of long-term selenium supplementation on the incidence of type 2 diabetes.\n Secondary analysis of a randomized, double-blind, placebo-controlled trial.\n Areas of low selenium consumption of the eastern United States.\n 1202 persons seen in dermatology clinics who did not have type 2 diabetes at baseline.\n Oral administration of selenium, 200 microg/d, or placebo.\n Incidence of type 2 diabetes.\n During an average follow-up of 7.7 years (SD, 2.7), type 2 diabetes developed in 58 selenium recipients and 39 placebo recipients (incidence, 12.6 cases per 1000 person-years vs. 8.4 cases per 1000 person-years, respectively; hazard ratio, 1.55 [95% CI, 1.03 to 2.33]). The lack of benefit of selenium supplementation on the incidence of type 2 diabetes persisted in analyses stratified by age, sex, body mass index, and smoking status. An exposure-response gradient was found across tertiles of baseline plasma selenium level, with a statistically significantly increased risk for type 2 diabetes in the highest tertile of baseline plasma selenium level (hazard ratio, 2.70 [CI, 1.30 to 5.61]).\n Diabetes was a secondary outcome in the parent trial. Diagnoses of diabetes were self-reported but were validated in most participants. The sample was mostly older and white.\n Selenium supplementation does not seem to prevent type 2 diabetes, and it may increase risk for the disease. Click here for related information on selenium.", "Selenium is an essential trace nutrient required for the synthesis of selenoproteins such as glutathione peroxidase and thioredoxin reductase, the major forms of selenium in the endothelium that have important functions relevant to inflammation and cardiovascular disease. Selenium deficiency is associated with cardiomyopathy and sudden cardiac death in animals, and a low selenium status is associated with cardiovascular disease in humans. Endothelial dysfunction, measured as the impaired flow-mediated vasorelaxation of the brachial artery, is a reliable indicator of future cardiovascular disease risk in healthy individuals. To test whether selenium supplementation affects endothelial function, we conducted a randomized, placebo-controlled trial in healthy men who were administered 300 microg of selenium a day as high-selenium yeast for 48 wk. Brachial artery responsiveness to transient occlusion was assessed at baseline and after 24 and 48 wk of supplementation. The supplementation increased the selenium concentration by more than half in blood plasma and erythrocytes. However, there was no effect of selenium on arterial diameter or blood flow rate before or after transient occlusion or on the maximum dilated diameter after the administration of nitroglycerin. This study indicates that selenium supplementation is not likely to improve endothelial function or peripheral arterial responsiveness in healthy North American men receiving adequate selenium from their diets." ]

[ "15027039", "17646620", "17353259", "15383747", "15722369", "17873681" ]

[ "Efficacy of rivastigmine in subjects with moderately severe Alzheimer's disease.", "Caregiver preference for rivastigmine patches versus capsules for the treatment of Alzheimer disease.", "Rivastigmine: a placebo controlled trial of twice daily and three times daily regimens in patients with Alzheimer's disease.", "A 12-month study of the efficacy of rivastigmine in patients with advanced moderate Alzheimer's disease.", "Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial.", "Does serotonin augmentation have any effect on cognition and activities of daily living in Alzheimer's dementia? A double-blind, placebo-controlled clinical trial." ]

[ "Cholinesterase (ChE) inhibitors are primarily used in the treatment of mild to moderate Alzheimer's disease (AD), but may also be effective in more severe disease.\n To evaluate the dual ChE inhibitor, rivastigmine, in more severe dementia.\n We retrospectively analysed pooled data from three randomised, placebo-controlled, double-blind, 6-month trials, involving 2126 AD subjects. Subjects were selected according to baseline Mini-Mental State Examination (MMSE) score to identify subjects with more severe cognitive impairment (10-12 MMSE points). One-hundred-and-seventeen subjects were included who had been treated with rivastigmine 6-12 mg/day or placebo. The AD Assessment Scale-Cognitive Subscale (ADAS-Cog), the MMSE, a six-item subscore of the Progressive Deterioration Scale (PDS) and the BEHAVE-AD assessed efficacy. Tolerability was assessed by recording adverse events (AEs) and the relative risk (RR) of discontinuation.\n This group of subjects responded well to rivastigmine. After 6 months, the mean ADAS-Cog score declined by 6.3 points in the placebo group and increased by 0.2 points in the rivastigmine group (observed cases; p<0.001). Clinical benefits were also observed with the MMSE, the six-item PDS score and items of the BEHAVE-AD. Rivastigmine showed the same pattern of AEs as in other studies, but the RR of dropping out due to AEs was lower than in subjects with milder AD.\n Current treatment guidelines do not recommend treating individuals with severe AD with ChE inhibitors. However, this retrospective analysis suggests that rivastigmine 6-12 mg/day may benefit subjects with more severe disease, as well as subjects with mild to moderate impairment.\n Copyright 2004 John Wiley & Sons, Ltd.", "Alzheimer disease (AD) has a significant impact on caregivers. Administering and managing medications is one of their many daily tasks. More effective modes of drug administration may benefit patient and caregiver, and may improve compliance. A prospective outcome of the IDEAL (Investigation of TransDermal Exelon in ALzheimer's disease) trial was to evaluate caregiver preference for rivastigmine patches compared with capsules. The 24-week, randomized, double-blind, double-dummy, placebo- and active-controlled IDEAL trial investigated once-daily rivastigmine patches vs twice-daily capsules in moderate AD patients. Caregivers rated patch adhesion throughout. The AD Caregiver Preference Questionnaire (ADCPQ) assessed patch vs capsule from caregivers' perspective, based on expectations, preferences, and satisfaction with treatment. A total of 1,059 caregivers completed the ADCPQ while their respective patients were on study drug. More than 70% of caregivers preferred the patch to capsules overall. The patch was preferred to capsules with respect to ease of use (p < 0.0001) and ease of following the schedule (p < 0.0001). Caregivers indicated greater satisfaction overall (p < 0.0001) and less interference with daily life (p < 0.01) with the patch vs capsules. The preference substudy of the IDEAL trial demonstrated that caregivers of AD patients preferred patches to capsules for drug delivery. Preference for the patch may indicate reduced caregiver stress, substantiated by greater satisfaction and less interference with daily life. These benefits may lead to improved compliance.", "To evaluate the efficacy and safety of rapidly titrated rivastigmine administered twice (BID) or three times (TID) daily in patients with mild to moderate Alzheimer's disease (AD).\n This was a 26 week international, randomised, double blind, placebo controlled study in which 678 patients with probable AD received placebo or rivastigmine 2-12 mg/day BID or TID. Primary outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog) and categorical analysis of the Clinician Interview Based Impression of Change incorporating caregiver information (CIBIC-Plus). Secondary outcomes were the CIBIC-Plus change from baseline, Progressive Deterioration Scale, ADAS-cogA, Mini-Mental State Examination and Global Deterioration Scale.\n At week 26, mean rivastigmine dose was 9.6 (2.76) mg/day in the TID group and 8.9 (2.93) mg/day in the BID group. Mean ADAS-cog changes from baseline in the TID and BID rivastigmine treated groups were -0.2 (SD 7.3) and 1.2 (SD 7.2) versus 2.8 (SD 7.2) for the placebo group (p<0.05). Differences between rivastigmine TID and placebo on the CIBIC-Plus categorical responder analysis were significant (31% vs 19%; p<0.05, intention to treat). No significant differences were seen between BID and placebo for this outcome measure. Adverse events were predominantly gastrointestinal, occurring mainly during dose titration. Withdrawal because of adverse events accounted for 17% of BID, 11% of TID and 9% of placebo patients.\n Rivastigmine administered as a BID or TID regimen significantly benefited cognitive, function and global performances in AD patients. The TID regimen showed a tendency for superior tolerability and permitted titration to higher doses, an outcome that is significant as the efficacy of rivastigmine is dose related.", "The efficacy of a centrally active cholinesterase inhibitor, rivastigmine tartrate (ENA 713), in patients with advanced moderate Alzheimer's disease (AD) was evaluated in a 12-month placebo-controlled study. We aimed to investigate whether there was any evidence for the benefits of rivastigmine in patients with severe disease. These patients were compared with matched controls. In this study, 24 patients with advanced moderate AD received rivastigmine for 12 months. Another 20 patients received placebo. Mean daily doses of rivastigmine in the higher-dose group at 3, 6, 9, and 12 months were 6.1 +/- 1.0, 8.3 +/- 1.2, 8.9 +/- 1.3, and 10.7 +/- 1.6 mg/day, respectively. Cognitive abilities were assessed using the 11-item cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). Forty-five percent of placebo-treated patients declined by at least 4 points on the ADAS-cog. Conversely, only 18.3% of patients treated with rivastigmine declined by 4 or more points. Functional disabilities, as assessed using the Disability Assessment for Dementia Scale, remained significantly superior in rivastigmine-treated patients compared with placebo-treated patients. Patients benefited from high-dose rivastigmine treatment on all outcome measures, including the Mini-Mental State Examination, Progressive Deterioration Scale, as well as the Global Deterioration Scale. Patients receiving rivastigmine for 12 months significantly improved compared with placebo-treated patients (p < 0.001). By 52 weeks, patients originally treated with 6-12 mg/day rivastigmine had a significantly better cognitive function than patients originally treated with placebo. Long-term rivastigmine treatment appeared to be well tolerated in patients with advanced moderate AD and significantly benefits the cognitive and functional symptoms of AD.\n Copyright 2005 S. Karger AG, Basel.", "To determine the respective efficacy of quetiapine and rivastigmine for agitation in people with dementia in institutional care and to evaluate these treatments with respect to change in cognitive performance.\n Randomised double blind (clinician, patient, outcomes assessor) placebo controlled trial.\n Care facilities in the north east of England.\n 93 patients with Alzheimer's disease, dementia, and clinically significant agitation.\n Atypical antipsychotic (quetiapine), cholinesterase inhibitor (rivastigmine), or placebo (double dummy).\n Agitation (Cohen-Mansfield agitation inventory) and cognition (severe impairment battery) at baseline and at six weeks and 26 weeks. The primary outcome was agitation inventory at six weeks.\n 31 patients were randomised to each group, and 80 (86%) started treatment (25 rivastigmine, 26 quetiapine, 29 placebo), of whom 71 (89%) tolerated the maximum protocol dose (22 rivastigmine, 23 quetiapine, 26 placebo). Compared with placebo, neither group showed significant differences in improvement on the agitation inventory either at six weeks or 26 weeks. Fifty six patients scored > 10 on the severe impairment battery at baseline, 46 (82%) of whom were included in the analysis at six week follow up (14 rivastigmine, 14 quetiapine, 18 placebo). For quetiapine the change in severe impairment battery score from baseline was estimated as an average of -14.6 points (95% confidence interval -25.3 to -4.0) lower (that is, worse) than in the placebo group at six weeks (P = 0.009) and -15.4 points (-27.0 to -3.8) lower at 26 weeks (P = 0.01). The corresponding changes with rivastigmine were -3.5 points (-13.1 to 6.2) lower at six weeks (P = 0.5) and -7.5 points (-21.0 to 6.0) lower at 26 weeks (P = 0.3).\n Neither quetiapine nor rivastigmine are effective in the treatment of agitation in people with dementia in institutional care. Compared with placebo, quetiapine is associated with significantly greater cognitive decline.", "Recent studies suggest that cholinergic dysfunction does not provide a complete account of age-related cognitive deficits, and other neuronal systems like monoaminergic hypofunction are involved. In several studies, selective serotonin reuptake inhibitors demonstrated promotion in neurogenesis in the hippocampus and enhanced memory and cognition. The aim of this study is to survey the effect of serotonin augmentation on cognition and activities of daily living in patients with Alzheimer's disease.\n The trial was designed as a 12-week randomized, placebo-controlled, double-blind study. One hundred twenty-two patients aged 55 to 85 years with mild-to-moderate Alzheimer's dementia were randomly allocated in 1 of the 3 treatment groups: fluoxetine plus rivastigmine, rivastigmine alone, or placebo group. Efficacy measures comprised assessments of cognition, activities of daily living, and global functioning. Hamilton Depression Scale also was used to assess changes in mood throughout the study.\n Fluoxetine plus rivastigmine and rivastigmine groups demonstrated improvement on measures of cognitive and memory without any significant difference; however, the former group did better in their activities of daily living and global functioning. Patients taking placebo had significant deterioration in all the efficacy measures. Patients taking rivastigmine or rivastigmine plus fluoxetine had improvements in Hamilton Depression Scale without significant differences.\n Concomitant use of selective serotonin-enhancing agents and acetyl cholinesterase inhibitors can provide greater benefit in activities of daily living and global functioning in patients with cognitive impairment. Because our study is preliminary, larger double-blind studies are needed to confirm the results." ]

[ "16819595", "6848154", "9516764", "2470768", "6555992", "2738549", "17942268", "10232210", "18398664", "18945572", "18676516", "19733100", "10315165", "18652000", "17284502", "1685595", "14507797", "8564589", "12071899", "11820354", "20385634", "21043788" ]

[ "Inhaler technique in Turkish people with poor English: a case of information discrimination?", "The value of demonstration and role of the pharmacist in teaching the correct use of pressurized bronchodilators.", "Evaluation of the long-term effectiveness of three instruction modes for inhaling medicines.", "Audiovisual demonstration for patient counselling in the use of pressurised aerosol bronchodilator inhalers.", "The effect of teaching on medication knowledge.", "Comparison between videotape and personalized patient education for anticoagulant therapy.", "Patient education about anticoagulant medication: is narrative evidence or statistical evidence more effective?", "Preoperative PCA teaching program to manage postoperative pain.", "Computer-assisted provision of emergency contraception a randomized controlled trial.", "Improving informed consent to chemotherapy: a randomized controlled trial of written information versus an interactive multimedia CD-ROM.", "A video game improves behavioral outcomes in adolescents and young adults with cancer: a randomized trial.", "Results of a randomized controlled trial of a brief behavioral intervention for pelvic inflammatory disease in adolescents.", "Tricyclic antidepressant education program and its evaluation.", "Evaluation of the addition of video-based education for patients receiving standard pre-chemotherapy education.", "Influence of an interactive computer-based inhaler technique tutorial on patient knowledge and inhaler technique.", "[Randomized evaluation of two teaching methods using aerosol dosers].", "Providing information on metered dose inhaler technique: is multimedia as effective as print?", "Failure of educational videotapes to improve medication compliance in a health maintenance organization.", "An interactive technology approach to educate older adults about drug interactions arising from over-the-counter self-medication practices.", "Delivering health information about self-medication to older adults: use of touchscreen-equipped notebook computers.", "Animated video vs pamphlet: comparing the success of educating parents about proper antibiotic use.", "Preventing prescription drug misuse: field test of the SmartRx Web program." ]

[ "(a) To compare metered dose inhaler (MDI) technique in users with poor English and fluent English, (b) to evaluate two interventions: a translated patient information leaflet (PIL) plus support from an translator (PIL + verbal) and a multimedia touch screen system (MTS) using video clips and own-language instruction.\n (a) Inhaler technique was videotaped and key steps rated blind for 105 fluent English-speakers (FE) and 69 Turkish-speakers with poor English (EP). (b) The EP group was randomised to receive information by MTS (n = 34) or PIL + verbal (n = 35). Inhaler technique was videotaped before and after information.\n (a) Global inhaler technique; (b) breathing-in time; (c) co-ordination of inspiration and inhaler actuation.\n Global technique, co-ordination and breath-holding were all significantly worse in MDI users with poor English. Only 17% of that group had adequate technique compared to over half (62%) of FE. The EP group were significantly less likely than the FE group to report ever seeing the practice nurse about their asthma. After information, global technique was rated as improved in 50% of the MTS group compared to 28% of those given a translated PIL. A further six people (17%) in the PIL group improved after subsequent verbal advice in their own language. Both information methods significantly increased inhaler shaking and mouthpiece checking, but co-ordination only improved in a small number of people.\n The study suggests that Turkish-speaking MDI users with poor English may be disadvantaged in terms of access to medicines information in the UK. The acceptability of pharmacy-based support services for this, and other specific language groups should be explored. Multimedia offers an alternative to a translator for brief explanations, particularly for first-time users, but improving poor co-ordination requires individualised \"hands on\" teaching from health professionals.", "The use of an improper technique with metered-dose inhalers decreases the efficacy of the bronchodilators being administered. There is evidently a need for patients to watch a demonstration. Twenty-nine adult asthmatic patients from an allergy clinic were divided into three groups, each receiving a different form of instruction: an information sheet, personal instruction or a videotape presentation. Subsequently each patient was tested for correct use of the inhaler. There was no difference in mean scores for inhalation technique between the groups instructed in person and by videotape, but both were significantly better than the mean score of the group given only an information sheet. There was also no significant change in the scores at a follow-up test in the groups who saw the technique demonstrated. These results indicate the need for and value of the demonstration of proper technique with pressurized inhalers. A pharmacy-generated education system using videotape equipment or personal instruction by a pharmacist could readily solve the problem.", "Inhaled medication is important in the treatment of chronic obstructive pulmonary disease (COPD). In this paper a comparison of the long-term efficacy of three instruction-models is presented. A total of 152 COPD-patients were randomized into one of four groups: Personal-, video-, group-instruction and a control group. Inhalation technique was assessed by means of checklists, on which essential inhalation manoeuvres were identified. Up to 9 months later, 148 patients returned for follow-up assessment. Prior to instruction 61% of patients in the control group had a perfect score on essential actions, compared to 62, 65 and 53% for those receiving group-, personal- and video-instruction respectively. At follow-up these percentages were 49, 97, 75 and 76%. For group-(35%) and video-instruction (24%) the increase from baseline was significant. Examining the different inhalers under investigation, it is striking, that only 24% of all patients with a Metered Dose Inhaler (MDI) performed all essential checklist items correctly, versus 96% for those using a Diskhaler. The fact that for the MDI this percentage improved to 90% post-instruction, shows that time spent on instruction, is time well spent. We conclude that group instruction seems superior to personal counselling, and equally effective or even better than video instruction. Personal instruction should not be dismissed and a combination with video instruction might prove to be effective as well.", "The use of video as a method of instructing subjects on correct inhaler technique was compared with the written and personal instruction of 150 volunteer subjects with no previous experience of such a device. Video was found to be as effective as personal tuition by a pharmacist and significantly (P less than 0.05) superior to the manufacturer's package insert in teaching correct inhaler technique. The technique was assessed by a panel of five investigators in each case and was found to deteriorate over a 2-week period regardless of the instruction method. The video, which was prepared 'in-house', was then assessed in both the hospital out-patient and the general practice pharmacy settings. Asthmatic patients found the video useful at identifying mistakes they were making and felt that this approach to their education should be more widely available.", "nan", "To assess the effectiveness of videotape patient education, 22 patients were randomized to receive either videotape or personalized teaching for oral anticoagulant (warfarin) therapy. Both groups scored significantly higher on a questionnaire designed to assess knowledge gained after instruction, with no significant difference between the two groups. Videotape instruction required substantially less nursing time. A second questionnaire assessed patient satisfaction with respect to both methods, which were rated equally effective and worthwhile. Videotape teaching is an effective and well-accepted alternative form of patient education requiring significantly less personnel time.", "To determine the relative impact of incorporating narrative evidence, statistical evidence or both into patient education about warfarin, a widely used oral anticoagulant medication.\n 600 patients receiving anticoagulant therapy were randomly assigned to view one of three versions of a video depicting a physician-patient encounter where anticoagulation treatment was discussed, or usual care (no video). The videos differed in whether the physician used narrative evidence (patient anecdotes), statistical evidence, or both to highlight key information. 317 patients completed both the baseline and post-test questionnaires. Questions assessed knowledge, beliefs and adherence to medication and laboratory monitoring regimens.\n All three approaches positively effected patients' warfarin-related knowledge, and beliefs in the importance of lab testing; there was also some indication that viewing a video strengthened belief in the benefits of warfarin. There was some indication that narrative evidence had a greater impact than statistical evidence on beliefs about the importance of lab testing and on knowledge. No other evidence of the differential effectiveness of either approach was found. No statistically significant effect was found on intent to adhere, or documented adherence to lab monitoring.\n Videos depicting a physician-patient dialogue about warfarin were effective in educating patients about anticoagulant medication, and had a positive impact on their beliefs. The use of narrative evidence in the form of patient anecdotes may be more effective than statistical evidence for some patient outcomes.\n Patients on oral anticoagulant therapy may benefit from periodic educational efforts reinforcing key medication safety information, even after initial education and ongoing monitoring. Incorporating patient anecdotes into physician-patient dialogues or educational materials may increase the effectiveness of the message.", "Patient-controlled analgesia (PCA) therapy was designed to provide patients with greater control in managing their pain. However, many patients continue to suffer from moderate to severe pain due to lack of knowledge about how to use PCA therapy. The results of this quasi-experimental study demonstrated that patients who received structured preoperative teaching had statistically significant higher knowledge regarding the use of PCA therapy and more positive attitudes toward using pain medicine. Patients who received the video teaching reported better pain control and satisfaction with pain management 4 and 8 hours following their surgical procedures.", "Emergency contraception (EC) can prevent unintended pregnancy. However, many women continue to lack information needed to use EC effectively and clinician time to counsel women about EC is limited.\n To evaluate whether computer-assisted provision of EC can increase knowledge and use of EC among women able to access EC without a prescription.\n We conducted a randomized controlled trial in which the intervention group received a 15-minute computerized educational session and 1 pack of EC. The control group received education about periconception folate supplementation, but no information about EC. Participants were contacted 7 months after enrollment.\n Four hundred forty-six women recruited from 2 urgent care clinics in San Francisco in 2005.\n Knowledge of EC, use of EC, and self-reported pregnancy.\n At follow-up, women in the intervention group answered an average of 2 more questions about EC correctly than they had at baseline, whereas women in the control group answered only 1 more item correctly (2.0 vs 1.2, p < .001). There was a trend toward more use of EC during the study period in the intervention group (10% vs 4% of women followed, p = .06; 6% vs 3%, p = .09 of women enrolled). Fewer women in the intervention group were pregnant at the time of follow-up (0.8% vs 6.5%, p = .01 of women followed; 0.5% vs 4.0%, p = .01 of women enrolled).\n Computer-assisted provision of EC in urgent care waiting areas increased knowledge of EC in a state where EC had been available without a prescription for 3 years.", "This randomized controlled trial aimed to determine whether an interactive CD-ROM improved cancer patients' recall of chemotherapy treatment information over standard written information, and whether demographic, cognitive, and psychological factors better predicted recall than this format of delivery.\n One-hundred-and-one new patients about to commence chemotherapy were randomized to receive written information or a CD-ROM containing treatment information before giving informed consent. Patients' recall, concentration, short-term memory, reading comprehension, anxiety, depression, and coping styles were assessed with standardized measures pre-treatment. Seventy-seven patients completed tests for recall of treatment information before their second chemotherapy session.\n Intention-to-treat analyses indicated no significant differences between the written information and CD-ROM groups across recall questions about number of drugs received (p=.43), treatment length (p=.23), and treatment goal (p=.69). Binary logistic regressions indicated that for groups combined different variables predicted each of the recall questions.\n An interactive CD-ROM did not improve cancer patients' recall of treatment information enough to warrant changes in consent procedures.\n Different variables predicted recall of different treatment aspects highlighting the complex nature of attempting to improve patient recall. Attending to the effect of depression on patient knowledge and understanding appears paramount.", "Suboptimal adherence to self-administered medications is a common problem. The purpose of this study was to determine the effectiveness of a video-game intervention for improving adherence and other behavioral outcomes for adolescents and young adults with malignancies including acute leukemia, lymphoma, and soft-tissue sarcoma.\n A randomized trial with baseline and 1- and 3-month assessments was conducted from 2004 to 2005 at 34 medical centers in the United States, Canada, and Australia. A total of 375 male and female patients who were 13 to 29 years old, had an initial or relapse diagnosis of a malignancy, and currently undergoing treatment and expected to continue treatment for at least 4 months from baseline assessment were randomly assigned to the intervention or control group. The intervention was a video game that addressed issues of cancer treatment and care for teenagers and young adults. Outcome measures included adherence, self-efficacy, knowledge, control, stress, and quality of life. For patients who were prescribed prophylactic antibiotics, adherence to trimethoprim-sulfamethoxazole was tracked by electronic pill-monitoring devices (n = 200). Adherence to 6-mercaptopurine was assessed through serum metabolite assays (n = 54).\n Adherence to trimethoprim-sulfamethoxazole and 6-mercaptopurine was greater in the intervention group. Self-efficacy and knowledge also increased in the intervention group compared with the control group. The intervention did not affect self-report measures of adherence, stress, control, or quality of life.\n The video-game intervention significantly improved treatment adherence and indicators of cancer-related self-efficacy and knowledge in adolescents and young adults who were undergoing cancer therapy. The findings support current efforts to develop effective video-game interventions for education and training in health care.", "The objective of this research was to examine the effectiveness of a brief behavioral intervention, provided at the time of diagnosis of pelvic inflammatory disease, on subsequent behaviors by patients who were urban adolescents in a community in which sexually transmitted infection was prevalent.\n 121 adolescents aged 15 to 21 years with mild to moderate pelvic inflammatory disease were enrolled in a randomized trial. All participants received standardized care, completed baseline audio computerized self-interviews, received full courses of medication at discharge, and were interviewed after the 2-week treatment course. The intervention group also watched a 6-minute intervention video.\n Medication completion, temporary sexual abstinence during the 14-day treatment period, partner notification, partner treatment, and return for 72-hour follow-up were studied. Data were evaluated using multivariate regression analysis.\n Of the participants, 61% were located and could participate in the 2-week interview by the disease intervention specialist. The intervention participants had higher rates of 72-hour follow-up (32% vs. 16%) and partner treatment (71% vs. 53%) in bivariate analyses at a P = 0.1 level. There were no differences in medication completion (66% vs. 66%), sexual abstinence (78% vs. 89%), or partner notification (88% vs. 92%). Only the partner-treatment finding persisted in multivariate models (AOR = 3.10; 95% CI, 1.03-9.39, P = .045).\n Adolescent girls randomized to a community-specific video intervention at diagnosis of pelvic inflammatory disease were three times more likely to have their partners treated than those in the control group. Given the value of partner treatment in secondary prevention of sexually transmitted diseases, this video may be an essential component of discharge programming in urgent care settings. Additional structural supports may be necessary to facilitate improved adherence to other key adherence behaviors.\n Copyright 2010 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.", "The objectives of this study were (1) to develop an individualized tricyclic audiovisual education program and (2) to compare the program's effectiveness with that of traditional education. The program is designed to increase short-term and long-term knowledge about tricyclic antidepressants and depression. The patient's dose was stabilized, and then a pretest was given. If the patient was in the study group, he received the seven-minute slide-tape program and a posttest within 72 hours. The control group received the posttest within five days of the pretest. Both groups were given knowledge tests at approximately four weeks. Statistical analysis of the data from this small study group revealed significance at the 95% confidence level for the following statement: the study group showed a greater increase in factual short-term and long-term knowledge about its tricyclic therapy as shown by differences in pretest, posttest, and scores of tests at four weeks. This study demonstrates an effective standardized alternative to traditional education which can be used to educate the majority of patients about tricyclic antidepressants and depression with a minimum time investment.", "Preparing cancer patients and their families for chemotherapy treatment is difficult. The challenge lies in finding ways to promote self-care and improve their ability to recall instructions. The aim of this study was to evaluate the usefulness of an educational video with regard to patients' ability to recall and report side effects of treatment. Patients referred for adjuvant chemotherapy for breast and colorectal cancer were randomized to receive standard pre-chemotherapy education or standard education plus addition of a video. Patients completed a base line questionnaire assessing existing knowledge and another questionnaire prior to the second chemotherapy cycle evaluating recall of information. Patients who watched the video were asked to assess the video after six cycles of chemotherapy. Telephone calls to the department reporting symptoms were monitored for both groups. The video group demonstrated trends towards higher recall in information concerning fever, mouth problems, low red cell count and prevention of constipation. They more commonly telephoned reporting medical problems of nausea, vomiting and signs of infection compared with the standard group. In summary, our study demonstrated inclusion of video to standard chemotherapy education improves retention of information regarding management of predictable chemotherapy side effects and reporting of treatment-related symptoms.", "Patient knowledge of correct inhaler technique is essential in the treatment of pulmonary disease. Computer delivery of educational content may augment existing teaching efforts.\n To determine whether a computer-based tutorial on inhaler technique could improve patients' knowledge and ability to correctly demonstrate inhaler technique.\n A total of 34 adults with pulmonary disease and experience using inhalers were randomized into the control or intervention groups. The intervention group viewed the tutorial, after which they demonstrated their inhaler technique and completed an Inhaler Technique Knowledge Test. Control group patients, who did not view the tutorial, were also evaluated on their demonstrated inhaler technique and technique knowledge. Additional information obtained included demographics, illness and treatment history, and patients' use of computers. Lastly, all patients who viewed the tutorial completed a brief questionnaire eliciting tutorial feedback. Control group patients were invited to view the tutorial after other data collection was complete. The 2 principal outcomes were the observed inhaler technique score and the inhaler technique knowledge test score. Comparisons between groups were conducted using Student's t-test and chi(2) test, with a p value less than 0.05 considered statistically significant.\n Eighteen subjects were enrolled in the computer group; 16 were in the control group. The intervention group demonstrated significantly better inhaler technique, with a mean Observed Inhaler Technique Score of 88.3 +/- 12.3 compared with 67.4 +/- 19.2 for the control group (p = 0.001). The intervention group also scored significantly higher on the Inhaler Technique Knowledge Test, with a score of 80.9 +/- 17.0 versus 67.4 +/- 11.8 for the control group (p = 0.01). Overall, the program appeared acceptable to patients.\n Patients in the tutorial group demonstrated better inhaler technique and scored higher on the Inhaler Technique Knowledge Test compared with those in a control group. This tutorial may be a useful educational tool to enhance patient education regarding inhaler technique.", "The administration of antiasthmatic drugs by pressurised aerosols is limited by the difficulties of the inhalation technique. The development of teaching aids may help their use. The aim of this study was to assess and to compare 2 educational methods of inhalation: a standardised inhalation card and a video film. Forty five asthmatic patients who were poor coordinators were separated randomly into 3 groups: education by card, education by video film and a third group served as a positive control and had been educated by video film and also an additional education in a room set aside for teaching inhalation techniques. The FEV1 (VEMS) had been read before the education session and 15 days after, and on each occasion before and after inhalation of a beta-2-mimetic. An inhalation score was measured on the same date. The 2 educational methods enabled an improvement in the score to be shown which was more marked in the video group than in the card group. The VEMS (mean + or - one standard deviation) before inhalation of beta-2-mimetics was significantly superior to J15 in relation to J1 in the video group (2.38 +/- 0.84 and 1.89 +/- 0.61 respectively) and in the control group (2.05 +/- 0.81 and 1.71 +/- 0.66 respectively) whilst the values did not differ in the card group (2.09 +/- 0.63 and 2.01 +/- 0.7 respectively). This study suggests the value of education of these patients and the superiority of video education in relation to reading a standardised card in the optimisation of treatment administered by the inhaled route.", "Metered dose inhalers (MDIs) are not easy to use well. Every MDI user receives a manufacturer's patient information leaflet (PIL). However, not everyone is able or willing to read written information. Multimedia offers an alternative method for teaching or reinforcing correct inhaler technique.\n The aim of this study was to compare the effects of brief exposure to the same key information, given by PIL and multimedia touchscreen computer (MTS).\n A single-blind randomized trial was conducted in 105 fluent English speakers (53% female; 93% White) aged 12-87 years in London general practices. All patients had had at least one repeat prescription for a bronchodilator MDI in the last 6 months. Inhaler technique was videotaped before and after viewing information from a PIL (n = 48) or MTS (n = 57). Key steps were rated blind using a checklist and videotape timings. The main outcome measures were a change in (i) global technique; (ii) co-ordination of inspiration and inhaler actuation; (iii) breathing-in time; and (iv) information acceptability.\n Initially, over a third of both groups had poor technique. After information, 44% (MTS) and 19% (PIL) were rated as improved. Co-ordination improved significantly after viewing information via MTS, but not after PIL. Breathing-in time increased significantly in both groups. Half the subjects said they had learned 'something new'. The MTS group were more likely to mention co-ordination and breathing.\n Short-term, multimedia is as least as effective as a good leaflet, and may have advantages for steps involving movement. MTS was acceptable to all age groups. The method could be used more widely in primary care.", "The value of mailed educational videotapes as a means of enhancing compliance with drug therapy was studied. Members of a health maintenance organization with a pharmacy claim for benazepril, metoprolol, simvastatin, or transdermal estrogen were randomly assigned to a study group or a control group. Subjects in the study group were mailed one of four videotape programs giving information on the drug prescribed and the inferred disease state. Control subjects received no educational materials. Subjects were enrolled from July 1, 1993, through January 2, 1994. Refill data were collected from July 1, 1993, through April 1, 1994. The medication possession ratio (MPR) was calculated as the total number of days' supply of a drug obtained by a member divided by the number of days between the time of enrollment and April 1, 1994, or the date the member was terminated from the plan. A subject was deemed compliant if his or her MPR was > or = 0.80. There were no significant differences in mean MPRs between the study group (n = 1993) and the control group (n = 2253). None of the mean MPRs was > or = 0.80, although 44% of control subjects and 46% of study-group subjects were compliant. Of 97 respondents to a survey mailed to a randomly selected subset of the study group, almost 87% reported that they had viewed the videotapes, and of these subjects, about 88% said they found them very useful or somewhat useful. A one-time mailing of videotapes to patients, with no individual follow-up, did not increase compliance with the medications monitored.", "An interactive computer program (Personal Education Program [PEP]) designed for the learning styles and psychomotor skills of older adults was used to teach older adults about potential drug interactions that can result from self-medication with over-the-counter (OTC) agents and alcohol. Subjects used the PEP on notebook computers equipped with infrared sensitive touchscreens. Subjects were recruited from senior centers. Those who met age, vision, literacy, independence, and medication use criteria were randomly assigned to one of three groups: (1) PEP plus information booklet; (2) information booklet only; or (3) control. A repeated measures (three time periods 2 weeks apart), three-group design was used. Users of PEP had significantly greater knowledge and self-efficacy scores than both the conventional and control groups at all three time points. The PEP group reported fewer adverse self-medication behaviors over time. Reported self-medication behaviors did not change over time for either the conventional or control groups. Subjects indicated a high degree of satisfaction with the PEP and reported their intent to make specific changes in self-medication behaviors.", "Preventing Drug Interactions in Active Older Adults is an educational intervention to prevent prescription and over-the-counter (OTC) drug and alcohol interactions in active, community-living older adults. The objectives of the program are to increase older adults' knowledge of potential interactions of prescription medications with OTC drugs and alcohol and to increase their confidence (self-efficacy) about how to avoid such interactions. An interactive multimedia computer software program (Personal Education Program or PEP) was designed for the learning styles and psychomotor skills of older adults. Focus groups of older adults evaluated PEP components in a formative manner during development. The program content dealing with antacids, calcium supplements, and acid reducers was pilot tested with 60 older adults recruited from local senior centers. Participants used the PEP on notebook computers equipped with infrared-sensitive touchscreens. Users of PEP had greater knowledge and self-efficacy scores than controls. Participants indicated a high degree of satisfaction with the PEP and reported their intent to make specific changes in self-medication behaviors.", "The objective was to create an animated video to teach parents about the appropriate use of antibiotics and to compare their knowledge to parents who were provided with the American Academy of Pediatrics pamphlet. We hypothesized that the video format would result in improved comprehension and retention.\n This prospective randomized, controlled trial was conducted in an urban pediatric emergency department. Parent subjects were randomly assigned to a control group, a pamphlet group, and a video group and completed a survey at 3 time points. Analysis included the nonparametric matched Friedman test, Kruskal-Wallis test, and the Mann-Whitney U test. A 2-sided P value of < .05 was required for significance, and a Bonferroni-corrected P value of < .017 was required for paired comparisons.\n Postintervention survey scores improved significantly in the pamphlet and video groups compared with baseline. The video group's follow-up scores were not significantly different from the postintervention-survey scores (P = .32). The pamphlet-group scores at follow-up were significantly lower than the postintervention-survey scores (P = .002). The control group's scores were similar at all 3 time periods. The pamphlet group had significantly better scores than the control group after the intervention (P < .001). The video-group scores exceeded the control-group scores at all 3 time periods.\n An animated video is highly effective for educating parents about the appropriate use of antibiotics in the emergency department setting and results in long-term knowledge retention. The results of this study provide a foundation to further evaluate the use of animated video in additional populations.", "Purpose of the project was to test a Web-based program designed to prevent prescription drug misuse. Study sample consisted of 346 working women randomized into either an experimental or wait-list control condition. Analysis of covariance and logistic regression were used to compare responses. Women receiving the intervention had greater knowledge of drug facts and greater self-efficacy in medication adherence and ability to manage problems with medications compared with controls. Women receiving the intervention also had reduced symptoms reported on the CAGE for prescription medications. Findings suggest that multimedia Web-based programs can be a beneficial addition to substance misuse prevention services. The study's limitations are noted." ]

[ "15659490", "10344555" ]

[ "Up-front tandem high-dose chemotherapy compared with standard chemotherapy with doxorubicin and paclitaxel in metastatic breast cancer: results of a randomized trial.", "[Intensive chemotherapy and autograft of hematopoietic stem cells in the treatment of metastatic cancer: results of the national protocol Pegase 04]." ]

[ "The role of high-dose chemotherapy (HDCT) in metastatic breast cancer remains controversial. Trials with late intensification HDCT have failed to show an advantage in overall survival. This study was initiated to compare up-front tandem HDCT and standard combination therapy in patients with metastatic breast cancer.\n Patients without prior chemotherapy for metastatic disease were randomly assigned to standard combination therapy with doxorubicin and paclitaxel (AT) or double HDCT with cyclophosphamide, mitoxantrone, and etoposide followed by peripheral-blood stem-cell transplantation. HDCT was repeated after 6 weeks. Patients were stratified by menopausal and hormone-receptor status. The primary objective was to compare complete response (CR) rates.\n A total of 93 patients were enrolled onto the trial. Intent-to-treat CR rates for patients randomized to HDCT and AT were 12.5% and 11.1%, respectively (P = .84). Objective response rates were 66.7% for patients in the high-dose group and 64.4% for patients in the AT arm (P = .82). In an intent-to-treat analysis, there were no significant differences between the two treatments in median time to progression (HDCT, 11.1 months; AT, 10.6 months; P = .67), duration of response (HDCT, 13.9 months; AT, 14.3 months; P = .98), and overall survival (HDCT, 26.9 months; AT, 23.4 months; P = .60). HDCT was associated with significantly more myelosuppression, infection, diarrhea, stomatitis, and nausea and vomiting, whereas patients treated with AT developed more neurotoxicity.\n This trial failed to show a benefit for up-front tandem HDCT compared with standard combination therapy. HDCT was associated with more acute adverse effects.", "We report hereby the results of the french multicentric randomized PEGASE 04 protocol established to evaluate the impact on survival of high-dose chemotherapy over conventional chemotherapy for MBC patients.\n Inclusion criteria were: age < or = 60 year, PS < 2, adenocarcinoma initially metastatic or in first relapse, chemosensitive disease. Randomization was done after 4-6 courses of conventionnal chemotherapy between high-dose (Mitoxantrone, 45 mg/m2, Cyclophosphamide: 120 mg/kg, Melphalan: 140 mg/m2), and the pursuit of the same conventionnal chemotherapy. Between 09/92 and 12/96, 61 chemosensitive patients were enrolled: 29 were referred to standard chemotherapy, 32 to intensive therapy. At randomization, 13 pts (21.3%) were in complete response and 48 in partial response.\n The median progression-free survivals were 20 and 35.3 months in the standard and intensive groups (p=0.06). The relapse rates were respectively 79.3% vs 50.8% at 3 years and 90.8% vs 90.7% at 5 years. The median overall survivals were 20 and 43.4 months, with an overall survival rate of 18.5% vs 29.8% at 5 years (p=0.12).\n The CMA regimen could prolong the progression-free survival of MBC patients, however without any significant impact on overall survival." ]

[ "12832708", "17907238", "16181565" ]

[ "Aquatic fitness training for children with juvenile idiopathic arthritis.", "The effects of vigorous exercise training on physical function in children with arthritis: a randomized, controlled, single-blinded trial.", "Is hydrotherapy cost-effective? A randomised controlled trial of combined hydrotherapy programmes compared with physiotherapy land techniques in children with juvenile idiopathic arthritis." ]

[ "To evaluate the effects of an aquatic training programme for JIA patients.\n Fifty-four patients with JIA (age range 5 to 13 yr) participated in this study and were randomized into an experimental (n = 27) and a control (n = 27) group. The children in the experimental group received a training programme consisting of a 1 h per week supervised training programme in a local pool of approximately 20 sessions. Effects were analysed on the following domains: functional ability, health-related quality of life, joint status and physical fitness.\n Although all measures improved more in the experimental group than the control group, none of the differences was statistically significant.\n The current research found no significant effect of an aquatic fitness training programme in children with JIA. Since there were no signs of worsening in health status, one can conclude that this was a safe exercise programme.", "To examine the effectiveness of high-intensity aerobic training compared with low-intensity training in terms of energy cost of locomotion, peak oxygen uptake, peak power, and self-reported physical function in children with juvenile idiopathic arthritis (JIA).\n Eighty children with JIA, ages 8-16 years, were enrolled in a randomized, single-blind controlled trial. Both groups participated in a 12-week, 3-times-weekly training program consisting of high-intensity aerobics in the experimental group and qigong in the control group. Subjects underwent exercise testing measuring submaximal oxygen uptake at 3 km/hour (VO(2submax)) as the primary outcome, maximal oxygen uptake, and peak power at the beginning and end of the program. Physical function was measured using the Child Health Assessment Questionnaire (C-HAQ).\n The exercise program was well tolerated in both groups. There was no difference in VO(2submax) or any other exercise testing measures between the groups through the study period and no indication of improvement. Both groups showed significant improvements in C-HAQ with no difference between the groups. Adherence was higher in the control group than the experimental group.\n Our findings suggest that activity programs with or without an aerobic training component are safe and may result in an important improvement in physical function. The intensity of aerobic training did not seem to provide any additional benefits, but higher adherence in the qigong program may suggest that less intensive regimens are easier for children with JIA to comply with, and provide a degree of benefit equivalent to more intensive programs.", "To compare the effects of combined hydrotherapy and land-based physiotherapy (combined) with land-based physiotherapy only (land) on cost, health-related quality of life (HRQoL) and outcome of disease in children with juvenile idiopathic arthritis (JIA). Also to determine the cost-effectiveness of combined hydrotherapy and land-based physiotherapy in JIA.\n A multicentre randomised controlled, partially blinded trial was designed with 100 patients in a control arm receiving land-based physiotherapy only (land group) and 100 patients in an intervention arm receiving a combination of hydrotherapy and land-based physiotherapy (combined group).\n Three tertiary centres in the UK.\n Patients aged 4-19 years diagnosed more than 3 months with idiopathic arthritides, onset before their 16th birthday, stable on medication with at least one active joint.\n Patients in the combined and land groups received 16 1-hour treatment sessions over 2 weeks followed by local physiotherapy attendances for 2 months.\n Disease improvement defined as a decrease of > or =30% in any three of six core set variables without there being a 30% increase in more than one of the remaining three variables was used as the primary outcome measure and assessed at 2 months following completion of intervention. Health services resource use (in- and outpatient care, GP visits, drugs, interventions, and investigations) and productivity costs (parents' time away from paid work) were collected at 6 months follow-up. HRQoL was measured at baseline and 2 and 6 months following intervention using the EQ-5D, and quality-adjusted life-years (QALYs) were calculated. Secondary outcome measures at 2 and 6 months included cardiovascular fitness, pain, isometric muscle strength and patient satisfaction.\n Seventy-eight patients were recruited into the trial and received treatment. Two months after intervention 47% patients in the combined group and 61% patients in the land group had improved disease with 11 and 5% with worsened disease, respectively. The analysis showed no significant differences in mean costs and QALYs between the two groups. The combined group had slightly lower mean costs (-6.91 pounds Sterling) and lower mean QALYs (-0.0478, 95% confidence interval -0.11294 to 0.0163 based on 1000 bootstrap replications). All secondary measures demonstrated a mean improvement in both groups, with the combined group showing greater improvements in physical aspects of HRQoL and cardiovascular fitness.\n JIA is a disease in which a cure is not available. This research demonstrates a beneficial effect from both combined hydrotherapy and land-based physiotherapy treatment and land-based physiotherapy treatment alone in JIA without any exacerbation of disease, indicating that treatments are safe. The caveat to the results of the cost-effectiveness and clinical efficacy analysis is that the restricted sample size could have prevented a true difference being detected between the groups. Nevertheless, there appears to be no evidence to justify the costs of building pools or initiating new services specifically for use in this disease. However, this conclusion may not apply to patients with unremitting active disease who could not be entered into the trial because of specified exclusion criteria. For this group, hydrotherapy or combined treatment may still be the only physiotherapy option. Further research is suggested into: the investigation and development of appropriate and sensitive outcome measures for use in future hydrotherapy and physiotherapy trials of JIA; preliminary studies of methodologies in complex interventions such as physiotherapy and hydrotherapy to improve recruitment and ensure protocol is acceptable to patients and carers; hydrotherapy in the most common paediatric user group, children with neurological dysfunction, ensuring appropriate outcome measures are available and methodologies previously tried; patient satisfaction and compliance in land-based physiotherapy and hydrotherapy and European studies of hydrotherapy in rare disorders such as JIA." ]

[ "6853874", "9212372", "886092", "10535230", "461602", "3571672", "3363075", "1852848", "3700808", "7381310", "11860044", "8436025", "11508042", "10784079", "8113483" ]

[ "Modification of anger in children by affective imagery training.", "School-based secondary prevention for children with disruptive behavior: initial outcomes.", "\"Think aloud\": a program for developing self-control in young aggressive boys.", "Initial impact of the Fast Track prevention trial for conduct problems: I. The high-risk sample. Conduct Problems Prevention Research Group.", "Cognitive self-instructional training approach for reducing disruptive behavior of young children.", "Improving the social behavior and peer acceptance of rejected boys: effects of social skill training with instructions and prohibitions.", "Effectiveness of assertiveness training in modifying aggressive behaviors of young children.", "Can disruptive boys be helped to become competent?", "Behavioral and cognitive effects of a moral reasoning development intervention for high-risk behavior-disordered adolescents.", "\"I must be good if i can teach!\" --- peer tutoring with aggressive and withdrawn children.", "A cognitive-ecological approach to preventing aggression in urban settings: initial outcomes for high-risk children.", "An attributional intervention to reduce peer-directed aggression among African-American boys.", "Training in social skills: an alternative technique for handling disruptive child behavior.", "Multi-method psycho-educational intervention for preschool children with disruptive behavior: preliminary results at post-treatment.", "Effectiveness of a social relations intervention program for aggressive and nonaggressive, rejected children." ]

[ "From a school population of normal children (third through fifth grades), thirty children initially identified as \"angry\" were randomly assigned to either an affective imagery training group, an attention group, or a control group. The treatment group received three sessions of affective imagery in which they focused on physiological changes and on their thoughts associated with prior emotional experiences. Teachers recorded pre-, post-, and short term follow-up aggressive behaviors for all thirty children. Cognitive perceptions and attributions were recorded at the same three occasions on the Affect Questionnaire. Results suggested that, as a result of affective imagery training, angry children's perceptions and cognitions shifted from \"angry\" towards \"sad,\" and there was a concomitant decrease in observed aggressive classroom behavior.", "First through fourth graders from 22 suburban elementary schools were screened for cross-setting disruptive behavior as eligibility criteria for participation in a longitudinal secondary prevention study aimed at reducing the risk for serious externalizing behavioral disorders. Three hundred nine subjects participated in either a multicomponent competence enhancement intervention (MCEI) or an information/attention control (IAC) condition over a 2-year period. Following baseline requirements, initial intervention effects were assessed at the end of intervention Year 1, at the beginning of intervention Year 2 (fall of the next school year), and at the end of intervention Year 2. Multisource assessments were not supportive of the efficacy of the MCEI over the IAC condition. Children in both groups rated themselves as improved over time in terms of increased adaptive skills and decreased school problems and internalizing symptoms. Teacher and parent ratings of externalizing behavior did not yield evidence of positive change, but teachers noted improved problem solving and observers noted a decrease in behavioral interference in both groups over time, possibly as a result of maturation.", "\"Think Aloud\" was designed as a training program to improve self-control in 6- to 8-year-old boys. It involved modeling and verbalization of cognitive activity to foster use of verbal mediation skills in dealing with both cognitive and interpersonal problems. It was hypothesized that this training would lead to improvement in test performance and teacher ratings of classroom behavior in hyperaggressive boys. Twelve aggressive second grade boys participated in daily, 30-minute, individual sessions for 6 weeks. Normal and aggressive control subjects received no intervention. Teachers rated both trained and untrained aggressive boys as improving in aggressive behaviors but they rated the experimental group as showing improvement on a significantly larger number of prosocial behaviors. The pattern of performance on cognitive tests also changed significantly in the experimental group. On pretest, their pattern differed from normals and resembled the aggressive control group, while on posttest their pattern resembled normals and differed from agressive controls. Suggestions were made concerning additional refinements needed in the program, but overall results indicated potential value in the present approach for providing assistance to aggressive boys in the early grades.", "Fast Track is a multisite, multicomponent preventive intervention for young children at high risk for long-term antisocial behavior. Based on a comprehensive developmental model, intervention included a universal-level classroom program plus social skills training, academic tutoring, parent training, and home visiting to improve competencies and reduce problems in a high-risk group of children selected in kindergarten. At the end of Grade 1, there were moderate positive effects on children's social, emotional, and academic skills; peer interactions and social status; and conduct problems and special-education use. Parents reported less physical discipline and greater parenting satisfaction/ease of parenting and engaged in more appropriate/consistent discipline, warmth/positive involvement, and involvement with the school. Evidence of differential intervention effects across child gender, race, site, and cohort was minimal.", "nan", "nan", "nan", "The Montréal Longitudinal Study of Disruptive Boys, an experimental study, was designed to understand boys who were considered disruptive in kindergarten. One part of the study involved assessing effects of a preventive treatment program carried out during the boys' early years in primary school. This paper reports on the outcome of the randomized treatment experiment 3 years after treatments ended. Disruptive boys were randomly allocated to a treated group and two nontreated groups. Treatment consisted of parent training and training of boys for social skills, fantasy play and television viewing. Results suggest that the treatment program had some positive effects. Some of the improvements were not evident immediately after treatment ended.", "nan", "nan", "A multiyear, multicontext aggression prevention intervention was provided during the early or late elementary school years in an inner-city and an urban poor community. Sixteen schools were randomly assigned to 1 of 4 conditions: (a) no-treatment control, (b) general enhancement classroom program, (c) general enhancement plus small-group peer-skills training, or (d) general enhancement plus small-group peer-skills training plus family intervention. This article reports on results for the high-risk subsample of 1,500 children. Results from hierarchical linear modeling indicate that comprehensive interventions, if provided in early grades, can be effective for children in schools in settings with resources adequate to support learning and development, but some unintended effects can occur in schools in the most distressed communities when delivered too late in development.", "An attributional intervention was designed to reduce aggressive males' tendency to attribute hostile intentions to peers following ambiguously caused peer provocations. African-American elementary school boys (N = 101), aggressive and nonaggressive, were randomly assigned to the attributional intervention, an attention training program, or a no-treatment control group. Data were collected on subjects' attributions about hypothetical and laboratory simulations of peer provocation, disciplinary referrals to the school office, and teacher ratings of aggressive behavior. Aggressive subjects in the attributional intervention were less likely to presume hostile intent by peers in hypothetical and laboratory simulations of ambiguous provocation. They were also less likely to endorse hostile retaliation on judgment measures and to engage in verbally hostile behaviors in the laboratory task. Further, intervention subjects were rated as less aggressive by their teachers following the treatment. Both the benefits of attributional change and its limitations in the African-American population are discussed.", "The purposes of this study were to examine the type of response to different situations displayed by children with or without conduct disorders and to assess the efficacy of the social skills training program herein proposed for modifying styles of interpersonal relationship in children. The sample included 315 children, 8 to 12 years of age. Those exhibiting conduct problems were 164 boys, and those having no conduct problems were 151 boys. All participants shared a low socioeconomic and cultural status and attended schools located in poor districts of Mendoza City in Argentina. Analysis showed that the groups trained in social skills improved in social interaction by reducing disruptive behaviors, whereas the groups without social skills training showed no behavioral changes. These data were confirmed by the teachers' assessments. These results suggest social skills training seems an efficient therapeutic approach to the attenuation of behavior disorders of boys.", "Annual screenings of preschool children at kindergarten registration identified 158 children having high levels of aggressive, hyperactive, impulsive, and inattentive behavior. These \"disruptive\" children were randomly assigned to four treatment conditions lasting the kindergarten school year: no treatment, parent training only, full-day treatment classroom only, and the combination of parent training with the classroom treatment. Results showed that parent training produced no significant treatment effects, probably owing largely to poor attendance. The classroom treatment produced improvement in multiple domains: parent ratings of adaptive behavior, teacher ratings of attention, aggression, self-control, and social skills, as well as direct observations of externalizing behavior in the classroom. Neither treatment improved academic achievement skills or parent ratings of home behavior problems, nor were effects evident on any lab measures of attention, impulse control, or mother-child interactions. It is concluded that when parent training is offered at school registration to parents of disruptive children identified through a brief school registration screening, it may not be a useful approach to treating the home and community behavioral problems of such children. The kindergarten classroom intervention was far more effective in reducing the perceived behavioral problems and impaired social skills of these children. Even so, most treatment effects were specific to the school environment and did not affect achievement skills. These findings must be viewed as tentative until follow-up evaluations can be done to determine the long-term outcomes of these interventions.", "A sample of 52 Black aggressive, rejected and nonaggressive, rejected children were randomly assigned to receive a social relations intervention or to be in a nonintervention control group. The school-based intervention for fourth-grade children focused on positive social skill training and cognitive-behavioral strategies to promote deliberate, nonimpulsive problem solving. At both the post-treatment and the 1-year follow-up assessments, the social relations intervention was found to be effective only with the aggressive, rejected children. Implications for the importance of assessing subtypes of rejected children are discussed." ]

[ "348228", "6387968", "19016569", "11750964" ]

[ "A controlled trial of puncture sites for amniocentesis.", "The role of hexoprenaline in suprapubic amniocentesis during late pregnancy. A pilot study.", "A randomized study to assess two different techniques of aspiration while performing transabdominal chorionic villus sampling.", "A randomised trial of progesterone prophylaxis after midtrimester amniocentesis." ]

[ "A controlled trial to determine a better site for amniocentesis was carried out over a 6-month period, involving 98 obstetric patients. The suprapubic and nuchal puncture site for amniocentesis were compared. The failure rate was found to be lower when the suprapublic site was used, and no significant difference in morbidity was found in the two groups.", "Suprapubic amniocentesis is often complicated by the fetal head being fixed in the pelvis, oligohydramnios or a hyperirritable myometrium. These factors limit the success rate associated with the procedure. If the myometrium is relaxed with a beta 2-stimulant, a higher success rate may be achieved. This was investigated in a randomized, prospective, double-blind pilot study using hexoprenaline. When four- or five-fifths of the fetal head was palpable above the pelvis, hexoprenaline (17 amniocenteses) showed no advantage over a placebo (16 amniocenteses). However, when three-fifths or less of the fetal head was palpable above the brim, 4 dry taps were obtained in the control group using a placebo (17 amniocenteses), while none occurred in the study group (19 amniocenteses) (P less than 0,05). Elevation of the fetal head was less difficult in the study group, but this difference was not statistically significant. These results suggest that hexoprenaline is not indicated for routine use during amniocentesis. When a dry tap is obtained or when marked difficulty is encountered in lifting the fetal head from the pelvis, 10 micrograms hexoprenaline administered intravenously 5 minutes before amniocentesis appears to facilitate successful completion of the procedure. However, a larger series is necessary to confirm this observation.", "The technique used to perform transabdominal chorionic villus sampling (CVS) is not standardized, but aspiration of villi is generally obtained by discontinuous vacuum created in a syringe, manually or by a hand-grip device. We evaluated the feasibility of a new method of performing CVS which employs a 4-mL Vacutainer connected to the needle, producing a continuous negative pressure.\n Two hundred pregnant women, whose gestational age ranged from 10 + 2 to 16 + 2 (mean, 12 + 1) weeks, entered the randomized study, which was powered to detect with 90% probability the absence of any difference in the size of chorionic samples obtained by using a 20-mL syringe with the vacuum obtained by a hand-grip device (Group 1) or by a vacutainer (Group 2). Four operators with different levels of experience performed all the procedures, which were done transabdominally using a freehand technique with a 20-gauge needle under ultrasound guidance.\n Maternal age, body mass index, gestational age and the way the needle was inserted within the chorion were similar in the two groups. The median amount of villi sampled was 20 mg, with no differences between the two groups. The rate of fetal loss was 1.7%. All losses occurred in women of Group 1 who had only one needle insertion. A second needle insertion was required more frequently while using the vacutainer.\n This new technique for performing transabdominal CVS uses a readily available device and is as effective as traditional sampling systems to aspirate villi. It has the advantage of being a one-operator procedure.", "Midtrimester amniocentesis to investigate fetal karyotype carries a small risk of fetal loss.\n To test the hypothesis that progesterone prophylaxis may reduce this.\n A randomised controlled trial comparing a short prophylactic treatment with progesterone after amniocentesis with untreated controls.\n There were no differences in frequency of miscarriage, preterm delivery or neonatal outcome.\n Prophylactic progesterone treatment after amniocentesis does not improve obstetric outcome." ]

[ "18509560" ]

[ "Specific exercises reduce brace prescription in adolescent idiopathic scoliosis: a prospective controlled cohort study with worst-case analysis." ]

[ "To compare the effect of Scientific Exercises Approach to Scoliosis (SEAS) exercises with \"usual care\" rehabilitation programmes in terms of the avoidance of brace prescription and prevention of curve progression in adolescent idiopathic scoliosis.\n Prospective controlled cohort observational study.\n Seventy-four consecutive outpatients with adolescent idiopathic scoliosis, mean 15 degrees (standard deviation 6) Cobb angle, 12.4 (standard deviation 2.2) years old, at risk of bracing who had not been treated previously.\n Thirty-five patients were included in the SEAS exercises group and 39 in the usual physiotherapy group. The primary outcome included the number of braced patients, Cobb angle and the angle of trunk rotation.\n There were 6.1% braced patients in the SEAS exercises group vs 25.0% in the usual physiotherapy group. Failures of treatment in the worst-case analysis were 11.5% and 30.8%, respectively. In both cases the differences were statistically significant. Cobb angle improved in the SEAS exercises group, but worsened in the usual physiotherapy group. In the SEAS exercises group, 23.5% of patients improved and 11.8% worsened, while in the usual physiotherapy group 11.1% improved and 13.9% worsened.\n These data confirm the effectiveness of exercises in patients with scoliosis who are at high risk of progression. Compared with non-adapted exercises, a specific and personalized treatment (SEAS) appears to be more effective." ]

[ "12383667", "11867823", "16096858", "17537764", "20442386", "16809416", "14519709", "19818694", "18701270" ]

[ "Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial.", "Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial.", "Autoantibodies against bactericidal/permeability-increasing protein (BPI-ANCA) in cystic fibrosis patients treated with azithromycin.", "Daily versus weekly azithromycin in cystic fibrosis patients.", "Effect of azithromycin on pulmonary function in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa: a randomized controlled trial.", "Long term effects of azithromycin in patients with cystic fibrosis: A double blind, placebo controlled trial.", "Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial.", "Long-term daily high and low doses of azithromycin in children with cystic fibrosis: a randomized controlled trial.", "Once-weekly azithromycin in cystic fibrosis with chronic Pseudomonas aeruginosa infection." ]

[ "The macrolide antibiotic azithromycin has anti-inflammatory properties potentially beneficial in cystic fibrosis. Since findings of open pilot studies seemed to show clinical benefit, we undertook a formal trial.\n 41 children with cystic fibrosis, aged 8-18 years, and with a median forced expiratory volume in 1 s (FEV1) of 61% (range 33-80%) participated in a 15-month randomised double-blind, placebo-controlled crossover trial. They received either azithromycin (bodyweight < or =40 kg: 250 mg daily, >40 kg: 500 mg daily) or placebo for 6 months. After 2 months of washout, the treatments were crossed over. The primary outcome was median relative difference in FEV1 between azithromycin and placebo treatment periods. Sputum cultures, sputum interleukin 8 and neutrophil elastase, exercise testing, quality of life, antibiotic use, and pulmonary exacerbation rates were secondary outcome measures. Side-effects were assessed by pure tone audiometry and liver function tests. Analysis was by intention-to-treat.\n Median relative difference in FEV1 between azithromycin and placebo was 5.4% (95% CI 0.8-10.5). 13 of 41 patients improved by more than 13% and five of 41 deteriorated by more than 13% (p=0.059). Forced vital capacity and mid-expiratory flow did not significantly change overall. 17 of 41 patients had 24 fewer oral antibiotic courses when on azithromycin than when taking placebo, and five had six extra courses (p=0.005). Sputum bacterial densities, inflammatory markers, exercise tolerance, and subjective well-being did not change. There were no noticeable side-effects.\n A 4-6-month trial of azithromycin is justified in children with cystic fibrosis who do not respond to conventional treatment. The mechanism of action remains unknown.", "Relentless chronic pulmonary inflammation is the major contributor to morbidity and mortality in patients with cystic fibrosis (CF). While immunomodulating therapies such as prednisolone and ibuprofen may be beneficial, their use is limited by side effects. Macrolides have immunomodulatory properties and long term use dramatically improves prognosis in diffuse panbronchiolitis, a condition with features in common with the lung disease of CF.\n To determine if azithromycin (AZM) improves clinical parameters and reduces inflammation in patients with CF, a 3 month prospective randomised double blind, placebo controlled study of AZM (250 mg/day) was undertaken in adults with CF. Monthly assessment included lung function, weight, and quality of life (QOL). Blood and sputum collection assessed systemic inflammation and changes in bacterial flora. Respiratory exacerbations were treated according to the policy of the CF Unit.\n Sixty patients were recruited (29 men) of mean (SD) age 27.9 (6.5) years and initial forced expiratory volume in 1 second (FEV1) 56.6 (22.3)% predicted. FEV1% and forced vital capacity (FVC)% predicted were maintained in the AZM group while in the placebo group there was a mean (SE) decline of -3.62 (1.78)% (p=0.047) and -5.73 (1.66)% (p=0.001), respectively. Fewer courses of intravenous antibiotics were used in patients on AZM (0.37 v 1.13, p=0.016). Median C reactive protein (CRP) levels declined in the AZM group from 10 to 5.4 mg/ml but remained constant in the placebo group (p<0.001). QOL improved over time in patients on AZM and remained unchanged in those on placebo (p=0.035).\n AZM in adults with CF significantly improved QOL, reduced CRP levels and the number of respiratory exacerbations, and reduced the rate of decline in lung function. Long term AZM may have a significant impact on morbidity and mortality in patients with CF. Further studies are required to define frequency of dosing and duration of benefit.", "Autoantibodies against bactericidal/permeability-increasing protein (BPI-ANCA) were found in patients with cystic fibrosis (CF). It is speculated that they represent a marker of the chronic endobronchial infection and sustained inflammatory response in CF. Our aim was to evaluate whether azithromycin (AZM), through its antiinflammatory effect, could affect the level of BPI-ANCA in CF patients. Eighteen patients with CF aged 5.5-36.3 years (median 15.1) were enrolled in a randomised, double-blind, placebo-controlled trial of AZM (250 mg twice a week to 10 patients) or placebo (8 patients) for 12 weeks. BPI-ANCA levels were recorded pre- and post-treatment and compared to a group of 18 matched healthy controls. Chi-square analysis, Kruskal-Wallis and Mann-Whitney tests were used to compare between the groups. Pre- and post-treatment values were compared using the Wilcoxon Signed-Ranked test. BPI-ANCA was found in 12 CF patients (67%) and four (22%) healthy subjects (P<0.001). The mean BPI-ANCA level was 3.94+/-6.15 U/ml (mean+/-SD) in healthy subjects and 38.11+/-42.34 U/ml in CF patients (P=0.023). The mean BPI-ANCA level was higher in patients with Pseudomonas aeruginosa compared to those without (64+/-35 U/ml and 25+/-41 U/ml respectively, P=0.032). No change in BPI-ANCA levels occurred in the AZM-treated patients [35 (0-127) U/ml (median (range) and 30 (0-120) U/ml, respectively] or in the placebo group [10 (0-66) U/ml and 13 (0-83) U/ml, respectively]. BPI-ANCA levels are significantly higher in patients with CF compared to healthy controls. BPIANCA levels are higher among patients colonised with P. aeruginosa. Twelve weeks of AZM therapy did not lower the BPI-ANCA level in patients with CF.", "Four randomised, placebo-controlled trials have previously documented the clinical benefits of azithromycin (AZM) in cystic fibrosis (CF) patients. The present study examined whether the beneficial effect of AZM is equivalent when administered daily or weekly. A double-blind, randomised study was carried out in 208 CF patients aged 6-58 yrs who were assigned to AZM either 250 mg daily (n = 103) or 1,200 mg weekly (n = 105) for 6 months, with assessments at baseline and at 1, 3, 6 and 7 months. Patients were taken from five adult and children CF centres in South-east Queensland, Australia. Equivalence was demonstrated between the two groups (daily versus weekly) with respect to improvements in lung function (forced expiratory volume in one second and forced vital capacity), C-reactive protein, days spent in hospital, admission rates and nutrition (body mass index, z-scores) using 95% confidence intervals with a tolerance interval of +/-10%. In patients aged <18 yrs the daily group had significantly better improvements in z-scores for height and weight after 6 months. In children, a nutritional advantage for daily administration was found. Gastro-intestinal adverse effects were more common with weekly therapy. Apart from these findings, daily and weekly administered azithromycin demonstrated similar outcomes for cystic fibrosis patients.", "Azithromycin is recommended as therapy for cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa infection, but there has not been sufficient evidence to support the benefit of azithromycin in other patients with CF.\n To determine if azithromycin treatment improves lung function and reduces pulmonary exacerbations in pediatric CF patients uninfected with P. aeruginosa.\n A multicenter, randomized, double-blind placebo-controlled trial was conducted from February 2007 to July 2009 at 40 CF care centers in the United States and Canada. Of the 324 participants screened, 260 were randomized and received study drug. Eligibility criteria included age of 6 to 18 years, a forced expiratory volume in the first second of expiration (FEV(1)) of at least 50% predicted, and negative respiratory tract cultures for P. aeruginosa for at least 1 year. Randomization was stratified by age of 6 to 12 years vs 13 to 18 years and by CF center.\n The active group (n = 131) received 250 mg (weight 18-35.9 kg) or 500 mg (weight > or = 36 kg) of azithromycin 3 days per week (Monday, Wednesday, and Friday) for 168 days. The placebo group (n = 129) received identically packaged placebo tablets on the same schedule.\n The primary outcome was change in FEV(1). Exploratory outcomes included additional pulmonary function end points, pulmonary exacerbations, changes in weight and height, new use of antibiotics, and hospitalizations. Changes in microbiology and adverse events were monitored.\n The mean (SD) age of participants was 10.7 (3.17) years. The mean (SD) FEV(1) at baseline and 168 days were 2.13 (0.85) L and 2.22 (0.86) L for the azithromycin group and 2.12 (0.85) L and 2.20 (0.88) L for the placebo group. The difference in the change in FEV(1) between the azithromycin and placebo groups was 0.02 L (95% confidence interval [CI], -0.05 to 0.08; P = .61). None of the exploratory pulmonary function end points were statistically significant. Pulmonary exacerbations occurred in 21% of the azithromycin group and 39% of the placebo group. Participants in the azithromycin group had a 50% reduction in exacerbations (95% CI, 31%-79%) and an increase in body weight of 0.58 kg (95% CI, 0.14-1.02) compared with placebo participants. There were no significant differences between groups in height, use of intravenous or inhaled antibiotics, or hospitalizations. Participants in the azithromycin group had no increased risk of adverse events, but had less cough (-23% treatment difference; 95% CI, -33% to -11%) and less productive cough (-11% treatment difference; 95% CI, -19% to -3%) compared with placebo participants.\n In children and adolescents with CF uninfected with P. aeruginosa, treatment with azithromycin for 24 weeks did not result in improved pulmonary function.\n clinicaltrials.gov Identifier: NCT00431964.", "Macrolides display immunomodulatory effects that may be beneficial in chronic inflammatory pulmonary diseases. The aim of the study was to document whether long term use of azithromycin may be associated with respiratory benefits in young patients with cystic fibrosis.\n A multicentre, randomised, double blind, placebo controlled trial was conducted from October 2001 to June 2003. The criteria for enrollment were age older than 6 years and forced expiratory volume in 1 second (FEV1) of 40% or more. The active group received either 250 mg or 500 mg (body weight < or > or =40 kg) of oral azithromycin three times a week for 12 months. The primary end point was change in FEV1.\n Eighty two patients of mean (SD) age 11.0 (3.3) years and mean (SD) FEV1 85 (22)% predicted were randomised: 40 in the azithromycin group and 42 in the placebo group. Nineteen patients were infected with Pseudomonas aeruginosa. The relative change in FEV1 at month 12 did not differ significantly between the two groups. The number of pulmonary exacerbations (count ratio 0.50 (95% CI 0.32 to 0.79), p < 0.005), the time elapsed before the first pulmonary exacerbation (hazard ratio 0.37 (95% CI 0.22 to 0.63), p < 0.0001), and the number of additional courses of oral antibiotics were significantly reduced in the azithromycin group regardless of the infectious status (count ratio 0.55 (95% CI 0.36 to 0.85), p < 0.01). No severe adverse events were reported.\n Long term use of low dose azithromycin in young patients with cystic fibrosis has a beneficial effect on lung disease expression, even before infection with Pseudomonas aeruginosa.", "Treatment strategies for cystic fibrosis (CF) lung disease include antibiotics, mucolytics, and anti-inflammatory therapies. Increasing evidence suggests that macrolide antibiotics might be beneficial in patients with CF.\n To determine if an association between azithromycin use and pulmonary function exists in patients with CF.\n A multicenter, randomized, double-blind, placebo-controlled trial conducted from December 15, 2000, to May 2, 2002, at 23 CF care centers in the United States.\n Of the 251 screened participants with a diagnosis of CF, 185 (74%) were randomized. Eligibility criteria included age 6 years or older, infection with Pseudomonas aeruginosa for 1 or more years, and a forced expiratory volume in 1 second (FEV1) of 30% or more. Participants were stratified by FEV1 (> or =60% predicted vs <60% predicted), weight of less than 40 kg vs 40 kg or more, and CF center.\n The active group (n = 87) received 250 mg (weight <40 kg) or 500 mg (weight > or =40 kg) of oral azithromycin 3 days a week for 168 days; placebo group (n = 98) received identically packaged tablets.\n Change in FEV1 from day 0 to completion of therapy at day 168 and determination of safety. Secondary outcomes included pulmonary exacerbations and weight gain.\n The azithromycin group had a mean 0.097-L (SD, 0.26) increase in FEV1 at day 168 compared with 0.003 L (SD, 0.23) in the placebo group (mean difference, 0.094 L; 95% confidence interval [CI], 0.023-0.165; P =.009). Nausea occurred in 17% more participants in the azithromycin group (P =.01), diarrhea in 15% more (P =.009), and wheezing in 13% more (P =.007). Participants in the azithromycin group had less risk of experiencing an exacerbation than participants in the placebo group (hazard ratio, 0.65; 95% CI, 0.44-0.95; P =.03) and weighed at the end of the study an average 0.7 kg more than participants receiving placebo (95% CI, 0.1-1.4 kg; P =.02).\n Azithromycin treatment was associated with improvement in clinically relevant end points and should be considered for patients with CF who are 6 years or older and chronically infected with P aeruginosa.", "Long-term administration of azithromycin (AZM) in children with cystic fibrosis (CF) has improved outcomes. However, the doses and schedule of administration are not very well studied in children with CF.\n A randomized controlled trial was conducted to compare the effect of two doses of azithromycin (5mg/kg/day and 15mg/kg/day) on FEV(1) and pulmonary exacerbations in children with cystic fibrosis. Enrolled children were randomly allocated to receive daily azithromycin (5mg/kg/day or 15mg/kg/day) for 6months. Clinical assessment and FEV(1) measurement were performed monthly.\n 56 children (28 in high dose group and 28 in low dose group) were enrolled. 47 (24 and 23 children in low and high dose groups) completed 12months of follow up. There was no difference in clinical scores, FEV(1), pulmonary exacerbation rates between two groups at baseline, 6months and at 12months. Per protocol analysis revealed that pulmonary exacerbation increased after discontinuing AZM and there was significantly more increase after 12months of enrolment in children getting high dose azithromycin. There was no improvement in FEV(1) in either group at the end of treatment period. Children tolerated daily low as well as high dose AZM well for 6months. There was no significant side effect of azithromycin.\n In this randomized controlled trial, we did not find differences in the effect of 2 doses (5mg/kg/day or 15mg/kg/day) of AZM on change in percentage predicted FEV(1), clinical scores, Pseudomonas colonization rates, pulmonary exacerbations and need for antibiotics. There was increase in exacerbations after stopping azithromycin in both the groups. Our results also suggest that the decrease in the incidence of LRTI persists only till 6months after discontinuing azithromycin.", "Data on the effects of long-term treatment with azithromycin (AZM) on inflammatory markers in cystic fibrosis patients chronically infected with Pseudomonas aeruginosa are scarce. So far there is no pharmacokinetic and clinical data on once-weekly dosage of AZM in CF patients.\n In a randomised double-blind, placebo-controlled trial, patients received AZM or placebo 1 per week for 8 weeks (AZM dosage--20-29 kg: 500 mg, 30-39 kg: 750 mg, 40-49 kg: 1000 mg and > or = 50 kg: 1250 mg) after a course of intravenous antipseudomonal antibiotics. Pulmonary function tests, the serum markers LPS-binding protein (LBP), interleukin-8 (IL-8), CRP, P. aeruginosa alginate in sputum samples and quality of life scores were evaluated.\n Thirty-eight patients (21 AZM/17 placebo) (mean age: 23.7 years; mean FEV(1): 62% of predicted) were recruited. After treatment (mean dose of 21.2 mg/kg body weight once a week) pulmonary function declined in both groups compared to baseline (i.e. after cessation of i.v. antibiotics). The AZM group was significantly better for mean changes in serum CRP (AZM: +0.9 mg/l, placebo: +21.6 mg/l, p=0.019), lipopolysaccharide binding protein in serum, LBP (AZM: +0.9 microg/ml, placebo: +7.0 microg/ml, p=0.015), serum interleukin-8 (AZM: -3.1 pg/ml, placebo: +2.9 pg/ml, p=0.001) and alginate in sputum (AZM: +85 microg/ml, placebo: +353 microg/ml, p=0.048). Quality of life was significantly better after AZM and there was no increase in treatment-related adverse events.\n Once-weekly azithromycin ameliorated inflammatory reactions and improved quality of life. A decline of pulmonary function after cessation of i.v. antibiotics could not be prevented." ]

[ "4378136" ]

[ "Live and inactivated adenovirus vaccines. Clinical evaluation of efficacy in prevention of acute respiratory disease." ]

[ "nan" ]

[ "2429622", "6174719", "2773843", "2438638", "7678046" ]

[ "Treatment with iron increases weight gain and psychomotor development.", "The effects of short-term oral iron therapy on developmental deficits in iron-deficient anemic infants.", "Infancy: mental and motor development.", "Iron deficiency anemia and iron therapy effects on infant developmental test performance.", "Reversal of developmental delays in iron-deficient anaemic infants treated with iron." ]

[ "Previous work at this hospital and elsewhere has shown that anaemia in toddlers is common and is associated with psychomotor delay. It seemed unclear, however, whether this association was cause and effect or merely due to the same underprivileged environment. A double blind randomised intervention study was, therefore, performed. After an initial assessment 97 children with anaemia (haemoglobin 8-11 g/dl) aged 17-19 months received either iron and vitamin C or vitamin C only (control group) for two months and were then reassessed. The children who received the iron had an increased rate of weight gain and more of them achieved the expected rate of development. While iron deficiency anaemia is unlikely to be the only factor in the slower development of children living in underprivileged circumstances, it can at least be easily identified and treated. Routine child health surveillance in such areas should include a haemoglobin determination.", "To assess the effects of iron therapy on developmental test scores in infants with iron deficiency anemia, 68 Guatemalan babies 6 to 24 months of age, with and without mild iron deficiency anemia, were tested with the Bayley Scales of Infant Development before and after one week of oral iron treatment. The two major findings of the study were developmental deficits in the anemic group prior to treatment, and lack of rapid improvement with short-term oral iron therapy. The mean pretreatment Mental Development Index of the anemic group was significantly lower than that of nonanemic infants. The anemic group's pretreatment Psychomotor Development Index was also lower than that of the nonanemic control group. In a double-blind randomized study, six to eight days of oral iron therapy did not reverse these deficits. Consequently, the deficits of the anemic group cannot be unequivocably attributed to iron lack. However, no significant differences were found between anemic and nonanemic groups in birth histories, socioeconomic level, or general nutritional status which might otherwise explain the lower developmental test scores of the anemic babies.", "In a prospective cohort study of 196 infants from birth to age 15 mo, the relationship of iron status to psychomotor development, the effect of a short-term trial of oral iron or placebo, and the effect of longer-term oral iron therapy was assessed. Development was assessed with the Bayley Scale of Infant Development in anemic, nonanemic, iron-deficient, and control children. Anemic infants had significantly lower indices than did control or nonanemic, iron-deficient infants. Control infants and nonanemic, iron-deficient infants performed comparably. No difference between the effect of oral administration of iron or placebo was noted after 10 d or 3 mo of iron therapy. A hemoglobin concentration of less than 105 g/L and anemia duration greater than 3 mo were correlated with significantly lower motor and mental scores, suggesting that when iron deficiency progresses to anemia, adverse influences in the performance of developmental tests appear and persist, despite iron therapy.", "The behavioral effects of iron deficiency and its treatment were evaluated in a double-blind randomized controlled community-based study of 191 Costa Rican infants, 12 to 23 months of age, with various degrees of iron deficiency. The Bayley Scales of Infant Development were administered before and both 1 week and 3 months after IM or oral administration of iron. Appropriate placebo-treated control infants were also tested. Infants with iron deficiency anemia showed significantly lower mental and motor test scores, even after considering factors relating to birth, nutrition, family background, parental IQ, and the home environment. After 1 week, neither IM nor oral iron treatments differed from placebo treatment in effects on scores. After 3 months, lower mental and motor test scores were no longer observed among iron-deficient anemic infants whose anemia and iron deficiency were both corrected (36%). However, significantly lower mental and motor test scores persisted among the majority of initially anemic infants (64%) who had more severe or chronic iron deficiency. Although no longer anemic, they still showed biochemical evidence of iron deficiency after 3 months of treatment. These persistent lower scores suggest either that iron therapy adequate for correcting anemia is insufficient to reverse behavioral and developmental disturbances in many infants or that certain ill effects are long-lasting, depending on the timing, severity, or chronicity of iron deficiency anemia in infancy.", "Iron-deficient anaemic infants perform worse in tests of mental and motor development than do iron-sufficient infants of a comparable age. A randomised, double-blind trial was done to monitor the effects of iron supplementation on performance in the Bayley scales of mental and motor development among 12-18-month-old infants in Indonesia. Iron-deficient anaemic infants (n = 50) were assigned randomly to receive dietary ferrous sulphate or placebo for 4 month. Similar treatment randomisation was done among nonanaemic iron-deficient (n = 29) and iron-sufficient (n = 47) infants. Before intervention, the mean mental and motor scores of the iron-deficient anaemic infants were significantly (p < 0.01) lower than those of the nonanaemic iron-deficient and iron-sufficient classes. After intervention, developmental delays were reversed among iron-deficient anaemic infants who had received iron but they remained the same among placebo-treated iron-deficient anaemic infants. Neither ferrous sulphate nor placebo had significant effects on the scores of the other two iron-status classes. The poor performance of 12-18-month-old iron-deficient anaemic infants in the Bayley scales of mental and motor development can be improved to the level of performance of iron-sufficient infants by treatment with ferrous sulphate." ]

[ "22043463", "12608675", "22092380", "20467596", "11021706", "20128828" ]

[ "Flapless versus open flap implant surgery in partially edentulous patients subjected to immediate loading: 1-year results from a split-mouth randomised controlled trial.", "Erbium:YAG laser application in the second phase of implant surgery: a pilot study in 20 patients.", "Clinical efficacy of a xenogeneic collagen matrix in augmenting keratinized mucosa around implants: a randomized controlled prospective clinical trial.", "Connective tissue grafts for thickening peri-implant tissues at implant placement. One-year results from an explanatory split-mouth randomised controlled clinical trial.", "A comparison of labial and crestal incisions for the 1-stage placement of IMZ implants: a pilot study.", "A comparison of two implant techniques on patient-based outcome measures: a report of flapless vs. conventional flapped implant placement." ]

[ "To evaluate the efficacy of flapless versus open flap implant placement in partially edentulous patients.\n Forty patients with two separate edentulous areas characterised by residual bone at least 5 mm thick and 10 mm in height had these sites randomised following a split-mouth design to receive at least one implant to each side after flap elevation or not. Implants were first placed in one site, and after 2 weeks in the other site freehand. Implants inserted with a torque >48 Ncm were immediately loaded with full occluding acrylic temporary restorations. Definitive single cemented crowns or screw-retained metal ceramic fixed dental prostheses were delivered after 2 months. Outcome measures were prosthesis and implant failures, complications, postoperative swelling and pain, consumption of analgesics, patient preference, surgical time, marginal bone level changes, and implant stability quotient (ISQ) values.\n Seventy-six implants were placed flapless and 67 after flap elevation. In the flapless group, four flaps had to be raised to control the direction of the bur, whereas one haemorrhage and one fracture of the buccal bone occurred in two patients of the flap elevation group. Four implants did not reach the planned stability (three belonging to the flapless group) and they were all immediately replaced by larger diameter ones. After 1 year, no drop-outs occurred. Two definitive bridges could not be placed when planned (one in each group) and two crowns had to be remade (one in each group). Two implants failed in each group, all in different patients. There were no statistically significant differences for prosthetic and implant failures, complications, ISQ values and marginal bone levels between groups. However, flapless implant placement required significantly less operation time (17 minutes less, saving almost two-thirds of the time for implant placement), induced less postoperative pain, swelling, analgesic consumption and was preferred by patients. Mean ISQ values of both groups significantly decreased over time.\n Implants can be successfully placed flapless and loaded immediately, reducing treatment time and patient discomfort.", "Conventional implant dentistry implies 2 surgical stages. In this context, pain is often present in the second stage, despite the fact that it is comparatively less aggressive for the patient. The present pilot study proposes application of Erbium:YAG (Er:YAG) laser for second-stage implant surgery.\n Twenty patients were studied with a total of 50 implants in which osseointegration was complete. The subjects were divided into 2 groups: a control group (10 patients with 25 implants), subjected to conventional second-stage surgery; and a group of 10 subjects (also with 25 implants) treated with the Er:YAG laser at second-stage implant surgery.\n The use of Er:YAG laser obviated the need for local anesthesia and minimized postoperative pain and time needed before starting the second stage. With regard to surgical duration, quality of hemostasis, and success in implant treatment, no differences were reported.\n In the second stage of implant surgery, different types of laser have been used, taking advantage of their bacteridal effect; disadvantages arise from inducing damage to the implant surface and adverse thermal effects.\n The advantages afforded by laser treatment include technical simplicity, the possibility of obviating local anesthesia, absence of postoperative pain and edema, and complete tissue healing by day 5, thus facilitating rapid prosthetic rehabilitation. The technique described can be used in all cases except situations where esthetic considerations prevail in anterior areas, or in the event of a lack of keratinized gingiva surrounding the implant.", "The aim of this controlled randomized clinical trial was to evaluate the efficacy of a xenogeneic collagen matrix (CM) to augment the keratinized tissue around implants supporting prosthetic restorations at 6 months when compared with the standard treatment, the connective tissue autograft, CTG).\n This randomized longitudinal parallel controlled clinical trial studied 24 patients with at least one location with minimal keratinized tissue (≤1 mm).\n The 6-month width of keratinized tissue. As secondary outcomes the esthetic outlook, the maintenance of peri-implant mucosal health and the patient morbidity were assessed pre-operatively and 1, 3, and 6 months post-operatively.\n At 6 months, Group CTG attained a mean width of keratinized tissue of 2.75 (1.5) mm, while the corresponding figure in Group CM was 2.8 (0.4) mm, the inter-group differences not being statistically significant. The surgical procedure in both groups did not alter significantly the mucosal health in the affected abutments. There was a similar esthetic result and significant increase in the vestibular depth in both groups as a result of the surgery. In the CM group it changed from 2.2 (3.3) to 5.1 (2.5) mm at 6 months. The patients treated with the CM referred less pain, needed less pain medication, and the surgical time was shorter, although these differences were not statistically significant when compared with the CTG group.\n These results prove that this new CM was as effective and predictable as the CTG for attaining a band of keratinized tissue.\n © 2011 John Wiley & Sons A/S.", "Nothing to declare.\n To evaluate whether connective tissue grafts performed at implant placement could be effective in augmenting peri-implant soft tissues.\n Ten partially edentulous patients requiring at least one single implant in the premolar or molar areas of both sides of the mandible were randomised to have one side augmented at implant placement with a connective soft tissue graft harvested from the palate or no augmentation. After 3 months of submerged healing, abutments were placed and within 1 month definitive crowns were permanently cemented. Outcome measures were implant success, any complications, peri-implant marginal bone level changes, patient satisfaction and preference, thickness of the soft tissues and aesthetics (pink aesthetic score) evaluated by an independent and blinded assessor 1 year after loading.\n One year after loading, no patients dropped out, no implants failed and no complications occurred. Both groups lost statistically significant amounts of peri-implant bone 1 year after loading (0.8 mm in the grafted group and 0.6 mm in the non-grafted group), but there was no statistically significant difference between groups. Soft tissues at augmented sites were 1.3 mm thicker (P < 0.001) and had a significantly better pink aesthetic score (P < 0.001). Patients were highly satisfied (no statistically significant differences between treatments) though they preferred the aesthetics of the augmented sites (P = 0.031). However, five patients would not undergo the grafting procedure again and two were uncertain.\n Connective tissue grafts are effective in increasing soft tissue thickness, thus improving aesthetics. Longer follow-ups are needed to evaluate the stability of peri-implant tissues over time.", "The aim of this study was to compare the crestal incision with the labial flap design when inserting a 2-stage implant system in a nonsubmerged manner.\n Ten consecutive edentulous patients with a severely resorbed mandible (Cawood Class V to VI) that resulted in reduced stability and insufficient retention of the lower denture were included. In all patients, 2 IMZ implants were inserted in a 1-stage procedure in the mandibular canine regions as part of an implant overdenture treatment. In 5 patients, the labial flap approach was used, and a crestal incision approach was used in the other 5 patients. Standardized evaluations were performed at 2, 6, and 12 weeks after implant placement and 12 months after placement of the new prosthesis.\n In the first postoperative weeks, more hyperplasia occurred around the implants inserted by the crestal incision than the labial flap. However, after 1 year of function, no striking differences between the 2 groups were present with regard to the clinical and radiographic parameters.\n From this pilot study, it was concluded that both the crestal incision and the labial flap approach are reliable procedures for insertion of IMZ implants in a 1-stage procedure. However, because of the smaller risk of soft tissue overgrowth, there is a preference for the labial flap approach.", "Flapless implant surgery is considered to offer advantages over the traditional flap access approach. There may be minimized bleeding, decreased surgical times and minimal patient discomfort. Controlled studies comparing patient outcome variables to support these assumptions, however, are lacking.\n The objective of this clinical study was to compare patient outcome variables using flapless and flapped implant surgical techniques.\n From January 2008 to October 2008, 16 consecutive patients with edentulous maxillas were included in the study. Patients were randomly allocated to either implant placement with a flapless procedure (eight patients, mean age 54.6 + or - 2.9 years) or surgery with a conventional flap procedure (eight patients, mean age 58.7 + or - 7.2 years). All implants were placed using a Nobel guide CT-guided surgical template. Outcome measures were the Dutch version of the Impact of Event Scale-Revised (IES-R), dental anxiety using the s-DAI and oral health-related quality of life (OHIP-14).\n Ninety-six implants were successfully placed. All implants were placed as two-phase implants and the after-implant placement dentures were adapted. No differences could be shown between conditions on dental anxiety (s-DAI), emotional impact (IES-R), anxiety, procedure duration or technical difficulty, although the flapless group did score consistently higher. The flap procedure group reported less impact on quality of life and included more patients who reported feeling no pain at all during placement.\n Differences found in the patient outcome variables do suggest that patients in the flapless implant group had to endure more than patients in the flap group." ]

[ "8995348", "12771852" ]

[ "Efficacy of Daflon 500 mg in venous leg ulcer healing: a double-blind, randomized, controlled versus placebo trial in 107 patients.", "Efficacy of a 6-month treatment with Daflon 500 mg in patients with venous leg ulcers associated with chronic venous insufficiency." ]

[ "The objective of this study was to evaluate the efficacy of Daflon 500 mg (Dios)* in venous ulcers. A multicenter, double-blind, randomized, controlled versus placebo (Plac) trial was conducted, with stratification according to the size of ulcer (< or = 10 cm and > 10 cm). The protocol called for a two-month treatment with Dios (one tablet = 450 mg micronized purified Diosmin) or a placebo, two tablets/day, in addition to compression therapy. Evaluations were performed every fifteen days, from D0 to D60. The primary endpoint, in accordance with Alexander House group requirements were: percentage of patients with complete ulcer healing, ie, comparison between Dios and Plac group at D60, and comparison of survival curves in each group between D0 and D60 (log rank test). Secondary endpoints included ulcer surface area assessed by computerized planimetric measurements, qualitative evaluation of ulcers, and symptoms. The patients were 105 men and women ranging in age from eighteen to eighty-five years, with standard compression stocking, who were undergoing standardized local care of ulcer and had no significant arterial disease (ankle/arm systolic pressure index > 0.8). Fifty-three patients received Dios, and 52 received Plac. The 2 groups were well matched for age (m +/- 1 SD = seventy-one +/- eleven years), gender, ulcer size, and associated disorders. Among patients with ulcer size < or = 10 cm (Dios = 44, Plac = 47) a significantly larger number of patients had a complete ulcer healing at two months in the Dios group (n = 14) in comparison with the Plac group (n = 6) (32% vs 13%, P = 0.028) with a significantly shorter time duration of healing (P = 0.037). No difference was shown for the secondary criteria, except for sensation of heavy legs (P = 0.039) and a less atonic aspect of ulcer (P = 0.030) in favor of Dios. Among the 14 patients with ulcer size > 10 cm (Dios = 9, Plac = 5), subjected to a descriptive analysis only, no ulcer healed. This study showed that a two-month course of Daflon 500 mg at a daily dose of two tablets, in addition to conventional treatment, is of benefit in patients with venous ulcer < or = 10 cm by accelerating complete healing.", "Epidemiological data show that standard compression therapy for leg ulceration in chronic venous insufficiency (CVI) often fails to effectively improve patients' condition. This study assesses the contribution of Daflon 500 mg added to conventional therapy in the healing of hypostatic ulcers of CVI patients.\n Patients of about 65 years were included, with ulcers > or = 2 and > or = 10 cm diameter on 1 or 2 limbs, Doppler ankle/arm pressure index > 0.9, and no recent history of skin graft. Controls (n=68) remained on compression alone while the tested group (n=82) also received Daflon 500 mg 2 tablets/day during 6 months. Treatment could be stopped as soon as the reference ulcer appeared fully healed. Primary endpoints were the rate of healed ulcers and the time to complete healing assessed by planimetry/photography and clinical examination. Variations of the ulcer surface, appearance of the skin, and clinical symptoms of CVI were the secondary criteria.\n Only 7% of Daflon 500 mg patients necessitated the full 6 month therapy. Whatever the lesion size, from W8 significantly more healed ulcers were observed under Daflon 500 mg (p=0.004), and the ulcer surface was more reduced (p=0.012). For large ulcers, the rate of healing was approximately 2-fold higher with Daflon 500 mg, and the percentage of ulcers healed before W24 was significantly higher (p=0.008). Heavy leg sensation was significantly improved by Daflon 500 mg from W4 (p < 0.05). No treatment-related side effects were reported and the acceptability was considered excellent by 85% of Daflon 500 mg patients.\n Six months of Daflon 500 mg in addition to compression significantly improve some clinical symptoms and accelerate the healing process in patients with ulcerous complications of CVI, with a good acceptability." ]

[ "7517477", "1369725", "3518547", "12555510", "6373217" ]

[ "An evaluation of patients with severe intermittent claudication and the effect of treatment with naftidrofuryl.", "Treatment of stage II chronic arterial disease of the lower limbs with the serotonergic antagonist naftidrofuryl: results after 6 months of a controlled, multicenter study.", "Naftidrofuryl in chronic arterial disease. Results of a six month controlled multicenter study using Naftidrofuryl tablets 200 mg.", "[Effect of naftidrofuryl on physiological walking distance in patients with intermittent claudication].", "[Naftidrofuryl in arterial occlusive disease. Controlled multicenter double-blind study with oral administration]." ]

[ "A randomized placebo-controlled study was undertaken in 188 patients with severe intermittent claudication attending two vascular clinics in Manchester and Liverpool. After a 4-week run-in period, patients received active or placebo treatment for 24 weeks. Patients were assessed on a treadmill prior to the 4-week run-in period, at randomization, and at 8, 16, and 24 weeks. Outcome was measured in terms of change in pain-free walking distance, maximum walking distance, and pressure indices. In this severe claudication population, in which the patients presented with a mean pain-free walking distance of 60 m, an intention-to-treat analysis demonstrated that the outcome in the naftidrofuryl-treated group was significantly better than in the group receiving placebo (p = 0.045). Additionally, 7% of patients in the naftidrofuryl group deteriorated compared with 22% in the placebo group (p = 0.005). Of the various risk factors that were recorded during the study--smoking habits, the presence of hypertension, diabetes, obesity, and duration of illness--only duration of illness had a significant influence on outcome. Maximum walking distances alone were not significantly influenced by treatment, but the use of a combined index of pain-free walking distance, maximum walking distance, and pressure indices to record success or failure confirmed a significant treatment effect (p = 0.047). A higher incidence of minor gastrointestinal symptoms was recorded in the naftidrofuryl-treated group. Treatment with naftidrofuryl was shown to prevent or slow the deterioration observed in a group of patients with severe claudication over a 24-week period.", "A study was carried out in patients with intermittent claudication (Fontaine's stage II). The atheromatous origin of the disease was confirmed and localized by angiography or Doppler. One hundred eight-three patients were selected initially (day -30) with a pain-free walking distance on a treadmill (at a speed of 3 km/h and a slope of 10%) ranging from 150 to 300 m. During the first month (washout period) all patients received two placebo tablets daily. At the end of this run-in period (day -30; day 0) and after checking walking distance stability (allowed variation: 20% between the two measurements), patients were included in the study. According to this criterion, 112 patients were selected and 94 remained during the whole study. The study was designed in double-blind, using two parallel, randomly selected groups. Fifty-two patients received naftidrofuryl (2 x 316.5 mg tablets daily with meals) for 6 months; 42 patients received placebo under the same conditions. During this period, clinical and paraclinical examinations were carried out every quarter (day 90 and day 180). After checking the initial homogeneity of the naftidrofuryl and placebo groups, the comparison between the two groups indicates a significant improvement in the naftidrofuryl group after 3 months and 6 months of treatment, for the pain-free walking distance. For the maximal walking distance, a significant improvement was found at day 180. Nonparametric analysis (chi 2 test) also indicated a significant improvement for the naftidrofuryl group. These results confirm that naftidrofuryl is beneficial in the treatment of patients with chronic arterial disease.", "The study was carried out on patients with intermittent claudication (Fontaine's stage II). The arterial and atheromatous origin of the disease was confirmed and localized by angiography or Doppler velocimetry examination. One hundred eighty-six patients were selected initially. Their pain-free walking distance on a treadmill (at a speed of 3 km/hour and an inclination of 10%) had to be 150-300 m. During the first month all patients received 3 placebo tablets daily. At the end of this run-in period (D-30; D 0) and after checking walking distance stability (allowed variation: +/- 20% between the two measurements) the patients were included in the study. One hundred fifty-four patients were selected and 118 remained during the whole study. The study was designed as a double-blind, using two parallel randomly selected groups. Sixty-four patients received for six months Naftidrofuryl (3 X 200 mg tablets daily with meals); 54 patients received placebo under the same conditions. During this period, clinical and paraclinical examinations were carried out every quarter (D 90 and D 180). After checking the initial homogeneity of the Naftidrofuryl and placebo-groups, the comparison between groups indicates a significant improvement in Naftidrofuryl group after 3 and 6 months of treatment. At the end of the study the observed differences in walking distance with Naftidrofuryl are approximately twice the difference in the reference group (D 90: p less than 0.05; D 180: p less than 0.02). The results of this study indicate that Naftidrofuryl is an efficient pharmacological tool for treatment of patients with chronic arterial disease (Fontaine's stage II).", "To evaluate the physiological walking distance measured with the Peripheral Arterial Disease Holter Control device (PADHOC) after 12 months of treatment with naftidrofuryl in a double blind placebo controlled, parallel group study, in patients presenting with intermittent claudication.\n The outpatients selected were of both sexes, aged 40 to 80, with a chronic, stable intermittent claudication and an ankle brachial index between 0.60 and 0.90. They received naftidrofuryl 200 mg tid or placebo for 12 months. Outcome measures included physiological painfree and maximal walking distances using the PADHOC device. The principle of this device is the measurement of the intermalleolar distances using ultrasound telemetry. The PADHOC measures the walking distance and the speed profile in an ambulatory subject.\n 182 patients were randomised and 168 entered the intention to treat analysis. The two groups were well matched for demographic variables, risk factors and history of vascular disease. After 12-month treatment, patients who received naftidrofuryl had a 107% improvement of geometric physiological pain-free walking distance versus 12% in the placebo group (P < 0.001) and 74% improvement of geometric maximal physiological walking distance versus 1% in the placebo group (P < 0.001).\n This study demonstrates the efficacy of naftidrofuryl versus placebo in patients with intermittent claudication using a new device measuring the walking distances of the patients in a more physiological way than the treadmill test.", "The efficacy of naftidrofuryl ( Dusodril ) for treatment of stage II arterial occlusive disease was evaluated in a controlled multi-centre study in a total of 104 out-patients with angiographically documented localization of occlusion. The therapeutic effect was assessed over three months by measurements of walking distance using standardized treadmill conditions. Further parameters were venoocclusive plethysmography and Doppler ultrasonography measurement of pressures. The complaint-free walking distance increased significantly during daily application of 600 mg naftidrofuryl orally (n = 54) during the 12-week assessment period when compared to the placebo group (n = 50). Taking the intraindividual variability of 17.2 m in assessment of walking distance into account, the increase of painless walking of 93 m after treatment for 12 weeks in the active-drug group is considered the result of treatment-induced increased performance." ]

[ "18372433", "12767646", "8761844", "2514430", "16787192", "2446877", "2115186", "9081136", "2609241", "3073766", "3470963", "9142008", "8044953", "10908215", "10870853", "9809945" ]

[ "A randomized trial of iloprost in patients with intermittent claudication.", "Treatment of intermittent claudication with beraprost sodium, an orally active prostaglandin I2 analogue: a double-blinded, randomized, controlled trial.", "A dose-effect study of beraprost sodium in intermittent claudication.", "Effects of taprostene, a chemically stable prostacyclin analogue, in patients with ischaemic peripheral vascular disease: a placebo controlled double-blind trial.", "The effects of prostaglandin E-1 in patients with intermittent claudication.", "Clinical effects of intravenous iloprost in patients with intermittent claudication.", "A double blind placebo controlled trial of intravenous prostacyclin (PGI2) in 108 patients with ischaemic peripheral vascular disease.", "Efficacy of a new prostaglandin E1 regimen in outpatients with severe intermittent claudication: results of a multicenter placebo-controlled double-blind trial.", "Effects of regular physical training in a supervised class and additional intravenous prostaglandin E1 and naftidrofuryl infusion therapy in patients with intermittent claudication--a controlled study.", "Intermittent intraarterial infusion therapy with PGE1 in patients with severe claudication--results of a randomized prospective double blind study.", "Clinical and haemorheological efficacy of i.a. PGE1 infusions in intermittent claudication.", "Randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of AS-013, a prostaglandin E1 prodrug, in patients with intermittent claudication.", "Intensive vascular training in stage IIb of peripheral arterial occlusive disease. The additive effects of intravenous prostaglandin E1 or intravenous pentoxifylline during training.", "Oral Beraprost sodium, a prostaglandin I(2) analogue, for intermittent claudication: a double-blind, randomized, multicenter controlled trial. Beraprost et Claudication Intermittente (BERCI) Research Group.", "Impact of a 4-week treatment with prostaglandin E1 on health-related quality of life of patients with intermittent claudication.", "Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease." ]

[ "Prostanoids, which promote vasodilation and reduce platelet aggregation, have been proposed as candidate therapies for intermittent claudication due to peripheral arterial disease (PAD). However, studies of these medications have yielded inconsistent results. This study tested the hypothesis that iloprost, an oral prostacyclin analogue, would improve walking distance and quality of life in patients with intermittent claudication. The study was a multi-center, randomized, double-blind, placebo-controlled trial comparing three doses of oral iloprost (50 microg, 100 microg, or 150 microg twice daily), pentoxifylline, or placebo in 430 patients with intermittent claudication. The primary outcome measure was improvement in absolute claudication distance (ACD) after 6 months. Secondary outcomes included initial claudication distance and quality of life assessment. Placebo increased ACD by 3.3%, and iloprost increased peak ACD by 7.7%, 8.8% and 11.2% at the 50 microg, 100 microg, and 150 microg twice-daily doses, respectively (all insignificant relative to placebo). Pentoxifylline increased ACD by 13.9% relative to placebo (p = 0.039). Neither iloprost nor pentoxifylline enhanced quality of life. These results indicate that oral iloprost is not effective in improving exercise performance or quality of life in patients with PAD who have intermittent claudication.", "In the current study, we hypothesized that beraprost would: 1) improve treadmill exercise performance and quality of life; and 2) decrease rates of ischemic events in patients with intermittent claudication.\n Previous trials with beraprost sodium, an orally active prostaglandin I(2) analogue, in the treatment of claudication in patients with peripheral arterial disease (PAD) have been inconsistent.\n Patients with intermittent claudication (n = 897) were randomized to receive either 40 microg three times a day of beraprost with meals (n = 385) or placebo (n = 377) in a double-blinded manner for one year. The primary efficacy parameter was treadmill-measured maximum walking distance, as assessed at three and six months after randomization. Secondary efficacy parameters included treadmill-measured pain-free walking distance and change in quality of life.\n There was no significant improvement in maximum walking distance in the beraprost group (16.7%) as compared with the placebo group (14.6%, p = NS). Administration of beraprost did not improve the pain-free walking distance (p = NS between treatment groups), and there was no improvement in the quality-of-life measures between the treatment groups. The incidence of critical cardiovascular events was 7.3% in the beraprost group and 11.4% in the placebo group (p = NS). There was a significant reduction in the combination of cardiovascular death and myocardial infarction in the beraprost group (p = 0.01).\n Despite previous investigations suggesting efficacy, these results indicate that beraprost is not an effective treatment to improve symptoms of intermittent claudication in patients with PAD. The potential benefit of beraprost on critical cardiovascular events would require confirmation in a larger prospective investigation.", "We compared the efficacy and safety of three doses of beraprost sodium, an epoprostenol analogue, with placebo in the treatment of intermittent claudication (Fontaine's stage II). One hundred sixty-four patients were randomized to receive either placebo, 20 micrograms beraprost sodium (BPS60 group), 40 micrograms beraprost sodium (BPS120 group), or 60 micrograms beraprost sodium (BPS180 group) three times daily administered orally in a double-blind manner for 12 weeks. Treadmill exercise tests were performed twice during an initial selection phase (D-28 and D0) at week 10 (at trough beraprost concentration) and week 12 (at peak beraprost concentration) of the treatment phase. At week 10, all groups showed an increase in pain-free walking distance, and this distance was greatest in the BPS60 and BPS120 groups (p = 0.055). At week 12, a similar pattern was observed, and the difference was significant between the groups (p = 0.023). The most frequent adverse events reported were gastrointestinal disorders, headaches, skin disorders, and flushes. Patients who received either 60 or 120 micrograms of beraprost sodium daily had an increased pain-free walking distance. Further studies are required to investigate why the highest dose used (180 micrograms daily) showed lower efficacy. Having both vasodilating and antiplatelet properties and being able to increase pain-free walking distance in the short term, beraprost sodium is a promising drug for the treatment of intermittent claudication.", "Thirty patients with ischaemic peripheral vascular disease and intermittent claudication were randomly allocated to receive either placebo or taprostene, a chemically stable prostacyclin analogue, intravenously at a rate of 25 ng/kg/min for 6 hours daily on 5 consecutive days. Taprostene produced a significant (p less than 0.05) increase in absolute walking time compared to placebo on one day after infusion and at 1, 4 and 8 weeks (14% vs 2.8%) later. Taprostene also produced a significant (p less than 0.05) increase in the pain-free walking time compared to placebo in the follow-up period (8 weeks after infusion: 23% vs 3.8%). During the infusion period systolic and diastolic blood pressure decreased (p less than 0.05) and heart rate was accelerated (p less than 0.05) in the taprostene treated group whereas no change was monitored in the placebo group. The ankle/brachial Doppler index was unaffected by taprostene. The platelet half-life was significantly (p less than 0.05) prolonged following taprostene-infusion (72.6 +/- 9.35 vs 77.9 +/- 7.44 hours). However, no change on platelet half-life was found in the placebo group (p less than 0.05). Various measures of platelet function parameters followed in vitro (ADP-induced aggregation, platelet sensitivity to PGI2, PGE1, PGD1 and taprostene, concentrations of platelet factor 4 and beta-thromboglobulin) showed no change with taprostene. Measures of circulating platelet aggregates and endothelial cells count showed no changes during the 2 months follow-up period too. It is assumed that taprostene may be of clinical benefit in patients with ischaemic peripheral vascular disease. However, future investigations have to be carried out to assess the optimal dose regime.", "Aim of the study is to evaluate the effects of Prostaglandin E-1 (PGE-1) in patients with peripheral arterial disease (PAD) at the 2nd b stage Fontaine's classification. The study, controlled, single blinded, enrolled 123 patients with intermittent claudication that were randomised in two groups; the first group received a treatment with PGE-1 while the second one received a pentoxifylline-buflomedil association by venous infusion. We evaluated: Pain Free Walking Distance (PFWD), Maximum Walking Distance (MWD), Rest Flow (RF), Peak Flow (PF), Basal (BVR) and Minimal Vascular Resistance (MVR) with a strain gauge plethysmograph, Resting Flow (RF), Peak Flow (PF), time to reach the Peak Flow (tPF) and time to recovery of the base values (tRF) with laser Doppler flowmeter. After a four weeks treatment, we observed an increase of 370% about PFWD and of 260% in the MWD in patients treated with PGE-1; the other group showed an increase of 110% and 118% respectively. Moreover, the patients of the first group showed a significant increase regarding the plethysmographic Peak Flow (from 9.75+/-1.37 to 16.21+/-1.75, p<0.001), greater than the one observed in the second group (from 9.53+/-1.41 to 13.47+/-1.53, p<0.05); also the laser Doppler parameters showed a significant reduction, more evident in the first group (tPF from 23.0+/-7.5 to 10.5+/-4.9, p<0.001; tRF from 73.5+/-22.7 to 48.3+/-13.5, p<0.001) than in the second one.", "In a randomized patient-blind study iloprost or hydroxy-ethyl starch 200/0.5 were given i.v. 5 h daily for 2 weeks to 24 patients suffering from severe intermittent claudication due to peripheral vascular disease. An increase in pain-free walking distance of more than 50% occurred in 6 of 11 patients after the iloprost infusions and in 7 of 12 patients after HES treatment. No significant effects on haemodynamic or clinical chemistry tests were observed.", "108 patients with ischemic peripheral vascular disease were randomly allocated to receive infusion of either PGI2 (6 ng/kg/min over 8 hours daily for 5 consecutive days) or placebo in a double-blind manner. All patients had Stage II disease (Fontaine classification). One month after infusion the absolute and relative walking times were significantly (p less than 0.05) longer in the PGI2- than in the placebo-treated group. Patients were further classified as treatment responders or non-responders on the basis of increase of absolute and relative walking times. After one month 44% (24 out of 54) of the PGI2- and 15% (8 out of 54) of the placebo-treated patients were positive treatment-responders (p less than 0.01).", "For the first time efficacy and safety of a new prostaglandin E1 (PGE1) regimen in the treatment of intermittent claudication were evaluated in a randomized, double-blind, placebo-controlled multicenter clinical trial. The study involved 213 outpatients with a maximum walking distance of 50 to 200 m measured on the treadmill (3 km/hr, 12% grade). After a 2-week run-in phase they received a 2-hour intravenous infusion of 60 micrograms PGE1 or placebo 5 days a week for 4 weeks. It was followed by a 4-week interval treatment with the same medication administered only twice a week. Patients were monitored for 3 months when they received no study medication. In the PGE1 group the intention-to-treat analysis (n = 208) revealed an increase in walking distance after 4 weeks of 75% (placebo, 43%). At the end of the interval treatment the walking distance had improved to 101% (placebo, 60%). The results remained virtually constant during follow-up (PGE1, 104%, placebo, 63%). Between-group comparisons showed significant differences in favor of PGE1 for all three time points of measurement (p < 0.05, p < 0.01, and p < 0.05). PGE1 was well tolerated; the rate of adverse reactions related to the treatment was 12.8% (placebo, 7.7%). In summary, these results show that the new PGE1 regimen is effective and safe in the treatment of outpatients with intermittent claudication.", "The aim of this study was to investigate if PGE1 i.v.-therapy after active physical training further increases the walking distance in PAOD stage IIb according to Fontaine. 48 outpatients with intermittent claudication underwent a standardized active walking training of about 6 months twice weekly. Afterwards patients were randomly given once daily an i.v. infusion of 60 micrograms PGE1 (3 ampoules prostavasin) or 600 mg naftidrofuryl. The therapy lasted for 3 weeks with the exception of Saturdays and Sundays. Besides laboratory and doppler parameters, painfree and maximum walking distance (treadmill, 10% incline, 3.5 km/h) were determined. Results: Under active physical training the patients' walking distance increased significantly to more than double the baseline levels. Further significant increase of the painfree walking distance was seen after a 3 week treatment with PGE1 from 136 to 270 m (99%) as well as with naftidrofuryl from 117 to 230 m (97%). While this difference was not significant there was a significant difference in favour to PGE1 after the follow-up period (p less than 0.01). In the PGE1-group the painfree walking distance showed a further increase (from 270m to 306m) whereas it decreased in the naftidrofuryl-group (from 230m to 210m). At the same time under PGE1 the ankle/arm index increased significantly in comparison to naftidrofuryl (p less than 0.01). Side effects differed significantly in respect of the frequency and severity. In the PGE1-group in 20.8% of the patients side effects occurred, whereas in 91.6% of the patients in the naftidrofuryl-group side effects were observed. In no case therapy had to be discontinued because of side effects.", "In a randomized prospective double blind study, intraarterial infusion therapy with prostaglandin E1 (PGE) was tested against infusion therapy with energy rich phosphates (ERP) in 40 patients with severe claudication. During the treatment period of three weeks, a significant increase of the painfree (PWD) and maximal walking distance (MWD) was observed. The improvement of PWD was of clinical relevance (PGE: 60----195 m; ERP: 69----170 m; p less than 0.001) and persisted during a 36 week post treatment observation period. The differences between the two drugs were not significant but showed a tendency in favour of the PGE therapy.", "nan", "Intermittent claudication due to peripheral arterial occlusive disease (PAOD) is a common cause of pain and disability in the middle-aged. Clinical trials of the potent vasodilator prostaglandin E1 have been disappointing. This is the first report of a controlled clinical trial of AS-0:3, a novel prodrug of prostaglandin E1 incorporated into lipid microspheres that has been developed to improve delivery of the active compound to blood vessel walls.\n Eighty patients with stenosis or occlusion, symptoms of intermittent claudication, and maximum walking distance of > or = 30 and < or = 300 m on a standard treadmill test were randomized to placebo or one of three dosage regimens of AS-013. Drug was administered by intravenous injection 5 d/wk for 4 weeks. Treadmill tests and other assessments were completed at weeks 0, 4, and 8. A statistically significant increase in maximum walking distance was observed at 4 weeks (for placebo: median, 4.5 m; interquartile range [IQR], 20; for active treatment: median, 28.0 m; IQR, 81; P < .01, Mann-Whitney test). A similar response was seen at 8 weeks (for placebo; median, -11.2 m; IQR, 35; for active treatment: median, 35 m; IQR, 68; P < .01, Mann-Whitney test). Dose-related improvements in pain-free walking distance and quality of life were observed. No serious safety issues were noted.\n These promising clinical data indicate that AS-013, a new prodrug of prostaglandin E1, could provide an effective and acceptable treatment for patients with intermittent claudication. Studies to investigate the optimal dosing regimen, duration of clinical benefit, and effects in more severe forms of peripheral arterial disease are warranted.", "In a randomized open study, the combination of either prostaglandin E1 (PGE1) or pentoxifylline with controlled vascular training was compared with vascular training alone in patients with peripheral arterial occlusive disease in stage IIb. Forty-four patients were randomly assigned to treatment either of intensive vascular training alone (n = 15) or in combination with either i.v. pentoxifylline (200 mg over 2 hours BID, n = 15) or PGE1 (40 micrograms over 2 hours BID, n = 14). The basic therapy was a well-defined routine for vascular training, which was identical for all groups. The duration of therapy was 4 weeks. In all three test groups, there was a significant increase in the walking distance. There was a 119% increase in symptom-free walking distance in the exercise-only group. In comparison with exercise alone, the additional administration of pentoxifylline produced no greater effect; the increase was 105%. In contrast, administration of PGE1 combined with exercise achieved a remarkable improvement of 604%. Between-group comparison revealed the significant superiority of treatment with PGE1 (P < .05). During the 1-year follow-up, there was a reduction in the walking performance in all groups, albeit of variable extent. In the exercise-only and the pentoxifylline groups, the maintained increase in walking distance was only 30% compared with baseline values before the beginning of therapy. In the PGE1 group, on the other hand, the maintained improvement was 149%. Nine of 14 patients were still in stage IIa of peripheral arterial occlusive disease 1 year after PGE1 therapy.", "Beraprost sodium (BPS) is a new stable, orally active prostaglandin I(2) analogue with antiplatelet and vasodilating properties. We report the results of a phase III clinical trial of BPS in patients with intermittent claudication.\n Patients (n=549) with a pain-free walking distance of between 50 and 300 m were entered into a 4-week single-blind placebo run-in phase. Patients whose pain-free walking distance had changed by <25% were then randomized to receive either BPS (40 microg TID, n=209) or placebo (n=213) in a double-blind manner for 6 months. Pain-free and maximum walking distances were measured on the occasion of treadmill exercise tests performed at baseline and 1.5, 3, 4.5, and 6 months after randomization. Success was defined as an improvement of >50% in pain-free walking distance at month 6 and in > or =1 earlier treadmill exercise test in the absence of critical cardiovascular events. Success was observed more frequently in the BPS group (43.5%) than in the placebo group (33.3%, P=0.036). Pain-free walking distances increased by 81.5% and 52.5%, respectively, in the BPS and placebo groups (P=0.001) and maximum walking distances by 60.1% and 35.0%, respectively (P=0.004). The incidence of critical cardiovascular events was 4.8% in the BPS group and 8.9% in the placebo group.\n These results show that BPS is an effective symptomatic treatment of patients with intermittent claudication. The beneficial effects of BPS on critical cardiovascular events should be confirmed in appropriate clinical trials.", "Intermittent claudication impairs functional status and quality of life in many patients by limiting walking capacity. The aim of this study was to evaluate the effects of a 4-week treatment with prostaglandin E1 (PGE1), a drug inducing vasodilation and inhibiting platelet aggregation, on improving functional status and health-related quality of life in patients with disabling intermittent claudication. Forty-two untrained outpatients (37 men and five women, mean age 64 +/- 8 years) with intermittent claudication,and maximum walking distance (MWD) of at least 50 and no more than 200 m on treadmill test (5% slope, 3 km/hr) were randomized to 4 weeks of double-blind treatment either with 60 mcg PGE1 daily given IV in 250 mL saline over a period of 2 hours (21 patients) or placebo (250 mL saline, 21 patients). Treatment-free follow-up was completed 8 weeks after the final infusion. Pain free walking distance (PFWD), MWD, and questionnaire evaluation were determined at baseline, after the 4-week treatment period, and at the end of the 8 weeks of the treatment-free follow-up period. After 4 weeks of treatment with PGE1 PFWD and MWD increased from 72 +/- 16 m to 135 +/- 33 m (+87%, p<0.001)and from 140 +/- 30 m to 266 +/- 62 m (+90%, p<0.001), respectively. Analysis of the Walking Impairment Questionnaire responses in the PGE1 group at 4 weeks demonstrated significant improvements in the walking impairment score (+19 percentage points, p<0.001), in the distance score (+25 percentage points, p<0.001), in the speed score (+24 percentage points, p<0.001), in the stair climbing score (+20 percentage points, p<0.001). The RAND survey responses showed improvements in physical function and bodily pain scores (+14 percentage points, p<0.001, and +15 percentage points, p<0.01, respectively). After the treatment-free follow-up period of 8 weeks, increases in PFWD and MWD were maintained (113 +/- 26 m, +57%, p<0.001, and 229 +/- 55 m, +63%, p<0.001, respectively). Similarly, at the end of the treatment-free follow-up, the walking impairment score (+16 percentage points, p<0.001), the distance score (+23 percentage points, p<0.001), the speed score (+22 percentage points, p<0.001), the stair climbing score (+18 percentage points, p<0.001) as well as the RAND physical function and bodily pain scores (+10 percentage points, p<0.001, and +13 percentage points, p<0.01, respectively) were still increased compared with baseline. No change from baseline was found in all the target parameters in the placebo group after 4 weeks of treatment and at the end of the treatment-free follow-up period. These data show that a 4-week treatment with PGE1 improves functional status and quality of life as well as treadmill performance in patients with disabling intermittent claudication as compared with placebo-treated patients. The improvements are also maintained for a period of 8 weeks beyond the end of the treatment. Additional studies are needed to determine the duration of functional benefits after the end of treatment.", "Administration of L-arginine improves nitric oxide (NO) formation and endothelium-dependent vasodilation in atherosclerotic patients.\n We investigated in this double-blind, controlled study whether prolonged intermittent infusion therapy with L-arginine improves the clinical symptoms of patients with intermittent claudication, as compared with the endothelium-independent vasodilator prostaglandin E1, and control patients.\n Thirty-nine patients with intermittent claudication were randomly assigned to receive 2 x 8 g L-arginine/day, or 2 x 40 microg prostaglandin E1 (PGE1)/day or no hemodynamically active treatment, for 3 weeks. The pain-free and absolute walking distances were assessed on a walking treadmill at 3 km/h, 12% slope, and NO-mediated, flow-induced vasodilation of the femoral artery was assessed by ultrasonography at baseline, at 1, 2 and 3 weeks of therapy and 6 weeks after the end of treatment. Urinary nitrate and cyclic guanosine-3', 5'-monophosphate (GMP) were assessed as indices of endogenous NO production.\n L-Arginine improved the pain-free walking distance by 230+/-63% and the absolute walking distance by 155+/-48% (each p < 0.05). Prostaglandin E1 improved both parameters by 209+/-63% and 144+/-28%, respectively (each p < 0.05), whereas control patients experienced no significant change. L-Arginine therapy also improved endothelium-dependent vasodilation in the femoral artery, whereas PGE1 had no such effect. There was a significant linear correlation between the L-arginine/asymmetric dimethylarginine (ADMA) ratio and the pain-free walking distance at baseline (r=0.359, p < 0.03). L-Arginine treatment elevated the plasma L-arginine/ADMA ratio and increased urinary nitrate and cyclic GMP excretion rates, indicating normalized endogenous NO formation. Prostaglandin E1 therapy had no significant effect on any of these parameters. Symptom scores assessed on a visual analog scale increased from 3.51+/-0.18 to 83+/-0.4 (L-arginine) and 7.0+/-0.5 (PGE1; each p < 0.05), but did not significantly change in the control group (4.3+/-0.4).\n Restoring NO formation and endothelium-dependent vasodilation by L-arginine improves the clinical symptoms of intermittent claudication in patients with peripheral arterial occlusive disease." ]

[ "6994086", "11444677", "7477801", "3973067", "7477800", "3511877", "9546003" ]

[ "Hunger, food intake and weight: the impact of clomipramine on a refeeding anorexia nervosa population.", "A single blind comparison of amisulpride, fluoxetine and clomipramine in the treatment of restricting anorectics.", "Combined cognitive-behavioral, psychopharmacological and nutritional therapy in eating disorders. 2. Anorexia nervosa--binge-eating/purging type.", "Amitriptyline in the treatment of anorexia nervosa: a double-blind, placebo-controlled study.", "Combined cognitive-behavioral, psychopharmacological and nutritional therapy in eating disorders. 1. Anorexia nervosa--restricted type.", "Anorexia nervosa. Treatment efficacy of cyproheptadine and amitriptyline.", "Does fluoxetine augment the inpatient treatment of anorexia nervosa?" ]

[ "This double-blind controlled study examines the impact of clomipramine when taken by an anorexia nervosa population, refeeding in hospital, over and above that generated by the established treatment programme. Of the 16 patients studied, all reached their target weights including three who asked to leave the study. Clomipramine was significantly associated with increased hunger, appetite and energy intake. It tended, though, to be associated with a reduced rate of weight gain, possibly because activity was increased. Patients receiving clomipramine were more stable in their eating habits and maintained body weight better than those on placebo after leaving the trial. These findings indicate the sensitivity of the hypothalamus to changes in body weight. Clomipramine, which is known to act at a hypothalamic level, seems to influence hunger, appetite and dietary intake according to the body weight of the patient. The threshold weights which have been shown to trigger hypothalamic sexual responses, may also influence hunger, appetite, motility and voluntary energy intake.", "1. The study evaluated the efficacy of amisulpride, fluoxetine and clomipramine at the beginning of the re-feeding phase of the treatment of restricting anorexia nervosa according to DSM-IV criteria. 2. 13 patients, mean weight 37.61 kg +/- 9.80 SD, were treated with clomipramine at a mean dosage of 57.69 mg +/- 25.79 SD; 10 patients, mean weight 40.90 kg +/- 6.98 SD, were treated with fluoxetine at a mean dosage of 28.00 mg +/- 10.32 SD; 12 patients, mean weight 38.41 kg +/- 8.33 SD, were treated with amisulpride at a mean dosage of 50.00 mg +/- 0.00 SD. 3. Clinical evaluation was carried out under single-blind condition at basal time and after three months by a structured clinical interview, the Eating Disorder Interview based on Long Interval Follow-up Evaluation (LIFE II BEI). 4. Patients treated with amisulpride showed a more significant increase (p=0.016) of mean weight. Concerning weight phobia, body image disturbance and amenorrhoea, no significant difference resulted.", "Thirteen women with anorexia nervosa, binge-eating/purging type (AN-BP), 17-43 years old, were treated with a 4-month course of combined cognitive-behavioral, nutritional and antidepressant therapy (7 with amineptine and 6 with fluoxetine). Patients were monitored before and after 1, 2 and 4 months of treatment for body mass index (BMI), for eating disorder symptoms by the Eating Disorder Inventory (EDI) and the Bulimic Investigation Test (BITE) and for depression and anxiety by the Hamilton Rating Scales for Depression and for Anxiety. BMI, EDI scores, depression and anxiety improved significantly and equally in the two groups during the 4 months of therapy, while BITE scores did not change.", "The tricyclic antidepressant drug amitriptyline was evaluated as a short-term treatment of anorexia nervosa patients. In a 5-week double-blind, placebo-controlled study 11 patients were given amitriptyline and 14 received placebo. In addition, 18 patients who refused to participate in the drug trial and received only psychosocial treatment were used as an additional comparison group. Overall, patients in the three groups showed little improvement. No statistically significant differences favoring amitriptyline were found in any of the outcome variables. Plasma levels varied widely among patients receiving similar doses. No association was found between plasma levels and improvement in either psychiatric symptomatology or weight. Amitriptyline patients did not manifest any tendency for a reduction of depressive symptomatology. In addition, amitriptyline treatment was associated with substantial discomfort and adverse affects.", "Twenty-two female patients with anorexia nervosa, restricted type, 14-35 years old, were treated with a 4-month course of combined cognitive-behavioral therapy, nutritional counselling and antidepressant drugs (nortriptyline for 7, fluoxetine for 15). Patients were monitored for body mass index (BMI), for eating disorder symptoms by the Eating Disorder Inventory (EDI) and the Bulimic Investigation Test (BITE) and for depression and anxiety by the Hamilton Rating Scales for Depression and for Anxiety (HRS-D and -A). The scores were determined before and after 1, 2 and 4 months of therapy. BMI, depression, anxiety and EDI scores improved significantly and equally in both groups during the 4 months of therapy, while BITE scores did not change.", "Patients with anorexia nervosa have concurrent problems of emaciation and depression. Therefore, treatment with medications affecting both weight gain and depression seemed reasonable. Seventy-two anorectic patients were randomly assigned in a double-blind study to receive cyproheptadine hydrochloride, a weight-inducing drug, amitriptyline hydrochloride, a tricyclic antidepressant, or placebo. Overall, cyproheptadine had a marginal effect on decreasing the number of days necessary to achieve a normal weight. There was a differential drug effect present in the bulimic subgroups of the anorectic patients: cyproheptadine significantly increased treatment efficiency for the nonbulimic patients and significantly impaired treatment efficiency for the bulimic patients when compared with the amitriptyline- and placebo-treated groups. The differential cyproheptadine effect on the anorectic bulimic subgroups is the first pharmacologic evidence of the validity of these subgroups. Cyproheptadine had an anti-depressant effect demonstrated by a significant decrease in the Hamilton depression ratings.", "While pharmacological interventions are of established utility in bulimia nervosa, medications have no clear role in the treatment of anorexia nervosa. Because patients with anorexia nervosa frequently exhibit mood disturbances and symptoms of obsessive-compulsive disorder, the authors tested the utility of fluoxetine in the treatment of women participating in an inpatient program for anorexia nervosa.\n The authors conducted a randomized, placebo-controlled, double-blind, 7-week study of fluoxetine at a target daily dose of 60 mg in 31 women with anorexia nervosa receiving treatment for their eating disorder on a clinical research unit. Body weight and measures of eating behavior and psychological state were obtained at baseline and at termination.\n There were no significant differences in clinical outcome on any measure between patients receiving fluoxetine and patients receiving placebo.\n Fluoxetine does not appear to add significant benefit to the inpatient treatment of anorexia nervosa." ]

[ "10777122", "8247075", "6986827", "1472183", "20423755", "9506565", "21688301" ]

[ "Cyclosporine A versus methotrexate in the treatment of polymyositis and dermatomyositis.", "A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis.", "Azathioprine with prednisone for polymyositis. A controlled, clinical trial.", "Controlled trial of plasma exchange and leukapheresis in polymyositis and dermatomyositis.", "Oral dexamethasone pulse therapy versus daily prednisolone in sub-acute onset myositis, a randomised clinical trial.", "Treatment of refractory myositis: a randomized crossover study of two new cytotoxic regimens.", "A randomized, pilot trial of etanercept in dermatomyositis." ]

[ "To determine the effectiveness and tolerance of treatment with cyclosporine A (CyA) or methotrexate (MTX) added to corticosteroids in patients with severe, active polymyositis (PM) and dermatomyositis (DM).\n Thirty-six patients (20 with DM, 16 with PM) were enrolled into the study and randomized in MTX (n = 17) and CyA (n = 19) groups. Muscle endurance and functional test (MEFT), clinical assessment (CA), global patient's assessment (GPA), muscle MRI, serum CK, myoglobin, IL-1Ra, and autoantibody status were used to assess the response to therapy after 1, 3, and 6 months.\n Significant improvement in MEFT, CA, GPA, and muscle MRI was found in both groups. Patients treated with MTX showed insignificantly better response than patients with CyA. CK levels in the MTX group decreased significantly after 1, 3, and 6 months, whereas a significant reduction in the CyA group was first observed after 6 months. IL-1Ra serum levels significantly dropped in the CyA group after two weeks, whereas in the MTX group the significant decrease was first seen after 3 months of treatment. Good correlation was found between each of the clinical parameters (MEFT, CA, and GPA), none of them showed any correlation with CK or IL-1Ra levels.\n Administration of MTX or CyA added to corticosteroids was associated with clinical and laboratory improvement. Changes in CK and IL-1Ra levels were not associated with parameters of clinical disease severity measured in this study.", "Dermatomyositis is a clinically distinct myopathy characterized by rash and a complement-mediated microangiopathy that results in the destruction of muscle fibers. In some patients the condition becomes resistant to therapy and causes severe physical disabilities.\n We conducted a double-blind, placebo-controlled study of 15 patients (age, 18 to 55 years) with biopsy-proved, treatment-resistant dermatomyositis. The patients continued to receive prednisone (mean daily dose, 25 mg) and were randomly assigned to receive one infusion of immune globulin (2 g per kilogram of body weight) or placebo per month for three months, with the option of crossing over to the alternative therapy for three more months. Clinical response was gauged by assessing muscle strength, neuromuscular symptoms, and changes in the rash. Changes in immune-mediated muscle abnormalities were determined by repeated muscle biopsies.\n The eight patients assigned to immune globulin had a significant improvement in sores of muscle strength (P < 0.018) and neuromuscular symptoms (P < 0.035), whereas the seven patients assigned to placebo did not. With crossovers a total of 12 patients received immune globulin. Of these, nine with severe disabilities had a major improvement to nearly normal function. Their mean muscle-strength scores increased from 74.5 to 84.7, and their neuromuscular symptoms improved. Two of the other three patients had mild improvement, and one had no change in his condition. Of 11 placebo-treated patients, none had a major improvement, 3 had mild improvement, 3 had no change in their condition, and 5 had worsening of their condition. Repeated biopsies in five patients of muscles whose strength improved to almost normal showed an increase in muscle-fiber diameter (P < 0.04), an increase in the number and a decrease in the diameter of capillaries (P < 0.01), resolution of complement deposits on capillaries, and a reduction in the expression of intercellular adhesion molecule 1 and major-histocompatibility-complex class I antigens.\n High-dose intravenous immune globulin is a safe and effective treatment for refractory dermatomyositis.", "A controlled, prospective, double-blind, therapeutic trial of azathioprine was conducted in the initial therapy of polymyositis. Sixteen patients received 60 mg prednisone per day plus either azathioprine (2 mg/kg of body weight per day) or placebo for a period of 3 months. Creatine phosphokinase (CPK) levels fell to normal slightly sooner in the placebo group, but not significantly so. The azathioprine group did not become significantly stronger (P = 0.58) and did not manifest significantly greater improvement of histopathologic features of muscle (P = 0.80) than the placebo group. Initial CPK elevations were significantly related to the degree of muscle inflammation (P = 0.037), but this was not the case at 3 months (P greater than 0.05). Normalization of the CPK could not be equated with disease control. Type II fiber atrophy, attributed to steroid therapy, was more marked in women than in men (P less than 0.03).", "The therapeutic options for patients with polymyositis or dermatomyositis that is resistant to corticosteroids are limited, unproved, and often toxic. Uncontrolled trials concluded that both plasma exchange and leukapheresis are beneficial, but despite the considerable use of these approaches, proof of their efficacy is lacking.\n Thirty-nine patients with definite polymyositis or dermatomyositis were randomly assigned to receive plasma exchange (replacement of one volume of plasma with 5 percent albumin in saline), leukapheresis (removal of 5 x 10(9) to 10 x 10(9) lymphocytes), or sham apheresis in a double-blind manner, with 12 treatments given over a one-month period. Muscle strength, functional capacity, and serum levels of muscle-associated enzymes were measured before and after the 12 procedures.\n In each group 3 of 13 patients had improvements in strength and functional capacity. The condition of 3 patients treated with leukapheresis and 1 treated with plasma exchange deteriorated, and it was unchanged in the other 26 patients. Adverse effects of apheresis included the need for a central venous catheter (9 patients), major vasovagal episodes (3 patients), and severe citrate reactions (2 patients). Despite the occurrence of significant reductions in the serum levels of muscle enzymes with plasma exchange (P less than 0.001) and significant decreases in lymphocyte counts with leukapheresis (P = 0.002), there were no significant differences among the three treatment groups in the final muscle strength or functional capacity of the patients.\n As treatments for corticosteroid-resistant polymyositis or dermatomyositis, leukapheresis and plasma exchange are no more effective than sham apheresis.", "To determine if high-dose pulsed dexamethasone is more effective and safer than daily high-dose prednisolone in treatment-naive adult patients with inflammatory myopathies (sporadic inclusion body myositis excluded) we performed a multicenter, double-blind randomised controlled clinical trial with 18 months follow-up. Sixty-two patients were randomised into 28-day cycles of oral high-dose dexamethasone or daily high-dose prednisolone. Primary outcome measures included (1) seven point composite score of six clinically relevant outcomes and (2) (time-to) remission and (time-to) relapse. No difference between both treatment groups on the composite score was found. Side-effects occurred significantly less frequently in the dexamethasone group. Median time to relapse was 60 (2.9) weeks in the prednisolone and 44 (4.7) weeks in the dexamethasone group (log-rank test p=0.03). In conclusion, pulsed high-dose oral dexamethasone is not superior to daily prednisolone as first-line treatment of idiopathic inflammatory myopathies, but is a good alternative by causing substantially fewer side-effects.", "To assess the clinical usefulness of 2 novel therapies for treatment-resistant myositis.\n Thirty patients with refractory myositis, of whom 25 had an inadequate or no response to previous cytotoxic therapy, were randomized to begin either a combination of weekly oral methotrexate and daily azathioprine (MTX/AZA) or intravenous methotrexate with leucovorin rescue (I.V. MTX) every 2 weeks for 6 months. Crossover to the alternate therapy occurred according to defined rules; evaluations of muscle strength and functional abilities were performed at the beginning, and after 3 and 6 months, of each treatment.\n Of the 15 patients initially randomized to oral MTX/AZA, 8 improved with oral therapy and 1 improved with I.V. MTX during the crossover period. Of the 15 patients initially randomized to I.V. MTX therapy, 3 improved with the I.V. therapy and 4 with the oral combination during the crossover period. Although the study lacked the power to directly compare both treatments, intention-to-treat analysis showed a trend in favor of those patients who first received oral combination therapy (P = 0.025). There were 0.09 adverse events per patient-month with oral combination therapy and 0.16 per patient-month with I.V. therapy (P = 0.09).\n Combination oral MTX/AZA may benefit patients with treatment-resistant myositis, including those who previously had inadequate responses to either MTX or AZA alone. I.V. MTX with leucovorin rescue may also benefit some patients with refractory myositis.", "The aims of this pilot study were to assess (1) the safety and tolerability of etanercept in dermatomyositis (DM); (2) the feasibility and safety of a forced prednisone taper; and (3) outcome measures, including those recommended by the International Myositis Assessment Clinical Study (IMACS) group.\n We conducted a randomized, double-blind, placebo-controlled trial of etanercept (50mg subcutaneously weekly) for 52 weeks in DM subjects. Subjects were tapered off prednisone in a standardized schedule as tolerated over the initial 24 weeks of the study. Principal outcomes included adverse events, time from randomization to treatment failure (inability to wean off prednisone on schedule), and average prednisone dosage after week 24.\n Sixteen subjects were randomized, 11 to etanercept and 5 to placebo. There were no significant differences in adverse event rates between the treatment groups, although 5 etanercept-treated and 1 placebo-treated subjects developed worsening rash. All 5 subjects receiving placebo were treatment failures (median time to treatment failure 148 days). In contrast, 5 of 11 subjects in the etanercept arm were successfully weaned off prednisone; the median time to treatment failure in this group was 358 days (p = 0.0002). The median of the average prednisone dosage after week 24 was 29.2mg/day in the placebo group and 1.2mg/day in the etanercept group (p = 0.02). IMACS and other outcome measures demonstrated excellent test-retest reliability (intraclass correlation coefficients 0.79-0.99). There was no significant treatment effect on functional outcome.\n The findings of no major safety concerns and a steroid-sparing effect in our study suggest that further investigation of etanercept as a treatment for DM is warranted.\n Copyright © 2011 American Neurological Association." ]

[ "18585831" ]

[ "Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease." ]

[ "To determine the clinical efficacy of combined vaccination with 23-valent pneumococcal vaccine (PV) and influenza vaccine (IV) against pneumonia and acute exacerbation of chronic lung diseases (CLD), we conducted an open-label, randomized, controlled study among 167 adults with CLD over a 2-year period. Subjects were randomly assigned to a PV+IV group (n=87) or an IV group (n=80). The number of patients with CLD experiencing infectious acute exacerbation (P=0.022), but not pneumonia (P=0.284), was significantly lower in the PV+IV group compared with the IV group. When these subjects were divided into subgroups, an additive effect of PV with IV in preventing infectious acute exacerbation was significant only in patients with chronic obstructive pulmonary diseases (P=0.037). In patients with CLD, the Kaplan-Meier survival curves demonstrated a significant difference for infectious acute exacerbation (P=0.016) between the two groups. An additive effect of PV with IV on infectious acute exacerbation was found during the first year after vaccination (P=0.019), but not during the second year (P=0.342), and was associated with serotype-specific immune response in sera of these patients who used PV during the same period." ]

[ "12556774", "11154484", "8536511", "12072597", "11600473", "15114302", "11473325", "15520997", "12865276", "14971818", "10029284", "9113010" ]

[ "Endoscopic sphincterotomy and endoscopic papillary balloon dilatation for bile duct stones: A prospective randomized controlled multicenter trial.", "A randomized trial of endoscopic balloon dilation and endoscopic sphincterotomy for removal of bile duct stones in patients with a prior Billroth II gastrectomy.", "Papillary dilation vs sphincterotomy in endoscopic removal of bile duct stones. A randomized trial with manometric function.", "What is an appropriate indication for endoscopic papillary balloon dilation?", "Can endoscopic papillary balloon dilation really preserve sphincter of Oddi function?", "Endoscopic papillary balloon dilation and endoscopic sphincterotomy for bile duct stones: long-term outcomes in a prospective randomized controlled trial.", "Endoscopic papillary balloon dilation vs. sphincterotomy for removal of common bile duct stones: a prospective randomized pilot study.", "Endoscopic balloon dilation compared with sphincterotomy for extraction of bile duct stones.", "Endoscopic balloon dilatation versus endoscopic sphincterotomy for the removal of bile duct stones: a prospective randomised trial.", "Endoscopic balloon dilatation is a safe method in the management of common bile duct stones.", "Comparing the treatment outcomes of endoscopic papillary dilation and endoscopic sphincterotomy for removal of bile duct stones.", "Randomised trial of endoscopic balloon dilation versus endoscopic sphincterotomy for removal of bileduct stones." ]

[ "Endoscopic papillary balloon dilatation may be an alternative to endoscopic sphincterotomy in the treatment of bile duct stones. However, there is a controversy as to the effectiveness and safety of endoscopic papillary balloon dilatation.\n Two hundred eighty-two patients with bile duct stones were enrolled and randomized to an endoscopic sphincterotomy or endoscopic papillary balloon dilatation group. The success rate for duct clearance as well as the frequency and types of complications were evaluated prospectively. Endoscopic sphincterotomy was performed in a standard manner. Endoscopic papillary balloon dilatation was carried out with gradual inflation of a 4-, 6-, or 8-mm diameter balloon.\n Complete duct clearance was achieved in 100% in the endoscopic sphincterotomy group and 99.3% in the endoscopic papillary balloon dilatation group (not significant). Complications occurred in 11.8% of patients in the endoscopic sphincterotomy group and 14.5% of those in the endoscopic papillary balloon dilatation group (not significant). No complication was severe; there was no mortality. The frequency of acute pancreatitis was higher in the endoscopic papillary balloon dilatation group than the endoscopic sphincterotomy group (respectively, 10.9% vs. 2.8%; p < 0.045). Hemorrhage occurred only in the endoscopic sphincterotomy group.\n Endoscopic sphincterotomy and endoscopic papillary balloon dilatation were approximately equal in terms of successful clearance of bile duct stones. They were also similar with respect to overall complications. Endoscopic papillary balloon dilatation is an alternative to endoscopic sphincterotomy as a treatment of bile duct stones.", "A prior Billroth II gastrectomy renders endoscopic sphincterotomy (EST) more difficult in patients with bile duct stones. Endoscopic balloon dilation (EBD) is a relatively easy procedure that potentially reduces the risk of bleeding and perforation.\n Thirty-four patients with bile duct stones and a previous Billroth II gastrectomy were randomized to EST or EBD. Complications were graded in a blinded fashion. Results were compared with those for a group of 180 patients with normal anatomy from a previously reported randomized trial of EBD versus EST.\n All stones were removed in 1 endoscopic retrograde cholangiopancreatography in 14 of 16 patients who underwent EBD versus 14 of 18 who had EST (p = 1.00). Mechanical lithotripsy was used in 3 EBD procedures versus 4 EST procedures (p = 1.00). Early complications occurred in 3 patients who had EBD versus 7 who underwent EST (p = 0.27). Three patients had bleeding after EST; 1 patient had mild pancreatitis after EBD. The median time required for stone removal was 30 minutes in both groups. Compared with patients with a normal anatomy, patients with a previous Billroth II gastrectomy had a significantly increased risk of bleeding after EST (17% vs. 2%, relative risk = 7.25, p < 0.05).\n A prior Billroth II gastrectomy renders EST more difficult and increases the risk of a complication. EBD in these patients is easy to perform and is not associated with an increased need for mechanical lithotripsy or a longer procedure time. The risk of bleeding is virtually absent after EBD and the risk of pancreatitis after EBD seems not significantly increased in these patients.", "To circumvent the long-term effects of papillary ablation for extracting common bile duct stones (< 12 mm in diameter) in endoscopic sphincterotomy (EST), endoscopic papillary dilation (EPD) was attempted in 20 patients. To evaluate papillary function before and after the procedures, manometry of the sphincter of Oddi was carried out in 13 with EPD and 10 of 20 patients with EST. Extraction of all stones was successful (100%) in both groups at an equal rate. Repeated numbers of procedures were common in both groups. However, the mean duration of the procedure was high in EPD compared to EST (63 min vs 42 min, P < NS). Adjunctive therapies like mechanical lithotripsy (ML), nasobiliary drainage, and choledochoscopy were included in EPD, while EST required a basket catheter and ML. There was no significant difference on manometry before and after the procedures (P = NS), although papillary function was found to have decreased after the EPD. In contrast, all patients in the EST group lost papillary function after the procedure. Thirty-day morbidity and mortality rate were absent in both groups. Immediate and 2.5-year follow up complications were uncommon in both groups. As a simple method, EPD may be an effective and safe alternative to EST in the management of patients with bile duct stones who require maintenance of papillary function.", "There are a number of views on the indication for endoscopic papillary balloon dilation (EPBD) in the management of bile duct stones. In this study, we have evaluated the efficacy and safety of EPBD compared with endoscopic sphincterotomy (EST).\n Prospective randomized trial.\n One university hospital and one general hospital.\n One hundred and forty patients were randomly allocated to EPBD or EST. Outcomes and complications were observed for a median period of 30 months.\n Both treatment approaches finally achieved similar success rates and needed similar numbers of treatment sessions for patients with stones less than 10 mm in diameter. However, for patients with stones of 10 mm or more, EPBD required a significantly greater mean number of treatment sessions than EST (2.4 vs 1.6, P < 0.01). Early complications occurred in seven EPBD (four pancreatitis, two cholangitis and one basket impaction) and eight EST (three pancreatitis, two bleeding and three cholangitis) patients. Late complications occurred in four EPBD (three recurrent bile duct stones and one cholecystitis) and six EST (three recurrent stones and three cholecystitis) patients.\n EPBD has little risk of bleeding. The technique removed small bile duct stones just as easily as did EST. These two procedures had approximately the same risk of pancreatitis and incidence of recurrent bile duct stones. Therefore, both procedures appear to be appropriate treatments for small bile duct stones. Whether or not EPBD becomes an established treatment will depend on further long-term studies.", "Endoscopic papillary balloon dilation (EPBD) is assumed to preserve sphincter of Oddi function because it causes little trauma to the papilla. However, few studies have addressed this issue specifically. In this study, we investigated whether EPBD can preserve sphincter function, and evaluated whether or not such preservation has clinical significance.\n Seventy patients with common bile duct (CBD) stones were randomly assigned to EPBD or endoscopic sphincterotomy (EST). Sphincter of Oddi (SO) function was measured by endoscopic manometry before, one week after, and one year after treatment. Incidence of pneumobilia and later complications were compared between the two groups at one year. Series manometric data were compared within each group and between the two groups. For a more detailed analysis of the cumulative incidence of later complications, retrospective cohorts were added to the study groups, giving a total number of 235 patients in the EPBD group and 126 in the EST group.\n Baseline characteristics did not differ significantly between the 35 EPBD and 35 EST patients. CBD stones were discharged successfully in all cases. CBD pressure, SO basal and peak pressures, and contraction frequency decreased significantly at one week in both groups. The damage was more severe in the EST group, and SO contraction completely disappeared in 23 patients in this group. The incidence of pneumobilia was significantly lower in the EPBD group than in the EST group (p<0.01) whereas CBD stones recurred and cholecystitis appeared at a similar rate in both groups at one year. A complete series of manometric data up to one year was obtained in 55 patients; 28 in the post-EPBD and 27 in post-EST groups. In the post-EPBD group, SO basal and peak pressures significantly recovered at one year compared with data at one week but these measures still remained significantly lower than those before EPBD (p< 0.01). In the post-EST group, SO contraction did not recover even after one year. A Kaplan-Meier analysis of 235 EPBD and 126 EST patients for a median follow up of 37 months revealed significantly lower incidences of biliary complications such as recurrent CBD stones and cholangitis, and cholecystitis in the EPBD group than in the EST group (p<0.05). The risk of pneumobilia was also significantly lower in the EPBD group (p<0.01).\n Preservation of papillary function after EPBD was not complete but remained somewhat reduced. However, preservation was more successful with EPBD than with EST. Such preservation may be clinically beneficial for the prevention of later complications.", "Little is known about the long-term outcome of endoscopic papillary balloon dilation for removal of bile duct stones. A randomized trial that compared long-term outcomes after endoscopic papillary balloon dilation and endoscopic sphincterotomy was conducted.\n Thirty-two patients with bile duct stones were randomized to endoscopic papillary balloon dilation or endoscopic sphincterotomy, with 16 patients in each group. Endoscopic papillary balloon dilation was performed by using an 8-mm-diameter balloon; endoscopic sphincterotomy was performed in the standard manner. The success rates for stone removal, as well as the frequency and types of early (<15 days), mid-term (<1 year), and long-term (1-6 years) post-procedure complications were evaluated.\n The success rates for stone removal and early complication rates were similar for both groups. The frequency of stone recurrence was approximately 4-fold higher in the endoscopic papillary balloon dilation group (25%) vs. the endoscopic sphincterotomy group (6.3%) at mid-term evaluation. However, over the long term, Kaplan-Meier estimated probability of stone recurrence tended to be higher in the endoscopic sphincterotomy group vs. the endoscopic papillary balloon dilation group; recurrent stones were found in, respectively, 26.7% vs. 6.3%. Complications occurred in 7 patients in each group.\n Long-term outcome of endoscopic papillary balloon dilation for bile duct stone removal is satisfactory, provided that consideration is given to recurrence of stones by early follow-up evaluation.", "Endoscopic sphincterotomy (EST) is the standard procedure for gaining access to the common bile duct for removal of bile duct stones. However, the procedure is associated with both short-term and long-term complications. Recent reports have described the use of endoscopic papillary balloon dilation (EBD) as an effective and safe alternative to EST. We conducted a prospective randomized pilot study to compare the efficacy and short-term complication rates of these two established methods for removing uncomplicated bile duct stones.\n Sixty patients were randomly assigned to receive either EST (n = 30) or EBD (n = 30) prior to removal of bile duct stones (maximum size 20 mm, maximum number five). The patient groups were comparable with regard to sex and age ratios, the size of the stones (EST: mean 10 +/- 4.7 mm; EBD: mean 7 +/- 3.5 min; not significant) and the numbers of stones (EST: mean 1.8 +/- 1.5 mm; EBD: mean 1.6 +/- 1.1 mm; not significant). EBD was carried out using a balloon-tipped biliary catheter (Maxforce, Microvasive, Boston, Massachusetts, USA) with a maximum diameter of 24 Fr for 45-60 s. Bile duct stones were removed using Dormia baskets or retrieval balloons, or both.\n The two methods were successful in all patients studied. Subsequent stone removal was possible in all 30 patients after EST (100%) and in 23 of the 30 who underwent EBD (77%), respectively (P<0.01). After conversion to EST, complete bile duct clearance was also achieved in the remaining seven EBD patients. The mean duration for the whole procedure was 17 +/- 12 min for EST and 29 +/- 15 min for EBD (not significant). Complications (WHO grades 2-4) were observed in five of the 30 EST patients (three cases of mild pancreatitis, two of hemorrhage) and in nine of the 30 EBD patients (three cases of cholangitis, four of mild pancreatitis, and two of severe pancreatitis), showing a trend toward higher complication rates in the EBD group. Postintervention hyperamylasemia was observed in six patients (three in each group).\n The results of this prospective randomized pilot study indicate that EST is superior to EBD in terms of stone removal, duration of the procedure, and complication rates. EST will therefore continue to be the standard procedure for stone removal in the near future. Further studies will be needed in order to compare the longer-term results with EST and EBD.", "Endoscopic retrograde cholangiopancreatography is commonly performed to remove bile duct stones. The aim of this study was to determine short-term outcomes of endoscopic balloon dilation of the sphincter of Oddi compared with sphincterotomy for stone extraction.\n A randomized, controlled multicenter study of 117 patients assigned to dilation and 120 to sphincterotomy was performed in a spectrum of clinical and academic practices.\n Characteristics of the patients, procedures, and endoscopists were similar except that dilation patients were younger. Procedures were successful in 97.4% and 92.5% of the dilation and sphincterotomy patients, respectively. Overall morbidity occurred in 17.9% and 3.3% ( P < .001; difference, 14.6; 95% confidence interval, 7-22.3) and severe morbidity, including 2 deaths, in 6.8% and 0%( P < .004; difference, 6.8; 95% confidence interval, 2.3-11.4) for dilation and sphincterotomy, respectively. Complications for dilation and sphincterotomy, respectively, included: pancreatitis, 15.4% and .8% ( P < .001; difference, 14.6; 95% confidence interval, 7.8-21.3); cystic duct fistula, 1.7% and 0%; cholangitis, .9% and .8%; perforation, 0% and .8%; and cholecystitis, 0% and .8%. There were 2 deaths (1.7%) due to pancreatitis following dilation and none with sphincterotomy. The study was terminated at the first interim analysis. Dilation patients required significantly more invasive procedures, longer hospital stays, and longer time off from normal activities.\n In a broad spectrum of patients and practices, endoscopic balloon dilation compared with sphincterotomy for biliary stone extraction is associated with increased short-term morbidity rates and death due to pancreatitis. Balloon dilation of the sphincter of Oddi for stone extraction should be avoided in routine practice.", "Endoscopic balloon dilatation (EBD) of the sphincter of Oddi has been proposed as an alternative therapy with possible advantages, as compared with endoscopic sphincterotomy (ES), for removal of bile duct stones.\n In a randomised study, we compared the efficacy and complication rate of the two techniques in 202 patients with common bile duct stones. Patients were followed up for 12 months.\n A total of 103 patients were randomised to the EBD group and 99 to the ES group. Overall duct clearance was 87.1% and did not differ between the two groups (EBD 87.4%; ES 86.9%). The complication rate at 24 hours was 6.8% in the EBD group and 3.0% in the ES group (NS). Complications during follow up were 11.7% and 15.2% respectively (NS). A multivariate logistic regression analysis showed only the size of the largest stone to be predictive of success for either technique.\n Endoscopic balloon dilatation offers no significant advantage over the well established technique of endoscopic sphincterotomy for the removal of bile duct stones.", "Endoscopic sphincterotomy is a widely accepted treatment for patients with common bile duct stones. Despite improvement in this technique, endoscopic sphincterotomy is still associated with some biliary complications. Endoscopic balloon dilatation is a less traumatic and sphincter preserving method for removal of common bile duct stones. However, the results of controlled studies in comparison with these two methods are contradictory. The aim of this study is to compare the safety and efficacy of endoscopic balloon dilatation and endoscopic sphincterotomy in Chinese patients.\n A total of 104 patients with common bile duct stones on endoscopic retrograde cholangiopancreatography were enrolled. They were randomly assigned to endoscopic balloon dilatation or endoscopic sphincterotomy. Endoscopic balloon dilatation was performed by using a balloon dilator to dilate the sphincter for 5 min. The common bile duct stones were then removed by a Dormia basket after endoscopic balloon dilatation or endoscopic sphincterotomy. Mechanical lithotripsy was performed if the stones were difficult to remove by Dormia basket. After discharge, patients were regularly followed up for biliary complications.\n The successful bile duct stone clearance rate was 94.1% in endoscopic balloon dilatation group and 100% in endoscopic sphincterotomy group. Post-procedural significant haemorrhage was higher in endoscopic sphincterotomy group than in endoscopic balloon dilatation group (14/53 versus 1/48, P < 0.001). The bleeding patient from endoscopic balloon dilatation group was a case of uremia and bleeding occurred 48 h after endoscopic balloon dilatation. All the patients with post-procedural haemorrhage were controlled endoscopically. The post-procedural serum amylase level showed no significant difference in both groups and none of them developed clinical pancreatitis. After a mean 16 months follow-up, three patients (6.3%) in endoscopic balloon dilatation group and four patients (7.5%) in endoscopic sphincterotomy group developed recurrent common bile duct stones. The recurrent common bile duct stones were multiple and muddy in consistency. They were successfully removed endoscopically.\n Both endoscopic balloon dilatation and endoscopic sphincterotomy are safe and effective techniques for the treatment of common bile duct stones. Endoscopic balloon dilatation can be safely applied in patients with coagulopathy and does not increase the incidence of pancreatitis or bleeding.", "To compare the clinical usefulness of endoscopic papillary dilation (EPD) and endoscopic sphincterotomy (EST) for removal of bile duct stones, 110 patients with stones up to 15 mm in diameter and less than 10 in number were randomly treated with either EPD (55 patients) or EST (55 patients). The patients were followed up for a median period of 23 months and endoscopic manometry with the administration of morphine was carried out in 17 patients who were observed more than 12 months after the procedures to evaluate the post-procedure papillary function. Duct clearance was achieved in 51 EPD (92.7%) and 54 EST patients (98.1%, not significantly different). Forty EPD (78.4%) and 51 EST patients (94.4%) achieved duct clearance in the initial procedure (P=0.02). Early complications occurred in one EPD (2.0%) and in three EST patients (5.6%, P=0.62). Complications during the follow-up period occurred in two EPD and eight EST patients. Recurrence of bile duct stones was observed in two EPD and three EST patients (P=0.98). Acute cholecystitis was observed in one EPD and five EST patients (P=0.06) and among patients with gall-bladder stones in situ, the rate of acute cholecystitis after EPD was significantly lower than that after EST (P=0.03). Endoscopic manometry showed the existence of a choledochoduodenal pressure gradient only after EPD, while papillary contractile function was observed after both procedures. In conclusion, both EPD and EST are safe therapeutic modalities, although EPD is more clinically effective in decreasing the risk of acute cholecystitis in patients with gall-bladder stones in situ and in preserving post-procedure papillary function.", "Endoscopic sphincterotomy (EST) for the removal of bileduct stones is associated with acute complications and a permanent loss of biliary-sphincter function. Endoscopic balloon dilation (EBD) causes less trauma to the biliary sphincter, but may be less effective in allowing stone removal.\n 218 consecutive patients with bileduct stones on endoscopic retrograde cholangiopancreatography (ERCP) were enrolled. 202 who met all eligibility criteria were randomly assigned EST or EBD. The patients were observed in hospital for at least 24 h and followed up at 1 month and 6 months. Complications were classified by an expert panel unaware of treatment allocation and outcome. Analysis was done by intention to treat.\n After a single ERCP, all stones were removed from 92 (91%) of 101 patients assigned EST and 90 (89%) of 101 assigned EBD (p = 0.81); in nine of the latter, successful removal required additional EST. Mechanical lithotripsy was used to fragment stones in 31 EBD procedures and 13 EST procedures (p < 0.005). Early complications (before 15 days) occurred in 24 EST patients and 17 EBD patients (p = 0.29). One patient died of retroperitoneal perforation after EBD. Four patients had bleeding after EST. Seven patients in each group had pancreatitis. Complications during follow-up occurred in 23 EST patients and 18 EBD patients (p = 0.48). Acute cholecystitis was observed in seven EST patients and one EBD patient (p < 0.05).\n The success rate of EBD was similar to that of EST. We found there is no evidence of the previously suggested higher risk of pancreatitis with EBD and suggest that EBD is preferred in patients at risk of bleeding after EST. Preservation of biliary-sphincter function after EBD may prevent long-term complications and reduce the risk of acute cholecystitis during follow-up. This procedure is a valuable alternative to EST in patients with bileduct stones." ]

[ "6362368", "13691281" ]

[ "The effects of procaine/haematoporphyrin on age-related decline: a double-blind trial.", "A controlled trial of \"gerioptil\"." ]

[ "A randomized, double-blind study of procaine/haematoporphyrin (KH3) has been carried out over two years in a selected population of healthy elderly subjects. The period of study exceeds 500 patient years. The trial population was weighted to contain a larger proportion of subjects aged over 75 years than a standard population; those receiving active KH3 had similar characteristics on entry to those receiving placebo. Over the course of two years, KH3 was shown to be an active substance in that: (a) decrement in the consolidation of new learning was prevented in the treatment group (less than 1.0%, as against 38% in the placebo group); (b) the prevalence of incontinence increased significantly in the placebo group, but not in the active group (P less than 0.05); (c) there was a significant increase in grip strength in the active treatment group (+22%, P less than 0.01 v. placebo); (d) more adverse reactions were observed on treatment with KH3 (P less than 0.005).", "nan" ]

[ "9817288", "6380281", "5338385", "2488674", "3528988", "3537160", "14701781" ]

[ "Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home.", "Combination therapy with ibuprofen and methadone for chronic cancer pain.", "A clinical comparison of the analgesic effects of methadone and morphine administered intramuscularly, and of orally and parenterally administered methadone.", "Does intravenous methadone provide longer lasting analgesia than intravenous morphine? A randomized, double-blind study.", "A comparative study of the efficacy and pharmacokinetics of oral methadone and morphine in the treatment of severe pain in patients with cancer.", "A randomized study on oral administration of morphine and methadone in the treatment of cancer pain.", "Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study." ]

[ "The aim of this study was to evaluate the analgesic and adverse effects and the doses of methadone in comparison to morphine.\n A prospective randomized study was performed in a sample of 40 patients with advanced cancer who required strong opioids for their pain management. Patients were treated with sustained-release morphine or methadone in doses titrated against the effect administered two or three times daily according to clinical need. Opioid doses, adjuvant medications, symptoms associated with opioid therapy, pain intensity, and pain mechanisms were recorded. The opioid escalation indices in percentage (OEI%) and milligrams (OEImg) were calculated. The effective analgesic score (EAS) that monitors the analgesic consumption-pain ratio was also calculated at fixed weekly intervals.\n differences in pain intensity were found. Patients treated with methadone reported values of OEI significantly less than those observed in patients treated with morphine. Seven patients in the methadone group maintained the same initial dosage until death, whereas only one patient in the morphine group did not require opioid dose escalation. A more stable analgesia in time in patients treated with methadone was shown by the low number of gaps in EASs reported. Symptom frequencies and intensities were similar in the two groups.\n Methadone is a drug of indisputable value in the treatment of cancer pain, and an unbalanced focus on the risks of inappropriate use rather than the benefits should not compromise the use of a relevant alternative to morphine in the management of cancer pain.", "This randomized double-blind crossover study compares the narcotic methadone alone with methadone in combination with the peripherally acting, antiprostaglandin agent ibuprofen (Motrin, Upjohn) in 28 patients with moderate to severe cancer-related pain, who were already using a narcotic for pain relief. Results show that the addition of 600 mg of ibuprofen to either 2.5 or 5 mg of methadone significantly increased analgesia, without concomitantly increasing side effects or euphoria.", "nan", "A prospective, randomized, double-blind trial was designed to compare the duration of analgesia produced by intravenous morphine and methadone. Patients with intractable cancer-related pain were studied for 5-6 days. One-eighth of the patient's daily opiate requirement was supplied as an i.v. infusion of either morphine or methadone over a period of 15 min. when initiated by the patient using a patient-controlled analgesia device. Dosing intervals, pain intensity assessments and toxicity were evaluated. Twenty-three patients were randomized; 18 were fully evaluable. Ten of the evaluable patients received morphine, 8 received methadone. Dosing intervals did not change over the 5 days for either group. The mean dosing interval for the last 10 doses was 3.9 +/- 0.85 h for patients receiving morphine and 3.9 +/- 1.6 h for patients receiving methadone (P = NS). One patient receiving morphine and one taking methadone required only 2-3 doses/day for pain control. Pain intensity and relief were similar for both groups. All patients had adequate analgesia as determined by at least a 50% difference in pain intensity at peak relief. The duration of pain relief when repeated intravenous doses of these analgesics were given was similar throughout the entire study period although morphine and methadone have different serum half-lives (3 vs. 25 h). Parenteral methadone does not offer a clinically significant increase in the duration of analgesia in patients with severe pain secondary to cancer.", "Eighteen patients suffering from cancer were entered into a study of the pharmacokinetics and efficacy of methadone and morphine in pain control. All patients had both clinical and radiological evidence of metastatic spread of their cancer and there were no significant differences in age, weight and sites of the primary cancer between the methadone (n = 9) and morphine (n = 9) groups. Blood opioid concentration, visual analogue pain scores (VAPS) and end-tidal percent carbon dioxide were measured before and after both an intravenous and oral dose of either methadone or morphine. Terminal half-lives (mean +/- S.D.) were 30.4 +/- 16.3 h and 2.7 +/- 1.2 h respectively for methadone and morphine while the clearance values (mean +/- S.D.) were 0.19 +/- 0.13 l/min and 1.16 +/- 0.47 l/min. The long half-life of methadone was associated with prolonged pain relief. However, the large variation in the half-life of methadone necessitated careful adjustment of the dosing interval in individual patients. There were pronounced differences in oral bioavailability between the two opioids: methadone, 79 +/- 11.7%, compared to morphine, 26 +/- 13% (mean +/- S.D.). Of greater clinical significance was the variability in these bioavailability estimates with a coefficient of variation of 15% for methadone compared to 50% for morphine. The combined effects of low and variable oral bioavailability for morphine may result in sub-therapeutic doses being administered as practitioners may be inhibited by the size of the effective oral morphine dose and may be confused by the variability in this dose compared to intramuscular doses. The initial oral dose of morphine varied from 15 mg 4 hourly to 150 mg 3 hourly, while the initial dose for methadone varied from 15 mg on alternate nights to 20 mg twice daily. There was no rapid escalation of daily opioid dose for either methadone or morphine when adequate pain control was provided rapidly at the start of treatment by the technique described in this study.", "nan", "To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain.\n Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks.\n A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups.\n Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain." ]

[ "9738217", "7857145", "11124554", "3510704", "8492040" ]

[ "[Is the stapled suture in visceral surgery still justified? A prospective controlled, randomized study of cost effectiveness of manual and stapler suture].", "Comparison of manually constructed and stapled anastomoses in colorectal surgery. West of Scotland and Highland Anastomosis Study Group.", "Long-term results of stapled and hand-sewn anastomoses in patients with Crohn's disease.", "A prospective randomized study of sutured versus stapled bowel anastomoses in patients with cancer.", "Ileocolonic anastomosis after right hemicolectomy for carcinoma: stapled or hand-sewn? A prospective, multicenter, randomized trial." ]

[ "Hospitals are facing increasing economic pressure. It therefore seems necessary to evaluate the efficiency and effectiveness of medical or surgical interventions. In this study 324 anastomoses (167 stapled and 157 hand-sewn) were performed after randomization during 200 elective operations [20.5% gastrectomies, 14% gastric resections (Billroth II), 15% Whipple's procedures, 4% segmental colonic resections, 18% right-sided hemicolectomies, 4% left-sided hemicolectomies, 22% sigmoid- or anterior rectal resections, 2.5% total colectomies with pouch-anal anastomoses] in 200 patients. Postoperative motility (time to full oral diet, time with naso-gastric tube) and hospitalization were comparable in both groups. Anastomotic insufficiency was observed in 2.1% of all patients, five after stapled and two after hand-sewn anastomoses. Hospital mortality was 1.5%. All stapled anastomoses were performed significantly (P < 0.001) faster. However, the cost of material for these anastomoses was significantly (P < 0.001) higher, resulting in significantly higher total costs for reconstruction. The time saving for the reconstruction did not influence the total operative time (except for stapled gastrectomy). Therefore, all operations with stapled reconstruction were more expensive than those with sutured reconstruction. The difference was significant for the gastrectomy (P < 0.01), colonic resection (P < 0.01) and sigmoid and rectal resection (P < 0.001) groups. Stapled and sutured anastomoses are equally effective. Stapled anastomoses are not efficient, however, and should be reserved for individual indications.", "The authors compared both the initial and the long-term outcomes of patients undergoing stapled and sutured colorectal anastomoses.\n Sutured and stapled large bowel anastomoses are perceived to be equally safe, but concern has been raised about increased rates of tumor recurrence with the use of stapling instruments.\n The outcome of patients with sutured and stapled colorectal anastomoses were compared in a prospective, multicenter, randomized study. Factors affecting long-term outcomes were assessed by both univariate and multivariate analysis.\n Seven hundred thirty-two patients were recruited. There was a significant increase in radiologic leakage in the sutured group (14.4% vs. 5.2%, p < 0.05), but there was no difference in clinical anastomotic leak rates, morbidity, or postoperative mortality. Tumor recurrence and cancer-specific mortality were higher in the sutured patients (7.5% and 6.7%, respectively) and in patients with anastomotic leaks.\n This study shows that suturing or stapling are equally safe in large bowel surgery. However, it also shows a long-term benefit of stapling in colorectal cancer patients.", "This study aimed at determining the reoperation rates of patients with anastomoses for Crohn's disease. The outcome of patients undergoing stapled anastomoses was compared with that of patients having hand-sewn anastomoses.\n Sixty-three patients undergoing intestinal resection for Crohn's disease at our institution from 1987 to 1996 were studied in a prospective, randomized trial. The group undergoing stapling comprised 30 patients and 37 anastomoses. The group with a hand-sewn anastomosis comprised 33 patients and 45 anastomoses. The median follow-up period was 87 (range 36-140) months.\n There were no significant differences in operative indications or patients' age and sex between the groups. There was a significant difference in cumulative recurrences between the groups (Cox-Mantel test: p = 0.022).\n A stapled anastomosis after resection for Crohn's disease may delay reoperation in patients with symptomatic recurrence.\n Copyright 2000 S. Karger AG, Basel.", "Eighty-eight cancer patients with the presence of one or more adverse factors for healing (carcinomatosis, adhesions, prior chemotherapy and radiation therapy, bowel obstruction, anemia, and low leukocyte count or albumin value) were prospectively randomized to undergo conventional two-layer hand suturing (45 patients) or mechanical stapling with a GIA/TA instrument (U.S. Surgical Corp., Norwalk, CT) (43 patients) of the large or small bowel anastomosis. Age, sex, complete blood count findings, and all biochemical plasma values were comparable in both groups. The anastomosis took an average of 19 minutes for the sutured and 9 minutes for the stapled technique (P = 0.0001), but the average length of operation, postoperative return of bowel function, and hospital stay were comparable in both groups. Bowel fistula was seen in one case of stapled anastomosis (P = not significant). The pulmonary and wound complication rates were the same in both groups. Of the four deaths (4.5%) due to causes unrelated to bowel anastomosis, three occurred in the stapled and one in the sutured group. It was concluded that a stapled anastomosis is as safe as a sutured one in patients with advanced-stage cancer. It saves time in anastomosis, but does not save time in postoperative return of the bowel function and hospital stay.", "440 patients were prospectively enrolled in a randomized, multicenter trial to compare 4 types of manual (84 interrupted end-to-end, 77 continuous end-to-end, 82 interrupted end-to-side, and 91 continuous end-to-side) (polyglycolic derived suture) and 1 type of stapled (106 side-to-side with GIA+TA devices) ileocolonic anastomosis after right hemicolectomy for carcinoma. The trial was designed according to Schwartz' pragmatic formulation. All 5 groups were well-matched, except for a lower rate of intraoperative sepsis in the stapled group (P < 0.02). The main end point was anastomotic leakage detected clinically or by routine sodium diatrizoate enema on the 8-10th postoperative day. Results showed that stapled ileocolonic anastomosis was associated with less anastomotic leakages (2.8%) than all the other techniques combined (8.3%). In spite of the fact that staples are approximately ten times more expensive, our results suggest performing side-to-side (GIA+TA) mechanical anastomosis after right resection for carcinoma." ]

[ "15803166" ]

[ "Long-term intraocular pressure control of eyes that developed encapsulated blebs following trabeculectomy." ]

[ "To evaluate the long-term intraocular pressure (IOP) control of eyes that developed an encapsulated bleb (EB) following trabeculectomy.\n Between 1994 and 1995, 25 eyes developed EBs and were randomized to medical treatment or needling without adjunct antimetabolites. Among the 25 patients who developed an EB, 21 were followed for at least 6 months. A control group of 21 consecutive eyes, which underwent trabeculectomy during the same period and that did not develop EBs was retrospectively selected. Success was defined as IOP <21 mmHg with or without medications. Kaplan-Meier survival analysis was performed to compare the groups.\n Among the 21 eyes that developed EBs, 12 (57%) had undergone transconjunctival needling and nine (43%) had received medical treatment. Mean follow-ups were 30.0 +/- 14.0 months, 33.3 +/- 18.5 months, and 37.4 +/- 2.6 months for the needling, medical treatment, and control groups, respectively (P = 0.19). Kaplan-Meier survival curves demonstrated that the control group showed a significantly lower chance of failure than both the needling and the medical treatment groups (P < 0.0001).\n Encapsulated blebs may be associated with an increased risk for surgical failure." ]

[ "9971864", "3560265", "3533203", "22168590", "9661685", "17442904", "20940381", "19389209", "10512433", "19656349", "13374186", "10532600", "7723158", "17894791", "16430668", "9293831", "1495291", "19237920" ]

[ "A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group.", "Influence of hematocrit on cardiopulmonary function after acute hemorrhage.", "Effect of early blood transfusion on gastrointestinal haemorrhage.", "Liberal or restrictive transfusion in high-risk patients after hip surgery.", "A pilot randomized trial comparing symptomatic vs. hemoglobin-level-driven red blood cell transfusions following hip fracture.", "Transfusion strategies for patients in pediatric intensive care units.", "Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial.", "The effects of liberal versus restrictive transfusion thresholds on ambulation after hip fracture surgery.", "Predonated autologous blood transfusions after total knee arthroplasty: immediate versus delayed administration.", "A randomized comparison of transfusion triggers in elective orthopaedic surgery using leucocyte-depleted red blood cells.", "The illness of trauma.", "Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome.", "Transfusion requirements in critical care. A pilot study. Canadian Critical Care Trials Group.", "A multicenter pilot-randomized controlled trial of the feasibility of an augmented red blood cell transfusion strategy for patients treated with induction chemotherapy for acute leukemia or stem cell transplantation.", "Silent myocardial ischaemia and haemoglobin concentration: a randomized controlled trial of transfusion strategy in lower limb arthroplasty.", "A prospective, randomized trial limiting perioperative red blood cell transfusions in vascular patients.", "Comparison of two transfusion strategies after elective operations for myocardial revascularization.", "The effect of red blood cell transfusion on cerebral oxygenation and metabolism after severe traumatic brain injury." ]

[ "To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients, we compared the rates of death from all causes at 30 days and the severity of organ dysfunction.\n We enrolled 838 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of less than 9.0 g per deciliter within 72 hours after admission to the intensive care unit and randomly assigned 418 patients to a restrictive strategy of transfusion, in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g per deciliter and hemoglobin concentrations were maintained at 7.0 to 9.0 g per deciliter, and 420 patients to a liberal strategy, in which transfusions were given when the hemoglobin concentration fell below 10.0 g per deciliter and hemoglobin concentrations were maintained at 10.0 to 12.0 g per deciliter.\n Overall, 30-day mortality was similar in the two groups (18.7 percent vs. 23.3 percent, P= 0.11). However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill -- those with an Acute Physiology and Chronic Health Evaluation II score of < or =20 (8.7 percent in the restrictive-strategy group and 16.1 percent in the liberal-strategy group; P=0.03) -- and among patients who were less than 55 years of age (5.7 percent and 13.0 percent, respectively; P=0.02), but not among patients with clinically significant cardiac disease (20.5 percent and 22.9 percent, respectively; P=0.69). The mortality rate during hospitalization was significantly lower in the restrictive-strategy group (22.3 percent vs. 28.1 percent, P=0.05).\n A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.", "The 'optimal' hematocrit to which patients should be resuscitated after shock and trauma is controversial. To test the hypothesis that sufficient oxygen delivery can be provided at a lower hematocrit without impairing oxygen consumption or hemodynamic function, 25 patients were prospectively studied immediately following injury and/or acute hemorrhage. Patients were randomized to have their hematocrits (HCT) maintained near 30% (29.7 +/- 0.4% (M +/- SEM); n = 12) or 40% (38.4 +/- 0.6%, n = 13). Cardiopulmonary parameters were measured twice a day for 3 days. Statistical analysis used a repeated measures analysis of variance with patient age, and ventilator parameters (FIO2, PEEP, and ventilator mode) as covariates. Arterial and venous O2 saturations were not significantly different at different hematocrits, although arterial and venous O2 contents were lower at 30% HCT (a = 14.1 +/- 0.2 m10(2)/dl, v = 10.1 +/- 0.3 m10(2)/dl; vs. a = 17.4 +/- 0.4 m10(2)/dl, v = 13.6 +/- 0.6 m10(2)/dl; p less than 0.05). This resulted in a lower oxygen delivery at the lower HCT. Between the two groups, there also was no significant difference in cardiac index (overall mean, 3.64 +/- 0.16 ml/min/m2), heart rate (99 +/- 4 bpm), systemic vascular resistance (1,058 +/- 55 dyne-sec/cm5), or left ventricular stroke work index (4.3 +/- 0.3 X 10(6) dyne-cm/m2). Intrapulmonary shunt was higher with higher hematocrit (22.6 +/- 2.4% at 40% HCT vs. 14.6 +/- 1.6% at 30% HCT; p less than 0.05) with no difference in end-expiratory pressure.(ABSTRACT TRUNCATED AT 250 WORDS)", "The effect of citrated stored blood on coagulation was studied initially in a pilot study where 25 patients with acute severe gastrointestinal haemorrhage had their whole blood coagulation measured using the Biobridge Impedance Clotting Time (ICT). This demonstrated that there is a hypercoagulable response to haemorrhage which was partially reversed by blood transfusion. Similar changes were noted in Kaolin Cephalin Clotting Times (KCCT). A further 50 patients were then randomized to receive, during the 24 h after admission, either at least 2 units of blood or no blood transfusion unless the haemoglobin fell below 8 g/dl or they were shocked. In the transfused group nine patients re-bled compared with only one in the non-transfused group (P less than 0.01, chi 2 with Yates' correction). Early blood transfusion appears to reverse the hypercoagulable response to haemorrhage thereby encouraging re-bleeding and hence the need for an operation.", "The hemoglobin threshold at which postoperative red-cell transfusion is warranted is controversial. We conducted a randomized trial to determine whether a higher threshold for blood transfusion would improve recovery in patients who had undergone surgery for hip fracture.\n We enrolled 2016 patients who were 50 years of age or older, who had either a history of or risk factors for cardiovascular disease, and whose hemoglobin level was below 10 g per deciliter after hip-fracture surgery. We randomly assigned patients to a liberal transfusion strategy (a hemoglobin threshold of 10 g per deciliter) or a restrictive transfusion strategy (symptoms of anemia or at physician discretion for a hemoglobin level of <8 g per deciliter). The primary outcome was death or an inability to walk across a room without human assistance on 60-day follow-up.\n A median of 2 units of red cells were transfused in the liberal-strategy group and none in the restrictive-strategy group. The rates of the primary outcome were 35.2% in the liberal-strategy group and 34.7% in the restrictive-strategy group (odds ratio in the liberal-strategy group, 1.01; 95% confidence interval [CI], 0.84 to 1.22), for an absolute risk difference of 0.5 percentage points (95% CI, -3.7 to 4.7). The rates of in-hospital acute coronary syndrome or death were 4.3% and 5.2%, respectively (absolute risk difference, -0.9%; 99% CI, -3.3 to 1.6), and rates of death on 60-day follow-up were 7.6% and 6.6%, respectively (absolute risk difference, 1.0%; 99% CI, -1.9 to 4.0). The rates of other complications were similar in the two groups.\n A liberal transfusion strategy, as compared with a restrictive strategy, did not reduce rates of death or inability to walk independently on 60-day follow-up or reduce in-hospital morbidity in elderly patients at high cardiovascular risk. (Funded by the National Heart, Lung, and Blood Institute; FOCUS ClinicalTrials.gov number, NCT00071032.).", "The indications for transfusion have never been evaluated in an adequately sized clinical trial. A pilot study was conducted to plan larger clinical trials.\n Hip fracture patients undergoing surgical repair who had postoperative hemoglobin levels less than 10 g per dL were randomly assigned to receive 1) symptomatic transfusion: that is, transfusion for symptoms of anemia or for a hemoglobin level that dropped below 8 g per dL or 2) threshold transfusion: that is, patients receive 1 unit of packed RBCs at the time of random assignment and as much blood as necessary to keep the hemoglobin level above 10 g per dL. Outcomes were 60-day mortality, morbidity, functional status, and place of residence.\n Among 84 eligible patients enrolled, mean (+/- SD) prerandomization hemoglobin was 9.1 (+/- 0.6) g/ dL. The median number of units transfused in the threshold transfusion group was 2 (interquartile range, = 1-2), and that in the symptomatic transfusion group was 0 (6; interquartile range, = 0-2) (p < 0.001). Mean hemoglobin levels were approximately 1 g per dL higher in the threshold group than in the symptomatic group: for example, on Day 2, 10.3 (+/- 0.9) g per dL versus 9.3 (+/- 1.2) g per dL, respectively (p < 0.001). At 60 days, death or inability to walk across the room without assistance occurred in 16 (39.0%) of the symptomatic transfusion group and 19 (45.2%) of the threshold transfusion group. Death occurred by 60 days in 5 (11.9%) of the symptomatic transfusion group and 2 (4.8%) in the threshold transfusion group (relative risk = 2.5; 95% CI, 0.5-12.2). Other outcomes were similar for the two groups.\n Symptomatic transfusion may be an effective blood-sparing protocol associated with the transfusion of appreciably fewer units of RBCs and lower mean hemoglobin levels than are associated with the threshold transfusion policy. However, it is unknown whether these two clinical strategies have comparable mortality, morbidity, or functional status. A definitive trial is needed.", "The optimal hemoglobin threshold for erythrocyte transfusions in critically ill children is unknown. We hypothesized that a restrictive transfusion strategy of using packed red cells that were leukocyte-reduced before storage would be as safe as a liberal transfusion strategy, as judged by the outcome of multiple-organ dysfunction.\n In this noninferiority trial, we enrolled 637 stable, critically ill children who had hemoglobin concentrations below 9.5 g per deciliter within 7 days after admission to an intensive care unit. We randomly assigned 320 patients to a hemoglobin threshold of 7 g per deciliter for red-cell transfusion (restrictive-strategy group) and 317 patients to a threshold of 9.5 g per deciliter (liberal-strategy group).\n Hemoglobin concentrations were maintained at a mean (+/-SD) level that was 2.1+/-0.2 g per deciliter lower in the restrictive-strategy group than in the liberal-strategy group (lowest average levels, 8.7+/-0.4 and 10.8+/-0.5 g per deciliter, respectively; P<0.001). Patients in the restrictive-strategy group received 44% fewer transfusions; 174 patients (54%) in that group did not receive any transfusions, as compared with 7 patients (2%) in the liberal-strategy group (P<0.001). New or progressive multiple-organ dysfunction syndrome (the primary outcome) developed in 38 patients in the restrictive-strategy group, as compared with 39 in the liberal-strategy group (12% in both groups) (absolute risk reduction with the restrictive strategy, 0.4%; 95% confidence interval, -4.6 to 5.4). There were 14 deaths in each group within 28 days after randomization. No significant differences were found in other outcomes, including adverse events.\n In stable, critically ill children a hemoglobin threshold of 7 g per deciliter for red-cell transfusion can decrease transfusion requirements without increasing adverse outcomes. (Controlled-trials.com number, ISRCTN37246456 [controlled-trials.com].).\n Copyright 2007 Massachusetts Medical Society.", "Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding optimal blood transfusion practice in patients undergoing cardiac surgery is lacking.\n To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery.\n The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n = 502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat.\n Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit ≥30%) or to a restrictive strategy (hematocrit ≥24%).\n Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at -8% (ie, 8% minimal clinically important increase in occurrence of the composite end point).\n Hemoglobin concentrations were maintained at a mean of 10.5 g/dL (95% confidence interval [CI], 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.0-9.2) in the restrictive-strategy group (P < .001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P < .001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% [95% CI, -6% to 4%]; P = .85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 [95% CI, 1.1-1.4]; P = .002).\n Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity.\n clinicaltrials.gov Identifier: NCT01021631.", "Perioperative anemia leads to increased morbidity and mortality and potentially inhibits rehabilitation after hip fracture surgery. As such, the optimum transfusion threshold after hip fracture surgery is unknown.\n A total of 120 elderly, cognitively intact hip fracture patients admitted from their own home were randomly assigned to receive transfusion at a hemoglobin threshold of 10.0 g per dL (liberal) versus 8.0 g per dL (restrictive) in the entire perioperative period. Patients were treated according to a well-defined multimodal rehabilitation program. Primary outcome was postoperative functional mobility measured with the cumulated ambulation score (CAS).\n Patients in the liberal group received transfusions more frequently than those in the restrictive group (44 patients vs. 22 patients; p < 0.01) and received more transfusions during hospitalization (median, 2 units [interquartile range, 1-2] vs. 1 [1-2]; p < 0.0001). There were no significant differences in postoperative rehabilitation scores (CAS: median, 9 [9-15] vs. 9 [9-13.5]; p = 0.46) or in length of stay (median, 18 days vs. 16 days, respectively; p = 0.46). There were fewer patients in the liberal transfusion group with cardiovascular complications (2% vs. 10%; p = 0.05) and a lower mortality (0% vs. 8%; p = 0.02).\n Although a liberal transfusion trigger did not result in increased ambulation scores, restrictive transfusion thresholds should be treated with caution in elderly high-risk hip fracture patients, until their safety has been proved in larger randomized studies.", "Efforts to avoid complications associated with transfusion of allogeneic blood have increased the use of preoperatively donated autologous blood (PAB). A major controversy has arisen: Should the same criteria be used for transfusion of autologous as allogeneic red cells? This study prospectively and randomly compared giving PAB immediately after total knee arthroplasty (TKA), beginning in the recovery room or delaying a transfusion until the patient's hemoglobin had fallen to less than a 9.0 g/dL transfusion trigger point. The results show that patients who received immediate transfusion had fewer nonsurgical complications (P < .002). Because TKAs are associated with an average blood loss of 1,400 mL, we recommend that PAB be used in the immediate postoperative period, especially in the elderly, in whom the risk for cardiac or nonsurgical complications is inherently increased.", "In elective orthopaedic hip- and knee replacement surgery patients, we studied the effect of implementation of a uniform transfusion policy on RBC usage.\n A randomized, controlled study. A new uniform, restrictive transfusion policy was compared with standard care, which varied among the three participating hospitals. Only prestorage leucocyte-depleted RBC(s) were used. Primary end-point was RBC usage, related to length of hospital stay. Secondary end-points were Hb levels, mobilization delay and postoperative complications.\n Six hundred and three patients were evaluated. Adherence to the protocol was over 95%. Overall mean RBC usage was 0.78 U/patient in the new policy group and 0.86 U/patient in the standard care policy group (mean difference 0.08;95% CI [-0.3; 0.2]; P = 0.53). In two hospitals, the new transfusion policy resulted in a RBC reduction of 30% (0.58U RBC/patient) (P = 0.17) and 41% (0.29 U RBC/patient) (P = 0.05) respectively. In the third hospital, however, RBC usage increased by 39% (0.31 U RBC/patient) (P = 0.02) with the new policy, due to a more restrictive standard care policy in that hospital. Length of hospital stay was not influenced by either policy.\n Implementation of a uniform transfusion protocol for elective lower joint arthroplasty patients is feasible, but does not always lead to a RBC reduction. Length of hospital stay was not affected.", "nan", "There is controversy regarding the application of transfusion triggers in cardiac surgery. The goal of this study was to determine if lowering the hemoglobin threshold for red cell (RBC) transfusion to 8 g per dL after coronary artery bypass graft surgery would reduce blood use without adversely affecting patient outcome.\n Consecutive patients (n = 428) undergoing elective primary coronary artery bypass graft surgery were randomly assigned to two groups: study patients (n = 212) received RBC transfusions in the postoperative period if the Hb level was < 8 g per dL or if predetermined clinical conditions required RBC support, and control patients (n = 216) were treated according to individual physician's orders (hemoglobin levels < 9 g/dL as the institutional guideline). Multiple demographic, procedure-related, transfusion, laboratory, and outcome data were analyzed. Questionnaires were administered for patient self-assessment of fatigue and anemia.\n Preoperative and operative clinical characteristics, as well as the intraoperative transfusion rate, were similar for both groups. There was a significant difference between the postoperative RBC transfusion rates in study (0.9 +/- 1.5 RBC units) and control (1.4 +/- 1.8 RBC units) groups (p = 0.005). There was no difference in clinical outcome, including morbidity and mortality rates, in the two groups; group scores for self-assessment of fatigue and anemia were also similar.\n A lower Hb threshold of 8 g per dL does not adversely affect patient outcome. Moreover, RBC resources can be saved without increased risk to the patient.", "To evaluate the effects of a restrictive and a liberal red blood cell (RBC) transfusion strategy on mortality and morbidity in critically ill patients.\n Multicenter, prospective, randomized clinical trial.\n Sixty-nine normovolemic critically ill patients admitted to one of five tertiary level intensive care units with hemoglobin values less than 90 g/L within 72 hours of admission.\n Patients were randomly allocated to one of two RBC transfusion strategies. Hemoglobin values were maintained between 100 and 120 g/L in the liberal transfusion group and between 70 and 90 g/L in the restrictive group.\n Primary diagnosis and mean +/- SD age (58.6 +/- 15 vs 59.0 +/- 21 years and Acute Physiology and Chronic Health Evaluation II score (20 +/- 6.2 vs 21 +/- 7.2) were similar in the restrictive and liberal groups, respectively. Daily hemoglobin values averaged 90 g/L in the restrictive group vs 109 g/L in the liberal group (P < .001). The restrictive group received 2.5 U per patient compared with 4.8 U per patient in the liberal group. This represents a 48% relative decrease (P < .001) in RBC units transfused per patient. The 30-day mortality rate was 24% in the restrictive group compared with 25% in the liberal group; the 95% confidence interval around the absolute difference was -19% to 21%. Similar observations were noted for intensive care unit mortality (P = .76) and 120-day mortality (P > .99). In addition, survival analysis comparing time until death in both groups did not reveal any significant difference (P = .93) between groups. Organ dysfunction scores were also similar (P = .44).\n In this small randomized trial, neither mortality nor the development of organ dysfunction was affected by the transfusion strategy, which suggests that a more restrictive approach to the transfusion of RBCs may be safe in critically ill patients. However, the study lacked power to detect small but clinically significant differences. Therefore, further investigations of RBC transfusion strategies are warranted.", "Anemia may be an important factor contributing to an increased risk of bleeding, particularly in patients with thrombocytopenia.\n A multicenter, single-blinded pilot randomized controlled trial (RCT) was performed to evaluate the feasibility of conducting a larger RCT to determine the effect of the hemoglobin (Hb) concentration on bleeding risk. Patients with acute leukemia receiving induction chemotherapy or those undergoing stem cell transplantation were assigned to one of two treatment groups: standard transfusion strategy (transfusion of 2 units of red blood cells [RBCs] when their Hb level was less than 80 g/L) or an augmented transfusion strategy (transfusion of 2 units of RBCs when their Hb level was less than 120 g/L).\n Sixty patients were enrolled: 29 in the control group and 31 in the experimental group. The proportions of patients experiencing clinically significant bleeding and the time to first bleed were not significantly different between the control and experimental groups. The experimental group received more RBC transfusions (transfusions/patient-day) than the control group (0.233 vs. 0.151; relative risk, 1.56; 95% confidence interval, 1.16-2.10; p = 0.003). The proportion of patient-days with platelet (PLT) transfusions was not different between the experimental and control groups. The mean number of donor exposures (PLT and RBC transfusions) was not different between experimental and control groups. Bleeding symptoms were systematically documented.\n This pilot study thus indicated that it would be feasible to enroll the required number of patients to enable the performance of a large RCT to investigate the effect of Hb on bleeding risk in thrombocytopenic patients.", "Red cell transfusion is commonly used in orthopaedic surgery. Evidence suggests that a restrictive transfusion strategy may be safe for most patients. However, concern has been raised over the risks of anaemia in those with ischaemic cardiac disease. Perioperative silent myocardial ischaemia (SMI) has a relatively high incidence in the elderly population undergoing elective surgery. This study used Holter monitoring to compare the effect of a restrictive and a liberal red cell transfusion strategy on the incidence of SMI in patients without signs or symptoms of ischaemic heart disease who were undergoing lower limb arthroplasty.\n We performed a multicentre, controlled trial in which 260 patients undergoing elective hip and knee replacement surgery were enrolled and randomized to transfusion triggers that were either restrictive (8 g/dl) or liberal (10 g/dl). Participants were monitored with continuous ambulatory electrocardiogram (ECG) (Holter monitoring), preoperatively for 12 h and postoperatively for 72 h. The tapes were analysed for new ischaemia by technicians blinded to treatment. The total ischaemia time in minutes was divided by the recording time in hours and an ischaemic load in min/h was calculated. Haemoglobin levels were measured preoperatively, postoperatively in the recovery room, and on days one, three and five after surgery.\n The mean postoperative haemoglobin concentration was 9.87 g/dl in the restrictive group and 11.09 g/dl in the liberal group. In the restrictive group, 34% were transfused a total of 89 red cell units, and in the liberal group 43% were given a total of 119 red cell units. A postoperative episode of silent ischaemia was experienced by 21/109 (19%) patients in the restrictive group and by 26/109 (24%) patients in the liberal group [mean difference -4.6%; 95% confidence interval (CI): -15.5% to 6%, P = 0.41). There was no significant difference (P = 0.53) between the overall ischaemic load in the restrictive group (median 0 min/h, range 0-4.18) and the liberal group (median 0 min/h, range 0-19.48). In those patients who did experience postoperative SMI, the mean ischaemic load was 0.48 min/h in the restrictive group and 1.51 min/h in the liberal group (ratio 0.32, 95% CI: 0.14-0.76, P = 0.011). The median postoperative length of hospital stay in the restrictive group was 7.3 days [range 5-11; interquartile range (IQR) 6-8] compared with 7.5 days (range 5-13; IQR 7-8) in the liberal group. The numbers were not large enough to conclude equivalence.\n In patients without preoperative evidence of myocardial ischaemia undergoing elective hip and knee replacement surgery, a restrictive transfusion strategy seems unlikely to be associated with an increased incidence of SMI. A proportion of these patients experience moderate SMI, regardless of the transfusion trigger. Use of a restrictive transfusion strategy did not increase length of hospital stay, and use of this strategy would lead to a significant reduction in red cell transfusion in orthopaedic surgery. Our data did not indicate any potential for harm in employing such a strategy in patients with no prior evidence of cardiac ischaemia who were undergoing elective orthopaedic surgery.", "Patients undergoing major arterial reconstruction have traditionally been transfused with red blood cells to keep hemoglobin concentrations above 10 g/dL in order to prevent anemia-induced myocardial ischemia. There are no data to support this practice. The hypothesis that vascular patients will tolerate a hemoglobin concentration of 9 g/dL was examined.\n Ninety-nine patients undergoing elective aortic and infrainguinal arterial reconstructions were prospectively randomized preoperatively to receive transfusions to maintain a hemoglobin level of either 10 g/dL or 9 g/dL.\n Despite significantly different postoperative hemoglobin levels of 11.0 +/- 1.2 versus 9.8 +/- 1.3 g/dL (P <0.0001), there were no differences in mortality or cardiac morbidity rates or length of hospital stay. There were no differences in hemodynamic parameters. Oxygen delivery was lower in the group with lower hemoglobin levels, but there was no difference in O2 consumption between the groups.\n A lower hemoglobin concentration was tolerated without adverse clinical outcome. Patients did not compensate for anemia by increased myocardial work, but by increasing O2 extraction in the peripheral tissues.", "We performed a prospective, randomized trial of two different strategies for postoperative packed red blood cell replacement in 39 autologous blood donors undergoing elective myocardial revascularization. The \"liberal\" group received blood to achieve a hematocrit value of 32%, and the \"conservative\" group received transfusions for a hematocrit value less than 25%. Although the groups had significantly different mean hematocrit values from the fourth postoperative hour (28.7% versus 31.2%) through the fifth postoperative day (28.4% versus 31.3%), there were no significant differences in fluid requirement, hemodynamic parameters, or hospital complications. Significantly fewer units of packed cells were required in the conservatively transfused group (20 units/20 patients) compared with the liberally transfused group (37 units/18 patients) (p = 0.012). Exercise tests were performed on the fifth and sixth postoperative days, with a transfusion being given to the conservative group between tests. Although a significant improvement in exercise endurance occurred in the conservative group receiving a transfusion (p = 0.008), no significant difference in duration or degree of exercise was demonstrated between the two groups on either day. In comparing these two groups of profoundly anemic patients, we identified no adverse consequence associated with the greater degree of hemodilution and could identify no correlation between hematocrit value and exercise capacity. We conclude that although the limits of hemodilution are still poorly defined, postoperative blood transfusion in revascularized patients should be guided by clinical indications and not by specific hematocrit values.", "There is evidence to suggest that anemia after severe traumatic brain injury (sTBI) is detrimental. However, there is a paucity of evidence supporting the use of transfusion of packed red blood cells in patients with sTBI. To understand the acute effect of packed red blood cell transfusion on cerebral oxygenation and metabolism in patients with sTBI.\n Prospective clinical study.\n Addenbrooke's Neurosciences Critical Care Unit, a 21-bed tertiary academic unit.\n Thirty patients with sTBI.\n Patients were randomized by computer random number generator to one of three transfusion thresholds: 8, 9, or 10 g/dL. When the patients' hemoglobin concentration fell below their assigned threshold, two units of packed red blood cells were transfused over 2 hours. A 1-hour period of stabilization was observed before final data collection.\n The primary outcome was change in brain tissue oxygen (Pbto2). Secondary outcomes included dependence of baseline hemoglobin concentration and baseline Pbto2 on the relationship of transfusion and Pbto2, and the effect of transfusion on lactate pyruvate ratio (LPR) and brain pH as markers of cerebral metabolic state. Fifty-seven percent of patients experienced an increase in Pbto2 during the course of the study, whereas in 43% of patients, Pbto2 either did not change or decreased. Multivariable generalized estimating equation analysis revealed change in hemoglobin concentration to significantly and positively associated with change in Pbto2 [0.10 kPa/(g/dL) 95% confidence interval 0.03-0.17, p = 0.003]. Improvement in Pbto2 was not associated with baseline hemoglobin concentration or low Pbto2 (<1 kPa). Fifty-six percent of patients experienced an increase in LPR. No significant relationship between change in LPR or transfusion on pHbt and change in hemoglobin could be demonstrated.\n Transfusion of packed red blood cells acutely results in improved brain tissue oxygen without appreciable effect on cerebral metabolism.\n ISRCTN89085577." ]

[ "6512000", "1106217", "7811160", "354733", "4942959", "7870975", "12826983", "7484202", "22058537", "6813888", "4936131", "2899186", "6722235", "1683094", "369472", "8793154", "10401914" ]

[ "Platelet monoamine oxidase response to lithium treatment in psychiatric patients.", "A placebo-controlled study of lithium combined with neuroleptics in chronic schizophrenic patients.", "Pharmacotherapy of impaired affect in recovering schizophrenic patients.", "Trials of lithium, chlorpromazine and amitriptyline in schizoaffective patients.", "A controlled study of lithium vs. chlorpromazine in acute schizophrenics.", "Addition of lithium to haloperidol in non-affective, antipsychotic non-responsive schizophrenia: a double blind, placebo controlled, parallel design clinical trial.", "Tolerability and efficacy of clozapine combined with lithium in schizophrenia and schizoaffective disorder.", "Lithium addition to neuroleptic treatment in chronic schizophrenia: a randomized, double-blind, placebo-controlled, cross-over study.", "Efficacy of lithium in schizophrenia.", "Lithium and chlorpromazine in psychotic inpatients.", "Comparative effects of lithium and chlorpromazine in the treatment of acute manic states.", "The Northwick Park \"functional\" psychosis study: diagnosis and treatment response.", "Lithium versus fluphenazine for prophylaxis in mainly schizophrenic schizo-affectives.", "Lithium carbonate in chronic schizophrenia--a brief trial of lithium carbonate added to neuroleptics for treatment of resistant schizophrenic patients.", "Combination of lithium carbonate and haloperidol in schizo-affective disorder: a controlled study.", "Adjunctive carbamazepine or lithium carbonate in therapy-resistant chronic schizophrenia.", "Lithium augmentation fails to reduce symptoms in poorly responsive schizophrenic outpatients." ]

[ "Platelet monoamine oxidase (MAO) activity was studied in bipolar and schizophrenic patients treated with lithium and was found to be increased as a nonspecific drug effect. Greater MAO increase in manic patients was correlated with lesser clinical improvement. There was no correlation of MAO activity with short-term outcome in schizophrenic patients. Change in MAO was not correlated with lithium dosage or plasma levels. Patients with baseline MAO values below the median had the largest activity increases. Platelet MAO might thus be characterized as a state variable, increased by lithium as a nonspecific pharmacologic effect, with the increase associated with poor clinical outcome in manic patients.", "Lithium combined with major tranquilizers was administered to 22 hospitalized chronic schizophrenic patients with minimal neurotoxicity or other side effects. Moreover, 10 of the patients benefited significantly with lithium as compared to placebo in terms of blind psychiatric and nursing ratings and nonblind clinical judgments of outcome. These results contrast with previous negative reports in the literature and the generally poor prognosis in chronic schizophrenic patients. The authors suggest that a trial combining lithium with psychotropic drugs is warranted in schizophrenic patients who do not respond satisfactorily to conventional treatment", "Prominent and persistent anxiety, depression, and/or negative features characterize a substantial minority of recovered or residually psychotic schizophrenic outpatients and contribute to poor outcome. Because extrapyramidal side effects of typical neuroleptic medications often resemble such features, we first systematically studied the contribution of extrapyramidal side effects to these problems and their treatment. For patients who remained distressed, controlled trials of supplemental thymoleptics were undertaken.\n In trial 1, 92 distressed (depressed and/or anxious) patients and 36 patients in a defect state (patients with negative symptoms) participated in a double-blind, intramuscular challenge that compared centrally acting benztropine mesylate with peripherally acting glycopyrrolate. In trial 2, 57 distressed patients and 22 patients in a defect state were randomly assigned to a double-blind, neuroleptic medication dose-reduction group. In trial 3, 57 chronically distressed patients who were maintained on a low dose of fluphenazine decanoate were randomly assigned to a supplemental desipramine hydrochloride, lithium carbonate, or placebo group under double-blind conditions for 12 weeks.\n For patients who were already maintained on antiparkinsonian medication, impaired affect was not resolved by additional benztropine. Only distressed patients with a family history of severe mental disorder (often affective) showed improvement with neuroleptic medication dose reduction. Patients in the defect-state group reported less dysphoria on a reduced neuroleptic medication dose, but negative symptoms persisted. Desipramine improved diverse aspects of mood and residual psychoticism, possibly as a prophylaxis against minor affective exacerbations. Depression improved in women only. Lithium positively affected multiple indexes of anxiety and anxious depression.\n Most often, persistent affective impairments are neither resistant extrapyramidal side effects nor characterological traits. Thymoleptics improve the nonphasic, chronic types of anxiety and depression in contrast to the acute, episodic forms, for which little support can be found in the literature.", "Two drug trials in schizoaffective patients are reported. Nineteen \"schizomanic\" patients were treated for one month, on a double blind basis, with chlorpromazine or lithium and 41 \"schizodepressive\" patients with amitriptyline, chlorpromazine or both. In the schizodepressive patients there was a trend to a better response to chlorpromazine, but drug response generally was poor, only 20 per cent of patients recovering within the month. In the schizomanic patients lithium seemed as effective as chlorpromazine, which supports the view that these patients were suffering from a variant of mania.", "nan", "This double-blind placebo controlled, parallel design clinical trial compared the therapeutic effects of the addition of lithium or placebo to haloperidol in 21 seriously ill state hospital patients with DSM-III-R schizophrenia, who did not have concurrent affective disorders and who had not responded to previous trials of conventional antipsychotic medication. During a baseline period of 6 weeks, patients were switched to a stable dose of haloperidol (mean +/- SD dose = 13.6 +/- 8.1 mg/day). Patients were then randomized to receive either lithium or placebo in addition to haloperidol for 8 weeks (mean +/- SD lithium level = 0.98 +/- 0.13 mEq/l). Symptoms and side effects were assessed weekly. Improvement in symptoms correlated with the non-blind adjustment of antipsychotic dose, but not with lithium or placebo treatment. Side effects ratings did not differ between the two groups, but one patient developed a reversible delirium associated with combined lithium/haloperidol treatment. For these long-term, severely ill patients, combined treatment afforded no advantage over treatment with haloperidol alone.", "The safety and tolerability of clozapine combined with lithium were investigated because of potential additive risks as well as frequent usage in clinical practice. Ten hospitalized schizophrenic and 10 schizoaffective patients receiving clozapine maintenance therapy with partial therapeutic response were studied in a randomized controlled trial. CGI and PANSS outcome ratings were employed and a cognitive battery was administered at baseline and after 4 weeks of lithium and placebo administration. Barnes and UKU side effect ratings and laboratory safety data were obtained. Combined lithium-clozapine treatment was well tolerated except for reversible neurotoxic reactions in two schizophrenic patients. Safety measures showed no significant variations, even during lithium toxicity. Total WBC and absolute granulocyte counts increased with lithium and declined with placebo. Schizoaffective patients improved with lithium on CGI and PANSS total and negative symptom scales and the cognitive measures, whereas schizophrenic patients did not. Lithium added to clozapine in treatment regimens for hospitalized, treatment-resistant, schizoaffective patients appears to afford potential benefit without harmful effects; for schizophrenic patients, however, it did not afford improvement but posed a risk of lithium toxicity.", "We studied the effect of lithium addition to neuroleptic treatment in chronic schizophrenia, for which contradictory results have been produced in previous studies. Twenty-one chronic schizophrenic inpatients received lithium in a study with randomized, double-blind, placebo-controlled, cross-over design consisting of 8 weeks each of treatment with lithium capsules and identical placebo capsules. The total Brief Psychiatric Rating Scale (BPRS) scores at week 8 of the lithium treatment were improved significantly compared with those at week 8 of the placebo treatment. Of the BPRS subscales, however, only anxiety-depression improved, whereas none of the subscales for anergia, thought disturbance, activation and hostile-suspiciousness improved. There was no significant difference between the total Scale for the Assessment of Negative Symptoms (SANS) scores at any time during lithium and placebo treatment. These results suggest that the addition of lithium to neuroleptic treatment improves anxiety-depression in chronic schizophrenia.", "60 Schizophrenic patients were given LiCo(3)/Chlorpromazine for 4 weeks, in a double blind cross over study with two placebo crossovers of 1 week before and two weeks after active treatment. Several core schizophrenic features showed significant reduction in severity with lithium. However, CPZ treatment was superior in terms of improvement, as compared to the other group on MBPRS and CGIS. Target symptoms may be one situation, where lithium could be tried and these results are discussed.", "A sample of recently hospitalized psychotic patients was assigned to treatment with lithium or chlorpromazine in a double-blind drug trial. Several diagnostic systems were used to characterize the patients. No relationship was found, regardless of criterion system used, between diagnosis and differences in drug effectiveness; specifically, the presence of \"schizophrenic\" symptoms did not predict a poor response to lithium. Among patients with physical overactivity, those treated with lithium terminated earlier and had poorer outcome than those treated with chlorpromazine. In patients who were not overactive, the two drugs were equally effective, and chronically psychotic patients had poorer outcomes regardless of drug. Lithium may be an effective treatment for acutely psychotic patients who are not overactive. The use of a lithium trial as a diagnostic tool may be unwarranted.", "nan", "Functional psychosis is conventionally subdivided into schizophrenia and manic depressive psychosis. Response to treatment is assumed to be a validating criterion for these diagnoses. The efficacy of pimozide (a dopamine antagonist neuroleptic), lithium, and a combination of the two was compared with that of placebo in a 4 week trial in 120 functionally psychotic patients each of whom was assessed for psychotic symptoms, manic symptoms, and depressive symptoms. The sample was subdivided into patients with predominantly elevated mood, predominantly depressed mood, and no consistent mood change. Pimozide reduced psychotic symptoms in all groups of patients. The only significant effect of lithium was to reduce elevated mood. Thus dopamine blockade seems relevant to the resolution of psychotic symptoms in all types of \"functional\" psychosis but the mode of action of lithium in psychotic patients concerns only mood. Application of standardised classifications of functional psychosis to these data did not change this conclusion.", "nan", "The value of lithium carbonate as an adjunctive treatment of resistant schizophrenia was tested in a 4-week clinical trial using a single-blind, randomized, consent design. Treatment and control groups were drawn from a population of detained patients in an English special (maximum security) hospital. The 2 groups were comparable in terms of age, sex, severity of symptoms, length of hospitalization and concurrent neuroleptic dosage. The addition of lithium carbonate to the treatment regimen did not result in symptomatic improvement in patients completing the treatment protocol. The ethical and practical difficulties raised by the trial are discussed.", "Lithium carbonate alone has been shown to be inferior to neuroleptics alone in the treatment of excited schizo-affective illness. However, in clinical practice, lithium carbonate and neuroleptics are often combined in this disorder. We report a double-blind five-week controlled trial of lithium carbonate plus haloperidol vs placebo plus haloperidol in the treatment of excited schizo-affective patients. Eighteen patients were studied in each treatment group. Modest but statistically significant differences in favor of lithium carbonate plus haloperidol were found by week 5, using the Brief Psychiatric Rating Scale. Lithium carbonate plus haloperidol was favored both for affective schizo-affectives and for schizophrenic schizo-affectives. Lithium carbonate benefit did not seem to be restricted to affective symptoms only. In the clinical treatment of acute schizo-affective illness, the modest benefits of added lithium carbonate must be weighed against the risks of the drug's toxicity.", "nan", "Nearly one third of patients suffering from schizophrenia do not fully respond to antipsychotic medication. Safe, effective, and cost-efficient methods to reduce symptoms are clearly needed; therefore, lithium as an adjunct to fluphenazine decanoate was tested in a placebo-controlled trial in outpatients who were part of the Treatment Strategies of Schizophrenia (TSS) study.\n Forty-one patients with DSM-III schizophrenia or schizoaffective disorder were assigned to either adjunctive lithium or placebo after at least 6 months of fluphenazine decanoate treatment to stabilize symptoms had failed. The trial was designed for 8 weeks of treatment, and patients assigned to placebo could afterward be administered lithium in an 8-week, open-label study.\n Assessment of the intent-to-treat analysis revealed no significant differences in demographic variables between the lithium and placebo groups. Although both groups showed significant (p = .00135) improvement as measured by total scores on the Brief Psychiatric Rating Scale (BPRS), there were no significant differences in response between the lithium and placebo groups. Patients originally treated with placebo added to neuroleptic did not have significantly greater improvement when receiving open-label adjunctive lithium.\n Although success with lithium augmentation therapy for persistent psychosis has been reported in the past, this study of well-characterized patients showed no benefit for this common strategy, thus indicating that care be used in utilizing lithium augmentation." ]

[ "3426824", "16599263", "6525812", "8874988", "7585833", "2456682", "7659614" ]

[ "[Initial experience with using phosphocreatine in patients in the early (up to 6 hours) period of myocardial infarction].", "Creatine supplementation improves muscle strength in patients with congestive heart failure.", "[Myocardial T1-201 scintigraphy in the study of the development of acute myocardial infarction. Evaluation of the effects of a drug with metabolic action: creatine phosphate].", "Hemodynamic effects of creatine phosphate in patients with congestive heart failure: a double-blind comparison trial versus placebo.", "Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance.", "Reduction of ventricular arrhythmias by phosphocreatine (Neoton) in patients with acute myocardial infarction.", "[Use of phosphocreatinine in treatment of acute heart failure]." ]

[ "A randomized study of 60 patients with myocardial infarction (MI) admitted to hospital in the first 6 hours of the disease was performed in order to study the effect of phosphocreatine (PC) on the course of MI. 30 patients were treated with PC; control group consisted also of 30 patients. PC infusion in the early period of MI resulted in the decreased frequency of ventricular arrhythmias (including paroxysms of ventricular tachycardia) and lowered likelihood of cardiac failure development. No reliable influence of PC on the central hemodynamics, heart rate, heart conduction and myocardial necrosis size was determined.", "Both, cardiac and skeletal muscle creatine levels are depressed in patients with congestive heart failure (CHF). Oral supplementation of creatine (Cr) could increase physical performance in healthy volunteers. We therefore hypothesized that oral creatine supplementation improves skeletal muscle strength, quality of live and symptom-limited performance in patients with CHF.\n In a double-blind, placebo-controlled and crossover-designed study, 20 patients suffering from congestive heart failure more than 6 months and a peak oxygen uptake (peak VO2) below 20 ml/min/kg received 4 x 5 g Cr daily vs. placebo for 6 weeks and were crossed over for the following 6 weeks. Peak VO2, VO2 at the anaerobic threshold (VO2AT), ejection fraction (EF), distance in 6-minute-walk-test (6 min W), and muscle strength (Modified Sphygmomanometer (MS)) were determined at baseline, after 6, and after 12 weeks. Dyspnoea after 6-minute-walk-test was measured using the Borg Scale. Quality of live was assessed with the Minnesota Living with Heart Failure Questionnaire (MLHFQ).\n 13 of 20 Patients finished the study. After 6 weeks of creatine supplementation there was a significant increase in body weight and muscle strength compared to baseline and placebo (p < 0.05). However, there was no significant change in peak VO2, VO2AT, walking distance, quality of life assessment and EF.\n Short-term creatine supplementation inaddition to standard medication in patients with CHF leads to an increase in body weight and an improvement of muscle strength. This effect is restricted to the time of supplementation.", "nan", "The use of metabolic drugs effective in addition to conventional therapy represents a significant challenge in patients with left ventricular dysfunction.\n The aim of this double-blind, placebo-controlled study was to investigate the hemodynamic effects of acute intravenous (i.v.) administration of creatine phosphate (CP) and of short-term treatment in patients with congestive heart failure (CHF) from ischemic heart disease (IHD) or dilated cardiomyopathy in addition to conventional therapy.\n We compared the hemodynamic effects of exogenous creatine phosphate (CP) and placebo in a double-blind, crossover design study in 13 hospitalized patients (12 men, 1 woman, mean age 52 +/- 8 years) with CHF. All patients were in New York Heart Association (NYHA) class II-III and received conventional pharmacologic therapy for CHF; this was not changed during the study period. The study design consisted of two treatment periods (CP or placebo and placebo or CP, respectively) of 4 days each, separated by a 2-day washout interval. The intravenous infusion consisted of 6 g CP or placebo (acute treatment) or 6 g CP or placebo daily for 4 days (short-term treatment) diluted in 50 ml of NaCl 0.9%; infusion duration was about 10 min. Mono-bidimensional echocardiographic examination (Hewlett Packard Sonos 1000, with a 2.5 MHz transducer) was performed at baseline, after acute infusion, and 12 h after the end of short-term treatment. Data were analyzed by ANOVA and Student's t-test for paired data; the results obtained after acute and short-term therapy were compared with the baseline values.\n After placebo therapy, no significant change was observed. The results after treatment with CP showed a significant reduction of end-systolic diameter [baseline: 4.5 +/- 0.6; acute: 4.2 +/- 0.5, (p < 0.001); short-term 4.3 +/- 0.6 cm, (p < 0.05)] and systemic vascular resistance (baseline: 1064.9 +/- 483.7; acute: 947.5 +/- 390.2 (p < 0.05); short-term: 950.7 +/- 394.3 dyne-s-cm-5 (p < 0.05); moreover, a significant increase of percent ejection fraction [baseline: 48 +/- 12%; acute 53 +/- 12% (p < 0.01); short-term 52 +/- 11% (p < 0.01)], and of percent fractional shortening [baseline: 25 +/- 7; acute 28 +/- 8 (p < 0.05); short-term 28 +/- 7% (p < 0.05)] was observed.\n CP was shown to improve cardiac function, even in the presence of a conventional CHF pharmacologic therapy.", "Cardiac creatine levels are depressed in chronic heart failure. Oral supplementation of creatine to healthy volunteers has been shown to increase physical performance.\n To evaluate the effects of creatine supplementation on ejection fraction, symptom-limited physical endurance and skeletal muscle strength in patients with chronic heart failure.\n With a double-blind, placebo-controlled design 17 patients (age 43-70 years, ejection fraction < 40) were supplemented with creatine 20 g daily for 10 days. Before and on the last day of supplementation ejection fraction was determined by radionuclide angiography as was symptom-limited 1-legged knee extensor and 2-legged exercise performance on the cycle ergometer. Muscle strength as unilateral concentric knee extensor performance (peak torque, Nm at 180 degrees/s) was also evaluated. Skeletal muscle biopsies were taken for the determination of energy-rich phosphagens.\n Ejection fraction at rest and at work did not change. Performance before creatine supplementation did not differ between placebo and creatine groups. While no change was seen in the placebo group compared to baseline, creatine supplementation increased skeletal muscle total creatine and creatine phosphate by 17 +/- 4% (P < 0.05) and 12 +/- 4% (P < 0.05), respectively. Increments were seen only in patients with < 140 mmol total creatine/kg d.w. (P < 0.05). One-legged performance (21%, P < 0.05), 2-legged performance (10%, P < 0.05), and peak torque, Nm (5%, P < 0.05) increased. Both peak torque and 1-legged performance increased linearly with increased skeletal muscle phosphocreatine (P < 0.05). The increments in 1-legged, 2-legged and peak torque were significant compared to the placebo group, (P < 0.05).\n One week of creatine supplementation to patients with chronic heart failure did not increase ejection fraction but increased skeletal muscle energy-rich phosphagens and performance as regards both strength and endurance. This new therapeutic approach merits further attention.", "On the basis of the positive results of recent experimental research, a clinical trial of phosphocreatine (Neoton) was carried out in 60 randomized patients with acute myocardial infarction (30 patients in the Neoton group and 30 patients in the control group). Neoton was given intravenously not later than 6 hours after the onset of symptoms, in a dose of 2 gm as a bolus injection, followed by a 2-hour infusion at the rate of 4 gm/hr. Holter monitoring for 24 hours showed a significant decrease in the frequency of ventricular premature beats: in the Neoton-treated group the total number of ventricular premature beats for 24 hours was 690 +/- 179 vs 2468 +/- 737 in the control group (p less than 0.02). During this period of time the number of ventricular tachycardia paroxysms was 6 +/- 2 in the treated group and 97 +/- 35 in the control group (p less than 0.01). No side effects or complications were found after administration of phosphocreatine. It is concluded that phosphocreatine may be a potentially important antiarrhythmic drug for treatment of patients with acute myocardial infarction.", "nan" ]

[ "6306192", "3246167", "3523457", "3895175", "16039333", "6323376", "8307046", "6322681", "6134039", "2467608", "3847486", "4073858", "3428132", "8685976", "3725653" ]

[ "Comparison of ceftriaxone with standard therapy for bacterial meningitis.", "Ceftriaxone alone compared to ampicillin and chloramphenicol in the treatment of bacterial meningitis.", "Ceftazidime vs. standard therapy for pediatric meningitis: therapeutic, pharmacologic and epidemiologic observations.", "Prospective comparative trial of ceftriaxone vs. conventional therapy for treatment of bacterial meningitis in children.", "Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study.", "Comparison of the efficacy and safety of ceftriaxone to ampicillin/chloramphenicol in the treatment of childhood meningitis.", "Ceftriaxone versus penicillin G in the short-term treatment of meningococcal meningitis in adults.", "Comparison of ceftriaxone and traditional therapy of bacterial meningitis.", "Ceftriaxone versus ampicillin and chloramphenicol for treatment of bacterial meningitis in children.", "Cefotaxime versus penicillin-chloramphenicol in purulent meningitis: a controlled single-blind clinical trial.", "A prospective randomized comparison of cefotaxime vs ampicillin and chloramphenicol for bacterial meningitis in children.", "Comparison of ceftriaxone and ampicillin plus chloramphenicol for the therapy of acute bacterial meningitis.", "Ceftriaxone compared with a combination of ampicillin and chloramphenicol in the treatment of bacterial meningitis in adults.", "Intravenous chloramphenicol plus penicillin versus intramuscular ceftriaxone for the treatment of pyogenic meningitis in Nepalese children.", "Cefotaxime vs. conventional therapy for the treatment of bacterial meningitis of infants and children." ]

[ "nan", "One hundred patients (71 males and 29 females) with bacterial meningitis were randomly assigned into two therapeutic regimens. Patients in group I were intravenously given ceftriaxone (CRO: Rocephin) to adults and intramuscularly to children once daily in a dose of 100 mg/kg/day. Patients in group II received ampicillin 160 mg/kg/day and chloramphenicol (AMCL) 100 mg/kg/day (i.v. to adults and i.m. to children) every 6 h. No significant difference was observed between the two therapeutic regimens with regard to mortality, time taken to become afebrile, fully alert and sequelae. Seven patients in the CRO group died compared to 10 in the AMCL group. The mean number of days taken to become afebrile were 3.4 and 3.5, and to become fully alert 3.9 and 3.5 for groups I and II, respectively. CRO administered in a single daily dose appears to be as effective as a combination of ampicillin and chloramphenicol given every 6 h in the treatment of acute bacterial meningitis. However, the once daily dose is more appropriate for use especially in areas where nursing care is limited.", "One hundred patients ages 1 month to 15 years received either ceftazidime (CZ) at a dose of 150 mg/kg/day divided every 8 hours or conventional treatment with chloramphenicol and ampicillin (CA). Seventy-eight had isolates recovered from the cerebrospinal fluid: 40 (51%) were Haemophilus influenzae (all ampicillin-susceptible); 16 (21%) were Streptococcus pneumoniae; 14 (18%) were Neisseria meningitidis; 3 (4%) were salmonellae; 1 (2%) was Pseudomonas; and 1 (2%) was Group B Streptococcus. Six patients with negative cerebrospinal fluid culture had positive latex agglutination (two H. influenzae, three N. meningitidis, one S. pneumoniae). Sixty-one patients had positive blood cultures. CZ inhibited 100% of H. influenzae at 0.78 micrograms/ml, S. pneumoniae at 0.39, N. meningitidis at 0.04 and salmonellae at 0.39 micrograms/ml. The mean peak serum concentration of CZ was 36.4 micrograms/ml with a mean cerebrospinal fluid level of 7.4 micrograms/ml. If one eliminates from the statistics those patients who died less than or equal to 24 hours after admission, five (10%) of 49 patients treated with CZ died, one (2%) improved and 43 (88%) were cured. Overall 29 patients died, 12 receiving CZ (20%) and 8 receiving CA (21%). There were no significant CZ-related toxicities. Gross neurologic sequelae were noted in 5% of 38 CZ patients and 4% of 28 CA patients. CZ compared favorably to CA for treatment of meningitis.", "Fifty children with bacterial meningitis were prospectively evaluated in a randomized comparative trial of twice daily ceftriaxone with conventional ampicillin and chloramphenicol therapy. The groups were comparable in age, sex, days of illness before admission, severity of illness at admission, etiology and admission cerebrospinal fluid (CSF) parameters and bacterial colony counts. The pathogens were Haemophilus influenzae type b (34 beta-lactamase-negative, 8 beta-lactamase-positive); Streptococcus pneumoniae (4); Neisseria meningitidis (3); and Streptococcus agalactiae (1). Initial CSF colony counts ranged from 2.5 X 10(2) to 1 X 10(10) colony-forming units/ml. In 44 children a lumbar puncture was repeated 10.5 to 18 hours after starting treatment; 16 of 24 (67%) ceftriaxone patients and 12 of 20 (60%) conventional therapy patients had sterile cultures. The reduction in the CSF bacterial colony counts (6.3 log10 colony-forming units/ml) was similar in both groups. Ceftriaxone CSF levels ranged from 1.0 to 8.0 micrograms/ml, representing a mean CSF penetration of 11.3% (range, 3.0 to 24.5%) of the simultaneous serum concentration. The median ceftriaxone bactericidal titer in CSF was 1:1024 compared with 1:4 achieved with conventional therapy. There were no significant differences in clinical responses or in frequency of complications, except for diarrhea which occurred in 59% of the ceftriaxone group and in 22% of the other (P less than 0.01). Despite one H. influenzae type b relapse occurring in the ceftriaxone group, ceftriaxone appears to be safe and as effective as conventional therapy for bacterial meningitis in children older than 2 months of age.", "In sub-Saharan Africa in the 1990s, more than 600,000 people had epidemic meningococcal meningitis, of whom 10% died. The current recommended treatment by WHO is short-course long-acting oily chloramphenicol. Continuation of the production of this drug is uncertain, so simple alternatives need to be found. We assessed whether the efficacy of single-dose treatment of ceftriaxone was non-inferior to that of oily chloramphenicol for epidemic meningococcal meningitis.\n In 2003, we undertook a randomised, open-label, non-inferiority trial in nine health-care facilities in Niger. Participants with suspected disease who were older than 2 months were randomly assigned to receive either chloramphenicol or ceftriaxone. Primary outcome was treatment failure (defined as death or clinical failure) at 72 h, measured with intention-to-treat and per-protocol analyses.\n Of 510 individuals with suspected disease, 247 received ceftriaxone, 256 received chloramphenicol, and seven were lost to follow-up. The treatment failure rate at 72 h for the intention-to-treat analysis was 9% (22 patients) for both drug groups (risk difference 0.3%, 90% CI -3.8 to 4.5). Case fatality rates and clinical failure rates were equivalent in both treatment groups (14 [6%] ceftriaxone vs 12 [5%] chloramphenicol). Results were also similar for both treatment groups in individuals with confirmed meningitis caused by Neisseria meningitidis. No adverse side-effects were reported.\n Single-dose ceftriaxone provides an alternative treatment for epidemic meningococcal meningitis--its efficacy, ease of use, and low cost favour its use. National and international health partners should consider ceftriaxone as an alternative first-line treatment to chloramphenicol for epidemic meningococcal meningitis.", "Ceftriaxone is a new cephalosporin with a broad spectrum of antibacterial activity and unique serum and CSF pharmacokinetics. The drug was compared in a randomized fashion with ampicillin and chloramphenicol in the treatment of 19 children with Haemophilus influenzae type b meningitis. Ceftriaxone was also administered non-randomly to six other patients including three children with Gram-negative meningitis. Among the children with H. influenzae meningitis, no deaths were noted and the outcomes of the study and the control groups were similar. Ninety per cent of the isolates of H. influenzae were inhibited by 0.0625, 1 and 1 mg/l of ceftriaxone, ampicillin and chloramphenicol respectively. One child with pneumococcal meningitis and two children with meningococcal meningitis recovered rapidly and without incident during ceftriaxone therapy. Three children with Gram-negative meningitis caused by multiply-drug resistant organisms were bacteriologically cured within five days of the onset of therapy. Persistent pleocytosis and neurological disabilities were noted in two at the conclusion of therapy. Ceftriaxone, as a single agent, was comparable in efficacy with traditional antimicrobial therapy usually employed in childhood meningitis.", "Short-term treatment with ceftriaxone 2 g once daily for two days (group 1) was compared to treatment with a standard regimen of penicillin G (group 2) for six days in adults with meningococcal meningitis. Thirty-six patients were allocated in a randomized fashion to a treatment group: 16 to group 1 and 20 to group 2. The clinical and microbiological results were comparable in the two treatment groups. In both groups cultures of cerebrospinal fluid were sterile after 24 hours. One patient in each group died. In group 1 one case of fulminant meningococcemia and one case of brain abscess required further antibiotic treatment. It is concluded that short-term treatment with ceftriaxone is feasible but patients with severe forms of meningitis would not be eligible for treatment with this regimen, and careful follow-up of the patients receiving ceftriaxone is necessary.", "Forty-five children (aged 1 day to 15 years) with bacterial meningitis were randomized to receive either traditional therapy (ampicillin and chloramphenicol or gentamicin, pending sensitivity) or ceftriaxone (100 mg/kg per day in two doses for a minimum of 10 days). The etiological agents involved were similar for the two groups and included Haemophilus influenzae type b, Neisseria meningitidis, Streptococcus pneumoniae, and group B streptococcus. Repeat spinal taps were carried out 24 to 48 h after admission. Organisms were seen on the Gram stain of one patient treated with ceftriaxone, but five patients in the traditional therapy group had organisms present on Gram stain of uncentrifuged spinal fluid or positive cultures of the spinal fluid (or both). Ceftriaxone entered the cerebrospinal fluid well, and the average cerebrospinal fluid bactericidal activity for ceftriaxone 1 h after a dose was at least 60 times greater than for ampicillin or chloramphenicol. In those patients who received treatment for a long enough period of time to permit evaluation, there was one death in each group, both due to S. pneumoniae. The length of fever and complications were similar for the patients in both groups. Ceftriaxone was well tolerated; diarrhea, seen in 5 of the 22 patients who received the drug, was the most commonly encountered adverse effect. It was mild, and in no case was it necessary to discontinue the drug. Ceftriaxone appears in this preliminary study to be a safe and acceptable single agent for the treatment of bacterial meningitis in children.", "78 patients with bacterial meningitis were evaluated in a prospective, randomised study comparing twice-daily ceftriaxone as single-drug therapy with ampicillin and chloramphenicol given every 6 h. The groups were comparable in age, sex, days of illness before admission, and bacterial colony counts in cerebrospinal fluid (CSF). The pathogens were Haemophilus influenzae type b (54 cases), streptococci (9 cases), meningococci (9 cases), and unknown (6 cases). In 40 CSF specimens obtained 4-12 h after initiation of therapy, cultures were negative in 57% of the ceftriaxone patients and in 42% of the others. The mean falls in the CSF bacterial colony counts were 4.7 and 5.0 log10 colony-forming units/ml, respectively. Mean bactericidal activity in CSF was significantly greater in the ceftriaxone than in the conventional treatment group at the beginning and end of therapy. There were no significant differences in clinical responses or in frequency of complications, except for mild diarrhoea, which occurred in 16 ceftriaxone patients and in 8 in the other group (p less than 0.05).", "In a prospective, controlled, randomized single-blind clinical trial, treatment with cefotaxime (CTX) was compared with that with standard therapy (ST), which consisted of a penicillin-chloramphenicol combination with or without sulphadiazine, in 31 patients (excluding neonates) with proven bacterial meningitis. The two groups of patients were comparable in age, sex, clinical presentation and causative pathogens. The case fatality rate was 12.5% for the CTX group and 20% for the ST group, but this difference was not significant. The times taken for the cerebrospinal fluid (CSF) to become sterile and the temperature to normalize, the mean duration of treatment, complications and adverse effects were similar for the two regimens. Neurological or developmental abnormalities on follow-up were not significantly different for the two groups. It is concluded that CTX is a suitable alternative for treatment of bacterial meningitis in infants and children.", "Fifty children with bacterial meningitis were prospectively randomized to receive cefotaxime (50 mg/kg/dose every 6 hours) or ampicillin and chloramphenicol in standard doses. Twenty-three patients received cefotaxime and 27 received standard therapy. Bacterial isolates included: Haemophilus influenzae (29), Streptococcus pneumoniae (eight), Neisseria meningitidis (eight), group B streptococci (three), and Salmonella enteritidis (two). Ten (34%) of the H. influenzae isolates were resistant to ampicillin, nine on the basis of beta-lactamase production. All strains were susceptible to cefotaxime. Clinical cure rates for the cefotaxime (100%) and standard therapy (96%) groups were similar; survival without detectable sequelae was similar, at 78% and 77%, respectively. The duration of therapy, 11.1 +/- 2.4 days (range 10 to 21 days) vs 11.9 +/- 3.9 days (range 10 to 21 days), and days to defervescence, 4.7 +/- 2.6 days (range 1 to 14 days) vs 5.6 +/- 2.9 days (range 2 to 17 days), were similar in the cefotaxime and standard therapy groups, respectively. No adverse drug reactions or side effects were noted in either group. Cefotaxime was found to be as safe and effective as standard therapy for the treatment of bacterial meningitis in children.", "Ceftriaxone, a new third-generation cephalosporin, appears to be promising for the therapy of acute bacterial meningitis. The 90% MBCs of ceftriaxone against 54 recent cerebrospinal fluid isolates of Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae were less than or equal to 0.06 to 0.25 micrograms/ml. We examined the efficacy and safety of ceftriaxone therapy of meningitis in Bahia, Brazil. The study was conducted in two phases; in phase A, ceftriaxone was coadministered with ampicillin. The mean cerebrospinal fluid concentrations of ceftriaxone 24 h after an intravenous dose of 80 mg/kg were 4.2 and 2.3 micrograms/ml on days 4 to 6 and 10 to 12 of therapy, respectively. These concentrations were 8- to more than 100-fold greater than the 90% MBCs against the relevant pathogens. In phase B, ceftriaxone (administered once daily at a dose of 80 mg/kg after an initial dose of 100 mg/kg) was compared with conventional dosages of ampicillin and chloramphenicol in a prospective randomized trial of 36 children and adults with meningitis. The groups were comparable based on clinical, laboratory, and etiological parameters. Ceftriaxone given once daily produced results equivalent to those obtained with ampicillin plus chloramphenicol, as judged by cure rate, case fatality ratio, resolution with sequelae, type and severity of sequelae, time to sterility of cerebrospinal fluid, and potentially drug-related adverse effects. The cerebrospinal fluid bactericidal titers obtained 16 to 24 h after ceftriaxone dosing were usually 1:512 to greater than 1:2,048 even late in the treatment course, compared with values of 1:8 to 1:32 in patients receiving ampicillin plus chloramphenicol. Ceftriaxone clearly deserves further evaluation for the therapy of meningitis; the optimal dose, dosing frequency (every 12 h or every 24 h), and duration of therapy remain to be determined.", "Thirty patients, 25 males and 5 females, aged 16-30 years (mean 21.8 years) with bacterial meningitis were assigned randomly into one of two therapeutic regimens. Patients in Group I received ceftriaxone 100 mg/kg (max 4 g) intravenously (i.v.) once daily. Those in Group II received ampicillin i.v. 160 mg/kg/day plus chloramphenicol i.v. 100 mg/kg/day every 6 h. Of the 15 patients in Group I, N. meningitidis was isolated from 11 patients and S. pneumoniae from 4; and of the 15 patients in Group II, N. meningitidis was isolated from 10 patients and S. pneumoniae from 5. Response to therapy as measured by mortality, time taken for defervescence and for patients to regain full consciousness were comparable in the two groups. One patient in each group died; both died within 24 h of initiation of therapy. The mean no. of days taken to become afebrile were 3.4 and 3.5 and to regain full consciousness were 3.9 and 3.5 for Groups I and II respectively. Ceftriaxone given i.v. appears to be as effective as a combination of ampicillin and chloramphenicol in the treatment of adult patients with meningitis due to N. meningitidis and S. pneumoniae. However, the once-daily schedule of ceftriaxone is more convenient, saving nursing time and expense.", "nan", "Eighty-five infants and children were prospectively randomized to receive cefotaxime or ampicillin and chloramphenicol for therapy of bacterial meningitis. The two therapy groups of patients were comparable as to sex, age, clinical status on admission, prior administration of antibiotics and etiology. Three infants (7%) died in each therapy group. Mean number of days of positive cerebrospinal fluid cultures, time to defervescence and duration of treatment and of hospital stay and complications developing during treatment were similar for the two treatment regimens. Median cerebrospinal fluid bactericidal titers against the patients' pathogens in cefotaxime-treated patients (1:64) were larger than those in patients who received conventional therapy (1:8). Mild to moderate motor sequelae were more frequent in those given conventional therapy at the time of discharge only, and not at 4 months or longer of follow-up. We conclude that cefotaxime has similar efficacy when compared with conventional therapy for the management of bacterial meningitis in pediatric patients." ]

[ "8564089", "1346410", "7589392" ]

[ "Double-blind, placebo-controlled study of cyclosporin A as a corticosteroid-sparing agent in corticosteroid-dependent asthma.", "Trial of cyclosporin in corticosteroid-dependent chronic severe asthma.", "Treatment of steroid-dependent bronchial asthma with cyclosporin." ]

[ "Patients with severe asthma who require long-term oral corticosteroid therapy are at risk of unwanted effects. Several immunosuppressive drugs have been assessed as corticosteroid-sparing agents in chronic asthma. We previously showed that cyclosporin A (CsA) administered for 12 wk improved lung function in corticosteroid-dependent patients. We have now investigated the corticosteroid-sparing properties of CsA over a 36-wk period. Following a 4-wk run-in period, 39 corticosteroid-dependent asthmatic patients were randomized to receive CsA (19 patients, initial doses 5 mg/kg/d) or matched placebo (20 patients) for 36 wk. Attempts were then made by a physician ignorant of the trial therapy to reduce their prednisolone dosages at 14-d intervals, provided that a patient's asthma remained stable or improved. Three patients receiving CsA had to be withdrawn from the study before they completed 12 wk of therapy. The remaining 16 patients achieved a statistically significant reduction in median daily prednisolone dosage of 62% (10 to 3.5 mg), compared with a decrease of 25% (10 to 7.5 mg) in the patients taking placebo (p = 0.043). This reduction was most pronounced during the last 12 wk of active therapy. In addition, morning peak expiratory flow rate (PEFR) improved significantly (mean 9.4%, SEM 3.0%) in the active-treatment group but not in the placebo group (p = 0.026 between groups). Predictable changes in renal function and blood pressure, and an increased incidence of hypertrichosis and paresthesia, were observed in the patients treated with CsA, but these did not necessitate withdrawal from the study, and were reversed during a 4-wk run-out period. Thus, low-dose CsA therapy, as compared with placebo, allowed a significant reduction in oral corticosteroid dosages in patients with severe asthma, and also improved lung function.", "The treatment of chronic severe asthma is unsatisfactory for many patients. In a randomised, double-blind, placebo-controlled, crossover trial we have tested whether cyclosporin, which is thought to act primarily by inhibition of T lymphocyte activation, improves lung function in corticosteroid-dependent asthmatics. After a 4-week run-in period, 33 patients with longstanding asthma (mean duration 27 years), and who had required continuous oral corticosteroids for a mean of 9.3 years, were randomised to receive either cyclosporin (initial dose 5 mg/kg per day) or placebo for 12 weeks, crossing over after a 2-week washout period. Mean baseline forced expiratory volume in 1 s (FEV1) was 60.1% of the predicted value. 2 patients failed to complete the protocol and 1 withdrew because of hypertrichosis. Cyclosporin therapy resulted in a mean increase above placebo of 12.0% in morning peak expiratory flow rate (PEFR; p less than 0.004) and 17.6% in FEV1 (p less than 0.001). The frequency of disease exacerbations requiring an increased prednisolone dose was reduced by 48% in patients on cyclosporin compared with placebo (p less than 0.02). Diurnal variation in PEFR decreased by a mean of 27.6% (p = 0.04). Cyclosporin for 12 weeks was well tolerated by this group of chronic asthmatics, in whom the mean whole-blood trough concentration was 152 micrograms/l. These findings provide further evidence of a role for activated T lymphocytes in the pathogenesis of asthma. Specific pharmacological targeting of this cell could form the basis of a novel approach to the treatment of asthma.", "The treatment of chronic severe asthma is unsatisfactory for many patients. The aim of the study was to determine the effects of treatment of steroid-dependent asthma with cyclosporin. We performed a double-blind, placebo-controlled, randomized, parallel group trial on the effect of cyclosporin on pulmonary function, asthma severity and tapering of prednisone in 34 steroid-dependent asthmatics (mean oral prednisone dose: 16 mg.day-1). The study consisted of: 1) baseline period (12 weeks); 2) experimental period divided into two parts: Part I (12 weeks) cyclosporin or placebo treatment; Part II (22 weeks) cyclosporin or placebo treatment and oral prednisone reduction; and 3) follow-up observation (8 weeks). Asthma symptoms score, pulmonary function tests (daily peak expiratory flow (PEF) and bi-weekly forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximal mid-expiratory flow (MEF50), biochemical profile and blood cyclosporin levels were monitored throughout the study. Following cyclosporin administration, a slight beneficial effect on some subjective parameters of asthma severity was observed. At the same time, no beneficial effect on pulmonary function was noted. The time trends analysis of mean daily prednisone doses between the treatment groups revealed a statistically significant difference indicating that, during prednisone reduction, cyclosporin seemed to be slightly more efficient than placebo in reducing the requirement for systemic corticosteroid, even though the steroid reduction was accompanied by slight impairment of some pulmonary function. However, there was no significant difference in the final dose reduction between the treatment groups. These data and the known toxicity of the drug suggest a limited place for cyclosporin treatment in steroid-dependent bronchial asthma." ]

[ "21979458" ]

[ "Laparoscopic compared with robotic sacrocolpopexy for vaginal prolapse: a randomized controlled trial." ]

[ "To compare conventional laparoscopic and robotic-assisted laparoscopic sacrocolpopexy for vaginal apex prolapse.\n This single-center, blinded randomized trial included participants with stage 2-4 posthysterectomy vaginal prolapse. Participants were randomized to laparoscopic or robotic sacrocolpopexy. The primary outcome was total operative time from incision to closure. Secondary outcomes were postoperative pain, functional activity, bowel and bladder symptoms, quality of life, anatomic vaginal support, and cost from a health care system perspective.\n A total of 78 patients enrolled and were randomized (laparoscopic n=38; robotic n=40). Total operative time was significantly longer in the robotic group compared with the laparoscopic group (+67-minute difference; 95% confidence interval [CI] 43-89; P<.001). Anesthesia time, total time in the operating room, total sacrocolpopexy time, and total suturing time were all significantly longer in the robotic group. Participants in the robotic group also had significantly higher pain at rest and with activity during weeks 3 through 5 after surgery and required longer use of nonsteroidal anti-inflammatory drugs (median, 20 compared with 11 days, P<.005). The robotic group incurred greater cost than the laparoscopic group (mean difference +$1,936; 95% CI $417-$3,454; P=.008). Both groups demonstrated significant improvement in vaginal support and functional outcomes 1 year after surgery with no differences between groups.\n Robotic-assisted sacrocolpopexy results in longer operating time and increased pain and cost compared with the conventional laparoscopic approach." ]

[ "3113475", "6541387", "9683309", "4890404", "15728164", "17934931", "16037757", "11304861", "10428529", "1761173", "3046105", "2089297", "8107615", "2079284", "2227611", "14716182", "11454122", "20236776", "8375632", "3908884", "8885906", "10955437" ]

[ "Treatment with oral piperazine oestrone sulphate for genuine stress incontinence in postmenopausal women.", "Urethral sphincteric insufficiency in postmenopausal females: treatment with phenylpropanolamine and estriol separately and in combination. A urodynamic and clinical evaluation.", "Heart and Estrogen/progestin Replacement Study (HERS): design, methods, and baseline characteristics.", "The use of quinestradol in elderly incontinent women, a preliminary report.", "Effects of estrogen with and without progestin on urinary incontinence.", "Presurgical promestriene therapy in postmenopausal women with stress urinary incontinence.", "Vaginal estrogen therapy and overactive bladder symptoms in postmenopausal patients after a tension-free vaginal tape procedure: a randomized clinical trial.", "Hormone replacement therapy plus pelvic floor muscle exercise for postmenopausal stress incontinence. A randomized, controlled trial.", "The effect of oestrogen supplementation on post-menopausal urinary stress incontinence: a double-blind placebo-controlled trial.", "[The effectiveness of intravaginal estriol tablet administration in women with urge incontinence].", "Estrogens and phenylpropanolamine in combination for stress urinary incontinence in postmenopausal women.", "[Transvaginal estrogen therapy in urinary stress incontinence].", "Oestriol in the treatment of postmenopausal urgency: a multicentre study.", "[Treatment of female urge incontinence by local estrogen therapy].", "Effect of combined treatment with phenylpropanolamine and estriol, compared with estriol treatment alone, in postmenopausal women with stress urinary incontinence.", "Efficacy of low-dose intravaginal estriol on urogenital aging in postmenopausal women.", "Effects of oral estrogen and progestin on the lower urinary tract among female nursing home residents.", "The use of oestradiol therapy in postmenopausal women after TVT-O anti-incontinence surgery.", "[Intravesical administration of estriol in sensory urge incontinence--a prospective study].", "Occurrence, nature and treatment of urinary incontinence in a 70-year-old female population.", "Efficacy of estrogen supplementation in the treatment of urinary incontinence. The Continence Program for Women Research Group.", "Oestradiol-releasing vaginal ring versus oestriol vaginal pessaries in the treatment of bothersome lower urinary tract symptoms." ]

[ "The use of oestrogens in the treatment of genuine stress incontinence was assessed by a double-blind prospective trial in 36 postmenopausal women with genuine stress incontinence who received 3 months of cyclical treatment with either piperazine oestrone sulphate or a matching placebo. Patients were assessed subjectively and objectively before and after treatment by 7-day bladder charts, urethral pressure profiles (UPP), the Urilos nappy test, vaginal cytology and hormone assays (plasma oestrogens and gonadotrophins). There was no statistical difference in the subjective response to treatment between the two groups. After 6 weeks of treatment there was a greater reduction in the number of pad changes/24 h in the oestrogen-treated patients that approached statistical significance but, because of a marked response in the placebo group, this difference was not significant after 3 months of treatment. There were also no significant differences between the two groups with respect to the UPP or Urilos measurements but the vaginal cytology and hormone profiles were significantly affected by oestrogens. In view of the possible risks of oestrogen therapy its use in genuine stress incontinence is limited.", "A randomized open comparative cross-over trial was carried out in 20 postmenopausal women, mean age 69 years, suffering from urinary incontinence due to urethral sphincteric insufficiency. They were treated with phenylpropanolamine (PPA) 50 mg p.o. twice daily or estriol vaginal suppositories 1 mg daily separately and in combination for periods of 4 weeks. Urodynamic investigations were carried out before and after each period of treatment. Both PPA and estriol increased the maximal urethral closure pressure and the continence area significantly compared to the initial values, but combined treatment was substantially more effective. The functional urethral length increased significantly while on estriol. No significant change was registered in the bladder pressure or in the pressure transmission ratio. PPA was clinically more effective than estriol, but not sufficient to obtain complete continence. With combined treatment 8 patients became completely continent, 9 were considerably improved and only 1 patient remained unchanged. 2 patients dropped out of the study because of side effects. Combined treatment with PPA and estriol represents a recommendable treatment to postmenopausal women with urinary incontinence due to urethral sphincteric insufficiency.", "The Heart and Estrogen/progestin Replacement Study (HERS) is a randomized, double-blind, placebo-controlled trial designed to test the efficacy and safety of estrogen plus progestin therapy for prevention of recurrent coronary heart disease (CHD) events in women. The participants are postmenopausal women with a uterus and with CHD as evidenced by prior myocardial infarction, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, or other mechanical revascularization or at least 50% occlusion of a major coronary artery. Between February 1993 and September 1994, 20 HERS centers recruited and randomized 2763 women. Participants ranged in age from 44 to 79 years, with a mean age of 66.7 (SD 6.7) years. Most participants were white (89%), married (57%), and had completed high school or some college (80%). As expected, the prevalence of coronary risk factors was high: 62% were past or current smokers, 59% had hypertension, 90% had serum LDL-cholesterol of 100 mg/dL or higher, and 23% had diabetes. Each woman was randomly assigned to receive one tablet containing 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate daily or an identical placebo. Participants will be evaluated every 4 months for an average of 4.2 years for the occurrence of CHD events (CHD death and nonfatal myocardial infarction). We will also assess other major CHD endpoints, including revascularization and hospitalization for unstable angina. The primary analysis will compare the rate of CHD events in women assigned to active treatment with the rate in those assigned to placebo. The trial was designed to have power greater than 90% to detect a 35% reduction in the incidence of CHD events, assuming a 50% lag in effect for 2 years and a 5% annual event rate in the placebo group. The design, analysis, and conduct of the study are controlled by the Steering Committee of Principal Investigators and coordinated at the University of California, San Francisco. HERS is the largest trial of any intervention to reduce the risk of recurrent CHD events in women with heart disease and is the first controlled trial to seek evidence of the efficacy and safety of postmenopausal hormone therapy to prevent recurrent CHD events.", "nan", "Menopausal hormone therapy has long been credited with many benefits beyond the indications of relieving hot flashes, night sweats, and vaginal dryness, and it is often prescribed to treat urinary incontinence (UI).\n To assess the effects of menopausal hormone therapy on the incidence and severity of symptoms of stress, urge, and mixed UI in healthy postmenopausal women.\n Women's Health Initiative multicenter double-blind, placebo-controlled, randomized clinical trials of menopausal hormone therapy in 27,347 postmenopausal women aged 50 to 79 years enrolled between 1993 and 1998, for whom UI symptoms were known in 23,296 participants at baseline and 1 year.\n Women were randomized based on hysterectomy status to active treatment or placebo in either the estrogen plus progestin (E + P) or estrogen alone trials. The E + P hormones were 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate (CEE + MPA); estrogen alone consisted of 0.625 mg/d of conjugated equine estrogen (CEE). There were 8506 participants who received CEE + MPA (8102 who received placebo) and 5310 who received CEE alone (5429 who received placebo).\n Incident UI at 1 year among women without UI at baseline and severity of UI at 1 year among women who had UI at baseline.\n Menopausal hormone therapy increased the incidence of all types of UI at 1 year among women who were continent at baseline. The risk was highest for stress UI (CEE + MPA: relative risk [RR], 1.87 [95% confidence interval {CI}, 1.61-2.18]; CEE alone: RR, 2.15 [95% CI, 1.77-2.62]), followed by mixed UI (CEE + MPA: RR, 1.49 [95% CI, 1.10-2.01]; CEE alone: RR, 1.79 [95% CI, 1.26-2.53]). The combination of CEE + MPA had no significant effect on developing urge UI (RR, 1.15; 95% CI, 0.99-1.34), but CEE alone increased the risk (RR, 1.32; 95% CI, 1.10-1.58). Among women experiencing UI at baseline, frequency worsened in both trials (CEE + MPA: RR, 1.38 [95% CI, 1.28-1.49]; CEE alone: RR, 1.47 [95% CI, 1.35-1.61]). Amount of UI worsened at 1 year in both trials (CEE + MPA: RR, 1.20 [95% CI, 1.06-1.36]; CEE alone: RR, 1.59 [95% CI, 1.39-1.82]). Women receiving menopausal hormone therapy were more likely to report that UI limited their daily activities (CEE + MPA: RR, 1.18 [95% CI, 1.06-1.32]; CEE alone: RR, 1.29 [95% CI, 1.15-1.45]) and bothered or disturbed them (CEE + MPA: RR, 1.22 [95% CI, 1.13-1.32]; CEE alone: RR, 1.50 [95% CI, 1.37-1.65]) at 1 year.\n Conjugated equine estrogen alone and CEE + MPA increased the risk of UI among continent women and worsened the characteristics of UI among symptomatic women after 1 year. Conjugated equine estrogen with or without progestin should not be prescribed for the prevention or relief of UI.", "Our study was aimed at evaluating the efficacy of therapy with promestriene, a synthetic diethyl-ether of estradiol with no distal hormonal effects, in patients undergoing surgical correction for stress urinary incontinence (SUI).\n Ninety-eight healthy, postmenopausal women, non-users of hormone replacement therapy, with a diagnosis of SUI and vulvovaginal dystrophy, were recruited and openly randomized into two main groups. Group I (48 patients) received promestriene 10 mg daily, by vaginal capsule, for 21 days before the operation. Group II (50 patients) underwent the surgical procedure with TVT (Tension-free Vaginal Tape) directly, without pharmacological preparation. The results were collected and analyzed using SAS software (version 8).\n The two groups were homogeneous in terms of age, parity and body mass index. There were no significant differences between the two groups with respect to the time required to accomplish the TVT, blood loss, length of hospital stay, blood component measurements and postoperative subjective symptoms. There were slight differences postoperatively in problems during intercourse and the appearance of new genital symptoms, but again they were not shown to be statistically significant.\n Our results, although preliminary and subjective, confirm the efficacy of remedial surgical treatment of SUI with TVT. Preoperative administration of promestriene seems to favor trophism and vascularization of the whole muscular and fascial support of the pelvic floor and facilitates performance of the operation, but is not supported statistically.", "To evaluate whether the frequency of overactive bladder (OAB) symptoms increases in menopause patients after a tension-free vaginal tape (TVT) procedure, and to determine if topical estrogen therapy can help prevent these symptoms.\n After undergoing a preoperative assessment, enrolled patients were randomly allocated to receive TVT plus postoperative vaginal estrogen therapy (ET group) or TVT without adjunctive medical treatment (No ET group). The pre- and postoperative assessments included: acquisition of a urogynecologic history with standardized questions regarding urinary function (including a 10-grade visual analogue scale score), urogynecologic clinical examination, and urodynamic assessment. Follow-up assessments were performed at 1, 3, and 6 months after surgery.\n Fifty-six of 59 patients were evaluable; 28 received topic vaginal estrogen after surgery (ET group) and 28 did not receive adjunctive medical treatment (No ET group). The overall OAB syndrome rate in menopause patients (No ET group) was 7% (2 of 28 patients) at baseline and 32% (9 of 28 patients) 6 months after surgery (P = 0.04). At the 6-month follow-up assessment, the incidence of urinary urgency was 4% (1 of 28 patients) and 29% (8 of 28 patients) in the ET and No ET groups, respectively (P = 0.01). Differences in frequency and nocturia were not statistically significant. Analysis of the visual analogue scale scores revealed that at the 6-month follow-up assessment, urgency significantly improved in the ET group compared with the No ET group (0.23 +/- 1.0 vs 2.30 +/- 3.7, respectively; P = 0.02).\n The TVT procedure seems to increase the frequency of OAB syndrome in menopause patients. Vaginal estriol therapy significantly reduces symptoms of urinary urgency, has a high rate of patient satisfaction, and can be used to treat postmenopausal women for at least 6 months after a TVT procedure.", "To investigate the effects of the combination of pelvic floor muscle exercise (PFME) and estriol on postmenopausal stress incontinence (SI).\n Sixty-six patients with postmenopausal SI were randomized to a group treated with a combination of estriol (1 mg/d) and PFME (group A, n = 32) and a group treated with PFME alone (group B, n = 34). Efficacy was evaluated every three months based on stress scores obtained from a urinary incontinence (UI) questionnaire.\n A significant decrease in stress score was observed in mild and moderate UI patients in both groups three months after the commencement of therapy (A and B, P < .0001). The therapeutic effect in group A was more prominent for up to 18 months in mild UI and for up to 12 months in moderate UI (A vs. B, P < .05). Kaplan-Meier analysis showed that the cumulative morbidity rate in mild SI patients was significantly lower in group A (0%) than in group B (12%, P < .005).\n Combination therapy with estriol plus PFME was effective and is capable of serving as first-line treatment for mild SI.", "To investigate the effect of hormone replacement therapy on post-menopausal urinary stress incontinence.\n Double-blind, placebo-controlled, randomised trial.\n University associated teaching hospital.\n Post-menopausal women with genuine stress incontinence, not taking hormone replacement therapy.\n Randomisation to six months therapy with oestradiol valerate 2 mg daily or placebo. Assessment prior to treatment and upon study completion with the SF-36 health status questionnaire, the Bristol Female Lower Urinary Tract Symptoms questionnaire, a one week urinary diary, one hour perineal pad test, cystometry and urethral profilometry.\n Sixty-seven women consented to participate, 33 were randomised to receive oestradiol. Mean age was 63 years. Five women failed to undergo repeat assessment, three of whom were receiving oestrogen. Six women receiving oestradiol experienced breakthrough bleeding during the six months and were subsequently treated with additional monthly progestogen. No significant effect of oestrogen over placebo was observed for any subjective or objective clinical outcome.\n This trial is one of the largest controlled studies yet reported, with the longest duration of treatment. No improvement in post-menopausal stress incontinence was demonstrated after six months therapy with oestradiol. This concurs with another study reported recently; it seems unlikely that oestrogen has a significant role to play in this condition.", "In postmenopausal patients, stress and urge incontinence often occur as a consequence of oestrogen deficiency. We performed a comparative study in a prospectively randomised and placebo controlled group of women with urge incontinence to investigate different dosages of intravaginally applied oestriol. Clinical and urodynamic parameters were also compared. 15 women (Group I) received 1 mg oestriol applied daily intravaginally over 3 weeks; 15 women (Group II) received a daily dosage of 3 mg and 10 women received a placebo. A complete clinical and urodynamic evaluation was carried out twice at a 4-week interval. The women receiving a daily dose of 3 mg oestriol applied intravaginally demonstrated a significant improvement of the parameters strong desire to void, pollakisuria, and nycturia. No improvement was seen in patients with motoric urge incontinence.", "Thirty-six postmenopausal women with objectively verified stress incontinence were treated with oral estriol (Triovex, 2 mg x 1) and phenylpropanolamine (Kontexin, 50 mg x 2) alone and in combination. After an initial four-week single-blind period with phenylpropanolamine (PPA), either estriol or estriol and PPA were given randomly in four-week periods, in a crossover design. PPA and estriol in combination as well as PPA alone, raised the intraurethral pressure and significantly reduced the urinary loss by 35 per cent in a standardized physical strain test. In women with an initial low urethral pressure estriol also induced pressure increase. The leakage episodes and the assessed leakage amounts were significantly reduced by both estriol and PPA given separately as single treatment (28%) or when given as combined therapy (40%). Most of the women preferred the combined treatment to either drug alone. Additive but no synergistic effects are indicated.", "Thirty-four postmenopausal stress incontinence patients were divided in two groups: 17 were treated with 0.5 mg oestriol vaginal cream for 90 days, 17 controls were treated with moisturizing cream. All had low urethral pressures and dystrophy. Treated patients showed improvement of maximum urethral pressure, urethral closure pressure, and volume at first sensation of fullness. Dystrophy was cured in most patients; in 17% incontinence was cured and in 41% subjectively improved.", "Oestrogen deficiency in postmenopausal women is thought to be important in the genesis of lower urinary tract symptoms, in particular the 'urge syndrome'. Evidence to support the use of oestrogen therapy in symptomatic postmenopausal women is, however, limited. Oestriol is a weak, naturally occurring oestrogen that may be beneficial to the urogenital tissues without stimulating the endometrium. We have investigated the use of oestriol in the treatment of postmenopausal sensory and motor urge incontinence. Materials and methods: A double-blind, placebo-controlled, randomised, multicentre study of 3 mg oral oestriol/day for 3 months in the treatment of women with urge incontinence was undertaken. Results and conclusions: Sixty-four women were recruited into the study. Although oestriol produced both subjective and objective improvement in lower urinary tract function, it was not significantly better than placebo. Some of the difficulties of running a multicentre study were encountered.", "nan", "Twenty-nine postmenopausal women with slight to severe stress urinary incontinence and estrogen deficiency symptoms in the urogenital tract were treated with estriol, p.o. 4 mg once daily, and either phenylpropanolamine (PPA), p.o. 50 mg twice daily, or placebo for periods of 6 weeks according to a randomized double-blind crossover schedule. At urodynamic recordings the maximum urethral closure pressure increased by 22% with combined treatment (p less than 0.001) and an additional effect of PPA to estriol was shown (p = 0.022). The pressure transmission ratio increased, by about 15%, with both treatments (p less than 0.07). The number of leakage episodes was reduced by 28% with combined treatment (p = 0.007), but not with estriol alone (p = 0.08). Both combined treatment and estriol alone reduced significantly (p less than 0.01) the urinary incontinence complaints. Twelve women (43%) preferred combined treatment, while 7 (25%) preferred estriol alone. In women with initially slight to very severe urine loss, combined treatment reduced also (p = 0.02) the amount of urine loss, measured at a standardized physical stress test. Signs of estrogen deficiency in vulva, vagina and urethra were reduced, 75% (p less than 0.001) or 65% (p = 0.001) with estriol given in combination with PPA or alone. Maturation index of both urethral and vaginal epithelium displayed significant changes. It is concluded that the combined treatment, PPA + estriol, by affecting both the muscular and mucosal factor of the urethra, is more effective than estriol alone for treatment of female stress urinary incontinence in the postmenopausal ages.", "To assess the efficacy and safety of intravaginal estriol administration on urinary incontinence, urogenital atrophy, and recurrent urinary tract infections in postmenopausal women.\n Eighty-eight postmenopausal women with urogenital aging symptoms were enrolled in this prospective, randomized, placebo-controlled study. Participants were randomly divided into two groups, with each group consisting of 44 women. Women in the treatment group received intravaginal estriol ovules: 1 ovule (1 mg) once daily for 2 weeks and then 2 ovules once weekly for a total of 6 months as maintenance therapy. Women in the control group received inert placebo vaginal suppositories in a similar regimen. We evaluated urogenital symptomatology, urine cultures, colposcopic findings, urethral cytologic findings, urethral pressure profiles, and urethrocystometry before as well as after 6 months of treatment.\n After therapy, the symptoms and signs of urogenital atrophy significantly improved in the treatment group in comparison with the control group. Thirty (68%) of the treated participants, and only seven (16%) of the control participants registered a subjective improvement of their incontinence. In the treated participants, we observed significant improvements of colposcopic findings, and there were statistically significant increases in mean maximum urethral pressure, in mean urethral closure pressure as well as in the abdominal pressure transmission ratio to the proximal urethra. Urethrocystometry showed positive but not statistically significant modifications.\n Our results show that intravaginal administration of estriol may represent a satisfactory therapeutic choice for those postmenopausal women with urogenital tract disturbances who have contraindications or refuse to undergo standard hormone therapy.", "To examine the effects of oral estrogen/progestin on incontinence and related lower urinary tract conditions among female nursing home (NH) residents.\n Randomized placebo-controlled trial.\n Five NHs.\n Thirty-two incontinent female residents of average age 88.\n Subjects were randomized to receive either oral estrogen (0.625 mg) combined with progesterone (2.5 mg) or placebo, daily for 6 months. Measures of incontinence severity, the clinical appearance of the vagina, vaginal and urethral cytology, and urine and vaginal cultures were made at baseline, 3 months, and 6 months. In addition to active drug or placebo, all subjects received regular toileting assistance (prompted voiding) by trained research aides during 3-day data-collection periods to compensate for mobility and cognitive impairments.\n At 3 and 6 months there were no significant differences between the groups in the severity of incontinence, the prevalence of bacteriuria, or the results of vaginal cultures. Several clinical findings associated with atrophic vaginitis improved more in the active than the placebo group and vaginal pH and vaginal and urethral cytology exhibited a partial estrogenic effect.\n Our results must be interpreted with caution because of the size and the select nature of our subject sample. Up to 6 months of oral estrogen had only a partial estrogenic effect on vaginal and urethral epithelium and no clinical effects in this patient population. We believe that future studies of estrogen for urinary incontinence in frail NH residents should utilize a topical preparation and consider targeting urinary tract infection as an additional outcome measure.", "To investigate whether patients who were treated with TVT-O procedure for urodynamic stress incontinence had a significant improvement in their urodynamic findings and their post-operative symptoms (frequency, urgency, nocturia) if they were treated post-operatively with vaginal oestradiol for 6 months compared to the non-treated group.\n Prospective randomised study. 190 patients were asked to participate in our study. Finally, a total of 92 patients in group 1 and 91 patients in group 2 completed the study. In group 1, which was the treatment group, patients having the TVT-O procedure for urodynamic stress incontinence were instructed to use post-operatively oestradiol tablets, 25 micrograms (Vagifem, Novo Nordisk) vaginally, once daily, nocte, for 2 weeks and then twice weekly for 6 months. The patients in group 2 (control group) had the TVT-O procedure only. All patients were reviewed in 2 months and again in 6 months time.\n There was no statistically significant difference between the two groups concerning pre-operative and post-operative haemoglobin, operative time, hospital stay or return to work. The within group analysis did not show significant differences between pre-operative and post-operative urodynamic data in both groups. Patients treated with vaginal estradiol post-operatively showed a statistically significant reduction in relation to the symptoms of urgency and frequency but not in relation to nocturia and urge incontinence compared to the non-treated group. There is no difference in relation to the efficacy of TVT-O procedure between the groups at 6 months follow-up.\n It appears that vaginal oestradiol treatment could be offered to postmenopausal patients after a TVT-O procedure having the symptoms of frequency and urgency provided they are aware of the lack of evidence regarding long term benefit.\n Copyright 2010. Published by Elsevier Ireland Ltd.", "Local intravaginal application of oestriol is part of the therapeutical programme of sensory urge-incontinence. The effectiveness of a new method--intravesical administration of 1 mg oestriol versus a placebo--has been proved in a prospective randomised study. 21 patients each were treated over a period of three weeks with oestriol or with the placebo-substance intravesically. The effectiveness of the administered therapy was checked with clinical and urodynamic parameters. The intravesical administration of 1 mg oestriol proved to be efficient and free of side effects in respect of the parameters such as imperative micturition, bladder capacity, of the maximum urethral closure pressure as well as the number of micturitions per diem. The intravesical administration of oestriol may be considered as additional method of therapy for treatment of sensory urge-incontinence.", "An intervention trial using oral oestriol to treat urinary incontinence was performed in a number of patients taken from a representative sample of 562 women aged 75 yr. The clinical series consisted of 34 patients who took part in a double-blind crossover study of the possible effects of oestriol, given in a single daily dose of 3 mg, and of a placebo over a period of 3 mth. The clinical examinations included bacteriological cultures and an assessment of the degree of atrophy of the surface membranes in the vagina. In most patients, oestriol was effective in reversing the atrophy. The clinical effect was excellent in urgency and mixed incontinence, but not in stress incontinence.", "To assess the efficacy of cyclic postmenopausal hormone replacement in treating urinary incontinence in hypoestrogenic women.\n Eighty-three hypoestrogenic women complaining of urinary incontinence were included. All patients were community-dwelling, age 45 years or older, with involuntary loss of urine occurring at least once a week and urodynamic evidence of genuine stress incontinence and/or detrusor instability. Evaluation consisted of a comprehensive clinical and urodynamic research protocol. The hypoestrogenic entry criterion was a plasma estradiol level of 30 pg/mL or less. Parabasal cells on vaginal smears were also monitored. The primary outcome was the number of incontinent episodes per week, as documented on a standardized urinary diary. Secondary outcomes were the quantity of fluid loss, voluntary diurnal and nocturnal micturition frequency, generic and condition-specific health-related quality of life measurements, and patient satisfaction. A randomized, placebo-controlled, double-blind design was used. Subjects in the treatment group were given conjugated equine estrogens (0.625 mg) and medroxyprogesterone (10 mg) cyclically for 3 months. Controls received placebo tablets.\n (All results are presented as mean +/- standard deviation.) Subjects were 67 +/- 9 years old. The menopause duration was 18 +/- 11 years. The duration of incontinence was 9 +/- 9 years. Estradiol level at baseline was 9 +/- 9 pg/mL, and the parabasal cell count was 42 +/- 44%. The number of incontinent episodes at baseline was 13 +/- 10 for the treatment group and 16 +/- 4 for controls. No significant changes occurred in the number of incontinent episodes after treatment: 10 +/- 10 for the treatment group, and 13 +/- 14 for the controls (P = .7). Also, fluid loss was not changed: 176 +/- 106 g for the treatment group and 64 +/- 88 g for the control group at baseline, and 101 +/- 150 and 51 +/- 69 g after treatment, respectively (P = .7). There were no significant differences for either diurnal or nocturnal voluntary micturition, quality of life measures, or patient's perception of improvement.\n Three-month cyclic hormone replacement therapy did not affect either clinical or quality of life variables of incontinent, hypoestrogenic women. Long-term effects are unlikely to be substantially different. The use of estrogen supplementation as preventive or adjuvant therapy was not evaluated in this study.", "To assess the efficacy of an oestradiol-releasing vaginal ring and oestriol pessaries in the alleviation of lower urinary tract symptoms occurring after the menopause.\n Randomised, parallel group, controlled trial.\n Twenty-six clinics of practising gynaecologists and one outpatient clinic at a department of obstetrics and gynaecology.\n Two hundred and fifty-one postmenopausal women, with a mean age of 66 years, reporting at least one bothersome lower urinary tract symptom.\n One hundred and thirty-four women were treated with the oestradiol-releasing ring for 24 weeks; 117 women were treated with oestriol pessaries 0.5 mg every second day for 24 weeks.\n Subjective scores of urgency, frequency, nocturia, dysuria, stress incontinence and urge incontinence.\n The two treatments were equally efficacious in alleviating urinary urgency (51% vs 56%), urge incontinence (58% vs 58%), stress incontinence (53% vs 59%) and nocturia (51% vs 54%). Dysuria was alleviated in 76% vs 67%, equivalence was not demonstrated. No statistically significant difference was found for any primary efficacy endpoint. Sixty percent of the participants rated the form of administration via the vaginal ring as excellent, compared with 14% for the pessaries (P < 0.0001).\n Low dose vaginally administered oestradiol and oestriol are equally efficacious in alleviating lower urinary tract symptoms which appear after the menopause. The form of administration of the vaginal ring, seems to be more acceptable than oestriol pessaries." ]

[ "9609334", "11851609", "20177294", "7738934", "12955343", "8261298" ]

[ "Use of a vaginal sponge during aerobic exercises in patients with stress urinary incontinence.", "A new intravaginal device for stress incontinence in women.", "Continence pessary compared with behavioral therapy or combined therapy for stress incontinence: a randomized controlled trial.", "Prevention of exercise incontinence with mechanical devices.", "A randomized controlled trial of the NEAT expandable tip continence device.", "The urethral plug II: an alternative treatment in women with genuine urinary stress incontinence." ]

[ "A newly marketed vaginal sponge intended to support the urethra was tested during aerobic exercise in a group of 6 women suffering from stress urinary incontinence. The patients performed half an hour of aerobic exercises on 2 consecutive days, with and without the vaginal sponge. A pad was worn during exercise and weighed before and after. Without the vaginal sponge the patients had a mean loss of 7 g (range 2-18 g) during exercise. With the vaginal sponge in situ there was no leakage. The sponge can be recommended for use during sports in patients with mild to moderate incontinence.", "To compare two versions of the same type of disposable intravaginal device (the Conveen Continence Guard, CCG, and the Contrelle Continence Tampon, CCT, Coloplast a/s, Humlebaek, Denmark) for treating stress incontinence in women.\n Women with the predominant symptom of stress incontinence were recruited from four centres in Denmark, Australia and the UK. The women were assessed using a 24-h pad-test, uroflowmetry, postvoid residual urine volume and a voiding diary before treatment, and after 5 weeks using each of the two devices. Vaginal swabs and specimens of urine were sent for culture, and a questionnaire about the subjective effect and adverse events completed at each visit. In all, 94 women were recruited, of whom 62 (66%) completed the study.\n Both devices reduced the amount of leakage significantly, but the CCT reduced urine loss significantly more than the CCG. Uroflowmetry values and residual urine volume were unchanged when using the two devices. Vaginal culture showed no abnormality during the study period, and only one woman was treated for a urinary tract infection. Side-effects were few and not serious. The women found both devices easy to prepare, insert and use; two-thirds preferred the CCT to the CCG.\n The new intravaginal device (CCT) is more effective for treating stress incontinence than the currently available version (CCG), and patient acceptability of the new device seems to be superior.", "To compare the effectiveness of a continence pessary to evidence-based behavioral therapy for stress incontinence and to assess whether combined pessary and behavioral therapy is superior to single-modality therapy.\n This was a multisite, randomized clinical trial (Ambulatory Treatments for Leakage Associated with Stress Incontinence [ATLAS]) that randomly assigned 446 women with stress incontinence to pessary, behavioral therapy, or combined treatment. Primary outcome measures, at 3 months, were Patient Global Impression of Improvement and the stress incontinence subscale of the Pelvic Floor Distress Inventory. A priori, to be considered clinically superior, combination therapy had to be better than both single-modality therapies. Outcome measures were repeated at 6 and 12 months. Primary analyses used an intention-to-treat approach.\n At 3 months, scores from 40% of the pessary group and 49% of the behavioral group were \"much better\" or \"very much better\" on the Patient Global Impression of Improvement (P=.10). Compared with the pessary group, more women in the behavioral group reported having no bothersome incontinence symptoms (49% compared with 33%, P=.006) and treatment satisfaction (75% compared with 63%, P=.02). Combination therapy was significantly better than pessary as shown on the Patient Global Impression of Improvement (53%, P=.02) and Pelvic Floor Distress Inventory (44%, P=.05) but not better than behavioral therapy; it was therefore not superior to single-modality therapy. Group differences were not sustained to 12 months on any measure, and patient satisfaction remained above 50% for all treatment groups.\n Behavioral therapy resulted in greater patient satisfaction and fewer bothersome incontinence symptoms than pessary at 3 months, but differences did not persist to 12 months. Combination therapy was not superior to single-modality therapy.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00270998.", "A prospective, randomized, single-blind study addressed the hypothesis that simple mechanical barriers are helpful in controlling urinary incontinence during exercise. Eighteen incontinent exercisers aged 33-73 participated in three 40-minute standardized aerobics sessions wearing either a Hodge pessary with support, a super tampon or no mechanical device. Urine loss was determined by a change in the weight of the pad worn while exercising. Statistical analysis of the log of urine loss revealed that women lost significantly less urine when exercising with either the pessary or the tampon than when exercising with no device. Thus, both devices studied are useful, nonsurgical alternatives for some women for the treatment of exercise incontinence.", "Urethral devices are one conservative management option for stress and mixed urinary incontinence, but there is little published data about their use. The aims of this study were to assess the safety and efficacy of a new urethral device (NEAT) and compare it with the Reliance Insert. The ease of use of both devices was then evaluated. Twenty-four women with mixed or stress urinary incontinence, patients at our tertiary care urogynecology unit and who met the inclusion and exclusion criteria, were enrolled in the study. Study subjects were blinded and randomly assigned to a device group. Device efficacy was assessed by pad weighing at 0 and 4 months. Success was defined as a 50% or greater reduction in urine loss using the formula 100[(pad weight without device -pad weight with device)/pad weight with device]. Safety was evaluated using urinalysis and urine cultures. Ease of use assessment scales were also completed. Eleven patients were randomized to the Reliance Insert and 13 to the NEAT device. There were no significant differences between the two groups in age, height, weight, duration of incontinence, pad weight, leakage score, parity or quality of life score. Based on the pad weight success formula, there was no significant difference in device success between the two groups at 4 months. Women who were postmenopausal had a trend towards a higher level of success in reduction of their pad weight. Previous treatment, diagnosis and hormone replacement therapy all had no relationship to device success. Leakage score data showed that subjects had a significant decrease in urine leakage when using either device. There was no statistically significant difference in ease of use between the two devices. Adverse symptoms most commonly noted were awareness of the device (62.5%), urgency (29.2%), and urethral discomfort or pain (20.8%). One urinary tract infection (UTI) was observed. The most common finding on urinalysis was trace hematuria (15.8%). Our conclusions are that the NEAT device appears to be at least as effective and safe as the Reliance Insert. Both devices are effective at decreasing urine leakage in patients with stress or mixed urinary incontinence. The risk of UTI is low, but these devices may cause trace hematuria.", "An improved design of the recently developed urethral plug was evaluated for the treatment of women with genuine urinary stress incontinence. The plug consists of an oval meatal plate, a soft stalk and 1 or 2 spheres along the stalk with fixed distances between the meatal plate and the spheres. Inside the stalk is a removable semi-rigid guide pin to ease insertion. Forty women were randomly allocated to treatment with either the 2-sphere or the 1-sphere plug during period 1 (2 weeks). In period 2 (2 weeks) the patients used the other plug. They then continued with what they judged to be the better plug in period 3 (2 months). Eighteen patients (45%) completed period 3 with the \"preference\" plug and 17 were subjectively and objectively continent or improved. Fourteen of these women preferred the 2-sphere device. The plugs were equally effective in patients with mild or severe incontinence. To accommodate variations in urethral length and to avoid the loss of plugs, the devices are available in different lengths. Six women developed urinary tract infections and 2 of these had a plug in the bladder. The urethral plug is an effective treatment in a group of women with stress incontinence. Removal by hand is advisable in order to avoid retention of plugs in the bladder." ]

[ "8153331", "2174575", "1848716", "15271870", "12517654", "3014408", "10644101", "16595242", "11779610", "2634468" ]

[ "Use of iotrolan versus ethiodized poppy-seed oil in hysterosalpingography.", "Pregnancy rates after the use of oil-based and water-based contrast media to evaluate tubal patency.", "Therapeutic effect of hysterosalpingography: oil- versus water-soluble contrast media--a randomized prospective study.", "The FLUSH trial--flushing with lipiodol for unexplained (and endometriosis-related) subfertility by hysterosalpingography: a randomized trial.", "Oil-soluble contrast during hysterosalpingography in women with proven tubal patency.", "Pregnancy rates after hysterosalpingography with oil- and water-soluble contrast media.", "Potential therapeutic effects of contrast materials in hysterosalpingography: a prospective randomized clinical trial. Kaiser Permanente Infertility Work Group.", "A randomized study of laparoscopic chromopertubation with lipiodol versus saline in infertile women.", "A randomized controlled trial of tubal flushing with lipiodol for unexplained infertility.", "The therapeutic effects of oil-soluble hysterosalpingography contrast medium following water-soluble hysterosalpingography contrast medium." ]

[ "To compare use of the water-soluble, nonionic isosmolar dimer iotrolan with that of ethiodized poppy-seed oil in hysterosalpingography with regard to side effects, diagnostic quality, and postexamination conception rates.\n A prospective randomized design was used in a study of 245 patients. Questionnaires and patient records were used to acquire information. All examinations and ratings of diagnostic quality were performed by the same three investigators. Statistical calculations were performed with the chi 2 test, including the Mantel-Haenszel variant, and the Kruskal-Wallis test.\n No substantial differences between the contrast media could be detected concerning pain during the procedure, delayed pain, or postexamination bleeding. Visualization of the uterine cavity and ampullary rugae was markedly better with use of iotrolan. The postexamination conception rate was higher with use of ethiodized poppy-seed oil (24.0%) but was not significantly different statistically (P = .44) from that seen after use of iotrolan (19.8%).\n The authors believe the use of iotrolan is preferable to that of ethiodized poppy-seed oil.", "Hysterosalpingography (HSG) has assumed a diagnostic and possibly therapeutic role in the evaluation of the infertile couple. The procedure is done using either an oil-based (OBCM) or a water-based (WBCM) contrast medium. Data from several retrospective studies suggest that higher pregnancy rates may be achieved when OBCM is used. Interpretation of these results, however, may be confounded by various methodologic flaws in study design and comparisons of heterogeneous populations. We sought to compare the therapeutic benefit of OBCM and WBCM in a prospective randomized study of infertile patients, controlling for pelvic anatomy by laparoscopic assessment. We used ethiodized oil (Ethiodol) or iothalamate meglumine (Conray 60) for tubal lavage at the time of laparoscopy only in patients with normal pelvic anatomy. Of the 225 patients who had diagnostic laparoscopy in the evaluation of infertility, 40 (18%) had normal pelvic anatomy and an otherwise unremarkable evaluation. Adequate follow-up was available on 29 patients randomized to receive either OBCM (n = 15) or WBCM (n = 14). A significant difference in pregnancy rates was noted between OBCM (40%) and WBCM (14%) by chi-square analysis. No short- or long-term adverse reactions were noted. Results of this study suggest that in patients with normal pelvic anatomy as assessed laparoscopically, OBCM may offer a therapeutic benefit not evident with WBCM.", "In a prospective randomized study, the number of pregnancies after hysterosalpingography (HSG) was estimated in 398 patients who had been infertile for longer than 1 year. Iohexol was used in 101 patients, ioxaglate in 102 patients, diatrizoate meglumine in 97 patients, and ethiodized poppy-seed oil in 98 patients. Ten months after HSG, the patient, referring physician, and/or hospital department was consulted for information about pregnancies. Questionnaires were obtained from the patients who became pregnant during the waiting period of 3 months. No differences in demographic parameters, infertility status, or diagnosis made with HSG were detected among the four contrast media groups. Significantly more patients became pregnant after HSG in the ethiodized poppy-seed oil group than in the three water-soluble contrast media groups (P less than .01). When only intrauterine pregnancies resulting in full-term births were considered, significant differences in pregnancy rates between the oil-soluble and the water-soluble contrast media groups became more obvious. In the group that received ethiodized poppy-seed oil, almost one-third of the infertile women had normal pregnancies and childbirths after HSG.", "To assess the effectiveness of flushing with the oil-soluble contrast medium lipiodol in women with unexplained infertility.\n An open randomized controlled trial design in a single centre secondary and tertiary level infertility service setting. A total of 158 women with unexplained infertility were stratified into two populations: 96 women without confirmed endometriosis and 62 women with endometriosis who had normal Fallopian tubes and ovaries. Randomization was computer-generated, with allocation concealment by opaque sequentially numbered envelopes. Lipiodol flushing was tested versus no intervention. The main outcome measures were clinical pregnancy (assessed at 6 months following randomization) and live birth.\n Lipiodol flushing resulted in a significant increase in pregnancy [48.0 versus 10.8%, relative risk (RR) 4.44, 95% confidence interval (CI) 1.61-12.21] and live birth (40.0 versus 10.8%, RR 3.70, 95% CI 1.30-10.50) rates versus no intervention for women with endometriosis, although there was no significant difference in pregnancy (33.3 versus 20.8%, RR 1.60, 95% CI 0.81-3.16) or live birth (27.1 versus 14.6%, RR 1.86, 95% CI 0.81-4.25) rates for women with unexplained infertility without confirmed endometriosis.\n Lipiodol flushing is an effective treatment for couples with unexplained infertility (based on meta-analysis data), but is particularly effective for women with endometriosis who have normal Fallopian tubes and ovaries.", "To determine if there are therapeutic advantages to oil-soluble contrast medium compared with water-soluble medium during hysterosalpingography.A randomized, controlled trial including 56 infertile patients undergoing hysterosalpingography was performed. After a hysterosalpingogram with water-soluble contrast demonstrated tubal patency, 30 patients were randomized to receive oil-soluble contrast medium (oil group) and 26 patients received no additional contrast medium (control group). The outcome was pregnancy and timing of pregnancy in relation to hysterosalpingography. There were 18 (64%) pregnancies in the oil group and 14 (56%) pregnancies in the control group. Mean time to achieve pregnancy was shorter in the oil group: 3.8 months in the oil group compared with 6.1 months in the control group (P =.06) There was a clinically meaningful improvement in pregnancy rates between the oil group and the control group at 1 month postprocedure (relative risk [RR] 2.1, 95% confidence interval [CI] 0.6, 7.2). However, at 12 months postprocedure, the advantage was diminished. (RR 1.3, CI 0.8, 2.1)Eighteen months after hysterosalpingography, contrast does not appear to influence cumulative pregnancy rates; however, the addition of oil-soluble contrast medium to water-soluble contrast medium may have the potential to reduce the time to conception.", "Hysterosalpingography can be accomplished with either oil or water-soluble contrast medium. This randomized prospective study compared pregnancy rates in women who had hysterosalpingography with either water- or oil-soluble contrast material and were followed for six months. Fifteen of 60 (25%) patients who received water-soluble dye conceived compared with 14 of 46 (30%) patients in the oil-soluble group, a statistically insignificant difference. Furthermore, no difference in pregnancy rates within each subgroup of fertility diagnosis was detected. Intravasation was more common in patients administered oil-based contrast materials (six of 46 versus one of 60 patients, P = .02), although no serious consequences occurred. No difference in the amount of pain as assessed by pain scoring was experienced by patients in each group. The authors conclude that pregnancy rates are similar after hysterosalpingography with oil- and water-soluble contrast material, during at least the first six months after the procedure.", "To evaluate the influence of the contrast material used in hysterosalpingography (HSG) on subsequent reproductive success, independent of other therapeutic interventions.\n In a prospective, multisite, randomized trial, 666 women who had been infertile for more than 1 year and were scheduled to undergo HSG as part of their evaluation were assigned to one of three groups: those receiving water-soluble contrast material (WSCM) (n = 260), those receiving oil-soluble contrast material (OSCM) (n = 273), and those receiving both OSCM and WSCM (n = 133). Possible causes of infertility and therapeutic interventions were abstracted from the medical records. Data on conception within 1 year and the outcome of conception were ascertained from multiple sources.\n Of 666 women, 204 (30.6%) had at least one pregnancy, and 136 (20.4%) had live births. The rates of live births were 20.4% (54 of 260) after HSG with WSCM, 19.4% (53 of 273) after HSG with OSCM, and 21.8% (29 of 133) after HSG with both WSCM and OSCM. Differences in reproductive outcome among contrast material groups were not statistically significant ((chi2)8 = 6.08, P = .64). Whatever the cause of infertility, the use of different contrast materials led to no significant differences in the rates of live births.\n There is no evidence to suggest that the choice of contrast material affects the rate of term pregnancy.", "Eighty-eight infertile patients undergoing laparoscopy were randomized to undergo chromopertubation with lipiodol or with normal saline. The cumulative probability of conception at 1, 3, and 6 months following laparoscopy was not statistically different between the lipiodol group (21%, 31% , and 43%, respectively) and the saline group (18%, 21%, and 33%, respectively).", "To test the hypothesis that, in couples with unexplained infertility, tubal flushing with an oil-soluble media (lipiodol) would increase the pregnancy rate within 6 months compared with expectant management.\n A prospective, randomized, controlled study in which couples were allocated to either a single treatment with lipiodol or no further action.\n Two tertiary referral centers for assisted reproduction.\n Couples with a diagnosis of primary or secondary unexplained infertility based on a normal semen analysis according to World Health Organization criteria, patent fallopian tubes at hysterosalpingography or laparoscopy, and ovulatory menstrual cycles based on midluteal phase progesterone levels or ultrasonic follicle tracking.\n In those patients randomized to lipiodol, a single treatment was performed.\n Biochemical (i.e., positive pregnancy test) and clinical (i.e., fetal heart on ultrasound scan) pregnancy rates.\n Seventeen couples were randomized to lipiodol and 17 to expectant treatment. The higher pregnancy rate after lipiodol was statistically significant. There were no complications after lipiodol treatment.\n There was a statistically significantly higher pregnancy rate in couples with unexplained infertility randomized to a single tubal flush with lipiodol compared with no treatment.", "Previous studies have revealed that patients who underwent hysterosalpingography (HSG) with an iol-soluble contrast medium (OSCM) rather than a water-soluble contrast medium (WSCM) had higher subsequent fertility rates. In this randomized prospective study, the fertility rates among 109 patients following HSG were found to be 31% (19/61) in the WSOM group and 38% (18/48) in the WSOM + OSCM group. No significant difference was noted between these two groups, whether their infertility was associated with endocrine factor, male factor, endometriosis, mechanical factor or some other unexplained factor." ]

[ "12176505", "12118900", "12742468", "10589950", "14694177", "12717205", "15385832", "12829890", "11267196" ]

[ "Randomized trial of three different immunosuppressive regimens to prevent chronic renal allograft rejection.", "Effects of sirolimus on lipids in renal allograft recipients: an analysis using the Framingham risk model.", "Bicêtre hospital experience with sirolimus-based therapy in human renal transplantation: the Sirolimus European Renal Transplant Study.", "Sirolimus reduces the incidence of acute rejection episodes despite lower cyclosporine doses in caucasian recipients of mismatched primary renal allografts: a phase II trial. Rapamune Study Group.", "Addition of sirolimus to cyclosporine delays the recovery from delayed graft function but does not affect 1-year graft function.", "Randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: results at 6 months.", "Everolimus therapeutic concentration range defined from a prospective trial with reduced-exposure cyclosporine in de novo kidney transplantation.", "A prospective randomized multicenter study of tacrolimus in combination with sirolimus in renal-transplant recipients.", "A single-center open label randomized trial of the safety and efficacy of the use of sirolimus versus azathioprine in one-haplotype living related kidney transplant recipients-preliminary results." ]

[ "nan", "This report describes the effects of sirolimus on plasma lipids, and uses the Framingham risk model to assess the clinical importance of these effects. Lipid data from two large controlled studies of 1295 renal transplant patients were analyzed retrospectively. Sirolimus 2 mg/day and 5 mg/day were compared with placebo or azathioprine, and administered concomitantly with steroids and cyclosporine over 12 months. Hypercholesterolemia and hypertriglyceridemia occurred in all treatment groups and were maximal at 2-3 months. The sirolimus groups evidenced higher lipid levels than the controls, but the elevations diminished over time. At 1 year, the patients given sirolimus 2 mg/day had a mean cholesterol level 17 mg/dL greater and a mean triglyceride level 59 mg/dL greater than the controls. Among the patients given sirolimus 5 mg/day, mean cholesterol was 30 mg/dL greater and mean triglycerides were 103 mg/dL greater than the controls. Treatment with statins and fibrates was effective in reducing cholesterol and triglyceride levels, respectively, in the sirolimus-treated patients. The Framingham risk model predicted that the 17 mg/dL elevation in cholesterol would increase the incidence of coronary heart disease (CHD) by 1.5 new cases per 1000 persons per year and CHD death by 0.7 events per 1000 persons per year. Lipid elevations observed in the sirolimus-treated patients were manageable, improved over time, and responded to lipid-lowering therapy. Based on the Framingham risk model, the CHD risks associated with these cholesterol elevations are small compared with the baseline risks of the transplant population.", "In 11 European centers, first cadaveric renal allograft recipients were randomized to CsA (n = 42) or sirolimus (n = 41). Dosing of these agents was concentration-controlled and open-labeled. All patients received corticosteroids and azathioprine. At 12 months, graft survival (98% sirolimus vs 93% CsA), patient survival (100% vs 98%), and incidence of biopsy-confirmed acute rejection (41% vs 38%) were similar. Serum creatinine was lower with sirolimus, significantly (P </=.05) so at 3 and 4 months, and serum uric acid and magnesium were normal. Laboratory abnormalities were reported significantly more often with sirolimus, which included hypertriglyceridemia (51% vs 12%), hypercholesterolemia (44% vs 14%), thrombocytopenia (37% vs 0%), leukopenia (39% vs 14%), and, of lesser importance, increased liver enzymes and hypokalemia. These abnormalities improved 2 months after transplantation when the sirolimus target trough level was lowered from 30 to 15 ng/mL. Occurrence of cytomegalovirus was comparable (14% vs 12%), but incidence of herpes simplex (24% vs 10%, P =.08) and pneumonia (17% vs 2%, P =.03) were higher with sirolimus. No gingival hyperplasia was seen with sirolimus, tremor was rare, and hypertension was less frequent (17% vs 33%). Two malignancies were observed with CsA, none with sirolimus. Results at 12 months suggest that sirolimus can be used as base therapy in the prophylaxis of acute renal transplant rejection, and has a safety profile that differs from that of CsA.", "The novel agent sirolimus (SRL; Rapamune; rapamycin) inhibits the immune response by a mechanism distinct from those of calcineurin antagonists or antimetabolites. This randomized, controlled, multicenter, single blind, phase II trial examined the combination of SRL, steroids, and full versus reduced doses of cyclosporine (CsA) for prophylaxis of acute renal allograft rejection.\n A total of 149 recipients of mismatched cadaveric- or living-donor primary renal allografts were randomized into six groups. Three groups received placebo or 1 or 3 mg/m2/day SRL, as well as steroids and full-dose CsA (Sandimmune). Three groups received steroids, reduced-dose CsA (target trough level 50% of full-dose range), and 1, 3, or 5 mg/m2/day SRL.\n The incidence of biopsy-proven acute rejection episodes within the first 6 months after transplant was reduced from 32.0% in the control group to 8.5% in patients receiving SRL (1 or 3 mg/m2/day) and full-dose Sandimmune CsA (P=0.018). Similar low rates of acute rejection episodes were observed among non-African-Americans, but not African-Americans, treated with SRL and reduced-dose Sandimmune CsA. Despite the augmented immunosuppression, 1-year patient and graft survival rates did not differ significantly across groups. Adverse effects attributable to CsA, including hypertension and new-onset diabetes mellitus, were not exacerbated by SRL. Except for an increased incidence of pneumonia among patients receiving full-dose CsA and 3 mg/m2/day SRL, the incidences of opportunistic infections were similar in all treatment groups. Although SRL produced more frequent, but reversible, hematological and lipid abnormalities, it had no apparent nephrotoxic effects to exacerbate CsA-induced renal dysfunction.\n SRL in combination with CsA and steroids not only lowers the incidence of biopsy-proven acute renal allograft rejection episodes, but also may permit CsA sparing, at least among Caucasian patients, without an increased risk of rejection.", "Delayed graft function (DGF) has long been identified as one of the main correlates of poor graft survival in cadaveric renal transplantation, but the factors that affect its onset and duration are not fully elucidated. The impact of two immunosuppressive protocols on the incidence and length of DGF among kidney transplant recipients of a suboptimal organ was evaluated. Patients were randomly treated with corticosteroids (CS); low-dose cyclosporine (CsA) and sirolimus (SRL; group 1; n = 42); or CS, full-dose CsA, and mycophenolate mofetil (group 2; n = 48). All recipients received immunoprophylaxis with basiliximab. After 3 mo, group 1 discontinued CsA and continued with SRL, whereas group 2 continued the same treatment. The incidence of DGF was similar in the two groups (group 1 = 52.4%; group 2 = 58.3%), whereas its duration was significantly higher in the group 1 (19.0 +/- 6.0 versus 10.3 +/- 3.2 d; P = 0.001). Both groups showed 100% actuarial graft and patient survival at 1-yr. Among DGF patients, serum creatinine (sCr) at discharge was significantly worse in group 1 (sCr, 3.0 +/- 1.0 versus 1.5 +/- 0.2 mg/dl; calculated creatinine clearance, 31.2 +/- 9.3 versus 61.1 +/- 10 ml/min; P = 0.001). During the first year, the former group displayed a significant improvement of graft function, such that at 1-yr, no difference could be measured between groups (sCr, 1.8 +/- 0.5 versus 1.7 +/- 0.4 mg/dl; calculated creatinine clearance, 51.5 +/- 10.2 versus 53.3 +/- 9.4 ml/min). In conclusion, in de novo renal transplanted patients, the administration of SRL, in combination with low-dose CsA, is associated with a delayed recovery from DGF but does not worsen 1-yr graft function.", "This is the first report of a randomized, multicenter, clinical trial comparing the combination of sirolimus or mycophenolate mofetil (MMF) with tacrolimus-based immunosuppression in kidney transplantation. Results at 6 months of follow-up are presented.\n Before transplantation, patients were randomized to receive tacrolimus plus corticosteroids with sirolimus (n=185) or MMF (n=176). The primary endpoint of the study was the incidence of biopsy-confirmed acute rejection. Patient and graft survival, renal function, and composite endpoints also were evaluated. Safety was assessed by monitoring laboratory parameters and adverse events.\n By 6 months of follow-up, the incidence of biopsy-confirmed acute rejection was similar in both treatment groups (13.0% tacrolimus+sirolimus vs. 11.4% tacrolimus+MMF; P=0.64 log-rank). Patient survival (97.3% tacrolimus+sirolimus vs. 97.7% tacrolimus+MMF) and graft survival (93.0% tacrolimus+sirolimus vs. 95.5% tacrolimus+MMF) were equivalent (P=0.53, overall survival log-rank). There was a significantly higher incidence of study drug discontinuation in patients receiving sirolimus (21.1% vs. 10.8%; P=0.008). Renal function was significantly better in the MMF-treatment group (serum creatinine 1.44+/-0.45 mg/dL vs. 1.77+/-1.42 mg/dL; P=0.018). Hyperlipidemia was significantly more prevalent in the sirolimus-treatment group. Diastolic blood pressure was significantly higher in sirolimus-treated patients. There were significantly more leukopenia and gastrointestinal adverse events in the MMF-treatment group. The incidence of posttransplant diabetes mellitus was 7.6% in the sirolimus group and 7.7% in the MMF group.\n Tacrolimus is equally effective in renal transplantation when combined with sirolimus or MMF. The tacrolimus-MMF combination may be superior in terms of improved renal function and improved cardiovascular risk factors including hyperlipidemia and hypertension.", "Prospective therapeutic drug monitoring of everolimus was performed in a 1-year multicenter trial in 237 de novo kidney transplant patients. Trough blood levels, rejection episodes, and safety parameters were evaluated to define an appropriate therapeutic concentration range for everolimus in this setting. Patients were randomized to everolimus starting doses of 0.75 mg bid (n = 112) or 1.5 mg bid (n = 125). Doses were then individualized based on everolimus trough blood levels (C0) in an attempt to maintain troughs > or = 3 ng/mL; no upper limit was specified. The regimen also contained corticosteroids and cyclosporine with an early dose reduction in months 2-3 posttransplant based on concentrations 2 hours postdose (C2). Cyclosporine C0 levels were also collected. Prospective therapeutic drug monitoring of everolimus C0 in patients starting at 0.75 mg bid led to dose adjustments in 52% of patients to an average long-term dose of 0.93 +/- 0.36 mg bid. This gave median (10th to 90th percentile) C0 levels of 5.3 (3.4-7.9) ng/mL. In patients starting at 1.5 mg bid, 55% had dose adjustments leading to an average long-term dose of 1.24 +/- 0.35 mg bid. This yielded C0 levels of 7.2 (4.4-11.6) ng/mL. Cyclosporine dosing began on average at 274 +/- 78 mg bid, was down-titrated in months 2-3 from 181 +/- 80 mg to 81 +/- 33 mg bid, and stabilized at 70 +/- 26 mg bid thereafter. This yielded median C2 levels of 1165 ng/mL in month 1, a down-titration with levels of 853 and 630 ng/mL in months 2 and 3, and a posttitration level of 472 ng/mL. The corresponding median cyclosporine C0 was 242 ng/mL initially and 70 ng/mL in the posttitration phase. In patients starting at 0.75 mg bid everolimus and an early down-titration of cyclosporine, everolimus C0 between 3 and 8 ng/mL was an effective and safe concentration range. Concentrations up to 12 ng/mL were tolerated over the first year posttransplant. This trial demonstrated that therapeutic monitoring of everolimus can be prospectively performed for dose individualization. Maintaining everolimus troughs in the range 3 to 8 ng/mL in the first posttransplant year with reduced-exposure cyclosporine is associated with good efficacy and safety profiles.", "Recently, sirolimus (SRL) was introduced as an immunosuppressant in solid-organ transplantation. This study evaluated combinations of SRL and tacrolimus (Tac).\n This 6-month study investigated the safety and efficacy of Tac and steroids in combination with three different doses of SRL in renal-transplant recipients. A total of 104 patients were randomized in four groups: one group received Tac and steroids (control n=28), and three groups also received the following daily SRL doses: 0.5 mg (TacSRL0.5, n=25), 1 mg (TacSRL1, n=25), or 2 mg (TacSRL2, n=26). Tac doses were adjusted to whole-blood trough levels. Steroids were tapered from 20 mg per day to 5 mg per day. The SRL groups underwent a second randomization to discontinue SRL at either month 3 or 5.\n At month 6, patient survival rates were 100%, 100%, 96.0%, and 100%, and graft survival rates were 96.4%, 84.0%, 88.0%, and 84.6%, respectively. The overall safety profile was similar in all groups. The incidences of infections during months 1 to 3 were similar in all groups (control 46.4%, TacSRL0.5 32.0%, TacSRL1 56.0%, TacSRL2 46.2%). The 3-month incidences of hypercholesteremia (cholesterol >240 mg/dL or low-density lipoprotein cholesterol >160 mg/dL) were 21.4%, 36.0%, 48.0%, and 50.0% (P=0.019). Lipid levels improved after withdrawal of SRL. The 3-month incidences of biopsy-proven acute rejection were 28.6% (control), 8.0% (TacSRL0.5), 8.0% (TacSRL1), and 3.8% (TacSRL2) (P=0.014).\n Tac in combination with low doses of SRL provides a very effective and safe regimen.", "nan" ]

[ "1875206", "11949239", "12216025", "9199073", "7902225", "11561502", "8581442", "8077977", "17162178", "9474633", "17592713", "7907012" ]

[ "Postoperative use of continuous passive motion, transcutaneous electrical nerve stimulation, and continuous cooling pad following total knee arthroplasty.", "A randomized, controlled trial comparing compression bandaging and cold therapy in postoperative total knee replacement surgery.", "Continuous-flow cold therapy after total knee arthroplasty.", "[Cryotherapy as analgesic technique in direct, postoperative treatment following elective joint replacement].", "The role of cold compression dressings in the postoperative treatment of total knee arthroplasty.", "Cryotherapy compared with Robert Jones bandage after total knee replacement: a prospective randomized trial.", "The effect of cold therapy on the postoperative course of total hip and knee arthroplasty patients.", "Cryotherapy for postoperative pain relief following knee arthroplasty.", "Postoperative cryotherapy after total knee arthroplasty: a prospective study of 86 patients.", "The use of cold compression dressings after total knee replacement: a randomized controlled trial.", "Cryotherapy temperature differences after total knee arthroplasty: a prospective randomized trial.", "Cold compressive dressing after total knee arthroplasty." ]

[ "Three rehabilitation modalities relating to in-hospital postoperative care following unilateral total knee arthroplasty (UTKA) were studied regarding their effect on pain management and UTKA outcome: (1) continuous passive motion (CPM); (2) CPM with transcutaneous electrical nerve stimulation (TENS); and (3) CPM with continuous cooling pad (CCP). Phase I: CPM. Twenty-two UTKA patients were randomized into two postoperative care groups: (1) 12 with CPM; and (2) 10 with no CPM. Total hospitalization pain medication consumption was significantly less for the CPM group (P less than .05). Phase II: CPM With TENS. Forty-eight UTKA patients were randomized into three postoperative care groups: (1) 18 with an ipsilateral thigh TENS unit delivering sensory threshold stimulation; (2) 18 with a subthreshold TENS unit; and (3) 12 with no TENS unit. All groups used CPM. No significant difference was found regarding pain medication consumption. Phase III: CPM With CCP. Thirty consecutive UTKA patients were divided into two postoperative care groups: (1) 15 with a CCP unit; and (2) 15 with no CCP unit. Both groups used CPM. No significant difference was found regarding total or intramuscular hospitalization pain medication consumption. However, oral hospitalization pain medication consumption was significantly less for the CCP group (P less than .01). This postoperative UTKA study demonstrates significantly decreased total in-hospital pain medication consumption when comparing CPM vs no CPM, significantly decreased oral in-hospital pain medication consumption when comparing CPM with CCP vs CPM without CCP, but no difference when comparing CPM with TENS vs CPM without TENS.(ABSTRACT TRUNCATED AT 250 WORDS)", "To examine the difference between compression bandaging and cold therapy after total knee arthroplasty.\n Eighty-four postoperative, unilateral, total knee replacement, surgical clients.\n Clients were randomized into two groups: those receiving compression bandaging, and those receiving cryo-pad technology. Subjects were assessed for total length of stay, blood loss, blood transfusion, swelling, flexion, pain, and opiate use.\n Unlike other studies, the results of these data showed no significant differences between groups on the measured outcomes. A simple cost benefit analysis shows that the compression bandage is cheaper and more labor efficient than the cold therapy as delivered by cryo-pad technology.", "Cryotherapy is widely used as an emergency treatment of sports trauma and postoperatively especially after anterior cruciate ligament reconstruction. Studies in the literature on the effect of cryotherapy after total knee arthroplasty (TKA) have been limited and controversial. In this prospective study, 60 primary TKAs were done on 30 patients (all staged bilateral TKAs). For every patient, 1 TKA had a continuous-flow cooling device applied over the surgical dressing immediately postoperatively. The other TKA in the same patient (control TKA) was done 6 weeks later and had no cooling device. The study compared the range of motion, the volume of hemovac output and blood loss, visual analog pain score, analgesic consumption, and wound healing in the 2 limbs of the same patient. This study showed that continuous-flow cold therapy is advantageous after TKA because it provides better results in all the areas compared.\n Copyright 2002, Elsevier Science (USA).", "The application of crushed ice or hydrogenated silicate, a micro-crystalline substitute has been used as a method to treat posttraumatic and postoperative irritations of the locomotor system for a long time. Closed systems using pumps can be viewed as further development as they enable continuous, water-free cooling of operating areas. The analgetic effect of postoperative cold therapy was evaluated in a prospective clinical trial, including 312 patients after total knee or hip arthroplasty. Conventional cold packs, consisting of microcrystalline silicate were compared to a continuous applicable closed system. Continuous cryotherapy resulted in a depression of skin temperature to 12 degrees C, whereas intermittent cooling only caused a mean temperature decrease of 1 degree C. Clinically continuous cold application leads to a more than 50% decrease of analgetic demands in both, systemic and regional application (p < 0.001). This observation was found in a significant correlation with patient's pain sensation as well as primary range of motion. Intermittent cryotherapy was found to be ineffective in postoperative pain relieve in hip- and adequate in knee arthroplasty patients. We could not report an influence on postoperative blood loss, as discussed in previous reports.", "A prospective randomized study was performed to evaluate the role of cold compressive dressings in the postoperative treatment of total knee arthroplasty (TKA). Eighty consecutive unilateral and ten bilateral primary total knee replacements were evaluated in terms of blood loss, pain relief, and range of motion. Patients in the cold compression group demonstrated an average of 548 ml in suction drainage, whereas those in the control group averaged 807 ml. This resulted in an average 3.1 mg hemoglobin drop in the cold compression group and 4.7 mg in the control group. When body habitus and weight were taken into account in the cold compression group, an average total blood loss of 1298 cc was calculated, with 744 ml arising from soft tissue extravasation. The corresponding total blood loss calculated average was 1908 ml in the control group, with 1101 ml attributed to soft tissue extravasation. Total injectable morphine per kilogram per initial 48 hours averaged 0.53 mg in the cold compression patients and 0.69 mg in the control patients. In the cold compression knees, range of motion averaged 86 degrees before operation, 53 degrees on postoperative day (POD) 7, and 77 degrees on POD 14. In the control knees, range of motion averaged 88 degrees before operation, 44 degrees on POD 7, and 65 degrees on POD 14. The use of cold compression in the postoperative period of TKA results in a dramatic decrease in blood loss. In addition, mild improvements are seen in early return of motion and injectable narcotic pain needs in the postoperative period.", "Sixty patients undergoing total knee replacement were randomized to receive either a cold compression dressing (Cryo/Cuff, Aircast, UK) or a modified Robert Jones bandage immediately after surgery. The cold compression dressing was used for a minimum of 6 h per day throughout the hospital stay, and the modified Robert Jones bandage remained in place for 48 h from the time of operation. The 2 groups of patients were compared during their hospital stay for blood loss, range of movement, pain scores and need for analgesia. No difference was found between the 2 groups except for less blood loss in the surgical drains in the cold compression group (P < 0.05). Postoperative complications were seen in both groups, but no complication was associated with either the cold compression dressing or the modified Robert Jones bandage.", "Fifty total hip arthroplasty (THA) patients and 24 total knee arthroplasty (TKA) patients were randomized in a controlled study to examine the effects of cold therapy (via thermal blankets) in the postoperative period. The postoperative hospital stay was significantly shorter for the cold-therapy (50 degrees F) compared with control (70 degrees F) groups (by 1.4 days, P = 0.03) for THA patients. There was a similar but nonsignificant trend observed in the TKA groups (1.5 days shorter, P = 0.19). Total knee arthroplasty patients using cold therapy achieved independent ambulation an average of 1 day sooner than TKA control patients, but this difference did not reach statistical significance (P = 0.08). There were no statistically significant differences between the control groups or the test groups for both THA and TKA patients in narcotic usage, postoperative range-of-motion (ROM), or rate of progression of ROM.", "Ninety consecutive patients undergoing primary knee arthroplasty received local cryotherapy 72 hours after surgery for pain relief. Thermal-pad circulating temperatures were randomly assigned to 50 degrees, 60 degrees, or 70 degrees F (room temperature). Pain relief was monitored using patient-controlled analgesia machines. The amount of morphine received and number of attempts per hour were statistically analyzed with relation to temperature group, age, sex, weight, side, and diagnosis. The amount of morphine injected was positively correlated to the number of attempts per hour and moderately correlated to body weight. There was no correlation between thermal-pad temperature or any other parameter and the amount of morphine injected after surgery.", "A study of 86 patients undergoing total knee arthroplasty (TKA) was performed to evaluate the role of cold compression. The patients were treated with cold compression or epidural analgesia for 3 days after TKA. Pain was measured on a visual analog scale, and total consumption of analgesics was recorded. Range of movement (ROM) was recorded before TKA until 3 weeks postoperatively. Weight bearing, blood loss, and time in hospital were recorded. Visual analog scale scores and analgesic consumption were equal in both groups. Range of movement at discharge was 75 degrees in the cold compression group vs 63 degrees in the control group. By 3 weeks' follow-up, ROM was 99 degrees vs 88 degrees. Mean Hb values averaged 120 mmol/L in the cold compression group vs 109 mmol/L in the control group after surgery. Mean time in hospital of patients with cold compression averaged 4.8 days vs 6.2 days in the control group. The study shows that cold compression therapy improves the control of pain and might thus lead to improvement in ROM and shorter hospital stay.", "This prospective, controlled study compared cold compressive dressings with wool and crepe in the postoperative management of patients undergoing total knee replacement (TKR). Forty TKR patients were assessed for blood loss, pain, swelling, and range of motion. Patients in the cold compression group had less blood loss through suction drainage (982 mL versus 768 mL). A higher proportion of patients in the treatment group did not require blood transfusion postoperatively. Mean opiate requirements were lower in the cold compression group (0.57 versus 0.71 mg/kg/48 hours). The cold compression device appeared to reduce blood loss and pain following TKR.", "In spite of its widespread use after orthopaedic procedures, the literature evaluating the clinical efficacy of cryotherapy is controversial. The purpose of this prospective randomized trial was to compare two different temperatures for administering cryotherapy after total knee arthroplasty with regards to short-term postoperative outcomes. Sixty-four subjects were assigned either the 45 degrees F group or the 75 degrees F group. Subjects in the 45 degrees group were as likely to report a lower pain score at the time of follow-up compared to the 75 degrees group. Our results demonstrate no additional analgesic effect associated with the lower temperature of cryotherapy. Postoperative narcotic consumption, postoperative drainage, self-reported knee function, and range of motion were not affected by the different cryotherapy temperatures. No adverse effects were reported with the cryotherapy treatment.", "The efficacy of a cold compressive dressing after total knee arthroplasty (TKA) was prospectively studied in 105 knees in 76 patients. All components were cemented. All patients were placed in continuous passive motion machines after operation. A cold compressive Cryocuff dressing was applied to 50 knees after operation. An ACE wrap and ice pack were applied to the knees of 55 control patients after operation. Postoperative range of motion was recorded as maximum active flexion at two to four days (interval one), at seven to 14 days (interval two), and four to six weeks (interval three). Swelling was measured at the same time intervals by circumference at the midpatella and circumference at the distal thigh one inch proximal to the superior pole of the patella. Use of postoperative narcotics was calculated for postoperative days zero to three and for postoperative days four to seven. Wound drainage was recorded for all knees. The use of a cold compressive dressing after TKA was not associated with an increase in range of motion at any point after the operation. The Cryocuff dressing did not appreciably reduce swelling around the knee after TKA. No significant difference was found in the amount of postoperative wound drainage between the two groups of patients. In patients undergoing unilateral TKA, no significant difference existed between the narcotic requirements of control patients and patients wearing the cold compressive dressing." ]

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[ "A comparison of the association of helicopter and ground ambulance transport with the outcome of injury in trauma patients transported from the scene.", "One year's trauma mortality experience at Brooke Army Medical Center: is aeromedical transportation of trauma patients necessary?", "The impact of advanced prehospital emergency care on the mortality of severely brain-injured patients.", "Factors improving survival in multisystem trauma patients.", "The effect of air medical transport on survival after trauma in Johannesburg, South Africa.", "Association of direct helicopter versus ground transport and in-hospital mortality in trauma patients: a propensity score analysis.", "Helicopter transport and blunt trauma mortality: a multicenter trial.", "The impact of a rotorcraft aeromedical emergency care service on trauma mortality.", "Helicopter evacuation of trauma victims in Los Angeles: does it improve survival?", "Impact of helicopter transport and hospital level on mortality of polytrauma patients.", "Air medical scene response to blunt trauma: effect on early survival.", "[The influence of transportation mode on mortality in polytraumatized patients. An analysis based on the German Trauma Registry].", "Effects of 2 patterns of prehospital care on the outcome of patients with severe head injury.", "Helicopters and the civilian trauma system: national utilization patterns demonstrate improved outcomes after traumatic injury.", "Helicopters improve survival in seriously injured patients requiring interfacility transfer for definitive care.", "Impact of emergency medical helicopter service on mortality for trauma in north-east Italy. A regional prospective audit.", "The impact of aeromedical response to patients with moderate to severe traumatic brain injury.", "Air versus ground transport of the major trauma patient: a natural experiment.", "Air versus ground transport of major trauma patients to a tertiary trauma centre: a province-wide comparison using TRISS analysis.", "Influence of prehospital treatment on the outcome of patients with severe blunt traumatic brain injury: a single-centre study.", "Reduced mortality in injured adults transported by helicopter emergency medical services.", "A comparison of ground paramedics and aeromedical treatment of severe blunt trauma patients.", "Effect of helicopter transport of trauma victims on survival in an urban trauma center.", "Emergency medical services intervals and survival in trauma: assessment of the \"golden hour\" in a North American prospective cohort.", "Effects of London helicopter emergency medical service on survival after trauma." ]

[ "Comprehensive emergency medical services and helicopter aeromedical transport systems have been developed based on the principle that early definitive care improves outcome. The purpose of this study was to compare outcomes between patients transported by helicopter and those transported by ground.\n Data were obtained from the North Carolina Trauma Registry for the period between 1987 and 1993 on all patients transported by helicopter and ground admitted to one of the eight state designated trauma centers. Study patients included only those who were transported directly from the scene of injury to the trauma center (interhospital transfers were excluded). Mortality (outcome) was compared after patient stratification by injury severity and transport time, using Cochran-Mantel-Haenszel statistics and logistic regression-derived probabilities of survival.\n One thousand three hundred forty-six patients (7.3% of the total) were transported from scene to trauma center by helicopter and 17,144 were transported by ground. In patients transported by helicopter, the mean Trauma Score was lower (12 +/- 3.6) versus 14.3 +/- 3.6 (p < 0.001) and the mean Injury Severity Score was higher (17 +/- 11.1) versus 10.8 +/- 8.4 (p < 0.001). A trend toward increased survival was observed among patients transported by helicopter with a higher Injury Severity Score. Statistical significance was achieved only for patients with a Trauma Score between 5 and 12 and Injury Severity Score between 21 and 30.\n The large majority of trauma patients transported by both helicopter and ground ambulance have low injury severity measures. Outcomes were not uniformly better among patients transported by helicopter. Only a very small subset of patients transported by helicopter appear to have any chance of improved survival based on their helicopter transport. This study suggests that further effort should be expended to try to better identify patients who may benefit from this expensive and risky mode of transport.", "The purpose of this study was to review whether air ambulance transportation of trauma patients to the Brooke Army Medical Center (BAMC) level I trauma center contributed to maintaining national mortality standards in the trauma care of these patients. Aeromedical transportation is considered a standard-of-care component of regional trauma systems throughout the United States. Pooled trauma database information from 792 consecutive ambulance-transported trauma patients received at BAMC during the fiscal year from October 1, 1995, to September 30, 1996, were reviewed. The 792 trauma patients were composed of 687 patients transported by ground ambulance and 105 patients who received helicopter aeromedical evacuation. Aeromedical evacuation was associated with increased levels of prehospital medical care and faster transportation than ground ambulance service. The mortality rates (immediate, early, and late deaths) of both ambulance groups were compared with national mortality standards using the internationally recognized Trauma and Injury Severity Score methodology, based on the Major Trauma Outcome Study in 1986 and validated in 1992. The Z test for independent populations demonstrated no statistically significant difference between BAMC trauma mortality rates for either ambulance group compared with national trauma mortality rates. The results suggest that aeromedical evacuation of the more severely injured patients farthest from the BAMC trauma center resulted in mortality rates that met national standards.", "The mortality of 128 consecutive severely brain-injured patients (Glasgow Coma Score less than or equal to 8) treated by a land advanced life support system and transported to a trauma center was compared to the mortality of 104 consecutive severely brain-injured patients treated during the same time period by an advanced care rotorcraft aeromedical emergency service and transported to the same trauma center. The two patient groups had statistically similar distribution of CNS lesions and Glasgow Coma Scores. The mortality of the patients treated by the land ALS system was 40%. The mortality of the patients treated by the aeromedical service was 31%. The 9% reduction in mortality in the patients treated by the aeromedical service was statistically significant (p less than 0.001). There was also a statistically significant (p less than 0.05) reduction in the Glasgow Outcome Scores of the patients treated by the aeromedical service compared with patients treated by the land advanced life support system.", "This report analyzes the effect of air versus ground interhospital transport on survival following multisystem injury. There were 136 air-transported patients versus 194 ground-transported patients. The groups were similar in trauma scores, ages, mechanism of injury, and organ systems injured. There was a statistically significant survival advantage for air-transported patients with trauma scores between 10 and 5 (82.8% survival vs. 53.5%, p = less than 0.001). The time interval between accident and admission to the authors' institution was similar for both groups. Important therapeutic interventions contributing to better survival by the air-transported group included higher incidences of endotracheal intubation (50% vs. 25%), blood transfusions (32% vs. 10%), larger volumes of electrolyte fluid (3.3 L per patient vs. 2.1 L per patient) as well as the use of MAST trousers (60.3% vs. 34.9%). Transport charges for both ground and air services were similar. However, helicopter charges met only 15% of the operational budget of the aeromedical service. The remainder of the costs were generated from hospital patient revenues. Overall, total hospital charges were similar for both groups and were influenced by the variability of length of stay, particularly for orthopedic patients.", "To assess the difference in survival of trauma patients transported to a trauma unit via either road or air in Johannesburg, South Africa.\n Prospective database analysis.\n Multicentre study utilising two trauma units.\n The study evaluated 428 subjects admitted to the two sites.\n Actual survival rates in each group (road and air) were compared with the predicted survival rates.\n In the road group, 38.96 people were predicted to die and 51 actually died, therefore 23.61% (or 12.04 people) died 'unnecessarily', i.e. they died after having been predicted to live. In the helicopter group, 38.15 people were predicted to die and 39 actually died, therefore 0.85 (39-38.15) people were not expected to die. The 0.85 people represent 2.18% (0.85/39) of the total number of dead in the helicopter group who died 'unnecessarily'. Therefore one could argue that introduction of helicopter transport reduces the number of dead by 21.43% (23.61-2.18).\n Patients with a certain injury severity are more likely to survive if transported by air to a trauma unit.", "Helicopter emergency medical services (HEMS) transport of trauma patients has been used for decades. Its use, however, is still a subject of debate, including issues such as high costs, increasing numbers of crashes, and conflicting results regarding effectiveness in reducing mortality. The aim of this study was to examine whether mode of transport (HEMS vs. ground EMS) is independently associated with mortality among trauma patients transported directly from the scene of injury to definitive care.\n All trauma patients transported directly to a Level I or Level II trauma center by either air or ground EMS over a 4-year period were selected from the Oklahoma State Trauma Registry. Multivariable logistic regression was used to develop propensity scores based on variables measured at the scene of injury. The propensity scores represented the predicted probabilities of a patient being transported by HEMS given a specific set of characteristics and were used as a composite confounding variable in subsequent models of the association of mortality and mode of transport. Along with the propensity scores, Injury Severity Scores (ISS), initial Revised Trauma Score (RTS), and distance from the trauma center were included in a Cox proportional hazards model of the association of mode of transport and 24-hour and 2-week mortality.\n Overall, the hazard ratio (HR) for 2-week mortality in patients transported by HEMS was 33% lower (HR = 0.67, 95% confidence interval [CI] = 0.54 to 0.84) than in patients transported by ground EMS from the scene of injury, after adjustment for the propensity score and other covariates. In subanalyses, the apparent association of a reduction in the hazard of early mortality among patients transported by HEMS was most evident for patients with an RTS based on injury scene vital signs of 3 to 7 (HR = 0.61, 95% CI = 0.46 to 0.82). The point estimate of the HR was similar (HR = 0.65 95% CI = 0.34 to 1.2) in the 75% of cases who had normal vital signs at the scene of injury, although it was no longer statistically significant because crude mortality was very low (1.7%) in this group. Among those with a RTS of 3 or less at the scene, crude mortality was 58%, and mode of transport was not associated with mortality (HR = 1.02, 95% CI = 0.68 to 1.6).\n Helicopter EMS transport was associated with a decreased hazard of mortality among certain patients transported from the scene of injury directly to definitive care. Refinements in scene triage and transport guidelines are needed to more effectively select patients that may benefit from HEMS transport from those unlikely to benefit.\n © 2011 by the Society for Academic Emergency Medicine.", "Despite many studies addressing potential impact of helicopter transport on trauma mortality, debate as to the efficacy of air transport continues.\n This retrospective study combined trauma registry data from five urban Level I adult and pediatric centers. Logistic regression assessed effect of helicopter transport on mortality while adjusting for age, sex, transport year, receiving hospital, prehospital level of care (Advanced Life Support vs. Basic Life Support), ISS, and mission type (scene vs. interfacility).\n The study database comprised 16,699 patients. Crude mortality for Air (9.4%) was 3.4 times (95% CI, 2.9-4.0, p < 0.001) that of Ground (3.0%) patients. In adjusted analysis, helicopter transport was found to be associated with a significant mortality reduction (odds ratio, 0.76; 95% CI, 0.59-0.98; p = 0.031).\n The results of this study are consistent with an association between helicopter transport mode and increased survival in blunt trauma patients.", "The mortality of 150 consecutive trauma patients treated at the site of injury and transported to a trauma center by standard land prehospital care services was compared with that of 150 consecutive trauma patients treated at the site of injury and transported to the same trauma center by a rotorcraft aeromedical service staffed by a physician and nurse. A statistical analysis designed to predict mortality based on injury severity revealed that the mortality of the land group was statistically no different from that of a large index trauma patient population treated at a major trauma center. There was a 52% reduction in predicted mortality of the aeromedical group, which was highly significant.", "The purpose of this study was to investigate the relationship between the method of transport after injury and survival among trauma patients admitted to a Level 1 trauma facility in Los Angeles, California.\n The trauma registry of LAC+USC Medical Center was reviewed to identify all injured patients evacuated by emergency medical service (EMS) from the injury scene from 1998 to 2007. The study population was divided into those who were airlifted (HEMS) and those who were transported by ground emergency medical service (GEMS) with transportation time that exceeded 30 minutes (GEMS > 30 minutes).\n During the 10-year study period, 1,836 patients were airlifted (helicopters for emergency medical service (HEMS)) and 1,537 patients were ground transported (GEMS > 30 minutes). HEMS patients suffered more frequently a penetrating injury (19% vs. 11%, p < 0.001), presented more often hypotensive to the emergency department (4% vs. 1%, p < 0.001), had more frequently a Glasgow Coma Scale (GCS) < or = 8 (9% vs. 3%, p < 0.001) and required more often an intubation at the injury scene (1.6% vs. 0.4%, p < 0.001). However, the transportation time and the total prehospital time were significantly shorter for airlifted patients. After multivariable analysis, the difference in mortality between the two transport modalities was not significant (adjusted odds ratio (95% confidence interval, 0.72 (0.22, 2.35); p = 0.596).\n In a metropolitan Los Angeles trauma system, EMS helicopter transportation of injured patients does not appear to improve overall adjusted survival after injury. There is however a potential benefit for severely injured subgroups of patients due to the shorter prehospital times.", "Despite numerous studies analyzing this topic, specific advantages of helicopter transport of blunt polytrauma patients as compared with ground ambulances have not yet been identified unequivocally.\n Four possible pathways in 403 polytrauma patients (Injury Severity Score [ISS] > 16) who were in reach of the helicopter emergency medical service (HEMS) Dresden were analyzed as follows: HEMS-UNI group (n = 140), transfer by HEMS into a university hospital; AMB-REG group (n = 102), transfer by ground ambulance into a regional (Level II or III) hospital; AMB-UNI group (n = 70), transfer by ground ambulance into the university hospital; and INTER group (n = 91), transfer by ground ambulance into a regional hospital, followed by transfer to the university hospital. Scores used were the ISS and the TRISS. Tests used for statistical analysis included chi2 and Fisher's tests. Statistical significance was set at p > 0.05.\n Age, gender, and mean ISS (range, 33.3-35.6) revealed extensive homogeneity of the groups. Mortality of the AMB-REG group was almost doubled (41.2%) compared with HEMS-UNI (22.1%) patients (p = 0.002). The AMB-UNI group displayed the lowest mortality (15.7%, p = not significant). TRISS analysis (PRE-Chart) revealed identical outcome for AMB-UNI and HEMS-UNI patients. Rescue time averaged 90 +/- 29 minutes for HEMS-UNI patients, 68 +/- 25 minutes for AMB-UNI patients, and 69 +/- 26 minutes for the AMB-REG group.\n Primary transfer by HEMS into a Level I trauma center reduces mortality markedly. In principle, this benefit can be attributed to superior preclinical therapy, primary admission to a Level I trauma center, or both. However, the identical probability of survival of the AMB-UNI and HEMS-UNI groups in this and comparable studies does not confirm generally better survival rates on account of a more aggressive on-site approach.", "nan", "Thirty years after its introduction in Germany, the benefits of the helicopter emergency medical service (HEMS) compared to ground ambulances (GA) still remain unclear. The aim of this study was to evaluate the influence of helicopter transport on rescue time and mortality based on the data of the German Trauma Registry.\n Data from patients with multiple injuries were documented prospectively between 1993 and 2003 in different trauma centers in Germany, Switzerland, Austria and The Netherlands. From these data, patients with an injury severity score (ISS)<16 were excluded. Patients who were transported to the hospital without a physician were also excluded. The data from included patients were evaluated for time to hospital and influence of transportation service on mortality.\n A total of 7,534 patients with multiple injuries were included. Of these, 3,870 patients were transported by HEMS and 3,664 reached the hospital by GA. There were 74.9% male patients in the HEMS group, and 71.3% male patients in the GA group. The mean ISS was higher in the HEMS group (31.4 vs 30.7; P<0.01); patients transported by GA were older (HEMS: 39.2; NEF:41.3; P<0.01). The GA arrived on the scene after 14.33 min, the HEMS after 18.18 min (P<0.01). Time at the scene was longer in the HEMS group (HEMS: 26:26 min; NEF: 22:29 min; P<0.01). Intubation rate in the HEMS group was about 80%, while patients transported by GA were intubated in 60% of cases. The overall mortality was 30.9%. Evaluation of the TRISS prediction of survival showed a benefit for patients transported with HEMS. In a multivariate analysis, intubated patients with ISS<or=60 had a lower mortality rate if transported with HEMS (NEF: 40.1%; HEMS 34.9%; P<0.01).\n Only minor differences in age and ISS were found between the groups. The time between the accident and arrival of the physician was longer in the HEMS group. The HEMS group also remained on the scene for longer, but had a higher rate of intervention. According to our analysis of the German Trauma Registry, patients with multiple injuries benefit from HEMS transportation.", "A pattern of prehospital care combining advanced life support, physician staffing, and helicopter transport improves the outcome of patients with severe brain injuries, compared with combined expanded basic life support, nurse staffing, and ground transport.\n Inception cohort from the data set of a population-based, prospective study on major trauma.\n Prehospital and hospital trauma systems of an Italian region.\n All patients with major trauma (Injury Severity Score, >or=16) and severe head injury (Abbreviated Injury Scale score for the head, >or=4) rescued alive from March 1, 1998, to February 28, 1999, who received either form of care. Patients with self-inflicted injuries were excluded. The 184 patients who met the entry criteria were divided equally between care groups.\n None.\n Mortality at 30 days and Glasgow Outcome Scale score of survivors.\n After verifying the comparability of the cohorts, no survival or disability benefit could be demonstrated (95% confidence interval [CI] of the odds ratio for mortality [helicopter/ambulance] [95% CI 1], 0.72 to 2.67; 95% CI of the difference in Glasgow Outcome Scale score medians between helicopter and ambulance groups [95% CI 2], 0.0 to 0.0). Similar results were derived from analyses restricted to the subgroups identified by low (<or=90 mm Hg) roadside systolic blood pressure (95% CI 1, 0.58 to 7.17; 95% CI 2, -1 to 2) and by need for urgent neurosurgical intervention (95% CI 1, 0.16 to 2.60; 95% CI 2, 0 to 2). Exclusion from the ambulance group of victims rescued in urban areas did not change the results (95% CI 1, 0.80 to 3.24; 95% CI 2, 0.0 to 0.0). Stratification by age, Injury Severity Score, and Glasgow Coma Scale score demonstrated a small survival benefit (95% CI 1, 1.12 to 2.12) in the ambulance subgroup with Glasgow Coma Scale score from 10 to 12. Multiple logistic regression analysis confirmed that the group did not affect mortality.\n This study was conceived to emphasize the supposed advantages of the combined helicopter, physician, and advanced life-support rescue. No increased benefit compared with the simpler rescue group could be demonstrated.", "The role of helicopter transport (HT) in civilian trauma care remains controversial. The objective of this study was to compare patient outcomes after transport from the scene of injury by HT and ground transport using a national patient sample.\n Patients transported from the scene of injury by HT or ground transport in 2007 were identified using the National Trauma Databank version 8. Injury severity, utilization of hospital resources, and outcomes were compared. Stepwise logistic regression was used to determine whether transport modality was a predictor of survival or discharge to home after adjusting for covariates.\n There were 258,387 patients transported by helicopter (16%) or ground (84%). Mean Injury Severity Score was higher in HT patients (15.9 ± 12.3 vs. 10.2 ± 9.5, p < 0.01), as was the percentage of patients with Injury Severity Score >15 (42.6% vs. 20.8%; odds ratio [OR], 2.83; 95% confidence interval [CI], 2.76-2.89). HT patients had higher rates of intensive care unit admission (43.5% vs. 22.9%; OR, 2.58; 95% CI, 2.53-2.64) and mechanical ventilation (20.8% vs. 7.4%; OR, 3.30; 95% CI, 3.21-3.40). HT was a predictor of survival (OR, 1.22; 95% CI, 1.17-1.27) and discharge to home (OR, 1.05; 95% CI, 1.02-1.07) after adjustment for covariates.\n Trauma patients transported by helicopter were more severely injured, had longer transport times, and required more hospital resources than those transported by ground. Despite this, HT patients were more likely to survive and were more likely to be discharged home after treatment when compared with those transported by ground. Despite concerns regarding helicopter utilization in the civilian setting, this study shows that HT has merit and impacts outcome.", "Helicopter transport (HT) is frequently used for interfacility transfer of injured patients to a trauma center. The benefits of HT over ground transport (GT) in this setting are unclear. By using a national sample, the objective of this study was to assess whether HT impacted outcomes following interfacility transfer of trauma patients.\n Patients transferred by HT or GT in 2007 were identified using the National Trauma Databank (version 8). Injury severity, resource utilization, and survival to discharge were compared. Stepwise logistic regression was used to determine whether transport modality was a predictor of survival after adjusting for covariates. Regression analysis was repeated in subgroups with Injury Severity Score (ISS)≤15 and ISS>15.\n There were 74,779 patients transported by helicopter (20%) or ground (80%). Mean ISS was higher in patients transported by helicopter (17±11 vs. 12±9; p<0.01) as was the proportion with ISS>15 (49% vs. 28%; odds ratio [OR], 2.53; 95% confidence interval [CI], 2.43-2.63). Patients transported by helicopter had higher rates of intensive care unit admission (54% vs. 29%; OR, 2.86; 95% CI, 2.75-2.96), had shorter transport time (61±55 minutes vs. 98±71 minutes; p<0.01), and had shorter overall prehospital time (135±86 minutes vs. 202±132 minutes; p<0.01). HT was not a predictor of survival overall or in patients with ISS≤15. In patients with ISS>15, HT was a predictor of survival (OR, 1.09; 95% CI, 1.02-1.17; p=0.01).\n Patients transported by helicopter were more severely injured and required more hospital resources than patients transported by ground. HT offered shorter transport and overall prehospital times. For patients with ISS>15, HT was a predictor of survival. These findings should be considered when developing interfacility transfer policies for patients with severe injuries.", "The hypothesis that high level on-the-field ATLS could influence mortality in severe trauma patients was tested by means of a prospective study. During a 7 month period, data of all the victims of severe involuntary trauma (road traffic accidents, work and sport accidents) in 3 Provinces of north-east Italy were entered in a database and analysed. The whole area is covered by a single emergency service which has direct control over all the ambulances and the Emergency Helicopter Service (EMHS). The area concerned by the study has a surface of 7,300 kmq with a population of 1 million inhabitants and is served by 12 first level hospitals and 4 second level institutions (trauma centres). All the patients who were still alive at the time of arrival of the first rescuers were considered, but only severe trauma patients with ISS > 15 were enclosed into the study. All the patients were followed up to their discharge from the ICUs (end point). There were three different rescue approaches: 82 Patients (GROUP A) were rescued by EMTs with BLS training, transported to the nearest level 1 hospital for stabilisation and subsequently transferred to a trauma center; 98 Patients (GROUP B) were rescued by EMTs and directly transported to a trauma centre which was the nearest institution; 42 Patients were rescued on the scene by the EMHS team including an anaesthesiologist with 10 years experience in trauma care and directly transported to a trauma centre after full on-the-field stabilisation (GROUP C) RESULTS: 222 severe trauma patients (ISS > 15) were considered. Mean ISS was 35.1 +/- 18.2 in group A, 33.4 +/- 19.6 in group B and 36.0 +/- 17.8 in group C. 67 patients died previous to ICU discharge (31%). 31 over the 82 pts in Group A (38%) died. 23 of them died even before reaching the trauma centre. The mean time elapsed between the first emergency call and the arrival at the trauma centre was 162 min (90'-300'). Mean ICU stay for patients who survived was 15 days. In Group B 31 over 98 patients (32%) died before ICU discharge. The mean time between the emergency call and hospital admission was 27'. Mean ICU stay for patients who were discharged, was 13 days. 5 over 42 patients rescued by the EMHS (Group C) died, none of them in the pre-hospital setting. Stabilisation included tracheal intubation in 34 cases (81%) and thoracic drainage in 6 (14%). All the patients arrived at the hospital with 2 i.v. line. The average amount of infused fluids were 600 mls of colloids and 810 mls of crystalloid. 13 patients with hypotension received and average of 1000 mls of colloids and 1200 mls of crystalloid. The average time elapsed between the emergency call and the final admission to the definitive care institution was 55'. Mean ICU stay was 11 days. Mortality rate in this group was 12%, significantly lower than in group A (p < 0.005) and group B (p < 0.05).", "Aeromedical crews offer an advanced level of practice and rapid transport to definitive care; however, their efficacy remains unproven. Previous studies have used relatively small sample sizes or have been unable to adequately control for the effect of other potentially influential variables. Here we explore the impact of aeromedical response in patients with moderate to severe traumatic brain injury.\n This was a retrospective analysis using our county trauma registry. All patients with head Abbreviated Injury Score of 3 or greater were included; interfacility transfers were excluded. The impact of aeromedical response was determined using logistic regression, adjusting for age, sex, mechanism, preadmission Glasgow Coma Scale score, head Abbreviated Injury Score, Injury Severity Score, and the presence of preadmission hypotension. Propensity scores were used to account for variability in selection of patients to undergo air versus ground transport. Patients with moderate and severe traumatic brain injury, as defined by head Abbreviated Injury Score and Glasgow Coma Scale score, were compared. Finally, aeromedical patients undergoing field intubation were compared with ground patients undergoing emergency department (ED) intubation.\n A total of 10,314 patients meeting all inclusion and exclusion criteria and with complete data sets were identified and included 3,017 transported by aeromedical crews. Overall mortality was 25% in the air- and ground-transported cohorts, but outcomes were significantly better for the aeromedical patients when adjusted for age, sex, mechanism of injury, hypotension, Glasgow Coma Scale score, head Abbreviated Injury Score, and Injury Severity Score (adjusted odds ratio [OR] 1.90; 95% confidence interval [CI] 1.60 to 2.25; P<.0001). Good outcomes (discharge to home, jail, psychiatric facility, rehabilitation, or leaving against medical advice) were also higher in aeromedical patients (adjusted OR 1.36; 95% CI 1.18 to 1.58; P<.0001). The primary benefit appeared to be in more severely injured patients, as reflected by head Abbreviated Injury Score and Glasgow Coma Scale score. Improved survival was also observed for air-transported patients intubated in the field versus ground-transported patients given emergency intubation in the ED (adjusted OR 1.42; 95% CI 1.13 to 1.78; P<.001).\n Here we analyze a large database of patients with moderate to severe traumatic brain injury. Aeromedical response appears to result in improved outcomes after adjustment for multiple influential factors in patients with moderate to severe traumatic brain injury. In addition, out-of-hospital intubation among air-transported patients resulted in better outcomes than ED intubation among ground-transported patients. Patients with more severe injuries appeared to derive the greatest benefit from aeromedical transport.", "1) To compare the outcomes of adult trauma patients transported to a level I trauma center by helicopter vs. ground ambulance. 2) To determine whether using a unique \"natural experiment\" design to obtain the ground comparison group will reduce potential confounders.\n Outcomes in adult trauma patients transported to a tertiary care trauma center by air were compared with outcomes in a group of patients who were accepted by the online medical control physician for air transport, but whose air missions were aborted for aviation reasons (weather, maintenance, out on a mission); these patients were subsequently transported by ground ambulance instead. Outcomes were also analyzed for a third ground control group composed of all other adult trauma patients transported by ground during this time period. Data were collected by retrospective database review of trauma patients transferred between July 1, 1997, and June 30, 2003. Outcomes were measured by Trauma Injury Severity Score (TRISS) analysis. Z and W scores were calculated.\n Three hundred ninety-seven missions were flown by LifeFlight during the study period vs. 57 in the clinical accept-aviation abort ground transport group. The mean ages, gender distributions, mechanisms of injury, and Injury Severity Scores (ISSs) were similar in the two groups. Per 100 patients transported, 5.61 more lives were saved in the air group vs. the clinical accept-aviation abort ground transport group (Z = 3.37). As per TRISS analysis, this is relative to the expected mortality seen with a similar group in the Major Trauma Outcomes Study (MTOS). The Z score for the clinical accept-aviation abort ground transport group was 0.4. The 1,195 patients in the third all-other ground control group had a higher mean age, lower mean ISS, and worse outcomes according to TRISS analysis (W = -2.02).\n This unique natural experiment led to better matched air vs. ground cohorts for comparison. As per TRISS analysis, air transport of the adult major trauma patient is associated with significantly improved survival as compared with ground transport.", "The purpose of this study was to compare the outcomes of adult (aged > 15 yr) blunt trauma patients with an Injury Severity Score (ISS) = 12 who were transported to a single tertiary trauma centre (TTC) by helicopter emergency medical service (HEMS) versus those transported by ground ambulance.\n We retrospectively analyzed all adult (aged > 15 yr) trauma patients between March 27, 1998 and March 28, 2002 with an ISS score = 12, as identified through the provincial trauma registry. We used the Trauma and Injury Severity Score (TRISS) methodology to determine a difference in outcomes between the 2 groups.\n We identified 823 patients; of these, we excluded 32 (3.9%) penetrating trauma patients. Of the blunt trauma cases (n = 791) 237 (30%) patients were transported by air and 554 were transported by ground (70%). A total of 770 (97.3%) patients were eligible for TRISS analysis. Using the TRISS methodology, the air group had a Z statistic of 2.77, yielding a W score of 6.40. This compared with the ground transport group, whose Z statistic was 1.97 and W score was 2.39.\n The transport of trauma patients with an ISS = 12 by a provincially dedicated rotor wing air medical service was associated with statistically significantly better outcomes than those transported by standard ground ambulance. This is the first large Canadian study to specifically compare the outcome of patients transported by ground with those transported by air.", "AIM, PATIENTS, AND METHODS: To compare retrospectively the outcomes of patients with severe traumatic brain injury (Injury Severity Score, ISS total >or=15; the Abbreviated ISS-head, aISS(head) >or=9) admitted to our Intensive Care Unit by helicopter (helicopter emergency medical service, HEMS group = 89) with those transported by ambulance (GROUND group = 105) from January 2002 to December 2007.\n The groups were comparable for age, Glasgow Coma Scale, ISS total, and aISS(head). The preadmission time of the HEMS group was significantly longer as compared with the GROUND group, but the interval from admission to definitive care was significantly shorter. In the prehospital phase, HEMS patients were more aggressively treated, as indicated by a significantly greater number of procedures performed (i.e. tracheal intubation and positioning of intravenous lines) and larger volumes of fluids infused. The overall mortality was lower in the HEMS than in the GROUND patients (21 vs. 25% respectively, P<0.05). The survival with or without only minor neurological disabilities was higher in the HEMS than in the GROUND group (54 vs. 44% respectively, P<0.05); among the survivors, the rate of severe neurological disabilities was lower in the HEMS than in the GROUND group (25 vs. 31%, P<0.05).\n In our experience, aggressive early treatment of patients with severe traumatic brain injury was associated with a better outcome likely because of the prevention of secondary brain injury and a shorter interval elapsing from the trauma to definitive care despite more time spent on the scene by the intervening team.", "Some studies have shown improved outcomes with helicopter emergency medical services (HEMS) transport, while others have not. Safety concerns and cost have prompted reevaluation of the widespread use of HEMS.\n To determine whether the mode of transport of trauma patients affects mortality.\n Data for 56,744 injured adults aged ≥ 18 years transported to 62 U.S. trauma centers by helicopter or ground ambulance were obtained from the National Sample Program of the 2007 National Trauma Data Bank. In-hospital mortality was calculated for different demographic and injury severity groups. Adjusted odds ratios (AOR) were produced by utilizing a logistic regression model measuring the association of mortality and type of transport, controlling for age, gender, and injury severity (Injury Severity Score [ISS] and Revised Trauma Score [RTS]).\n The odds of death were 39% lower in those transported by HEMS compared with those transported by ground ambulance (AOR = 0.61, 95% confidence interval [CI] = 0.54-0.69). Among those aged ≥ 55 years, the odds of death were not significantly different (AOR = 0.92, 95% CI = 0.74-1.13). Among all transports, male patients had a higher odds of death (AOR = 1.23, 95% CI = 1.10-1.38) than female patients. The odds of death increased with each year of age (AOR = 1.040, 95% CI = 1.037-1.043) and each unit of ISS (AOR = 1.080, 95% CI = 1.075-1.084), and decreased with each unit of RTS (AOR = 0.46, 95% CI = 0.45-0.48).\n The use of HEMS for the transport of adult trauma patients was associated with reduced mortality for patients aged 18-54 years. In this study, HEMS did not improve mortality in adults aged ≥ 55 years. Identification of additional variables in the selection of those patients who will benefit from HEMS transport is expected to enhance this reduction in mortality.", "This study compared a hospital-based aeromedical program to a ground paramedic service in order to determine whether the element of prehospital time or prehospital care is the major contributor towards improved survival. One hundred twenty-six severe blunt trauma patients were studied. There were 93(73.81%) transported by air and 33(26.19%) transported by ground. Utilizing the TRISS methodology, the air patients had a probability of survival of 2.23 SD better than the national norm, and the ground patients had a -2.69 SD below the national norm. The air patients had a higher percentage of intubated patients (42% vs 3%) and use of PASG(56% vs 30%). There was no significant difference in the prehospital times of either the air or ground services once they had arrived at the scene. Since the scene time of both services is similar, the improved survival of the air patients may be due to the technical intervention procedures performed.", "This paper reports a retrospective analysis of patients with serious yet substantially survivable injuries represented by ISS scores from 20 to 39 and whether or not survival was influenced by the use of helicopters. A review of 606 of these patients with blunt trauma was performed for the period from 1983 through 1986. When the group was evaluated there were 451 patients in the ISS cohort of 20-29 and 155 in the 30-39 group. The mean age was 30.5 years and 76% were males. A total of 259 patients were transported by ambulance and 347 by helicopter. Characteristics of the two groups were similar. The mean TS was 12.7 for ambulance and 12.1 for helicopter patients. Mean GCS was 10.4 in the ambulance group and 9.6 for helicopter patients. Overall the mortality for ambulance transported patients was 13% compared to 18% for the helicopter group. We conclude that there is no survival advantage in the helicopter transported group in an urban area with a sophisticated prehospital care system. Patients of rural origin deserve further study.", "The first hour after the onset of out-of-hospital traumatic injury is referred to as the \"golden hour,\" yet the relationship between time and outcome remains unclear. We evaluate the association between emergency medical services (EMS) intervals and mortality among trauma patients with field-based physiologic abnormality.\n This was a secondary analysis of an out-of-hospital, prospective cohort registry of adult (aged > or =15 years) trauma patients transported by 146 EMS agencies to 51 Level I and II trauma hospitals in 10 sites across North America from December 1, 2005, through March 31, 2007. Inclusion criteria were systolic blood pressure less than or equal to 90 mm Hg, respiratory rate less than 10 or greater than 29 breaths/min, Glasgow Coma Scale score less than or equal to 12, or advanced airway intervention. The outcome was in-hospital mortality. We evaluated EMS intervals (activation, response, on-scene, transport, and total time) with logistic regression and 2-step instrumental variable models, adjusted for field-based confounders.\n There were 3,656 trauma patients available for analysis, of whom 806 (22.0%) died. In multivariable analyses, there was no significant association between time and mortality for any EMS interval: activation (odds ratio [OR] 1.00; 95% confidence interval [CI] 0.95 to 1.05), response (OR 1.00; 95% CI 9.97 to 1.04), on-scene (OR 1.00; 95% CI 0.99 to 1.01), transport (OR 1.00; 95% CI 0.98 to 1.01), or total EMS time (OR 1.00; 95% CI 0.99 to 1.01). Subgroup and instrumental variable analyses did not qualitatively change these findings.\n In this North American sample, there was no association between EMS intervals and mortality among injured patients with physiologic abnormality in the field.\n Copyright (c) 2009 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.", "To assess the effect of the London helicopter emergency medical service on survival after trauma.\n Prospective comparison of outcomes in cohorts of seriously injured patients attended by the helicopter and attended by London ambulance service land ambulances crewed by paramedics.\n Greater London.\n 337 patients attended by helicopter and 466 patients attended by ambulance who sustained traumatic injuries and died, stayed in hospital three or more nights, or had other evidence of severe injury and who were taken to any one of 20 primary receiving hospitals.\n Survival at six months after the incident.\n After differences in the nature and severity of the injuries in the two cohorts were accounted for the estimated survival rates were the same (relative risk of death with helicopter = 1.0; 95% confidence interval 0.7 to 1.4). An analysis with trauma and injury severity scores (TRISS) found 16% more deaths than predicted in the helicopter cohort but only 2% more in the ambulance cohort. There was no evidence of a difference in survival for patients with head injury but a little evidence that patients with major trauma (injury severity score > or = 16) were more likely to survive if attended by the helicopter. An estimated 13 (-5 to 39) extra patients with major trauma could survive each year if attended by the helicopter.\n Any benefit in survival is restricted to patients with very severe injuries and amounts to an estimated one additional survivor of major trauma each month. Over all the helicopter caseload, however, there is no evidence that it improves the chance of survival in trauma." ]

[ "15718847", "11344201", "15764959", "15562367" ]

[ "Reversal of HIV-1-associated osteoporosis with once-weekly alendronate.", "Osteopenia in eugonadal men with acquired immune deficiency syndrome wasting syndrome.", "Alendronate, vitamin D, and calcium for the treatment of osteopenia/osteoporosis associated with HIV infection.", "Alendronate reduces bone resorption in HIV-associated osteopenia/osteoporosis." ]

[ "HIV-1-infected patients with osteoporosis were randomly assigned to alendronate 70 mg once-weekly plus dietary counselling (n = 11) or diet counselling alone (n = 14). At week 96, 27% of patients on alendronate versus 96% of controls presented with osteoporosis. Spine bone mineral density (BMD) increases were detected at week 48, and progressed thereafter. Improvements in trochanter BMD were obtained after 2 years. Once-weekly oral alendronate may be an effective and safe treatment for HIV-1-associated osteoporosis.", "Multiple endocrine and metabolic consequences of human immunodeficiency virus (HIV) infection exist that may contribute to bone loss in men with the acquired immune deficiency syndrome (AIDS) wasting syndrome. Recent studies suggest that anabolic strategies can increase lean body mass in men with AIDS wasting. Prior studies have not examined the effects of anabolic agents on bone mineral density (BMD) or bone turnover in these men. To determine the effects of testosterone and progressive resistance training on BMD and bone turnover in eugonadal men with AIDS wasting, we randomly assigned 54 eugonadal men with AIDS wasting (weight < 90% IBW or weight loss >10% from preillness baseline) to receive either testosterone enanthate (200 mg/week, im) or placebo and to progressive resistance training (3 times/week) or no training in a 2 x 2 factorial study design for 3 months. The BMD of the lumbar spine, proximal femur, and total body; lean body mass; and fat mass were measured by dual energy x-ray absorptiometry. Total body scans were repeated after 12 weeks of therapy. Baseline bone turnover and BMD were compared with those in 35 age-matched healthy non-HIV-infected control subjects. Compared with controls, lumbar spine BMD (1.021 +/- 0.018 vs. 1.084 +/- 0.025 g/cm(2); P = 0.04) and total hip BMD (0.951 +/- 0.017 vs. 1.070 +/- 0.019 g/cm(2); P < 0.0001) were reduced in men with AIDS wasting. T-scores were lower in men with AIDS wasting at the lumbar spine (-0.62 +/- 0.17 vs. -0.07 +/- 0.23, P = 0.05) and total hip (-0.65 +/- 0.11 vs. +0.20 +/- 0.014, P < 0.0001). Total hip T scores were less than -1.0 in 33% of men with AIDS wasting. Neither the use of protease inhibitors nor the duration of protease inhibitors use correlated with BMD. Serum osteocalcin levels were lower (3.63 +/- 0.29 vs. 4.54 +/- 0.31 nmol/L; P < 0.04) and urinary N-telopeptide excretion was higher (45.4 +/- 4.5 vs. 26.8 +/- 3.0 nmol BCE/mmol creatinine; P = 0.004) in men with AIDS wasting than in controls. Lumbar spine BMD, as assessed on regional total body dual energy x-ray absorptiometry scan, increased over the 12-week treatment period in response to testosterone (+2.4 +/- 1.3 vs. -1.3 +/- 1.0%, testosterone vs. placebo, respectively; P = 0.02), but not in response to training (+0.8 +/- 1.0 vs. +0.4 +/- 1.3%, training vs. no training; P = 0.70). Lumbar spine and total hip BMD are reduced in eugonadal men with AIDS wasting. Biochemical markers of bone turnover suggest that bone formation and bone resorption are uncoupled in these men. Testosterone administration, but not resistance training, over 3 months increases lumbar spine BMD in eugonadal men with AIDS wasting.", "Osteopenia and osteoporosis are frequent complications of HIV infection and/or its treatment. Alendronate is the only bisphosphonate approved for the treatment of osteoporosis in men and women. We conducted a 48-week prospective, randomized, open-label study to evaluate the effects of alendronate, vitamin D, and calcium supplementation on bone mineral density (BMD) in patients with HIV infection.\n Thirty-one HIV-infected subjects with lumbar spine BMD t-scores less than -1.0 on antiretroviral therapy for a minimum of 6 months were randomized to receive (n = 15) or not to receive (n = 16) 70 mg of alendronate weekly for 48 weeks. All subjects received calcium (1000 mg daily as calcium carbonate) and vitamin D supplementation (400 IU daily). The study was powered to detect 3% changes in BMD in the lumbar spine within arms at 48 weeks.\n Thirty-one patients were enrolled; most were male, with an average length of HIV infection of 8 years. Eighty-four percent had an HIV RNA load below 400 copies/mL, with a current median CD4+ T-cell count of 561 cells/mm3 (median nadir CD4 cell count of 167 cells/mm). At baseline, the median t-score in the lumbar spine was -1.52 and the median t-score in the hip was -1.02. Alendronate in combination with vitamin D and calcium increased lumbar spine BMD by 5.2% (95% confidence interval [CI]: 1.3-6.4) at 48 weeks compared with an increase of 1.3% (95% CI: -2.4 to 4.0) in subjects receiving vitamin D and calcium alone. One subject discontinued treatment in each arm. There were no serious adverse events.\n Alendronate, vitamin D, and calcium are safe and potentially useful in the treatment of osteopenia/osteoporosis associated with HIV infection.", "To evaluate the effects of alendronate, vitamin D, and calcium supplementation on bone metabolism and bone mineral density (BMD) in both HIV-infected men and women treated with highly active antiretroviral therapy (HAART).\n We performed a 52-week prospective, multicenter, randomized, open-label clinical trial. Eligible participants were on stable HAART and had BMD values at the femoral neck or lumbar spine that corresponded to a t score less than -1. Patients were randomized to receive alendronate 70 mg weekly or no alendronate; calcium 1000 mg daily and vitamin D 500 IU daily were provided to all study recipients. Primary endpoint of the study was the change in bone metabolism evaluated by N-telopeptide of type 1 collagen and bone-specific alkaline phosphatase; the secondary endpoint was BMD variation.\n 18 patients were randomized to the alendronate and 23 to the no-alendronate group (controls). The alendronate-treatment group compared to controls had a significant decrease in serum N-telopeptides, 1914 +/- 1433.4 vs. 3967 +/- 1650.5 pM/L (p = .005) after 1 year. Lumbar spine BMD increased by 4% in the alendronate group (p = .004) vs. 3.7% (p = .062) in controls, compared to baseline values. Femoral neck BMD decreased by 0.5% in the alendronate group (p = .05) and by 3.5% in the control group (p = .04). No between-groups differences for BMD were found (Delta lumbar-BMD 0.0351 +/- 0.0406 in cases and 0.0356 +/- 0.073 in controls [p = .977], Delta femoral-BMD -0.085 +/- 0.160 in cases and -0.100 +/- 0.165 in controls [p = .795]).\n Alendronate plus vitamin D and calcium was effective in reducing bone resorption. Alendronate improved lumbar BMD and minimized femoral BMD decrease after 52 weeks compared to treatment with vitamin D and calcium alone in patients on HAART with osteopenia/osteoporosis." ]

[ "14990637" ]

[ "Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines." ]

[ "To determine whether an angiotensin-converting enzyme (ACE) inhibitor, enalapril, prevents cardiac function deterioration (defined using maximal cardiac index [MCI] on exercise testing or increase in left ventricular end-systolic wall stress [LVESWS]) in long-term survivors of pediatric cancer.\n This was a randomized, double-blind, controlled clinical trial comparing enalapril to placebo in 135 long-term survivors of pediatric cancer who had at least one cardiac abnormality identified at any time after anthracycline exposure.\n There was no difference in the rate of change in MCI per year between enalapril and placebo groups (0.30 v 0.18 L/min/m(2); P =.55). However, during the first year of treatment, the rate of change in LVESWS was greater in the enalapril group than in the placebo group (-8.59 v 1.85 g/cm(2); P =.033) and this difference was maintained over the study period, resulting in a 9% reduction in estimated LVESWS by year 5 in the enalapril group. Six of seven patients removed from random assignment to treatment because of cardiac deterioration were initially treated with placebo (P =.11), and one has died as a result of heart failure. Side effects from enalapril included dizziness or hypotension (22% v 3% in the placebo group; P =.0003) and fatigue (10% v 0%; P =.013).\n Enalapril treatment did not influence exercise performance, but did reduce LVESWS in the first year; this reduction was maintained over the study period. Any theoretical benefits of LVESWS reduction in this anthracycline-exposed population must be weighed against potential side effects from ACE inhibitors when making treatment decisions." ]

[ "12761422", "12424684", "78382", "19864673", "322082", "1095132", "15078003", "18977988", "4066562", "2085111" ]

[ "[Long-term Cefadroxil prophylaxis in children with recurrent urinary tract infections].", "[Prophylaxis of recurrent urinary tract infections in children. Results of an open, controlled and randomized study about the efficacy and tolerance of cefixime compared to nitrofurantoin].", "Controlled trial of prophylactic treatment in childhood urinary-tract infection.", "Antibiotic prophylaxis and recurrent urinary tract infection in children.", "Prevention of recurrent urinary tract infections in girls.", "Duration of treatment for urinary tract infections in children.", "Comparison of trimethoprim-sulfamethoxazole, cephadroxil and cefprozil as prophylaxis for recurrent urinary tract infections in children.", "Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial.", "Comparison of long-term, low-dose pivmecillinam and nitrofurantoin in the control of recurrent urinary tract infection in children. An open, randomized, cross-over study.", "Nitrofurantoin versus trimethoprim prophylaxis in recurrent urinary tract infection in children. A randomized, double-blind study." ]

[ "The aim of the study was to evaluate the efficacy and safety of low-dose, long-term cefadroxil prophylaxis in preventing recurrent urinary tract infections in children. A prospective, randomized trial in 33 children (32 female, 1 male) aged 2-14 years (mean 8.1+/-2.8) was conducted. Children with recurrent urinary tract infections were commenced to six-month prophylaxis with cefadroxil at the dosage of 12.5-15.0 mg/kg at bedtime administered every night (group I, n=15) or alternate night (group II, n=18). Escherichia coli was the most frequently isolated agent (90.9%), followed by Proteus mirabilis (3.0%) and Klebsiella oxytoca (3.0%) and Staphylococcus epidermidis (3.0%). Cefadroxil prophylaxis was effective in 80% of patients in group I and in 78% patients in group II. Reinfection occurred in 3/15 (20%) patients in-group I and in 4/18 (22.2%) patients in-group II (odds ratio--1.14; 95% confidence interval--0.16-8.3). The difference of reinfection rate between the groups was not significant (p=0.88). The rate of day- and night-time wetting in both groups before prophylaxis of urinary tract infections was high. It decreased significantly at the end of prophylactic treatment with cefadroxil (from 42.4% to 9.1% and from 39.4% to 6.1% respectively). Mild adverse reaction (nausea) was observed in 1/33 patient. In conclusion our study shows that cefadroxil is an effective, well-tolerated and safe agent in the urinary tract infections prophylaxis. Prophylaxis of recurrent urinary tract infections in children with cefadroxil on alternate night regimen might reduce the cost of the treatment.", "Urinary tract infections are quite frequent in children. Urinary tract obstruction combined with recurrent urinary tract infections increase the risk for renal impairment. Therefore prophylaxis of reinfection is an important nephroprotective procedure. The aim of this open, controlled, randomised pilot study was to compare the efficacy and tolerance of a low dose prophylaxis with Cefixime versus Nitrofurantoin. 60 girls aged 1 to 11 years with at least 2 urinary tract infections within the preceding year were included in the study. The minimum duration of therapy was 6 months and was extended to 12 months for most of the children. The number of recurrent infections was the main criteria for efficacy evaluation, whereas adverse events were analysed to evaluate tolerance. Statistical significant differences between the two treatment groups, regarding recurrence rates could not be demonstrated. Tolerance was comparable in both groups. The influence on gut flora of cefixime given as a low dose regimen over a long period of time corresponds with already published results and was not correlated with a higher number of gastrointestinal side effects.\n Low-dose Cefixime (2 mg/kg bodyweight) is effective and well tolerated in the prophylaxis of recurrent urinary tract infections. Efficacy and tolerance of cefixime were comparable to the results obtained with nitrofurantoin. Due to the small number of patients this study was only a pilot study. Low-dose cefixime, however, could become an alternative to standard regimens in the prophylaxis of recurrent urinary tract infections. This should be investigated in further studies.", "nan", "Antibiotics are widely administered to children with the intention of preventing urinary tract infection, but adequately powered, placebo-controlled trials regarding efficacy are lacking. This study from four Australian centers examined whether low-dose, continuous oral antibiotic therapy prevents urinary tract infection in predisposed children.\n We randomly assigned children under the age of 18 years who had had one or more microbiologically proven urinary tract infections to receive either daily trimethoprim-sulfamethoxazole suspension (as 2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight) or placebo for 12 months. The primary outcome was microbiologically confirmed symptomatic urinary tract infection. Intention-to-treat analyses were performed with the use of time-to-event data.\n From December 1998 to March 2007, a total of 576 children (of 780 planned) underwent randomization. The median age at entry was 14 months; 64% of the patients were girls, 42% had known vesicoureteral reflux (at least grade III in 53% of these patients), and 71% were enrolled after the first diagnosis of urinary tract infection. During the study, urinary tract infection developed in 36 of 288 patients (13%) in the group receiving trimethoprim-sulfamethoxazole (antibiotic group) and in 55 of 288 patients (19%) in the placebo group (hazard ratio in the antibiotic group, 0.61; 95% confidence interval, 0.40 to 0.93; P = 0.02 by the log-rank test). In the antibiotic group, the reduction in the absolute risk of urinary tract infection (6 percentage points) appeared to be consistent across all subgroups of patients (P > or = 0.20 for all interactions).\n Long-term, low-dose trimethoprim-sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children. The treatment effect appeared to be consistent but modest across subgroups. (Australian New Zealand Clinical Trials Registry number, ACTRN12608000470392.)\n 2009 Massachusetts Medical Society", "Eighteen girls between the ages of 3 and 13 years--with a history of at least three culture-documented episodes of bacteriuria in the previous year, but without radiologic evidence of major urinary tract abnormality--were placed on a double-blind, crossover study comparing the effectiveness of nitrofurantoin macrocrystals against a placebo in preventing the recurrence of bacteriuria. Each child was placed on a daily low dose of nitrofurantoin (1.2 to 2.4 mg/kg/day) or an identical-appearing placebo for six months. Each child was then placed on the opposite capsule for a similar period. There were 35 episodes of bacteriuria (4.2 episodes/patient/yr) in the patients taking the placebo, which compared with a rate of 3.8 episodes/patient/yr during the year prior to the study. Only two episodes (0.2 episodes/patient/yr) occurred in the patients taking the drug. The difference in the rate of recurrent bacteriuria between the girls on placebo and on medication is significant at the 0.01 level using the Wilcoxin matched-pairs test. There were no adverse reactions to the drug. Nitrofurantoin macrocrystals in a single daily low dose appear to be a safe, effective method of preventing recurrent bacteriuria in girls at high risk.", "In a double-blind trial 45 children aged 6 months to 14 years with Escherichia coli infections of the urinary tract were given co-trimoxazole for two weeks and then allotted at random to one of two treatment groups for the remainder of six months; one continued with the active drug and the other with dummy tablets of identical appearance. Of the 24 children who took co-trimoxazole for two weeks and the 21 who took it for six months, 11 and 10, respectively, remained without further infections for at least a year. Over 90% of the reinfections occurred within five months of stopping the antibiotics, and the longer treatment did not cause any delay in their appearance. Thus probably a six-month course of treatment is no more likely to achieve a cure than a two-week course; nevertheless, no infection occurred during treatment, and there may be an advantage in continuing with antibiotics in small dosage.", "The aim of this study was to compare the efficacy of prophylactic trimethoprim-sulfamethoxazole (TMP/SMZ), cefprozil and cephadroxil treatments in children who have recurrent urinary tract infection, but no urinary tract pathology. After acute urinary tract infections (UTIs) were treated, the patients were divided into 3 groups randomly and TMP/SMZ was given to 21 patients, cephadroxil was given to 25 patients and cefprozil was given to 34 patients for 3 months--one dose at night. All patients were followed for 6 months following prophylaxis. The frequency of symptomatic UTIs among groups during prophylaxis was not statistically different, however the number of symptomatic UTIs in the cephadroxil group was lower than the other groups. Asymptomatic bacteriuria episodes were detected in TMP/SMZ and cefprozil groups, whereas no asymptomatic bacteriuria episodes were seen in the cephadroxil group. The number of patients with symptomatic UTI during the follow-up period was not different between groups, however all the asymptomatic bacteriuria episodes were encountered in the cefprozil group. In conclusion, in this study cephadroxil was found to be slightly superior to TMP/SMZ and cefprozil in preventing asymptomatic bacteriuria episodes and symptomatic UTIs in children with recurrent UTI and normal urinary tract system.", "Febrile urinary tract infections are common in children and associated with the risk for renal scarring and long-term complications. Antimicrobial prophylaxis has been used to reduce the risk for recurrence. We performed a study to determine whether no prophylaxis is similar to antimicrobial prophylaxis for 12 months in reducing the recurrence of febrile urinary tract infections in children after a first febrile urinary tract infection.\n The study was a controlled, randomized, open-label, 2-armed, noninferiority trial comparing no prophylaxis with prophylaxis (co-trimoxazole 15 mg/kg per day or co-amoxiclav 15 mg/kg per day) for 12 months. A total of 338 children who were aged 2 months to <7 years and had a first episode of febrile urinary tract infection were enrolled: 309 with a confirmed pyelonephritis on a technetium 99m dimercaptosuccinic acid scan with or without reflux and 27 with a clinical pyelonephritis and reflux. The primary end point was recurrence rate of febrile urinary tract infections during 12 months. Secondary end point was the rate of renal scarring produced by recurrent urinary tract infections on technetium 99m dimercaptosuccinic acid scan after 12 months.\n Intention-to-treat analysis showed no significant differences in the primary outcome between no prophylaxis and prophylaxis: 12 (9.45%) of 127 vs 15 (7.11%) of 211. In the subgroup of children with reflux, the recurrence of febrile urinary tract infections was 9 (19.6%) of 46 on no prophylaxis and 10 (12.1%) of 82 on prophylaxis. No significant difference was found in the secondary outcome: 2 (1.9%) of 108 on no prophylaxis versus 2 (1.1%) of 187 on prophylaxis. Bivariate analysis and Cox proportional hazard model showed that grade III reflux was a risk factor for recurrent febrile urinary tract infections. Whereas increasing age was protective, use of no prophylaxis was not a risk factor.\n For children with or without primary nonsevere reflux, prophylaxis does not reduce the rate of recurrent febrile urinary tract infections after the first episode.", "Thirty-five children with a history of vesicoureteric reflux or with recurrent urinary tract infections were randomly allocated to low-dose prophylactic treatment with pivmecillinam or nitrofurantoin. After 6-10 months they were crossed over to the alternate drug for another 6 months, but only 24 completed the study because of lack of compliance or intolerance to nitrofurantoin. There was no significant difference in the long-term prophylactic effect between the two drugs, the overall infection rate being 0.7/patient-year. Pivmecillinam was significantly better tolerated than nitrofurantoin (P = 0.01). Nitrofurantoin effected no major change in the faecal flora, and nearly all urinary infections occurring during long-term treatment were caused by Escherichia coli. In contrast, a marked reduction of E. coli and a marked increase in Gram-positive cocci were found in the faecal flora during treatment with pivmecillinam. Seventy per cent of infections were caused by Streptococcus faecalis and only 20% by E. coli during pivmecillinam treatment (P = 0.001).", "The efficiency of nitrofurantoin and trimethoprim prophylaxis in preventing recurrent urinary tract infections (UTI) was compared by means of actuarial percentage recurrence-free curves in a randomized, double blind study in 130 children (126 girls, 4 boys) aged 1 to 14 years (mean 7.5). The children received the antibiotics for 6 months. Nitrofurantoin proved to be the most efficient prophylactic drug in patients with abnormal urography and/or reflux (n = 60) as evaluated by actuarial percentage recurrence-free analysis (p = 0.0025). However, no differences was found in patients without urinary tract abnormalities. Nitrofurantoin prophylaxis altered neither the pattern of resistance nor the bacteriological constellation, while patients receiving trimethoprim prophylaxis had 76% trimethoprim resistant bacteria during prophylaxis, compared with 8% before (p less than 0.0001) and 17% after (p less than 0.0001) prophylaxis. The percentage of recurrences due to E. coli (70-80%) was unaffected by trimethoprim prophylaxis, but the proportion due to trimethoprim resistant E. coli was significantly higher during prophylaxis (65%) than before (6%, p less than 0.0001) and after (11%, p less than 0.001). The percentage of Staphylococcus epidermidis UTI was significantly higher during trimethoprim prophylaxis (27%) than before (2%, p less than 0.0003). Following prophylaxis there was no difference in the actuarial percentage recurrence-free curves of the two regimens. Side effects occurred more frequently in the nitrofurantoin group (37%) than in the trimethoprim group (21%) (p = 0.05). The majority of side effects in the nitrofurantoin group derived from gastrointestinal symptoms. In conclusion, nitrofurantoin is recommended as the first choice prophylactic treatment of children with recurrent UTI and urinary tract abnormalities." ]

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[ "Being controlled by normative influences: self-determination as a moderator of a normative feedback alcohol intervention.", "Brief motivational interventions for heavy college drinkers: A randomized controlled trial.", "Reducing alcohol use in college students: a controlled trial of two brief interventions.", "A controlled trial of web-based feedback for heavy drinking college students.", "Web-based screening and brief intervention for hazardous drinking: a double-blind randomized controlled trial.", "Randomized controlled trial of a web-based primary care intervention for multiple health risk behaviors.", "A multisite randomized trial of social norms marketing campaigns to reduce college student drinking.", "Randomized controlled trial of web-based alcohol screening and brief intervention in primary care.", "Indicated prevention for incoming freshmen: personalized normative feedback and high-risk drinking.", "Optimizing personalized normative feedback: the use of gender-specific referents.", "Results of a social norm intervention to prevent binge drinking among first-year residential college students.", "A randomized trial of motivational interviewing and feedback with heavy drinking college students.", "Brief intervention for heavy-drinking college students: 4-year follow-up and natural history.", "Relative efficacy of a brief motivational intervention for college student drinkers.", "Mailed personalized normative feedback as a brief intervention for at-risk college drinkers.", "Developing discrepancy within self-regulation theory: use of personalized normative feedback and personal strivings with heavy-drinking college students.", "Screening and brief intervention for high-risk college student drinkers: results from a 2-year follow-up assessment.", "Two brief alcohol interventions for mandated college students.", "Effects of a brief motivational intervention with college student drinkers.", "Brief group alcohol interventions with college students: examining motivational components." ]

[ "The objectives of this research were to evaluate the efficacy of computer-delivered personalized normative feedback among heavy drinking college students and to evaluate controlled orientation as a moderator of intervention efficacy. Participants (N = 217) included primarily freshman and sophomore, heavy drinking students who were randomly assigned to receive or not to receive personalized normative feedback immediately following baseline assessment. Perceived norms, number of drinks per week, and alcohol-related problems were the main outcome measures. Controlled orientation was specified as a moderator. At 2-month follow-up, students who received normative feedback reported drinking fewer drinks per week than did students who did not receive feedback, and this reduction was mediated by changes in perceived norms. The intervention also reduced alcohol-related negative consequences among students who were higher in controlled orientation. These results provide further support for computer-delivered personalized normative feedback as an empirically supported brief intervention for heavy drinking college students, and they enhance the understanding of why and for whom normative feedback is effective.", "In this randomized controlled trial, the authors evaluated brief motivational interventions (BMIs) for at-risk college drinkers. Heavy drinking students (N = 509; 65% women, 35% men) were randomized into 1 of 6 intervention conditions formed by crossing the baseline Timeline Followback (TLFB) interview (present versus absent) and intervention type (basic BMI, BMI enhanced with a decisional balance module, or none). Assessments completed at baseline, 1, 6, and 12 months measured typical and risky drinking as well as drinking-related problems. Relative to controls, the TLFB interview reduced consumption but not problems at 1 month. The basic BMI improved all drinking outcomes beyond the effects of the TLFB interview at 1 month, whereas the enhanced BMI did not. Risk reduction achieved by brief interventions maintained throughout the follow-up year.\n Copyright 2006 APA, all rights reserved.", "This study tested two forms of alcohol reduction programming for college students. Thirty-seven moderate to heavy drinkers completed measures of quantity/frequency, drinking consequences, and attitude questionnaires. Participants were randomly assigned to one of three groups: 1) a two-hour information and motivation session plus mailed personal feedback on their drinking; 2) mailed feedback only; or 3) no treatment. At a 6-week follow-up session, the feedback-only group decreased drinks per month as compared to control. No other differences were statistically significant, though decreases favored the treatment conditions about equally over control. Implications for research and treatment are discussed.", "Alcohol consumption has been a growing concern at U.S. colleges, particularly among first-year students, who are at increased risk for problems. This study tested the efficacy of the \"electronic Check-Up to Go\" (e-CHUG), a commercially-available internet program, at reducing drinking among a group of at-risk college freshman.\n The design was a randomized controlled trial: 106 freshmen students who reported heavy episodic drinking were randomly assigned to receive feedback or to assessment only. Assessment measures were completed at baseline, 8 weeks, and 16 weeks.\n At 8 weeks, the feedback group showed a significant decrease in drinks per week and peak BAC over control. By 16 weeks, the control group also declined to a point where there were no differences between groups. Changes in normative drinking estimates mediated the effect of the intervention. An additional 245 abstainers and light drinkers who were also randomized to condition did not show any intervention effect.\n This study provides preliminary support for the efficacy of this intervention at reducing short-term drinking among at-risk students.", "Strong evidence exists for the efficacy of screening and brief intervention for reducing hazardous drinking. However, problems have been highlighted with respect to its implementation in health-care systems, not least of which is a reluctance of some doctors to discuss alcohol proactively with their patients.\n To determine the efficacy of a novel web-based screening and brief intervention (e-SBI) to reduce hazardous drinking.\n A double-blind randomized controlled trial.\n A university student health service.\n A total of 167 students (17-26 years) were recruited in the reception area and completed a 3-minute web-based screen including the Alcohol Use Disorder Identification Test (AUDIT) questionnaire. Of these, 112 tested positive, and 104 (52 females) who consented to follow-up were included in the trial.\n Drinking frequency, typical occasion quantity, total volume, heavy episode frequency (females > 80 g ethanol, males > 120 g ethanol), number of personal problems, an academic problems score.\n Participants were randomized to 10-15 minutes of web-based assessment and personalized feedback on their drinking (intervention, n = 51) or to a leaflet-only control group (n = 53).\n Mean baseline AUDIT scores for control and intervention groups were 16.6 (SD = 6.0) and 16.6 (SD = 5.7). At 6 weeks, participants receiving e-SBI reported significantly lower total consumption (geometric mean ratio = 0.74; 95% confidence interval: 0.56-0.96), lower heavy episode frequency (0.63; 0.42-0.92) and fewer personal problems (0.70; 0.54-0.91). At 6 months personal problems remained lower (0.76; 0.60-0.97), although consumption did not differ significantly. At 6 months, academic problems were lower in the intervention group relative to controls (0.72; 0.51-1.02).\n e-SBI reduced hazardous drinking among university students, to an extent similar to that found for practitioner-delivered brief interventions in the general population. e-SBI offers promise as a strategy to reduce alcohol-related harm in a way that is non-intrusive, appealing to the target group, and capable of being incorporated into primary care. Research is required to replicate the findings, to determine the duration of intervention effects, and to investigate the mechanisms by which the intervention operates.", "Physical inactivity, low fruit and vegetable intake, hazardous drinking, and smoking are leading risk factors for disease and injury. The aim of this study was to obtain estimates of efficacy in reducing the first three of these behaviors.\n The design was a randomized controlled trial: 218 patients (17-24 years) attending a student health service at a New Zealand university in 2003 were assigned to: (A) web-based assessment and personalized feedback (n = 72); or (B) assessment only (n = 74); or (C) minimal contact (n = 72). Outcome measures were the proportion meeting recommendations for fruit and vegetable consumption, physical activity, and alcohol consumption 6 weeks later.\n Follow-up assessments were attained for 86% of participants, with no evidence of differential attrition. There were significant differences in the proportion meeting recommendations for fruit and vegetable consumption and physical activity in group A relative to C. Hazardous drinking prevalence did not vary significantly by group.\n Differences appear attributable to the intervention. The intervention could be routinely provided in primary care, and its efficacy could be assessed in a large randomized controlled trial.", "An 18-site randomized trial was conducted to determine the effectiveness of social norms marketing (SNM) campaigns in reducing college student drinking. The SNM campaigns are intended to correct misperceptions of subjective drinking norms and thereby drive down alcohol consumption.\n Institutions of higher education were randomly assigned to treatment and control groups. At the treatment group institutions, SNM campaigns delivered school-specific, data-driven messages through a mix of campus media venues. Cross-sectional student surveys were conducted by mail at baseline (n = 2,771) and at posttest 3 years later (n = 2,939). Hierarchical linear modeling was applied to examine multiple drinking outcomes, taking intraclass correlation into account.\n Controlling for other predictors, having an SNM campaign was significantly associated with lower perceptions of student drinking levels and lower alcohol consumption, as measured by a composite drinking scale, recent maximum consumption, blood alcohol concentration for recent maximum consumption, drinks consumed when partying, and drinks consumed per week. A moderate mediating effect of normative perceptions on student drinking was demonstrated by an attenuation of the Experimental Group x Time interaction, ranging from 16.4% to 39.5% across measures. Additional models that took into account the intensity of SNM campaign activity at the treatment institutions suggested that there was a dose-response relationship.\n This study is the most rigorous evaluation of SNM campaigns conducted to date. Analysis revealed that students attending institutions that implemented an SNM campaign had a lower relative risk of alcohol consumption than students attending control group institutions.", "There is compelling evidence supporting screening and brief intervention (SBI) for hazardous drinking, yet it remains underused in primary health care. Electronic (computer or Web-based) SBI (e-SBI) offers the prospects of ease and economy of access. We sought to determine whether e-SBI reduces hazardous drinking.\n We conducted a randomized controlled trial in a university primary health care service. Participants were 975 students (age range, 17-29 years) screened using the Alcohol Use Disorders Identification Test (AUDIT). Of 599 students who scored in the hazardous or harmful range, 576 (300 of whom were women) consented to the trial and were randomized to receive an information pamphlet (control group), a Web-based motivational intervention (single-dose e-SBI group), or a Web-based motivational intervention with further interventions 1 and 6 months later (multidose e-SBI group).\n Relative to the control group, the single-dose e-SBI group at 6 months reported a lower frequency of drinking (rate ratio [RR], 0.79; 95% confidence interval [CI], 0.68-0.94), less total consumption (RR, 0.77; 95% CI, 0.63-0.95), and fewer academic problems (RR, 0.76; 95% CI, 0.64-0.91). At 12 months, statistically significant differences in total consumption (RR, 0.77; 95% CI, 0.63-0.95 [equivalent to 3.5 standard drinks per week]) and in academic problems (RR, 0.80; 95% CI, 0.66-0.97) remained, and the AUDIT scores were 2.17 (95% CI, -1.10 to -3.24) points lower. Relative to the control group, the multidose e-SBI group at 6 months reported a lower frequency of drinking (RR, 0.85; 95% CI, 0.73-0.98), less total consumption (RR, 0.79; 95% CI, 0.64-0.97 [equivalent to 3.0 standard drinks per week]), reduced episodic heavy drinking (RR, 0.65; 95% CI, 0.45-0.93), and fewer academic problems (RR, 0.78; 95% CI, 0.65-0.93). At 12 months, statistically significant differences in academic problems remained (RR, 0.75; 95% CI, 0.62-0.90), while the AUDIT scores were 2.02 (95% CI, -0.97 to -3.10) points lower.\n Single-dose e-SBI reduces hazardous drinking, and the effect lasts 12 months. Additional sessions seem not to enhance the effect. Trial Registration www.anzctr.org.au Identifier:ACTRN012607000103460.", "This research evaluated the efficacy of a computerized, freshmen-specific personalized normative feedback (PNF) intervention on reducing alcohol consumption among high-risk drinking freshmen. Students (N=316; 53.8% female) completed measures of perceived drinking norms and drinking behavior. After completing the baseline assessment, students were randomly assigned to receive either freshmen-specific PNF that was gender-specific or gender-neutral, or to assessment only control. Findings demonstrated that students exhibited normative misperceptions for typical freshmen drinking behavior and that perceptions of typical same-sex freshmen drinking were positively associated with riskier drinking behavior. At follow-up, students randomly assigned to receive PNF reduced perceptions of typical freshmen drinking behavior and personal drinking behavior relative to those who did not receive PNF. Findings extend previous evaluations of computer-based PNF and suggest that computer-based PNF for incoming freshmen utilizing freshmen-specific norms that are gender-specific may constitute a promising prevention strategy.", "Many brief interventions include personalized normative feedback (PNF) using gender-specific or gender-neutral referents. Several theories suggest that information pertaining to more socially proximal referents should have greater influence on one's behavior compared with more socially distal referents. The current research evaluated whether gender specificity of the normative referent employed in PNF related to intervention efficacy.\n Following baseline assessment, 185 college students (45.2% women) were randomly assigned to one of three intervention conditions: gender-specific feedback, gender-neutral feedback, or assessment-only control. Immediately after completing measures of perceived norms, alcohol consumption, and gender identity, participants in the gender-neutral and gender-specific intervention conditions were provided with computerized information detailing their own drinking behavior, their perceptions of student drinking, and actual student drinking.\n After a 1-month follow-up, the results indicated that normative feedback was effective in changing perceived norms and reducing alcohol consumption for both intervention groups for women and men. The results provide support, however, for changes in perceived gender-specific norms as a mediator of the effects of normative feedback on reduced drinking behavior for women only. Additionally, gender-specific feedback was found to be more effective for women higher in gender identity, relative to the gender-neutral feedback. A post-assessment follow-up telephone survey administered to assess potential demand characteristics corroborated the intervention effects.\n Results extend previous research documenting efficacy of computer delivered PNF. Gender specificity and gender identity appear to be important elements to consider for PNF intervention efficacy for women.", "The effects of a primary prevention social norm intervention on binge drinking among 1st-year residential college students were examined. Six hundred thirty-four students attending a medium-sized public university in the South were randomly assigned to receive a two-phase social norm intervention or the standard campus psychoeducational prevention program. At posttest, no differences were found between intervention and control group students on any of the alcohol use and alcohol-use risk factor measures. Significant subgroup differences were found by stage of initiating binge drinking behaviors, for frequency of alcohol use, F(3, 507) = 3.69, p = .01; quantity of alcohol use, F(3, 507) = 2.51, p = .05; and social norms, F(3, 505) = 2.53, p = .05. These findings suggest the need for tailoring social norm binge drinking interventions to students' stage of initiating heavy drinking and carefully monitoring for potential negative, as well as positive, effects of norm-based prevention messages.", "Motivational interviewing (MI) is a brief intervention that has been shown to reduce heavy drinking among college students. Because all college studies of MI to date have included a personalized feedback report, it remains unclear which of the components is necessary to produce behavior change. This study evaluated the separate and collective effects of MI and feedback among 122 \"binge\" drinking college students. Participants were randomized to: (1) MI with feedback, (2) MI without feedback, (3) Mailed feedback only, (4) MI with mailed feedback, or (5) Assessment only control. At an eight-week follow-up, all groups reduced their consumption, peak BAC, consequences, and dependence symptoms. For females, there were reductions in consequences and dependence symptoms in groups that received feedback, as compared to groups that did not receive feedback. For females, there was an effect of the feedback on consequences and dependence symptoms, but was no overall effect of MI on any outcome measure.", "This study examined long-term response to an individual preventive intervention for high-risk college drinkers relative to the natural history of college drinking.\n A single-session, individualized preventive intervention was evaluated within a randomized controlled trial with college freshmen who reported drinking heavily while in high school. An additional group randomly selected from the entire screening pool provided a normative comparison. Participant self-report was assessed annually for 4 years.\n High-risk controls showed secular trends for reduced drinking quantity and negative consequences without changes in drinking frequency. Those receiving the brief preventive intervention reported significant additional reductions, particularly with respect to negative consequences. Categorical individual change analyses show that remission is normative, and they suggest that participants receiving the brief intervention are more likely to improve and less likely to worsen regarding negative drinking consequences.\n Brief individual preventive interventions for high-risk college drinkers can achieve long-term benefits even in the context of maturational trends.", "The authors evaluated the efficacy of Brief Alcohol Screening and Intervention for College Students (BASICS: L. A. Dimeff, J. S. Baer, D. R. Kivlahan, & G. A. Marlatt, 1999), a single session of drinking-related feedback intended to reduce heavy drinking and related harm. College student drinkers (N = 99) were assigned to BASICS, an educational intervention, or an assessment-only control group. At 3 months postintervention. there were no overall significant group differences, but heavier drinking BASICS participants showed greater reductions in weekly alcohol consumption and binge drinking than did heavier drinking control and education participants. At 9 months, heavier drinking BASICS participants again showed the largest effect sizes. BASICS participants evaluated the intervention more favorably than did education participants. This study suggests that BASICS may be more efficacious than educational interventions for heavier drinking college students.", "The current study examined the efficacy of mailed personalized normative feedback (PNF) as a brief alcohol intervention for at-risk college drinkers, and investigated discrepancy as a possible mediator of the intervention effect.\n Participants consisted of 100 at-risk college drinkers who completed an alcohol-use assessment at baseline, 6-week posttest and 6-month follow-up. Measures included number of drinks consumed per heaviest drinking week, frequency of heavy-drinking episodes, peak blood alcohol concentration and number of alcohol-related problems, all for the last month. Participants were randomly assigned to either a mailed brief intervention (MBI; n = 49) or attention-control (C; n = 51) group. The MBI group received mailed PNF that was based on baseline responses to the drinking measures; the C group received a psychoeducational brochure about alcohol.\n Mixed-model, repeated measures ANOVAs were used to examine the effects of time, group and gender on discrepancy and the drinking variables. Following the intervention, the MBI group reported significantly higher perceived discrepancy between self and others' drinking than the C group. The MBI group reported consuming significantly fewer drinks per heaviest drinking week and engaging in heavy episodic drinking less frequently than the C group at the 6-week posttest; however, these differences were no longer evident at the 6-month follow-up. Hierarchical regression analyses did not provide evidence for the hypothesized mediating effect of discrepancy.\n Mailed PNF may be a cost- and time-efficient means of developing discrepancy and temporarily reducing heavy alcohol consumption among at-risk college drinkers.", "Efforts to reduce the frequency of high-risk drinking have included the use of motivational interventions. Both the technique used in motivational interventions and an underlying theory of behavior change (i.e., self-regulation theory) invoke the construct of discrepancy development. This study was designed to determine whether techniques purported to develop discrepancy actually do so and to compare methods of developing discrepancy on indices of intention to reduce alcohol use. Male and female college drinkers (N=92) were selected if they reported two or more binge episodes in the last month, or scored 4 or higher on the Rutgers Alcohol Problem Index (RAPI). Participants were randomly assigned by gender to three conditions all conducted in a small group format: attention-control, personalized normative feedback (PNF), and personal strivings assessment (PSA). Personalized normative feedback was designed to develop discrepancy based on behavioral comparisons of self and others. Personal strivings assessment was designed to develop discrepancy between current and ideal self. It was hypothesized that participants who engage in discrepancy building activities would experience discrepancy specific to the activity in which they engaged, and that all participants who developed discrepancy would show higher levels of intention to reduce alcohol use. Results indicated that only the personalized normative feedback increased discrepancy and intention to reduce alcohol use.", "This randomized controlled trial evaluated the efficacy of a brief intervention designed to reduce the harmful consequences of heavy drinking among high-risk college students. Students screened for risk while in their senior year of high school (188 women and 160 men) were randomly assigned to receive an individualized motivational brief intervention in their freshman year of college or to a no-treatment control condition. A normative group selected from the entire screening pool provided a natural history comparison. Follow-up assessments over a 2-year period showed significant reductions in both drinking rates and harmful consequences, favoring students receiving the intervention. Although high-risk students continued to experience more alcohol problems than the natural history comparison group over the 2-year period, most showed a decline in problems over time, suggesting a developmental maturational effect.", "Encouraging but limited research indicates that brief motivational interventions may be an effective way to reduce heavy episodic drinking in college students. At 2 campuses, students (83% male) mandated to a substance use prevention program were randomly assigned to 1 of 2 individually administered conditions: (a) a brief motivational interview (BMI; n = 34) or (b) an alcohol education session (AE; n = 30). Students in the BMI condition reported fewer alcohol-related problems than the AE students at 3-and 6-month assessments. Trends toward reductions in number of binge drinking episodes and typical blood alcohol levels were seen in both groups. Process measures confirmed the integrity of both interventions. The findings demonstrate that mandated BMIs can reduce alcohol problems in students referred for alcohol violations.\n ((c) 2005 APA, all rights reserved).", "This study consisted of a randomized controlled trial of a 1-session motivational intervention for college student binge drinkers. Sixty students who reported binge drinking 2 or more times in the past 30 days were randomly assigned to either a no-treatment control or a brief intervention group. The intervention provided students with feedback regarding personal consumption, perceived drinking norms, alcohol-related problems, situations associated with heavy drinking, and alcohol expectancies. At 6-week follow-up, the brief intervention group exhibited significant reductions on number of drinks consumed per week, number of times drinking alcohol in the past month, and frequency of binge drinking in the past month. Estimates of typical student drinking mediated these reductions. This study replicates earlier research on the efficacy of brief interventions with college students and extends previous work regarding potential mechanisms of change.", "The utility of brief interventions with at-risk college drinkers would be enhanced if they could also be delivered in group settings without the need for risk prescreening. The current study therefore explored whether components of brief interventions could be effectively administered to mixed groups of drinking and non-drinking students. Specifically, the outcomes of two methods aimed toward increasing motivation for change were compared to controls. One intervention focused on enhancing actual-ideal drinking behavior discrepancy through a structured group discussion, while the other focused on enhancing self-norm drinking behavior discrepancy through the provision and discussion of didactic information. Among at-risk drinkers, significant reductions in heavy drinking episode frequency at four-week follow-up were found for the self-norm (S-N) group only, while reductions in alcohol problems were obtained in both the S-N and control groups. Results suggest that self-norm discrepancy enhancement strategies may be more effective than actual-ideal discrepancy strategies when used with a mixed drinking group." ]

[ "949896", "11102587", "2975583", "16171729", "19838585", "694638", "8605778", "22445431", "9886517", "16485589", "19766950", "10494483", "1764941", "15451329" ]

[ "A study of glucose tolerance, serum transaminase and lipids in women using depot-medroxyprogesterone acetate and a combination-type oral contraceptive.", "Depo-provera associated with weight gain in Navajo women.", "Acceptability of injectable contraceptives in Assiut, Egypt.", "Adolescent use of the monthly contraceptive injection.", "[Variation of weigth among users of the contraceptive with depot-medroxyprogesterone acetate according to body mass index in a six-year follow-up].", "Efficacy and acceptability of injectable medroxyprogesterone. A comparison of 3-monthly and 6-monthly regimens.", "A comparative study of one-year weight gain among users of medroxyprogesterone acetate, levonorgestrel implants, and oral contraceptives.", "Body weight and composition in users of levonorgestrel-releasing intrauterine system.", "The performance of levonorgestrel rod and Norplant contraceptive implants: a 5 year randomized study.", "Weight changes in clients on hormonal contraceptives in Zaria, Nigeria.", "A longitudinal comparison of body composition changes in adolescent girls receiving hormonal contraception.", "Effects of DMPA on weight and blood pressure in long-term acceptors.", "Progestagen-only oral contraceptives: comparison of the metabolic effects of levonorgestrel and norethisterone.", "Contraceptive efficacy and safety of DMPA-SC." ]

[ "nan", "Depo-medroxyprogesterone acetate (DMPA) is an increasingly popular contraceptive choice among Navajo women. Weight gain is cited as a common side effect and major reason for discontinuation of DMPA. No controlled trials have evaluated the association between weight gain and DMPA in Navajo women. We aimed to clarify whether DMPA is associated with weight gain in Navajo women and to quantify the magnitude of weight gain. A cohort of 172 Navajo women who had used DMPA continuously for one or 2 years comprised the study group. A cohort of 134 Navajo women who used a non-progestin method or no method over 1 or 2 years comprised the comparison group. Initial weight, one-year weight and 2-year weights were recorded for all patients. Study subjects gained a mean of 6 pounds over one year and 11 pounds over 2 years relative to the comparison group (p < 0.001) after controlling for possible confounding variables including age, parity and initial weight. Use of DMPA is associated with significant weight gain in Navajo women. This weight gain is greater than that reported in previous uncontrolled studies in non-Navajo populations. This information should be utilized in counseling Navajo women about the side effects of DMPA.", "The present work was a randomized comparative study of two injectable progestogen-only contraceptives. The first group (200 subjects) received 150 mg of depotmedroxyprogesterone acetate (Depoprovera) every 84 +/- 7 days and the second (200 subjects) received 200 mg of norethisterone enanthate (Noristerat) every 56 +/- 7 days. Acceptors of injectable contraceptives in Assiut, Egypt, were mainly women looking for fertility termination. Menstrual disruption was the main side effect among both treatment groups. Amenorrhoea was the commonest menstrual complaint and was the main reason for discontinuation in both groups. Only one pregnancy occurred during NET-EN use; two more pregnancies occurred, one in each of the two groups but there were indications that conception preceded the first injection. Menstrual irregularities were generally more frequent with DMPA users. However, DMPA had better one-year continuation rates than NET-EN (68.8 +/- 3.5 and 57.1 +/- 3.6 per 100 women, respectively).", "To compare weight and continuation among adolescents using monthly medroxyprogesterone acetate (MPA)/ethinyl estradiol cypionate (E2C), tri-monthly depot MPA (DMPA), and daily oral contraceptive pills (OCP).\n Medical records were reviewed for body mass index, demographics, and sexual history at baseline; and weight and continuation at 3, 6, 9, and 12 months. Bivariate analyses were performed by method, and continuation functions were compared by the log-rank and Wilcoxon tests. The effect of method on use duration was assessed by Cox regression.\n Hospital adolescent clinic.\n 12- to 21-year-old patients who initiated MPA/E2C, DMPA, or OCPs in 2001.\n Weight gain and method continuation.\n MPA/E2C was initiated by 40 (18%) patients, DMPA by 63 (28%), and OCPs by 119 (54%, P < 0.001). OCP users were younger (P = 0.005) and more likely to be white, privately insured, and in school (P < 0.004) than MPA/E2C or DMPA users. Previous DMPA and OCP use, pregnancy, and sexually transmitted infections (STI) were more common among MPA/E2C than DMPA or OCP users (P < or = 0.001). Baseline BMI was lowest (P = 0.06) among DMPA users, and MPA/E2C users were most likely to be overweight (P = 0.03). There were non-significant differences in weight change. Continuation functions differed by the method only in the first three months of use (P = 0.03). Leading reasons for discontinuation were unavailability of MPA/E2C (20%), bleeding with DMPA (22%), and forgetting OCPs (17%). Duration of use was independently associated with white race (P < 0.005) and STI-never (P < 0.0001) but not with method type.\n Although MPA/E2C use was associated with overweight status and early discontinuation, it also was associated with previous use of other methods. For all methods, poor continuation at one year supports the ongoing search for effective contraceptive alternatives.", "To determine weight variation in women with different Body Mass Index (BMI) in use of trimestral injections of depot-medroxyprogesterone acetate (DMPA), and compare it to women users of a non-hormonal method.\n Retrospective study with the chart review of 226 DMPA users and 603 controls, users of DIU TCu380A. Women were distributed in categories, according to their initial BMI, as having normal weight (<25 kg/m(2)), overweight (25 to 29,9 kg/m(2)) and being obese (>or=30 kg/m(2)), and were followed-up for six years, with yearly measurements of weight and BMI. The statistic test ANOVA was used to measure the weight variation among the groups in each BMI category every year.\n The average age at the onset of the method employed was higher in the study group than in the controls, in all the BMI categories: 31.6+/-SD 7.1 X 27.4+/-SD 5.5 in the normal weight category (p<0.0001); 37.3+/-SD 6.8 X 29.2+/-SD 6.0 in the overweight category (p<0.0001); and 35.3+/-SD 6.4 X 29.7+/-SD 5.8 among obese women (p<0.0001). DMPA users showed weight increase as compared to the controls in the overweight category (p=0.0082); and the weight increase along the observation period was also higher among the DMPA users than among the controls, for the normal weight (p<0.0001) and overweight (p=0.0008) categories. In the obese group, there was no BMI variation between the groups, nor along the period during which they were using the method.\n There was no change in weight gain among DMPA users from the obese category. Prospective studies should be done with metabolic tests to establish the determining factors of weight gain in normal and overweight women.", "Five hundred Black Rhodesian women given injections of 150 mg Depo-Provera every 3 months (group A) and 500 women given an injection of 450 mg Depo-Provera every 6 months (group B) were reviewed after 6 months. Group B had a significantly lower rate of defaulters. There was no significant difference between the groups with regard to weight gain, systolic and diastolic blood pressure increase, overall abnormal bleeding patterns and complaints of side-effects. Among those women who reported abnormal bleeding patterns, significantly more in group B had amenorrhoea. There was no significant increase of prolonged bleeding in group B. Among those women who complained of side-effects, significantly more in group B complained of headaches and a bloated abdomen. No pregnancies occurred in either group. The increased annual cost of the 450 mg injections, which was the main reason for women not accepting this regimen, is outweighed by convenience and reduced travel costs. Depo-Provera 450 mg given by 6-monthly injection is well tolerated and effective, and appears to be even more satisfactory as regards continued acceptance than 150 mg given every 3 months.", "With the recent introduction and growing popularity of Depo-Provera Contraceptive Injection, concern about the potential for weight gain during treatment has been raised. The purpose of the present study was to determine whether or not Depo-Provera Contraceptive Injection is associated with greater weight gain, and incidence thereof, than Norplant implants or oral contraceptives. A retrospective chart review of patients seen at a state- and federally-funded clinic was conducted. Fifty women in each treatment group who met the study criteria were identified and included in the study evaluation. Mean one-year weight gain for subjects in each group was as follows: -2.0 pounds in the oral contraceptive group, -1.8 pounds in the Norplant implants group, and +0.1 pounds in the Depo-Provera Contraceptive Injection group. While results among treatment groups differed slightly, no significant weight change occurred in any of the treatment groups.", "There is little information about body weight and body composition (BC) among users of the levonorgestrel-releasing intrauterine system (LNG-IUS). The aim of this study was to evaluate body weight and BC in LNG-IUS users compared to users of the TCu380A intrauterine device (IUD).\n A prospective study was done with 76 new users of both contraceptive methods. Women were paired by age (±2 years) and body mass index (BMI, kg/m², ±2). Body weight and BC (% lean mass and % fat mass) were evaluated by a trained professional at baseline and at 1 year of contraceptive use. The BC measurements were obtained using Lunar DXA equipment. Weight and BC were evaluated in each woman at baseline and at 12 months and analyzed as the mean change within each woman. Then, the changes in weight and BC for each woman were calculated and then compared between LNG-IUS and TCu380A IUD users (paired data for each woman). The central-to-peripheral fat ratio was calculated by dividing trunk fat by the upper and lower limb fat.\n There were no significant differences at time of IUD insertion between LNG-IUS and TCu380A IUD users regarding age (mean±SD) (34.4±7.5 vs. 33.9±8.0 years), BMI (25.3±4.1 vs. 25.9±4.1) and number of pregnancies (1.9±0.2 vs. 1.7±0.2), respectively. Mean body weight gain of 2.9 kg was observed among LNG-IUS users at 12 months (p=.0012), whereas the body weight of TCu380A IUD users only increased by 1.4 kg (p=.067). There was no significant difference in body weight change between the two groups of users at 12 months. The variation in the central-to-peripheral fat ratio was the same between the two groups (-1.6% vs. -0.2%; p=.364). LNG-IUS users showed a 2.5% gain in fat mass (p=.0009) and a 1.4% loss of lean mass, whereas TCu380A IUD users showed a loss of 1.3% of fat mass (p=.159) and gain of 1.0% of lean mass (p=.120). TCu380A IUD users gained more lean mass than LNG-IUS users (p=.0270), although there was no significant difference between the two groups after 12 months of use.\n Although an increase in mean fat mass among LNG-IUS users at 12 months of use was observed, it should be noted that an increase of body weight was also observed in both groups after 1 year of insertion of the device. However, a study with a larger number of women and long-term evaluation is necessary to evaluate these body changes.\n Copyright © 2012 Elsevier Inc. All rights reserved.", "A new contraceptive (LNG rod implants, Jadelle, Leiras Oy's registered trademark for rod implants) was prospectively evaluated in randomized 5 year comparison with Norplant (Population Council's registered trademark for contraceptive implants releasing levonorgestrel) capsule implants. The study involved 1198 women at seven centres. No pregnancies occurred in the first 4 years. At 5 years, the cumulative pregnancy rate was 1 per 100 users or less for each regimen. Annual discontinuation rates averaged 11-12 per 100 users (P > 0.05), corresponding to 5 year continuation rates of 55.1 for rods and 53.0 per 100 for capsules. Mean annual discontinuation rates for menstrual disturbances were 3.5 and 4.2 per 100 for rod and capsule implants respectively (P > 0.05), and mean annual removal rates for medical problems were 3.5 and 3.0 per 100 (P > 0.05) respectively. Apart from menstrual problems, headache, weight gain and acne were the principal medical reasons for removal. In proportional hazard analyses, family formation variables, age, parity and desire/non desire for another child, recorded at admission, significantly affected discontinuation rates for major decrement categories and for all reasons combined. Mean rod removal time was half that of Norplant (P < 0.01); complications of rod removal were at a lower rate. With these contraceptives indistinguishable in performance except for ease and speed of removal, LNG rod implants appear to be preferable to Norplant for use through 5 years by virtue of relative ease of removal.", "Misconceptions exist in Nigeria about the effects of hormonal contraceptives on weight, which may have negative effects on contraceptive use. Data from case notes of clients attending the reproductive health centre at the Ahmadu Bello University Teaching Hospital, Zaria, between 1993 and 1995, were analysed to determine the effects of hormonal contraceptives on body weight, comparing them to clients using intrauterine contraceptive devices. Weight changes were not significantly different in clients using hormonal contraceptives and those using intrauterine contraceptive devices. This information will be beneficial in contraceptive counselling for clients in this environment and provide a baseline for further research.", "The objective of this study was to examine body composition changes in adolescent girls initiating depot medroxyprogesterone acetate (DMPA), oral contraceptives, or no hormonal contraceptive method. At 6 months, DMPA resulted in significant increases in adiposity with concomitant decreases in lean body mass. Supplemental estrogen may lessen these DMPA effects.", "The study of effects on weight and blood pressure in long term DMPA acceptors is reported. The objectives were to study body weight and blood pressure changes in long term DMPA users compared with intrauterine device (IUD) acceptors. A total of 50 healthy women who had been using DMPA for 120 months were compared with 50 IUD acceptors who had been using an IUD for 120 months. Age, parity, income, body weight, and blood pressure at the initiation of contraception were matched. The mean +/- SD body weight at 120 months in the DMPA and IUD groups were 60.9 +/- 7.5 kg and 62.1 +/- 9.3 kg. No difference in mean body weight was demonstrated. The blood pressure change between DMPA and IUD acceptors also was not different. It is suggested that long term DMPA use does not have unfavorable effects on weight or blood pressure.", "A 6-month single-blind study compared the use of a progestagen-only oral contraceptive containing norethisterone 350 micrograms/day (NE 350) with one containing levonorgestrel 30 micrograms (LN 30), to assess the metabolic effects. At the end of 6 months, there were no significant differences between the two groups with respect to plasma cholesterol, lipoproteins including HDL subfractions, triglycerides or glucose concentration. Levels of fibrinogen, plasminogen, Factor VII, Factor X and antithrombin III were also similar. Women changing from a combined oral contraceptive to LN 30 showed a significant fall in Factor X. Mean blood pressure fell on LN 30 by 7/9 mmHg, but the 6-month reading did not differ significantly from that in women on NE 350. Acceptability, and the metabolic effects of the two preparations were similar in this study. Further larger studies are warranted.", "DMPA-SC 104 mg/0.65 mL is a new, low-dose subcutaneous (SC) formulation of Depo-Provera contraceptive injection (150 mg/mL medroxyprogesterone acetate injectable suspension) that provides efficacy, safety and immediacy of onset equivalent to Depo-Provera intramuscular (IM) injection. Two large, open-label, Phase 3 studies assessed the 1-year contraceptive efficacy, safety and patient satisfaction with DMPA-SC administered every 3 months (12-13 weeks). Zero pregnancies were reported in both studies, which included a total of 16,023 woman-cycles of exposure to DMPA-SC and substantial numbers of overweight or obese women. DMPA-SC was well-tolerated and adverse events were similar to those reported previously with Depo-Provera IM. Thus, DMPA-SC offers women a new, highly effective and convenient long-acting contraceptive option.\n Copyright 2004 Elsevier Inc." ]

[ "12023410", "14716693", "15590953", "15965198" ]

[ "Donepezil for cognitive impairment in Parkinson's disease: a randomised controlled study.", "Randomized placebo-controlled trial of donepezil in cognitive impairment in Parkinson's disease.", "Rivastigmine for dementia associated with Parkinson's disease.", "Donepezil for dementia in Parkinson's disease: a randomised, double blind, placebo controlled, crossover study." ]

[ "To study the safety and efficacy of the cholinesterase inhibitor donepezil in patients with Parkinson's disease (PD) and cognitive impairment.\n This was a double blind, randomised and placebo controlled, crossover study in which 14 patients with PD and cognitive impairment received donepezil (5 or 10 mg per day) or matching placebo during two sequential periods lasting 10 weeks each. The primary outcome measures were the mini mental state examination (MMSE) score, the clinician's interview based impression of change plus caregiver input (CIBIC+) score, and the motor subscale of the unified Parkinson's disease rating scale (UPDRS).\n Two patients on donepezil (14%) dropped out after one and four weeks of the first treatment period because of peripheral cholinergic side effects, otherwise the adverse effects were few and not severe. Carryover or residual effects were not observed. Parkinsonism did not increase during donepezil treatment. After 10 weeks of treatment, the mean MMSE score was increased by 2.1(SD 2.7) points on donepezil and 0.3 (SD 3.2) points on placebo, and the CIBIC+ score was 3.3 (SD 0.9) on donepezil and 4.1 (SD 0.8) on placebo. Statistical analysis of the repeated measurements and crossover study design showed significant effects of donepezil compared with placebo for MMSE (p=0.013) and CIBIC+ (p=0.034). Five (42%) patients on donepezil and two (17%) on placebo were rated as improved on the basis of the CIBIC+ score.\n Donepezil improves cognition, and seems to be well tolerated and not to worsen parkinsonism in patients with cognitive impairment.", "To evaluate the efficacy and safety of donepezil, an acetylcholinesterase inhibitor, as a treatment for cognitive impairment and dementia in patients with Parkinson' s disease (PD).\n Using a randomized, double-blind, placebo-controlled design, nine patients received placebo and seven patients received donepezil (2.5-10 mg/day) for a mean (SD) duration of 15.2 (3.4) weeks. The primary efficacy outcomes were derived from a neuropsychological battery that assessed global cognitive status as well as memory, attention, psychomotor speed, and visuospatial and executive functions. Secondary efficacy outcomes were psychiatric symptom and activities of daily living ratings. Primary safety measures were motor signs and assessments of adverse effects.\n Patients on donepezil showed selective and significant (p<0.05) improvement on the memory subscale of the Dementia Rating Scale. There was also a trend toward improvement on a measure of psychomotor speed and attention. There were no group differences in psychiatric status, motor function, or activities of daily living as measured at baseline or end-point. Adverse effects resulted in premature withdrawal of four patients on donepezil, two for peripheral cholinergic effects and one for increased parkinsonism. Side effects were associated with dosage increases.\n Donepezil has a beneficial effect on memory and may improve other cognitive deficits in patients with PD and cognitive impairment. However, variable tolerability in our sample underscores the need for careful monitoring when prescribing donepezil to patients with PD, especially with dosage increases.\n Copyright 2004 John Wiley & Sons, Ltd.", "Cholinergic deficits are prominent in patients who have dementia associated with Parkinson's disease. We investigated the effects of the dual cholinesterase inhibitor rivastigmine in such patients.\n Patients in whom mild-to-moderate dementia developed at least 2 years after they received a clinical diagnosis of Parkinson's disease were randomly assigned to receive placebo or 3 to 12 mg of rivastigmine per day for 24 weeks. Primary efficacy variables were the scores for the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC). Secondary clinical outcomes were the scores for the Alzheimer's Disease Cooperative Study-Activities of Daily Living, the 10-item Neuropsychiatric Inventory, the Mini-Mental State Examination, Cognitive Drug Research power of attention tests, the Verbal Fluency test, and the Ten Point Clock-Drawing test.\n A total of 541 patients were enrolled, and 410 completed the study. The outcomes were better among patients treated with rivastigmine than among those who received placebo; however, the differences between these two groups were moderate and similar to those reported in trials of rivastigmine for Alzheimer's disease. Rivastigmine-treated patients had a mean improvement of 2.1 points in the score for the 70-point ADAS-cog, from a baseline score of 23.8, as compared with a 0.7-point worsening in the placebo group, from a baseline score of 24.3 (P<0.001). Clinically meaningful improvements in the scores for the ADCS-CGIC were observed in 19.8 percent of patients in the rivastigmine group and 14.5 percent of those in the placebo group, and clinically meaningful worsening was observed in 13.0 percent and 23.1 percent, respectively (mean score at 24 weeks, 3.8 and 4.3, respectively; P=0.007). Significantly better outcomes were seen with rivastigmine with respect to all secondary efficacy variables. The most frequent adverse events were nausea (affecting 29.0 percent of patients in the rivastigmine group and 11.2 percent of those in the placebo group, P<0.001), vomiting (16.6 and 1.7 percent, P<0.001), and tremor (10.2 and 3.9 percent, P=0.01).\n In this placebo-controlled study, rivastigmine was associated with moderate improvements in dementia associated with Parkinson's disease but also with higher rates of nausea, vomiting, and tremor.\n Copyright 2004 Massachusetts Medical Society.", "To study the safety and efficacy of a cholinesterase inhibitor, donepezil hydrochloride, for the treatment of dementia in Parkinson's disease (PD).\n This was a randomised double blind, placebo controlled, crossover study in 22 subjects with PD and dementia. Participants were randomised to receive either donepezil followed by identical placebo, or placebo followed by donepezil. Donepezil was administered at 5-10 mg/day. Treatment periods were 10 weeks with a washout period of 6 weeks between the two periods. The primary outcome measure was the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAScog).\n Donepezil was well tolerated and most adverse events were mild. There was no worsening of PD symptoms as measured by the total or motor sections of the Unified Parkinson's Disease Rating Scale.There was a 1.9 point trend toward better scores on the ADAScog on treatment compared with placebo that was not statistically significant. The secondary cognitive measures showed a statistically significant 2 point benefit on the Mini Mental Status Examination and no change on the Mattis Dementia Rating Scale (MDRS). The Clinical Global Impression of Change (CGI) showed a significant 0.37 point improvement on donepezil. No improvement was observed on the MDRS or the Brief Psychiatric Rating Scale. Carryover between treatment periods was observed but was not statistically significant.\n Donepezil was well tolerated and did not worsen PD. There may be a modest benefit on aspects of cognitive function. The possible clinical benefit measured by CGI was reflected in only one of the cognitive scales used in this study." ]

[ "16966982", "17283347", "12972224", "3390235", "10519687", "21205050", "2858246", "16203349", "18054445", "10522717", "17784901", "16456433" ]

[ "Effectiveness of brief interventions after alcohol-related vehicular injury: A randomized controlled trial.", "Brief intervention for medical inpatients with unhealthy alcohol use: a randomized, controlled trial.", "Implementing an effective intervention for problem drinkers on medical wards.", "Intervention of heavy drinking--a prospective and controlled study of 438 consecutive injured male patients.", "A study of minimal interventions for problem drinkers in acute care settings.", "Randomized controlled trial of a brief intervention for unhealthy alcohol use in hospitalized Taiwanese men.", "Counselling problem drinkers in medical wards: a controlled study.", "Effects of brief counselling among male heavy drinkers identified on general hospital wards.", "Brief alcohol intervention for general hospital inpatients: a randomized controlled trial.", "Alcohol interventions in a trauma center as a means of reducing the risk of injury recurrence.", "The effect of brief interventions on alcohol consumption among heavy drinkers in a general hospital setting.", "Trauma center brief interventions for alcohol disorders decrease subsequent driving under the influence arrests." ]

[ "Because 40% of motor vehicle fatalities in the United States are alcohol-related, interventions delivered by trauma clinicians targeted to reduce drinking are of particular importance to public health. The objective of this study was to test the effectiveness of hospital-based brief intervention strategies to reduce alcohol consumption and other health-related outcomes in the year after an alcohol-related vehicular injury. Brief interventions are clinically based strategies including assessment and direct feedback about drinking alcohol, goal setting, behavioral modification techniques, and the use of a self-help manual.\n The study was a randomized controlled trial of two types of brief intervention with a 12-month follow-up. Participants with alcohol-related vehicular injury who were admitted to Level I trauma centers were eligible for enrollment. Enrolled participants were randomized to a control, simple advice, or brief counseling condition. Primary outcome variables were alcohol consumption (standard drinks/month, binges/month), adverse driving events (driving citations, traffic crashes), and changes in health status (hospital and emergency department admissions).\n The study enrolled 187 participants at baseline and retained 100 across 12 months. Participants had a significant decrease in alcohol consumption and traffic citations at 12 months as compared with baseline. Mean standard drinks/month declined from 56.80 (SD 63.89) at baseline to 32.10 (SD 53.20) at 12 months. Mean binges/month declined from 5.79 (SD 6.98) at baseline to 3.21 (SD 6.17) at 12 months. There were no differences in alcohol consumption, adverse driving events, or health status by condition.\n Whether the reductions in alcohol consumption and traffic citations were a result of the crash, hospitalization for injury, screening for alcohol use, or combination of these factors is difficult to determine. Further work is needed to understand the mechanisms involved in reductions of health-related outcomes and the role of brief intervention in this population.", "The efficacy of brief intervention in reducing alcohol consumption is well established for selected outpatients but not for medical inpatients.\n To determine whether brief intervention improves alcohol outcomes in medical inpatients who were identified by screening as having unhealthy alcohol use.\n Randomized, controlled trial.\n Medical service of an urban hospital.\n 341 medical inpatients who were drinking risky amounts of alcohol (defined for eligibility as >14 drinks/wk or > or =5 drinks/occasion for men and >11 drinks/wk or > or =4 drinks/occasion for women and persons > or =66 y); 77% had alcohol dependence as determined by the Composite International Diagnostic Interview Alcohol Module.\n A 30-minute session of motivational counseling given by trained counselors during a patient's hospitalization (n = 172) versus usual care (n = 169).\n Self-reported primary outcomes were receipt of alcohol assistance (for example, alcohol disorders specialty treatment) by 3 months in dependent drinkers and change in the mean number of drinks per day from enrollment to 12 months in all patients.\n The intervention was not significantly associated with receipt of alcohol assistance by 3 months among alcohol-dependent patients (adjusted proportions receiving assistance, 49% for the intervention group and 44% for the control group; intervention-control difference, 5% [95% CI, -8% to 19%]) or with drinks per day at 12 months among all patients (adjusted mean decreases, 1.5 for patients who received the intervention and 3.1 for patients who received usual care; adjusted mean group difference, -1.5 [CI, -3.7 to 0.6]). There was no significant interaction between the intervention and alcohol dependence in statistical models predicting drinks per day (P = 0.24).\n Baseline imbalances existed between randomized groups. Patients who received usual care were assessed and advised that they could discuss their drinking with their physicians.\n Brief intervention is insufficient for linking medical inpatients with treatment for alcohol dependence and for changing alcohol consumption. Medical inpatients with unhealthy alcohol use require more extensive, tailored alcohol interventions.", "Many medical inpatients have alcohol related problems but evidence of the feasibility of instituting a brief intervention is incomplete. An alcohol counsellor trained nurses on five general medical wards to screen patients routinely for alcohol problems. She counselled appropriate patients using one or two counselling sessions. Efficacy of the counselling was assessed at interview six months following the admission. We found that 19.6% of male and 4.8% of female medical patients were drinking more than 50 units (U) or 33 drinks per week (male) or 35 U or 23 drinks per week (female). Counselling, with one or two sessions led to a reduction from a median of 74 U (49 drinks) per week at admission to 26 U (17 drinks) per week at six months follow-up. A second counselling session after discharge showed no advantage over a single one administered while the patient was in the ward. The barriers to developing a successful alcohol screening and counselling service in medical wards can be overcome provided there is also adequate support and training of the ward nursing staff.", "We studied 120 injured male patients of working age who were heavy drinkers or alcoholics, obtaining seven points or more in the Michigan Alcoholism Screening Test (MAST). They were randomly allocated either to an intervention group (IG) or to a control group (CG). In addition to the MAST interview, the consumption of alcohol during the previous week prior to hospital admission was calculated and laboratory measures (serum GGT, ASAT and ALAT) were obtained. Counselling of the patients in the IG was carried out by a trained assistant nurse and a physician. Forty-nine patients in IG and 40 patients in CG were re-examined after 6 months. In the IG 45% and in the CG 20% of the patients were improved (Chi square test, P less than 0.05). Improvement criteria were a decrease in alcohol consumption by at least one-third and decrease of S-GGT by at least 20% during the follow-up period. In respect to the laboratory measures the groups were identical at the beginning of the study and after 6 months' follow-up. Our results are encouraging and suggest that the assessment of heavy drinking should be a routine in the treatment of alcohol-related injuries and that education and counselling must be intensive to be effective.", "This article reports an investigation of three minimal interventions for potential problem drinkers in general hospital wards. The interventions were: (a) brief advice; (b) the provision of health education literature; (c) a combination of both the advice and literature. One year after recruitment the mean levels of alcohol consumption and the number of alcohol-related problems reported by the cohort was significantly reduced. These reductions were supported by reductions in the mean levels of GGT and AST, but not in mean MCV. No statistically significant treatment effects were found. The results are presented and implications for nursing are discussed.", "To evaluate the effectiveness of a brief intervention in hospitalized Taiwanese men to reduce unhealthy alcohol consumption.\n Randomized controlled trial.\n Medical/surgical wards of a medical centre in Taipei, Taiwan.\n Of 3669 consecutive adult male in-patients, 616 were identified as unhealthy alcohol users (>14 drinks/week) and assigned randomly to either usual care (n = 308) or a brief intervention (n = 308).\n Primary outcomes were changes in alcohol consumption at 4, 9 and 12 months, including self-reported weekly alcohol consumption, drinking days and heavy drinking episodes assessed by 7-day time-line follow-back. Secondary outcomes were (i) self-reported alcohol problems, (ii) health-care utilization (hospital days and emergency department visits), (iii) self-reported seeking of speciality treatment for alcohol problems and (iv) 3-month Quick Drinking Screen.\n Based on intention-to-treat analyses, the intervention group consumed significantly less alcohol than the control group among both unhealthy drinkers and the subgroup of alcohol-dependent participants over 12 months, on both 7-day and 3-month assessments. Adjunctive analyses of only those who completed all assessments found that total drinks consumed did not remain significant. Significantly more participants with alcohol use disorders in the intervention than in the control group (8.3%, 19 of 230 versus 2.1%, four of 189) consulted specialists by 12 months (P = 0.01). However, alcohol-related problems and health-care utilization did not differ significantly in the two groups during follow-up.\n Data from Taiwan confirm that brief in-hospital intervention can result in a reduction in alcohol intake by men who drink heavily or are diagnosed with an alcohol use disorder.\n © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.", "Seven hundred and thirty one men admitted to medical wards were interviewed to identify problem drinkers who had not received previous treatment for alcoholism and who had some social support. One hundred and sixty one met the diagnostic criteria; 156 agreed to a follow up interview and were allocated to one of two groups. One group received a session of counselling about their drinking habits from a nurse while the other received only routine medical care. Both groups reported a reduction in alcohol consumption when interviewed 12 months later, but the counselled group had a significantly better outcome than the control group. It is concluded that systematic screening for alcohol consumption and related problems should become a routine part of medical assessment and that advice on drinking habits is effective if given before irreversible physical or psychosocial problems have developed.", "Although the prevalence of heavy alcohol consumption among patients of general hospitals is well documented, no study has yet reported an effect of counselling on the ward in reducing the level of consumption among such patients after discharge. This study was designed to evaluate brief counselling to reduce alcohol consumption among male heavy drinkers identified on general hospital wards. Male patients were screened on wards of four teaching hospitals in Sydney, Australia. Identified heavy drinkers (n = 174) showing predominantly low levels of alcohol dependence were allocated to one of two forms of brief counselling (skills-based counselling or brief motivational interviewing) or to a non-intervention control group. Blind follow-up for 123 patients (71%) was carried out approximately 6 months after discharge from hospital and self-reports of alcohol consumption were compared with collateral sources of information. Patients who received counselling showed a significantly greater mean reduction in a quantity-frequency measure of weekly alcohol consumption than controls but there were no significant differences in reduced consumption between the two intervention groups. However, patients who were deemed \"not ready to change\" showed greater reductions if they had received brief motivational interviewing than if they had received skills-based counselling. The implications of these findings for counselling male in-patients to reduce alcohol consumption are discussed.", "To test the effectiveness of a brief alcohol intervention among non-dependent general hospital inpatients with alcohol problems, delivered by either a specialized liaison service or hospital physicians.\n All inpatients of 29 wards from four general hospitals of one region in Germany were screened for alcohol problems (n=14,332). Of those screening positive, 595 patients were included in a randomized controlled group design using a time-frame. Patients with alcohol dependence were not considered in this study. Patients received Motivational Interviewing based counselling either by a specialized liaison service, by hospital physicians trained under routine conditions or received hospital treatment as usual without additional counselling. One year later, alcohol consumption, motivation and well-being were assessed. Sample survey analyses and generalized estimating equations were conducted.\n At baseline, the three groups differed regarding motivation, with higher motivation among the controls. At follow-up, the groups did not differ regarding alcohol consumption, alcohol-related problems and well-being. All groups decreased their alcohol consumption significantly. Regarding motivation, longitudinal analyses revealed significant interaction effects of time and intervention (p<0.05), indicating a stronger increase of readiness to change drinking and a less profound drop of readiness to seek help among those who received intervention compared to the controls.\n The intervention was not effective in reducing alcohol consumption or in increasing well-being 12 months after hospitalization. It had a positive effect on readiness to change drinking and on readiness to seek formal help for alcohol problems. The intervention groups compensated their lag of motivation.", "Alcoholism is the leading risk factor for injury. The authors hypothesized that providing brief alcohol interventions as a routine component of trauma care would significantly reduce alcohol consumption and would decrease the rate of trauma recidivism.\n This study was a randomized, prospective controlled trial in a level 1 trauma center. Patients were screened using a blood alcohol concentration, gamma glutamyl transpeptidase level, and short Michigan Alcoholism Screening Test (SMAST). Those with positive results were randomized to a brief intervention or control group. Reinjury was detected by a computerized search of emergency department and statewide hospital discharge records, and 6- and 12-month interviews were conducted to assess alcohol use.\n A total of 2524 patients were screened; 1153 screened positive (46%). Three hundred sixty-six were randomized to the intervention group, and 396 to controls. At 12 months, the intervention group decreased alcohol consumption by 21.8+/-3.7 drinks per week; in the control group, the decrease was 6.7+/-5.8 (p = 0.03). The reduction was most apparent in patients with mild to moderate alcohol problems (SMAST score 3 to 8); they had 21.6+/-4.2 fewer drinks per week, compared to an increase of 2.3+/-8.3 drinks per week in controls (p < 0.01). There was a 47% reduction in injuries requiring either emergency department or trauma center admission (hazard ratio 0.53, 95% confidence interval 0.26 to 1.07, p = 0.07) and a 48% reduction in injuries requiring hospital admission (3 years follow-up).\n Alcohol interventions are associated with a reduction in alcohol intake and a reduced risk of trauma recidivism. Given the prevalence of alcohol problems in trauma centers, screening, intervention, and counseling for alcohol problems should be routine.", "(i) To evaluate the effect of receiving one of two brief interventions in reducing alcohol consumption among general hospital patients compared with usual care. (ii) To assess whether a brief intervention of self-efficacy enhancement was superior to a self-help booklet in reducing alcohol consumption.\n A three-arm cluster randomized controlled trial.\n Seven general medical, six general surgical, one dermatology and two otolaryngology wards of a large teaching hospital covering a large urban and rural area.\n A total of 215 of 789 in-patients aged 18-75 years, who screened positive for alcohol consumption in excess of national recommended limits according to a 7-day retrospective drinking diary.\n Participants were allocated to receive one of three interventions: (i) face-to-face self-efficacy enhancement; (ii) a self-help booklet; or (iii) usual care.\n The primary outcome measure was change in reported alcohol consumption at 6-month follow-up as measured by a 7-day retrospective drinking diary. Secondary outcomes were change in: number of alcohol drinking days in last week; the maximum units of alcohol consumed on any one day in last week; and Drinking Refusal Self-efficacy Expectancy Questionnaire score.\n Compared to the usual care group the self-efficacy enhancement group (-10.1 units 95% CI -16.1 to -4.1) and the self-help booklet group (-10.0 units 95% CI -16.0 to -3.9) had greater reductions in self-reported weekly alcohol consumption. There was no evidence that self-efficacy enhancement was superior to the self-help booklet (P = 0.96).\n Brief interventions delivered in hospital offer simple means of helping heavy drinkers to reduce their alcohol consumption.", "A substantial number of trauma center admissions are related to driving under the influence (DUI); however, there has been no prior report of brief intervention (BI) after injury reducing subsequent DUI arrests. The hypothesis of this study was that injured patients receiving BI would have a lower risk of DUI arrest within 3 years of discharge than those receiving standard care (SC).\n This prospective, randomized clinical trial randomly allocated patients involved in motor vehicle collisions to receive SC or a BI regarding alcohol use. The primary outcome measure was DUI arrest within 3 years of hospital discharge. DUI arrests were documented by matching demographic information to state traffic safety data.\n After randomization (N = 126), BI and SC groups were similar in age, prior DUI arrests, and alcohol screening score. BI sessions lasted an average of 30 minutes and were performed by either a social worker or a trauma surgeon. Approximately one in six participants (n = 21, 16.7%) had a DUI arrest within 3 years of hospital discharge. Within 3 years of hospital discharge, 14 of 64 patients (21.9%) in the SC group had an arrest for DUI compared with only 7 of 62 patients (11.3%) who received the BI. Multivariate analysis demonstrated that BI was the strongest protective factor against DUI arrest (odds ratio [OR], 0.32; 95% confidence interval < or =CI], 0.11-0.96). Prior number of DUIs (OR, 1.43; 95% CI, 1.03-2.01) and age (OR, 0.94; 95% CI, 0.88-0.99) were also associated with DUI arrest post-hospitalization, but alcohol screening score (OR, 1.06; 95% CI, 0.99-1.13) was not. The absolute risk reduction implies that only nine patients would need to receive a BI to prevent one DUI arrest.\n Patients who receive BI during a trauma center admission are less likely to be arrested for DUI within 3 years of discharge. BI represents a viable intervention to reduce DUI after trauma center admission." ]

[ "6615094", "8978226", "16026656", "16423095", "16244510", "10361649", "7994223", "10098823", "9584539", "18067552", "11832254", "9335919", "314119", "11302295", "15818198", "15784786", "7083525" ]

[ "The group counseling v exercise therapy study. A controlled intervention with subjects following myocardial infarction.", "Psychological rehabilitation after myocardial infarction: multicentre randomised controlled trial.", "Psychological effects of a short behavior modification program in patients with acute myocardial infarction or coronary artery bypass grafting. A randomized controlled trial.", "Improving psychologic adjustment to chronic illness in cardiac patients. The role of depression and anxiety.", "Psychological and quality-of-life outcomes from a comprehensive stress reduction and lifestyle program in patients with coronary artery disease: results of a randomized trial.", "Effect of relaxation therapy on cardiac events after myocardial infarction: a 5-year follow-up study.", "Effects of a health education programme with telephone follow-up during cardiac rehabilitation.", "Behavioral effects of a comprehensive, multifactorial program for lifestyle change after percutaneous transluminal coronary angioplasty: a prospective, randomized controlled study.", "Effect of intervention for psychological distress on rehospitalization rates in cardiac rehabilitation patients.", "Effects of a stress management program on vital exhaustion and depression in women with coronary heart disease: a randomized controlled intervention study.", "Guideline-based early rehabilitation after myocardial infarction. A pragmatic randomised controlled trial.", "Management after myocardial infarction: a controlled trial of the effect of group psychotherapy.", "Brief group therapy in myocardial infarction rehabilitation: three- to four-year follow-up of a controlled trial.", "Psychosocial nursing therapy following sudden cardiac arrest: impact on two-year survival.", "Women's hearts--stress management for women with ischemic heart disease: explanatory analyses of a randomized controlled trial.", "Effects of treating exhaustion in angioplasty patients on new coronary events: results of the randomized Exhaustion Intervention Trial (EXIT).", "Feasibility of altering type A behavior pattern after myocardial infarction. Recurrent Coronary Prevention Project Study: methods, baseline results and preliminary findings." ]

[ "One hundred six postmyocardial infarction subjects who either achieved a mean work load of less than seven mets on treadmill testing, who were rated as anxious and/or depressed, or who met both criteria, participated in a controlled study comparing the rehabilitation effectiveness of exercise therapy and group counseling. Each intervention lasted 12 weeks. Follow-up evaluations were scheduled at three months, six months and one year. Exercise substantially increased mean work capacity, decreased fatigue, lessened anxiety and depression, and promoted independence and sociability. Counseling substantially reduced depression and promoted a sense of friendliness, and decreased interpersonal friction as well as greater independence and sociability. The control group reported no substantial change on any measured factor. Neither counseling nor exercise had an effect on mortality though subjects in the exercise group reported fewer major cardiovascular sequelae.", "To evaluate rehabilitation after myocardial infarction.\n Randomised controlled trial of rehabilitation in unselected myocardial infarction patients in six centres, baseline data being collected on admission and by structured interview (of patients and spouses) shortly after discharge and outcome being assessed by structured interview at six months and clinical examination at 12 months.\n Six district general hospitals.\n All 2328 eligible patients admitted over two years with confirmed myocardial infarction and discharged home within 28 days.\n Rehabilitation programmes comprising psychological therapy, counselling, relaxation training, and stress management training over seven weekly group outpatient sessions for patients and spouses.\n Anxiety, depression, quality of life, morbidity, use of medication, and mortality.\n At six months there were no significant differences between rehabilitation patients and controls in reported anxiety (prevalence 33%) or depression (19%). Rehabilitation patients reported a lower frequency of angina (median three versus four episodes a week), medication, and physical activity. At 12 months there were no differences in clinical complications, clinical sequelae, or mortality.\n Rehabilitation programmes based on psychological therapy, counselling, relaxation training, and stress management seem to offer little objective benefit to patients who have experienced myocardial infarction compared with previous reports of smaller trials.", "The effects of a short intervention on behavioral risk factor modification in patients with coronary artery disease (CAD) on Type A behavior, vital exhaustion, and depression were studied in a randomized controlled trial.\n Acute myocardial infarction patients or patients who underwent coronary artery bypass grafting (CABG) were randomly assigned to an 8-week multiple risk modification group program (n = 94) or to a control group (n = 90) that received usual care with standard physical exercise training. Patients were assessed before intervention, directly after intervention, and at 9-month follow-up.\n The intervention was effective in reducing hostility and total Type A behavior at postintervention (P = .01) and at 9-month follow-up (P = .03). The intervention had no overall impact on vital exhaustion and depression, measured by the Beck Depression Inventory (BDI), whereas we unexpectedly found that the percentage of patients with major depression was reduced in the control group but not in the intervention group.\n The results indicate that a short behavioral intervention for coronary patients can result in relatively large and persistent reductions in cognitive aspects of Type A behavior and hostility, in particular. In view of the unwanted findings on the diagnosis of depression, however, we do not unequivocally advise the intervention to the general population of AMI and CABG patients.", "Poor mood adjustment to chronic medical illness is often accompanied by decrements in function.\n To evaluate the effectiveness of a telephone-based intervention for psychologic distress and functional impairment in cardiac illness.\n Randomized, controlled trial.\n We recruited survivors of acute coronary syndromes using the Hospital and Anxiety Depression Scale (HADS) with scores indicative of mood disturbances at 1-month postdischarge. Recruited patients were randomized to experimental or control status. Intervention patients received 6 30-minute telephone counseling sessions to identify and address illness-related fears and concerns. Control patients received usual care. Patients' responses to the HADS and the Workplace Social Adjustment Scale (WSAS) were collected at baseline, 2, 3, and 6 months using interactive voice recognition technology. At baseline, the PRIME-MD was used to establish diagnosis of depression. We used mixed effects regression to study changes in outcomes.\n We enrolled 100 patients. Mean age was 60; 67% of the patients were male. Findings confirmed that the intervention group had a 27% improvement in depression symptoms (P=.05), 27% in anxiety (P=.02), and a 38% improvement in home limitations (P=.04) compared with controls. Symptom improvement tracked those for WSAS measures of home function (P=.04) but not workplace function.\n The intervention had a moderate effect on patient's emotional and functional outcomes that were observed during a critical period in patients' lives. Patient convenience, ease of delivery, and the effectiveness of the intervention suggest that the counseling can help patients adjust to chronic illness.", "Stress reduction and comprehensive lifestyle modification programs have improved atherosclerosis and cardiac risk factors in earlier trials. Little is known about the impact of such programs on quality-of-life (QoL) and psychological outcomes. Given recent significant improvements in cardiac care, we evaluated the current benefit of stress reduction/lifestyle modification on QoL and emotional distress in patients with coronary artery disease (CAD).\n 101 patients (59.4 +/- 8.6 years, 23 female) with CAD were randomized to a 1-year lifestyle/stress management program (n = 48) or written advice (n = 53). QoL and psychological outcomes were assessed with the SF-36, Beck Depression, Spielberger State/Trait Anxiety, Spielberger State/Trait Anger and Perceived Stress Inventories. Group repeated-measures analyses of variance were performed for all measures.\n Adherence to the program was excellent (daily relaxation practice 39 +/- 5 vs. 5 +/- 8 min, respectively; p < 0.001). Both groups improved comparably in most dimensions of QoL, and significantly greater improvements for the lifestyle group were found for physical function and physical sum score (p = 0.046 and p = 0.045). Depression, anxiety, anger and perceived stress were reduced similarly in both groups. However, intervention x gender interaction effects revealed greater benefits among women in the lifestyle intervention vs. advice group for depression and anger (p = 0.025 and p = 0.040), but no effects for men.\n A comprehensive lifestyle modification and stress management program did not improve psychological outcomes in medically stable CAD patients. The program did appear to confer psychological benefits for women but not men. Further trials should investigate gender-related differences in coronary patient responses to behavioral interventions.\n Copyright (c) 2005 S. Karger AG, Basel.", "Evidence suggests that breathing and relaxation therapy may influence cardiac events in persons after acute myocardial infarction (MI). The authors studied the effects of breathing and relaxation therapy on rates of cardiac events and cost effectiveness in past MI patients.\n Patients (n = 156) were chosen randomly to receive either exercise training plus relaxation therapy (relaxation group; n = 76) or exercise training only (control group; n = 80). The occurrence of major cardiac events and cardiac rehospitalizations in the two treatment groups was compared.\n At 5-year follow-up, 12 cardiac deaths had occurred, 5 in the relaxation group and 7 in the control group, reinfarction occurred in 10 and 12 patients, and cardiac surgery was performed in 2 and 11, respectively. In total, 15 (20%) and 26 (33%) patients, respectively, experienced at least one cardiac event (odds ratio [OR] for the relaxation group: 0.55, 95% confidence interval [CI] 0.29-1.05; adjusted for risk factors OR 0.52, 95% CI 0.28-0.99). Regarding all cardiac rehospitalizations, in the relaxation group, 30 patients (39%) had experienced 52 cardiac events, for which the patients were hospitalized for a total of 476 days. In the control group, 38 patients (48%) had experienced 78 cardiac events (OR 0.72; 95% CI 0.38-1.36), comprising 719 days of hospitalization. The total number of hospitalizations was reduced by 31% as a result of relaxation instruction.\n In the long-term, the disease course after myocardial infarction is influenced favorably by giving relaxation therapy in addition to cardiac rehabilitation. The extra costs of the therapy are compensated by a decrease in hospitalization for cardiac problems.", "A health education and counselling programme was offered to myocardial infarction patients during and after hospitalization. A randomized pre-test-post-test control group design was used to evaluate the effects of the experimental intervention. During hospitalization the intervention consisted of two individual counselling sessions and two group health education sessions focusing on medication, healthy habits, anxiety and depression. On completion of these sessions, weekly telephone calls were made to patients for a period of six weeks after discharge from hospital. The intervention was offered to 30 myocardial infarction patients and their partners (the experimental group) in addition to standard medical care. Thirty control patients received standard medical care only. Two months after myocardial infarction, patients in the experimental condition reported a significantly greater increase in physical activity, and a significantly greater decrease in unhealthy eating habits. No effects were found regarding smoking cessation, anxiety and depression. Twelve months after discharge from hospital patients in the experimental condition reported a significantly greater decrease in unhealthy eating habits. No effects were found regarding smoking cessation, physical activity, anxiety and depression. In addition, two months after myocardial infarction, it was found that patients whose partners participated in the health education sessions showed a significantly greater decrease in smoking and unhealthy eating habits and a significantly greater increase in physical activity than patients with no partner participating. Twelve months after discharge the only significant result favouring the patients whose partner participated in the health education sessions concerned smoking cessation.", "A group of 93 coronary patients recently treated with percutaneous transluminal coronary angioplasty (PTCA) were randomly assigned to either an intervention or a control group. Subjects in the intervention group participated in a comprehensive behaviorally oriented program aimed at achieving significant long-term changes in risk factor-related lifestyle behavior. Assessments of lifestyle behaviors, psychological factors, biological risk factors, and rehabilitation as well as secondary prevention endpoints were carried out, at inclusion and after 12 months. Results showed that the intervention patients, as compared with controls, improved significantly on measures assessing smoking, exercise, and diet habits. These self-rated changes were confirmed by weight reductions and improved exercise capacity, as well as by between-group differences in subclinical chest pain during an exercise test. However, few effects were found on the different psychological variables, as well as on morbidity or return to work.", "Psychosocial factors affect the development of coronary heart disease and morbidity and mortality of patients with known coronary heart disease. A prior study has shown that psychological distress in patients with known coronary heart disease increased medical and economic costs. This study examined the effects of commonly available psychological interventions offered to patients entering cardiac rehabilitation after hospitalization for angina, myocardial infarction, angioplasty, or coronary artery bypass grafting. A total of 380 patients were screened with the Symptom Checklist-90-Revised (SCL-90-R). Those with T-scores > or = 63 (> or = 91 percentile) on the General Severity Index (GSI) subscale were randomly assigned to usual care or special intervention. Special intervention included a psychiatric evaluation, plus one to seven sessions of behavioral therapy. The percentage of patients rehospitalized for cardiac symptoms within 12 months of psychological evaluation was 43% for special intervention and 40% for usual care (NS). A correction for crossover between the treatment groups resulted in a favorable trend toward intervention, with 35% of the psychologically treated patients rehospitalized vs. 48% of the untreated patients (NS). Although there was a nonsignificant reduction of the SCL-90-R's GSI T-score, the depression score was significantly reduced in the special intervention group.", "Psychosocial factors, including depression and vital exhaustion (VE) are associated with adverse outcome in coronary heart disease (CHD). Women with CHD are poor responders to psychosocial treatment and knowledge regarding which treatment modality works in them is limited. This randomized controlled clinical study evaluated the effect of a 1-year stress management program, aimed at reducing symptoms of depression and VE in CHD women.\n Patients were 247 women, < or =75 years, recruited consecutively after a cardiac event and randomly assigned to either stress management (20 2-h sessions) and medical care by a cardiologist, or to obtaining usual health care as controls. Measurements at; baseline (6-8 weeks after randomization), 10 weeks (after 10 intervention sessions), 1 year (end of intervention) and 1-2 years follow-up.\n For VE, intention to treat analysis showed effects for time (P < 0.001) and time x treatment interaction (P = 0.005), reflecting that both groups improved over time, and that the decrease of VE was more pronounced in the intervention group. However, the level of VE was higher in the intervention group than amongst controls at baseline, 22.7 vs. 19.4 (P = 0.036) but it did not differ later. The change in depressive symptoms did not differ between the groups.\n CHD women attending our program experienced a more pronounced decrease in VE than controls. However, as they had higher baseline levels, due to regression towards the mean we cannot attribute the decrease in VE to the intervention. Whether the program has long-term beneficial effects needs to be evaluated.", "To determine the effectiveness of individualised educational behavioural treatment delivered by cardiac nurses in hospital compared to usual care for patients following acute myocardial infarction.\n One hundred and fourteen consecutive patients were randomised to receive the intervention or usual care. Outcome assessment was by self-report questionnaire (the Hospital Anxiety and Depression Scale and Dartmouth COOP Health Status), interview at 1 month, and self-report at 3 and 12 months. The primary outcome was improvement in the Dartmouth COOP total score from baseline to 3 months.\n Four patients needed to be treated to give an additional patient with improvement in health status at 3 months (number needed to treat [NNT] 4, 95% confidence intervals [CIs] 3 to 12). The intervention group were more confident about returning to activities 1 month after discharge from hospital. Treated patients had fewer further treatment needs.\n An individualised educational behavioural treatment delivered by cardiac nurses in hospital may have substantial benefits. A large-scale pragmatic RCT is needed.", "nan", "A trial of brief group therapy as part of a rehabilitation program for postmyocardial infarction (MI) patients was carried out. Forty-four patients surviving their first MI were randomly allocated to either group therapy or control group status and were followed over 4 years. An additional group of 17 patients were referred for post-MI group therapy sessions after the termination of the controlled experiment and were followed for 3 years. Patients who received group therapy had significantly less follow-up coronary morbidity and mortality, and returned to work at significant higher percentages than control patients. Although neither group therapy nor control group patients meaningfully altered conventional coronary risk factors, group therapy patients (in the controlled trial) successfully altered selected coronary-prone behaviors. Educational information regarding the physiological and psychological aspects of coronary heart disease, presented in the group therapy sessions, was forgotten over follow-up. It is concluded that the supportive aspects of the group therapy experience played the most important role in determining the rehabilitation advantages seen for treatment patients.", "Although psychosocial therapy has been shown to reduce mortality after myocardial infarction, it is unknown whether the benefits of psychosocial therapy on mortality reduction extend to out-of-hospital sudden cardiac arrest, a main cause of cardiovascular mortality.\n Describe efficacy of psychosocial therapy on two-year cardiovascular mortality in sudden cardiac arrest survivors.\n Survivors of out-of-hospital ventricular fibrillation or asystole (N = 129), documented by electrocardiograms from registries of a citywide Medic One unit and two countywide emergency units, were randomized into a two group, experimental, longitudinal design. The intervention consisted of 11 individual sessions, implementing three components: physiologic relaxation with biofeedback training focused on altering autonomic tone; cognitive behavioral therapy aimed at self-management and coping strategies for depression, anxiety, and anger; and cardiovascular health education. The primary outcome measure was cardiovascular mortality.\n Risk of cardiovascular death was significantly reduced 86% by psychosocial therapy, p = .03. Six of the seven cardiovascular deaths in the control group were caused by ventricular arrhythmias. The cardiovascular death in the therapy group was due to stroke. Controlling for depression, previous myocardial infarction, low ejection fraction, decreased heart rate variability, and ventricular ectopic beats had little impact on estimated treatment effect. The risk of all-cause mortality was reduced by 62% in the therapy group, p = .13. There were a total of three deaths in the therapy group and eight deaths in the control group.\n Psychosocial therapy significantly reduced the risk of cardiovascular death in sudden cardiac arrest survivors.", "This randomized controlled study aimed to evaluate the effects on psychosocial variables of a 1-year group-based cognitive-behavioral stress management program developed specifically for women with ischemic heart disease.\n The present explanatory (per protocol) analyses include 80 women who were randomized to a 1-year cognitive-behavioral stress management program and 86 who were randomized to usual care (age = 35-77 years). Data were obtained before randomization and after 1 year, when the intervention group had completed the program.\n There were no statistically significant differences between the intervention and usual care groups in the psychosocial endpoints at randomization. Both groups improved in all psychosocial variables during the 1-year study period, but the rate of improvement was significantly greater in the intervention group for self-rated stress behavior (P = .006) and vital exhaustion (P = .03). Although changes were in favor of the treatment group also for depressive mood and quality of life, the rates of improvement between the 2 groups did not reach statistical significance (P = .23 and P = .10, respectively).\n A 1-year cognitive-behavioral stress management program designed specifically for women improved psychological well-being in some aspects in comparison with usual care.", "Extreme fatigue is a common complaint in percutaneous coronary intervention (PCI) patients, and is associated with an increased risk for new cardiac events. The objective of the Exhaustion Intervention Trial (EXIT) was to determine whether a behavioral intervention on exhaustion reduces the risk of a new coronary event after PCI.\n Seven hundred ten consecutive patients, ages 35 to 68 years, who felt exhausted after PCI were randomized into an intervention group and a usual-care group. The intervention was based on group therapy focusing on stressors leading to exhaustion, and on support for recovery by promoting rest and making rest more efficient. One month after PCI, 50% of the patients felt exhausted. The intervention reduced the odds of remaining exhausted at 18 months by 56% in those without a previous history of coronary artery disease (CAD) (OR = 0.44; 95% CI 0.29-0.66), but had no effect on exhaustion in those with a history of CAD (OR = 0.93; 95% CI 0.56-1.55; p = .78). The intervention did not reduce the risk of a new coronary event within 2 years (RR = 1.14; 95%CI 0.82-1.57). Post-hoc analyses suggest that the effect of the intervention was limited by a positive history of CAD, the presence of a chronic, painful condition (especially rheumatism), and by opposite effects on early and late cardiac events.\n A behavioral intervention in PCI patients has a beneficial effect on feelings of exhaustion. It could not be demonstrated that the intervention reduces the risk of a new coronary event within 2 years.", "We studied 1035 consecutive postinfarction patients to determine the feasibility of altering type A behavior and the effect such alteration might have on subsequent rates of infarction and cardiovascular death. Approximately 300 subjects were enrolled in small groups and primarily received cardiologic counseling on the usually accepted coronary risk factors. Six hundred subjects received, in addition to cardiologic counseling, advice and instructions designed to diminish the intensity of their type A behavior. The remaining subjects, serving as controls, received no counseling, but were examined and interviewed annually, as were those who dropped out of counseling groups. More than 98% of the 1035 subjects exhibited moderate-to-severe type A behavior during a videotaped structured interview. After the first year of this 5-year study, the rates of infarction and cardiovascular death were lower (p less than 0.01 and p less than 0.05, respectively) among subjects who received both cardiologic and behavioral counseling than among the control subjects. The rate of nonfatal infarction was lower (p less than 0.05) among subjects who received behavioral counseling than among those who received only cardiologic counseling or those who dropped out of either counseling group. The circumstances that most often preceded recurrent infarction or cardiovascular death were emotional crisis, excess physical activity, ingestion of a single fatty meal or a combination of these phenomena." ]

[ "6139668", "8208677", "6235453", "2961818", "8165854", "6111671", "3794300" ]

[ "Efficacy of heat-inactivated hepatitis B vaccine in haemodialysis patients and staff. Double-blind placebo-controlled trial.", "[Recombinant vaccine and extracting vaccine against hepatitis B in patients with kidney insufficiency: comparative immunogenicity].", "Hepatitis B vaccine in patients receiving hemodialysis. Immunogenicity and efficacy.", "Hepatitis B vaccines in patients with chronic renal failure before dialysis.", "Comparison of two immunization schedules with recombinant hepatitis B vaccine and natural immunity acquired by hepatitis B infection in dialysis patients.", "Randomised placebo-controlled trial of hepatitis B surface antigen vaccine in french haemodialysis units: II, Haemodialysis patients.", "Immunogenicity of recombinant hepatitis B vaccine in dialysis patients." ]

[ "The efficacy of a heat-inactivated hepatitis B vaccine, 3 micrograms of surface antigen (HBsAg), given at 0, 1, 2, and 5 months, was evaluated in 401 haemodialysis patients in 18 centres by a placebo-controlled, double-blind, randomised trial. The attack-rate of hepatitis B virus (HBV) infections in the control group was 18% over 435 days. The protective efficacy rate of the vaccine was 78% against all HBV infections in the entire study (p = 0.00016), and 94% against HBsAg-positive hepatitis more than 3 months after day 0. Those patients in whom HBV developed showed no evidence of vaccine-acquired anti-HBs. Among 152 similarly randomised staff members receiving three monthly injections, all 5 HBsAg-positive infections occurred in the placebo group (p = 0.022). The vaccine induced anti-HBs in 88% of the patients and 100% of the staff. Immediately after the fourth injection, anti-HBs levels were as high in responding patients as in staff. There were no serious side effects. In the four-dose schedule the vaccine provides dialysis patients with protection of the same order as that given by other hepatitis B vaccines to normal subjects.", "Patients with chronic renal failure respond rather poorly to hepatitis B vaccines. A better response could be expected from recombinant vaccines including both the S and the pre-S2 antigens. We therefore prospectively compared the immunogenicity of plasma-derived Hevac B vaccine (H) with that of recombinant GenHevac B vaccine (G).\n Vaccinations were performed in 120 non-dialyzed patients with chronic renal failure. The patients were randomly divided into two groups. Group G included 60 patients (24 males, mean age 58 +/- 16 years, mean creatinine clearance 25.3 +/- 12.6 ml/min) who were given the Hevac B vaccine at the dose of 5 micrograms. Group H included 60 patients (31 males, mean age 60 +/- 15 years, mean creatinine clearance 24.4 +/- 11.1 ml/min) who were given GenHevac B vaccine at the dose of 20 micrograms. All vaccinations were repeated at 0, 1, 2, 4 and 12 months.\n Following the fourth injection, seroconversion (anti-Hbs > or = 2 mlU/ml) was observed in 50/59 (85%) of the patients in group G versus 38/58 (67%) in group H (p < 0.02). Seroprotection (> or = 10 mlU/ml) was obtained in 42/59 (71%) vs 34/58 (59%), (NS) in the two groups respectively with a geometric mean titer of 112 versus 229 mlU/ml (NS) in responders. Following the booster injection at the 12th month, seroconversion was achieved in 48/51 (94%) vs 40/53 (76%) (p < 0.01) and seroprotection in 84% vs 70% (p = 0.053) respectively. The mean geometric titers were 879 and 1001 mlU/ml.\n Recombinant GenHevac B vaccine elicits seroconversion and seroprotection in a higher proportion of patients with chronic renal failure than the plasma-derived Hevac B vaccine, with comparably high antibody titers in responders. Therefore, GenHevac B vaccine should be recommended for vaccinating patients with chronic renal failure against hepatitis B.", "We evaluated the immunogenicity and efficacy of hepatitis B vaccine (Heptavax-B) in a randomized, double-blind, placebo-controlled trial involving 1311 patients receiving hemodialysis in the United States. After three doses of vaccine (40 micrograms each) had been administered, 63 per cent of the patients were antibody-positive. After correction for possible passive transfer of antibodies by blood transfusion, only 50 per cent of vaccine recipients were considered vaccine responders. The incidence of hepatitis B viral infection during the 25 months of the trial was much lower than had been anticipated and was virtually the same in the vaccine and placebo recipients (6.4 and 5.4 per cent, respectively). Four cases of hepatitis B occurred in patients who had an apparent antibody response to the vaccine, but in each case either antibody had reached low or undetectable levels before hepatitis B surface antigen was detected or the patient had been receiving immunosuppressive therapy. This study did not demonstrate the efficacy of the vaccine in a population of patients receiving dialysis in whom both the rate of antibody response to hepatitis B vaccine and the viral attack rate were low. Other measures to control transmission of hepatitis B virus in dialysis units, including surveillance for hepatitis B surface antigen and isolation of patients who are positive for the antigen, must be continued.", "Hepatitis B remains a significant risk to patients receiving chronic hemodialysis, but no certain method of prevention has been identified. We tested two vaccines, plasma-derived vaccine (40-micrograms dose) and recombinant-derived vaccine (40-micrograms and 20-micrograms doses), in 61 patients with chronic renal failure who were not yet dependent on dialysis. Patients were followed up clinically and with laboratory tests of kidney function and hepatitis B virus serology for one year. Significantly more recipients of plasma-derived vaccine responded to vaccination; they also achieved a higher titer of antibody to hepatitis B virus than did recipients of recombinant-derived vaccine when evaluated at 6, 7, 9, and 12 mo after vaccination. No serious side effects were observed with any vaccine preparation, nor were excessive adverse effects observed in any group. Compared with the dialysis patients previously studied, patients with renal failure who were not yet dependent on dialysis responded more favorably to the hepatitis B virus vaccine.", "In a prospective study over a 2-year period we compared two practical dosage schedules to vaccinate dialysis patients against hepatitis B virus (HBV) infection using a yeast-derived recombinant hepatitis B vaccine (Engerix-B). In addition, the natural history of this acquired immunity was compared with that developed through HBV infection in dialysis patients and healthy subjects. Patients on dialysis treatment (haemo or peritoneal) who were tested to be negative for hepatitis B surface antigen (HBsAg), anti-HBs and anti-HB core were allocated at random to receive HB vaccine according to one of the two schedules. The two groups receiving the vaccine were matched for age, sex, mean duration on dialysis and the form of dialysis treatment received. The group of patients who received a four-dose schedule (at 0, 1, 2 and 6 months) of 40 micrograms of HB vaccine each time (group 2) achieved a seroconversion rate of 79% 1 month after the last dose (at month 7) compared with a seroconversion rate of 55% in those who received three doses (at 0, 1 and 6 months) of 40 micrograms each (group 1). Healthy controls who received half the amount of vaccine on a three-dose schedule (group 3) attained 100% seroconversion (p < 0.05). When retested at 24 months, 30% of seroconverters in group 1 had lost their protective immunity, compared with only 6% in group 2 and 15% in group 3. The magnitude of antibody response (total and anti-(a)-specific) was assessed in the vaccinees at 24 months and compared with that of two other control groups, dialysis patients (group 4) and healthy volunteers (group 5), who had acquired immunity from HBV infection. In general, the total and anti-(a)-specific HBs titres in the dialysis patients (groups 1, 2 and 4) were lower than in their corresponding healthy controls (groups 3 and 5), irrespective of whether the protective immunity was acquired by vaccination or HBV infection. However, the anti-HBs titres in dialysis patients who received four doses were significantly higher than in those who received only three doses (p < 0.05), which indicated a better protective immunity in favour of the former regime. The magnitude of antibody response in the vaccinees of groups 2 and 3 compared well with their respective controls, groups 4 and 5, who had acquired their immunity through HBV infection. This implied that the yeast-derived vaccine was sufficiently immunogenic and provided lasting protection in patients and healthy subjects vaccinated by an appropriate dosage schedule.(ABSTRACT TRUNCATED AT 400 WORDS)", "A vaccine against hepatitis B surface antigen (Institut Pasteur Production) was assessed in 138 haemodialysis patients in a placebo-controlled randomised double-blind trial. In an interim analysis, hepatitis B infections were observed in 21% of the vaccine group and 45% of the placebo group (p less than 0.02). 2 of the infections in the vaccine group and 12 of the infections in the placebo group occurred after the third injection. 60% of the vaccine recipients had an immune response. 4 months after the first injection the mean titre of anti-HBs was 120 mlU/ml.", "Eighty-eight dialysis patients were vaccinated with recombinant hepatitis B vaccine prepared in yeast. Fourty-nine patients were immunized 3 times (months 0, 1, 6) intragluteally with 40 micrograms hepatitis B surface antigen (HBsAg) per dose. Only 32 of them (65.3%) showed anti-HBs concentrations above 10 IU/l with a geometric mean titer (GMT) of 180.7 IU/l after 3 vaccinations, whereas all of the 16 healthy controls, vaccinated 3 times with a 10-micrograms dose of the same vaccine batch, had specific antibodies higher than 10 IU/l (GMT 897.4 IU/l). Responses of patients were slightly higher than those of dialysis patients vaccinated in an earlier study with plasma-derived vaccine according to the same schedule. Results in 20 patients immunized 6 times intragluteally with 40 micrograms HBsAg/dose in monthly intervals were not better (at month 7, 65% showed anti-HBs concentrations greater than 10 IU/l; GMT = 126.6 IU/l), and 19 patients receiving 6 times 20 micrograms HBsAg monthly showed significantly lower responses (anti-HBs greater than 10 IU/l in 42% of vaccinees, GMT = 89.5 IU/l). The vaccine was tolerated well; side-effects were slight, and no serious adverse reactions were observed. In conclusion, recombinant hepatitis B vaccine is comparable to plasma-derived vaccine also in the case of dialysis patients; a 6-dose schedule does not seem to have much advantage compared to the conventional 3-dose regimen." ]

[ "17433319", "15589870", "9848316" ]

[ "A comparison of follicular response of ovaries to ovulation induction after laparoscopic ovarian cystectomy or fenestration and coagulation versus normal ovaries in patients with endometrioma.", "A prospective, randomized study comparing laparoscopic ovarian cystectomy versus fenestration and coagulation in patients with endometriomas.", "Randomized clinical trial of two laparoscopic treatments of endometriomas: cystectomy versus drainage and coagulation." ]

[ "In a comparison of follicular responses to controlled ovarian hyperstimulation (COH) between normal ovaries and ovaries previously treated by different laparoscopic techniques for ovarian endometrioma in 65 patients with unilateral endometrioma, laparoscopic ovarian fenestration and coagulation was performed in 24 cases (group 1) and laparoscopic ovarian cystectomy in the other 41 (group 2). In 16 patients with bilateral endometrioma (group 3), cystectomy was done in one ovary and fenestration and coagulation in the contralateral side. The results indicate that the response of ovaries to COH after laparoscopic ovarian cystectomy or fenestration and coagulation was the same and that there was no difference in response to COH between normal ovaries and those operated on by the laparoscopic techniques mentioned above.", "To determine the difference between two laparoscopic methods for the management of endometriomas with regard to recurrence of signs and symptoms and pregnancy rate.\n Prospective, randomized clinical trial.\n Infertility and gynecologic endoscopy units of two medical university hospitals.\n One hundred patients with endometriomas who had either infertility or pelvic pain.\n Patients were randomly divided into two groups; one group underwent cystectomy (group 1), and fenestration and coagulation were performed for the other (group 2).\n A comparison of recurrence of signs and symptoms of endometriomas and pregnancy rates in two groups.\n Fifty-two patients were studied in group 1 and 48 in group 2. The recurrence of symptoms, such as pelvic pain and dysmenorrhea, was 15.8% in group 1 and 56.7% in group 2 after 2 years. The rate of reoperation was 5.8% in group 1 and 22.9% in group 2 and these differences were statistically significant. The cumulative pregnancy rate was significantly higher in group 1 (59.4%) than in group 2 (23.3%) at 1-year follow-up.\n Laparoscopic cystectomy of endometriomas is a better choice than fenestration and coagulation because the former technique leads to a lower recurrence of signs and symptoms and a lower rate of reoperation and a higher cumulative pregnancy rate than the latter.", "To assess the efficacy of two laparoscopic methods for the management of endometriomas with regard to pain relief, pregnancy rate, and disease recurrence.\n Prospective, randomized clinical trial.\n Tertiary care hospital.\n Sixty-four patients with advanced stages of endometriosis.\n Patients were randomly allocated at the time of laparoscopy to undergo either cystectomy of the endometrioma (group 1) or drainage of the endometrioma and bipolar coagulation of the inner lining (group 2).\n Pain relief and pregnancy rate.\n Thirty-two patients were enrolled in each group. The 24-month cumulative recurrence rates of dysmenorrhea, deep dyspareunia, and nonmenstrual pelvic pain were lower in group 1 than in group 2 (dysmenorrhea: 15.8% versus 52.9%; deep dyspareunia: 20% versus 75%; nonmenstrual pelvic pain: 10% versus 52.9%). The median interval between the operation and the recurrence of moderate to severe pelvic pain was longer in group 1 than in group 2 (19 months [range, 13.5-24 months] versus 9.5 months [range, 3-20 months]). The 24-month cumulative pregnancy rate was higher in group 1 than in group 2 (66.7% versus 23.5%).\n For the treatment of ovarian endometriomas, a better outcome with a similar rate of complications is achieved with laparoscopic cystectomy than with drainage and coagulation." ]

[ "15749447", "2696324", "10872363", "10622480", "11706726", "7446041", "11764421", "8458140", "9043599", "12012035", "10738874" ]

[ "Gait and clinical measurements in patients with knee osteoarthritis after surgery: a prospective 5-year follow-up study.", "Early knee mobilization after osteotomy for gonarthrosis.", "Open-wedge osteotomy by hemicallotasis or the closed-wedge technique for osteoarthritis of the knee. A randomised study of 50 operations.", "Changes in osseous correction after proximal tibial osteotomy: radiostereometry of closed- and open-wedge osteotomy in 33 patients.", "High tibial osteotomy versus unicompartmental joint replacement in unicompartmental knee joint osteoarthritis: 7-10-year follow-up prospective randomised study.", "High tibial osteotomy with overcorrection of varus malalignment in medial gonarthrosis.", "Open-wedge osteotomy of the proximal tibia with hemicallotasis.", "The electrical stimulation of tibial osteotomies. Double-blind study.", "Does arthroscopic abrasion arthroplasty promote cartilage regeneration in osteoarthritic knees with eburnation? A prospective study of high tibial osteotomy with abrasion arthroplasty versus high tibial osteotomy alone.", "Valgus high tibial osteotomy. Comparison between an Ilizarov and a Coventry wedge technique for the treatment of medial compartment osteoarthritis of the knee.", "The incidence of thrombosis in high tibial osteotomies with and without the use of a tourniquet." ]

[ "The aim of this prospective follow-up study was to determine if gait measurements and/or clinical measurements could detect differences in treatment outcome between two surgical interventions in patients with knee osteoarthritis (OA). The patients were followed for 5 years after surgery. Forty patients, 55-70 years of age, with unilateral knee OA were included. The patients were treated either with a high tibial osteotomy (HTO) (n=18) or a unicompartmental knee arthroplasty (UKA) (n=22). Clinical outcome measures were the British Orthopaedic Association (BOA) score, pain during walking, passive range of knee motion (PROM) and patients' subjective opinion. The gait variables were free walking speed, step frequency, step length and single and double-stance phase for each leg. The patients were examined before surgery and 3 months, 1 year and 5 years after surgery. The time-distance variables of gait could detect differences in treatment outcome, 3 months after surgery, while the clinical outcome measures, as given here, could not detect any differences between the two groups of patients. Measurements of free walking speed could be recommended for clinical evaluation, after surgical interventions, in patients with knee OA.", "In a prospective study, 32 knees in 32 patients were randomized to either a cylinder plaster cast (17 knees) or hinged cast-brace (15 knees) after high tibial osteotomy for medial gonarthrosis. At 6 weeks, 3 months, and still 1 year after surgery, the range of motion was better in the cast-brace group. There was no difference in the other clinical results at 3 months and at 1 year after surgery, nor in changes of osseous correction or in the final knee alignment. All the patients in the cast-brace group were satisfied with early motion.", "We describe the results of 50 operations carried out on 46 patients with medial osteoarthritis of the knee of Ahlbäck grade 1 to 3. Patients were randomised either to a closed-wedge high tibial osteotomy (HTO) or an open-wedge procedure based on the hemicallotasis technique (HCO). Their median age was 55 years (38 to 68). The preoperative median hip-knee-ankle (HKA) angle was 171 degrees (164 to 176) in the HTO group and 173 degrees (165 to 179) in the HCO group. After six weeks, the median HKA angle was 185 degrees (176 to 194) in the HTO group and 184 degrees (181 to 188) in the HCO group. In the HTO group, seven patients were within the range of 182 degrees to 186 degrees compared with 21 in the HCO group (p < 0.001). One year later, ten HTO patients were within this range while the HKA angulation in the HCO group was unchanged. At two years the numbers were 11 and 18, respectively. We evaluated the clinical results on the Hospital for Special Surgery, Lysholm and Wallgren-Tegner activity scores, and patients completed part of the Nottingham Health Profile questionnaire. An impartial observer at the two-year follow-up concluded that all scores had improved, but found no clinical differences between the groups.", "33 patients (22 men), median age 54 (40-68) years, with medial gonarthrosis grades 1-3, were treated by closed-wedge osteotomy (high tibial osteotomy = HTO, n 16) or open-wedge osteotomy by hemicallotasis (hemicallotasis osteotomy = HCO, n 19). 2 patients were operated on bilaterally. The patients were studied by RSA (radiostereometric analysis) for measuring 3-D changes in the correction achieved. In the HTO group the RSA measurements were obtained at the time of plaster removal, 1 month later and 1 year after surgery. In the HCO group, the RSA measurements were performed at the time of removal of the external fixator, 1 month later and 1 year after surgery. After removal of the fixation, HTO was associated with increased medial/lateral and distal translation of the proximal segment, compared to HCO. In addition, the tibial plateau rotated more around the longitudinal axis of the tibia after HTO.", "The clinical outcome of patients treated either by high tibial osteotomy or unicompartmental arthroplasty for medial unicompartmental osteoarthritis of the knee was compared in a prospective randomised study. In total, 32 patients received a high tibial osteotomy (HTO) and 28 patients a unicompartmental arthroplasty (UKA). More intra- and postoperative complications were observed after HTO. Patients were assessed at an average of 2.5 (1.6-5), 4.5 (3.6-7), and 7.5 years (6.6-10) after the operation. Using the Knee Society Score, 71% (15) of patients after osteotomy and 65% (13) after replacement had a knee score of excellent or good 7-10 years postoperatively. The Kaplan-Meier survival analysis 7-10 years postoperatively showed a survivorship of 77% for UKA and 60% for HTO. Although the unicompartmental prosthesis used in this series has not shown promising results, we conclude that with the advanced design of unicompartmental prosthesis today, UKA offers better long-term success.", "Seventy-eight knee joints with varus malalignment were examined preoperatively using three-point measurement. Operation was performed with or without 5 degrees overcorrection of the varus deformity using random selection. The overcorrection group showed significantly better results than the normal-correction group.", "Conventional high tibial osteotomy for losteoarthritis of the medial compartment of the knee with closed-wedge or dome osteotomy (DMO) may produce shortening of the patellar tendon and loss of inclination of the proximal tibial plateau or of the offset of the tibial condyle relative to its bony axis. This can make subsequent total knee arthroplasty technically demanding. We undertook a prospective study comparing these changes after DMO with those after using open-wedge osteotomy hemicallotasis (HCO). A total of 50 knees with arthritis of the medial compartment in 46 consecutive patients was randomly allocated to either DMO or HCO. There were no significant differences between the groups with regard to age, gender, femorotibial angle before operation or the angle of correction. Radiological studies showed that HCO caused little change in the length of the patellar tendon or the inclination angle of the tibial plateau, while after DMO both gradually decreased. The degree of tibial condylar offset increased in both groups, but less so in the HCO group.", "The effect of electromagnetic field stimulation was investigated in a group of 40 consecutive patients treated with valgus tibial osteotomy for degenerative arthrosis of the knee. All patients were operated on by the same author and followed the same postoperative program. After surgery, patients were randomly assigned to a control group (dummy stimulators) or to a stimulated one (active stimulators). Four orthopedic surgeons, unaware of the experimental conditions, were asked to evaluate the roentgenograms taken 60 days postoperatively and to rate the osteotomy healing according to four categories (the fourth category being the most advanced stage of healing). In the control group, 73.6% of the patients were included in the first and second category. In the stimulated group, 72.2% of the patients were included in the third and fourth category. On a homogeneous group of patients, electromagnetic field stimulation had positive effects on the healing of tibial osteotomies.", "The purpose of this prospective study was to determine whether or not abrasion arthroplasty promotes cartilage regeneration in osteoarthritic (OA) knees with eburnation. Patients with OA knees were divided into a group of 51 knees treated by osteotomy with abrasion arthroplasty (Group A) and another group of 37 knees treated by osteotomy alone (Group B). Regeneration of cartilage was compared between the groups both arthroscopically and histologically. The Outerbridge classification was used for arthroscopic grading with Grade 0 being normal and Grade IV representing eburnation. On arthroscopic examination, around 12 months after surgery, Group A showed a significantly higher incidence of Grade II repair (a smooth articular surface and small fissures) and a lower incidence of Grade IV repair than Group B on both the femoral (P < .001) and tibial (P < .01) joint surfaces. Age was the only factor influencing the grade of tibial cartilage in Group A. Histological examination showed that 64% of the regenerated tissue studied consisted of fibro-cartilage at around 12 months after surgery. There was no difference in the clinical outcome at 2 to 9 years postoperatively between Groups A and B.", "A matched-pair comparative analysis was done comparing outcomes between a Coventry-type closing wedge valgus high tibial osteotomy (HTO) and an HTO using an Ilizarov apparatus. Thirty patients were treated with a mean follow-up interval of 28.1 months. Functional outcomes were evaluated using the Western Ontario and McMaster University (WOMAC) osteoarthritis index. Clinical and radiographic assessment of the index knee, complications, and over-all satisfaction of the patients were assessed. The procedures were performed between 1994 and 1997. The two groups were equal with respect to baseline demographics - age, sex, body mass index, smoking status. The patients undergoing an Ilizarov HTO had a significantly greater decrease in pain and increase in function at final follow-up assessment. Eleven of the 15 patients in the Ilizarov group were satisfied with the procedure compared to five in the closing wedge HTO group. The treatment of medial compartment osteoarthritis in genu varum of the knee with an Ilizarov apparatus produces outcomes that are comparable to the standard lateral closing wedge osteotomy.", "In a prospective randomised study, 65 high tibial osteotomies were performed in cases of varus osteoarthritis of the knee, and the incidence of thrombosis with and without the use of a tourniquet was studied. With an average incidence of thrombosis of 10.8%, no statistically significant differences between these two groups were seen." ]

[ "16796157", "9122640", "9517526", "10943958", "10992331", "11335732", "10440307" ]

[ "Standard WHO-ORS versus reduced-osmolarity ORS in the management of cholera patients.", "Reduced osmolarity oral rehydration salt in Cholera.", "Efficacy of oral hyposmolar glucose-based and rice-based oral rehydration salt solutions in the treatment of cholera in adults.", "Evaluation of oral hypo-osmolar glucose-based and rice-based oral rehydration solutions in the treatment of cholera in children.", "Controlled trial of hypo-osmalar versus World Health Organization oral rehydration solution.", "Multicenter, randomized, double-blind clinical trial to evaluate the efficacy and safety of a reduced osmolarity oral rehydration salts solution in children with acute watery diarrhea.", "Efficacy and safety of oral rehydration solution with reduced osmolarity in adults with cholera: a randomised double-blind clinical trial. CHOICE study group." ]

[ "The study compared the safety and efficacy of an oral rehydration salts (ORS) solution, containing 75 mmol/L of sodium and glucose each, with the standard World Health Organization (WHO)-ORS solution in the management of ongoing fluid losses, after initial intravenous rehydration to correct dehydration. The study was conducted among patients aged 12-60 years hospitalized with diarrhoea due to cholera. One hundred seventy-six patients who were hospitalized with acute diarrhoea and signs of severe dehydration were rehydrated intravenously and then randomly assigned to receive either standard ORS solution (311 mmol/L) or reduced-osmolarity ORS solution (245 mmol/L). Intakes and outputs were measured every six hours until the cessation of diarrhoea. During maintenance therapy, stool output, intake of ORS solution, duration of diarrhoea, and the need for unscheduled administration of intravenous fluids were similar in the two treatment groups. The type of ORS solution that the patients received did not affect the mean serum sodium concentration at 24 hours after randomization and the relative risk of development of hyponatraemia. However, patients treated with reduced-osmolarity ORS solution had a significantly lower volume of vomiting and significantly higher urine output than those treated with standard WHO-ORS solution. Reduced-osmolarity ORS solution was as efficacious as standard WHO-ORS solution in the management of cholera patients. The results indicate that reduced-osmolarity ORS solution is also as safe as standard WHO-ORS solution. However, because of the limited sample size in the study, the results will have to be confirmed in trials, involving a larger number of patients.", "In a controlled clinical trial conducted in 34 adults with severe cholera diarrhoea, the use of a relatively dilute oral rehydration salt (ORS) solution (sodium 67, potassium 20, chloride 66, citrate 7, glucose 89 mmol/l, osmolality 249 mOsmol/kg) caused a 29% (p=0.003) reduction in stool output over the first 24 h and a 37% (p=0.001) reduction over the first 48 h compared with 29 controls who received the hyperosmolar WHO/UNICEF ORS. No controls but 3 study-group patients had marked but asymptomatic hyponatraemia (sodium <125 mmol/l) at 24 h. Twenty-four % of controls and 12% of patients receiving the dilute ORS needed unscheduled intravenous therapy for recurrence of dehydration. The ORS intake was twice the 48 h stool volume in controls and 3 times in the study group. The test ORS with a reduced glucose and sodium concentration is more efficient than the WHO/UNICEF ORS in preserving net intestinal fluid balance in severe cholera.", "Recent animal experiments and clinical trials have shown that both osmolarity and rice as the organic components are important factors for net intestinal absorption of an oral rehydration salt solution.\n In a controlled clinical trial 123 male adult patients with severe cholera, after initial rehydration with intravenous Ringer's lactate solution, were randomly assigned to receive one of the four oral rehydration salt solutions: WHO ORS, ORS containing 70 mmol/l Na+ and 16.2 g/l glucose, rice ORS containing 50 g/l rice and 90 mmol/l Na+, and rice ORS containing 50 g/l rice and 70 mmol/l Na+. All patients received 300 mg of doxycycline as a single dose.\n Patients who received rice-low-sodium ORS subsequently had lower (P < 0.05) stool output, ORS consumption, and diarrhoea duration than the other three ORS groups.\n We conclude that rice-based low-sodium ORS is superior for treating adult cholera.", "In a randomized controlled clinical trial, the efficacy of a low-sodium low-glucose oral rehydration solution (ORS) and a low-sodium rice-based ORS was compared with standard WHO glucose ORS in the treatment of severe cholera in children aged 2-10y. In total, 120 children were evaluated for the study, of whom 58 patients were positive for Vibrio cholerae and were included in the study. Of these 58 cases, 19 received rice-based hypo-osmolar ORS, 20 received WHO-ORS and 19 received glucose-based hypo-osmolar ORS. The clinical characteristics (age, preadmission duration of diarrhoea, frequency of stool before admission, incidence of vomiting, body weight and volume of initial fluid requirement) were comparable in the three treatment groups. All patients received tetracycline in a dose of 50 mg/kg/d of body weight in 4 divided doses for 3 d.\n Patients who received rice-based hypo-osmolar ORS had subsequently reduced (p < 0.05) stool output, ORS consumption and diarrhoea duration than the patients who received either WHO-ORS or glucose-based hypo-osmolar ORS.", "To compare the safety and efficacy of a hyposmolar oral rehydration solution (H-ORS) (245 mmol/liter) with the World Health Organization oral rehydration solution (WHO ORS) in cholera and acute non-cholera diarrhea.\n Controlled clinical trial.\n Diarrhea training and treatment unit.\n Thirty-five culture proven cholera and 135 acute non-cholera diarrheal patients randomly received H-ORS or WHO-ORS. Intake and output were measured every 4 hours.\n Analysis of the total cases revealed rehydration phase (p=0.048, 95% CI 0.64-0.99) and overall (p=0.046, 95% CI 0.70-0.99) frequency of stools to be significantly less in the H-ORS group. In the severely malnourished, the rehydration phase (p=0.032, 95% CI 0.55-97), maintenance phase (p=0.035, 95% CI 0.51-0.97) and overall (p=0.011; 0.95% CI 0.55-0.93) stool frequency were significantly decreased in the H-ORS group. The amount of ORS consumed in the maintenance phase of the cholera cases was significantly (p=0.04, 95% CI 0.44-0.98) less in the H-ORS group. All other parameters, despite showing a decreasing trend, were statistically comparable in the cholera, non-cholera and total cases. The amount of intravenous fluid needed was significantly more in the noncholera and total cases on H-ORS. In the non-breastfed cases, under two years of age, the total duration of diarrhea was significantly decreased (p=0.03; 95% CI 11.07-11.45) but the need for intravenous fluids significantly increased (p=0.02; 95% CI 109.8-112.1) in the H-ORS group. The proportion of children vomiting, the weight gain, urine passed in 24 hours, serum sodium, caloric intake and failure rate were comparable.\n H-ORS is as safe and effective as the WHO-ORS and may have some additional benefits in malnourished children.", "To compare the efficacy of a reduced osmolarity oral rehydration salts (ORS) solution (75 mmol/L of sodium [Na], 20 mmol/L of potassium [K], 65 mmol/L of chloride, 10 mmol/L of citrate, and 75 mmol/L of glucose; osmolarity, 245 mosm/L) with that of the standard World Health Organization (WHO) ORS solution.\n A multicenter, double-blind, randomized, controlled clinical trial conducted in children with acute diarrhea in 5 developing countries to measure mean stool output in the 24 hours after randomization, proportion of children who required unscheduled intravenous therapy, proportion of children who vomited in the first 24 hours, and diarrhea duration after randomization.\n A total of 675 children who ranged in age from 1 to 24 months and who had acute diarrhea and dehydration were enrolled in the trial; 341 were randomized to receive reduced osmolarity ORS solution, and 334 were randomized to receive the WHO ORS solution. The mean (SE) stool output (g/kg) in the first 24 hours (reduced osmolarity ORS solution vs WHO ORS solution = 114 [4] vs 125 [5]) and during the total study period (reduced osmolarity ORS solution vs WHO ORS solution = 320 [18] vs 331 [18]) were comparable. The proportion of children who vomited in the first 24 hours (reduced osmolarity ORS solution vs WHO ORS solution = 58% vs 62%) and the diarrhea duration in the 2 treatment groups, compared by log rank test, were similar. The proportion of children who required unscheduled intravenous therapy was significantly lower in children who received reduced osmolarity ORS solution (10%) as compared with those who received the WHO ORS solution (15%; odds ratio = 0.6, 95% confidence interval = 0.4-1.0). There was no significant difference in the incidence of hyponatremia (serum Na <130 mmol/L) at 24 hours between the 2 treatment groups (11% in reduced osmolarity ORS solution group vs 9% in the WHO ORS solution group; odds ratio = 1.3; 95% confidence interval = 0.8-2.2). The frequency of patients with serum Na <125 mmol/L at 24 hours was 13 of 341 (4%) in children who were treated with reduced osmolarity ORS solution versus 7 of 334 (2%) in children who received the WHO ORS solution.\n Treatment with reduced osmolarity ORS solution was associated with a 33% reduction in the need for unscheduled intravenous therapy and had no apparent effect on stool output and illness duration when compared with treatment with the standard WHO ORS solution. Children with acute diarrhea, therefore, may benefit from a reduced osmolarity ORS solution. The results of trials that examine the efficacy and safety of reduced osmolarity ORS solution in adult patients with cholera have to be taken into consideration before consensus on composition of oral rehydration formulation can be reached.", "The effects of oral rehydration solution (ORS) with reduced osmolarity on children with acute watery diarrhoea are known, but little is known about the effects of such ORS on adults with cholera. We aimed to compare the efficacy and safety of an ORS with reduced osmolarity with that of standard WHO ORS in adults with cholera.\n We undertook a double-blind, controlled clinical trial in adults with severe cholera at the International Centre for Diarrhoeal Disease Research, Bangladesh. Our primary outcomes were mean stool output in the 24 h after randomisation, proportion of patients who needed unscheduled intravenous therapy, and proportion of patients with biochemical hyponatraemia 24 h after randomisation.\n 147 patients received ORS with reduced osmolarity and 153 received standard WHO ORS. There was no significant difference between the two groups in terms of main outcome variables: mean initial 24 h and total stool output (reduced osmolarity vs standard WHO ORS 212 [SE 8] vs 207 [8] and 284 [13] vs 273 [13] g/kg respectively), duration of diarrhoea (46 [1.5] vs 43 [1.5]). The proportion of patients vomiting during the first 24 h and the proportion who received unscheduled intravenous infusion during the first 24 h was similar between groups. More patients on reduced osmolarity ORS than on standard WHO ORS developed hyponatraemia during the first 24 h, defined as serum sodium concentration below 130 mmol/L (29 of 142 vs 16 of 150; odds ratio 2.1 [95% CI 1.1-4.1]). However, all hyponatraemic patients in both groups were symptom-free and the proportion of patients with serum sodium concentration below 125 mmol/L was similar between groups.\n There was no difference in clinical outcome between cholera patients treated with reduced osmolarity ORS solution and those treated with standard WHO ORS. The risk of increased incidence of symptom-free hyponatraemia in patients with cholera treated with an ORS with reduced osmolarity should be further assessed by meta-analysis. The risk should be taken into account when choice of ORS is made in areas in which cholera is endemic." ]

[ "12110735", "8452573", "8666628" ]

[ "A controlled trial of arthroscopic surgery for osteoarthritis of the knee.", "A randomized, controlled trial of arthroscopic surgery versus closed-needle joint lavage for patients with osteoarthritis of the knee.", "Articular debridement versus washout for degeneration of the medial femoral condyle. A five-year study." ]

[ "Many patients report symptomatic relief after undergoing arthroscopy of the knee for osteoarthritis, but it is unclear how the procedure achieves this result. We conducted a randomized, placebo-controlled trial to evaluate the efficacy of arthroscopy for osteoarthritis of the knee.\n A total of 180 patients with osteoarthritis of the knee were randomly assigned to receive arthroscopic débridement, arthroscopic lavage, or placebo surgery. Patients in the placebo group received skin incisions and underwent a simulated débridement without insertion of the arthroscope. Patients and assessors of outcome were blinded to the treatment-group assignment. Outcomes were assessed at multiple points over a 24-month period with the use of five self-reported scores--three on scales for pain and two on scales for function--and one objective test of walking and stair climbing. A total of 165 patients completed the trial.\n At no point did either of the intervention groups report less pain or better function than the placebo group. For example, mean (+/-SD) scores on the Knee-Specific Pain Scale (range, 0 to 100, with higher scores indicating more severe pain) were similar in the placebo, lavage, and débridement groups: 48.9+/-21.9, 54.8+/-19.8, and 51.7+/-22.4, respectively, at one year (P=0.14 for the comparison between placebo and lavage; P=0.51 for the comparison between placebo and débridement) and 51.6+/-23.7, 53.7+/-23.7, and 51.4+/-23.2, respectively, at two years (P=0.64 and P=0.96, respectively). Furthermore, the 95 percent confidence intervals for the differences between the placebo group and the intervention groups exclude any clinically meaningful difference.\n In this controlled trial involving patients with osteoarthritis of the knee, the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure.", "To compare arthroscopic surgery and closed-needle joint lavage for patients with non-end-stage osteoarthritis (OA) of the knee under controlled, experimental conditions.\n Thirty-two subjects who met specific clinical, radiologic, medical, and rehabilitation criteria were randomized to receive arthroscopic surgery (n = 18) or joint lavage (n = 14). Outcome measures evaluated at baseline and at 3 and 12 months of followup included 3 standard clinical parameters, self-reported pain and functional status (by the Arthritis Impact Measurement Scales), 50-foot walk time, 2 global scales, and direct and indirect medical costs.\n At 3 months of followup, there were no significant between-group differences in pain, self-reported and observed functional status, and patient and \"blinded\" physician global assessments. The arthroscopic procedure cost $3,840 more than did closed-needle joint lavage. After 1 year, there were no between-group differences in medication costs, utilization of medical services, or indirect costs related to employment or use of household help. After 1 year, 44% of subjects who underwent arthroscopy reported improvement and 58% of subjects who underwent joint lavage improved. Patients with tears of the anterior two-thirds of the medial meniscus or any lateral meniscus tear had a higher probability of improvement (by \"blinded\" physician assessment) after arthroscopic surgery (0.63) than did patients with other intraarticular pathology (0.20).\n The search for and removal of soft tissue abnormalities via arthroscopic surgery does not appear justified for all patients with non-end-stage OA of the knee who fail to respond to conservative therapy, but it may be beneficial for certain subgroups.", "In a prospective randomised trial 76 knees with isolated degenerative changes in the medial femoral condyle of grades 3 or 4 were treated by either arthroscopic debridement (40) or washout (36). All knees were followed up for at least one year and 58 for five years. The mean follow-up time was 4.5 years in the debridement group and 4.3 years in the washout group. At one year 32 of the debridement group and five of the washout group were painfree and at five years 19 of a total of 32 survivors in the debridement group and three of the 26 in the washout group were also free from pain. The mean improvement in a modified Lysholm score was 28 for the debridement group at one year and 21 at five years. In the washout group it was only 5 at one year and 4 at five years. For knees with lesions of the medial femoral condyle of grades 3 or 4, arthroscopic debridement appears to be the treatment of choice with over half the patients free from pain after five years." ]

[ "10212082", "9831683", "10099142" ]

[ "Randomised controlled study of early use of inhaled corticosteroid in preterm infants with respiratory distress syndrome.", "Inhaled budesonide in ventilator-dependent preterm infants: a randomized, double-blind pilot study.", "Early inhaled glucocorticoid therapy to prevent bronchopulmonary dysplasia." ]

[ "To investigate the therapeutic efficacy of inhaled fluticasone propionate, started on day 1 of age, on ventilated preterm infants with respiratory distress syndrome.\n Starting within 24 hours of age, ventilated preterm infants (gestation < 32 weeks, birthweight < 1.5 kg) with respiratory distress syndrome were given a 14 day course (two puffs, 12 hourly) of either fluticasone propionate (250 microg/puff) (group 1, n=27) or placebo (group 2, n=26) with a metered dose inhaler-spacer device. Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age, changes in respiratory system mechanics, death, occurrence of chronic lung disease, and other neonatal complications.\n More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group (17/27 vs 8/26; p = 0.038). The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life. The two groups, however, did not differ significantly in their need for systemic steroids after day 14 of age, death, or the occurrence of chronic lung disease. The treatment was not associated with any increase in neonatal complications, including those attributable to steroid induced side effects.\n These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress. Further study of its use in a large scale randomised trial is warranted.", "The aim of this randomized, double-blind pilot study was to evaluate the short-term efficacy of early inhalation therapy with budesonide in ventilator-dependent preterm infants. The primary outcome variable was the duration of artificial ventilation; secondary outcome variables were the need for supplemental oxygen and the release of several inflammatory mediators in the tracheobronchial aspirate fluid. The infants of the budesonide group could not be weaned earlier from the ventilator. The ventilatory parameters on day 14 of life and the need for supplemental oxygen were similar in both groups. The release of inflammatory mediators was not reduced in the budesonide group. No adverse side effects were observed in either group. In conclusion, aerosolized budesonide failed to demonstrate significant short-term pulmonary improvement in ventilator-dependent preterm infants.", "The safety and efficacy of inhaled glucocorticoid therapy for asthma stimulated its use in infants to prevent bronchopulmonary dysplasia. We tested the hypothesis that early therapy with inhaled glucocorticoids would decrease the frequency of bronchopulmonary dysplasia in premature infants.\n We conducted a randomized, multicenter trial of inhaled beclomethasone or placebo in 253 infants, 3 to 14 days old, born before 33 weeks of gestation and weighing 1250 g or less at birth, who required ventilation therapy. Beclomethasone was delivered in a decreasing dosage, from 40 to 5 microg per kilogram of body weight per day, for four weeks. The primary outcome measure was bronchopulmonary dysplasia at 28 days of age. Secondary outcomes included bronchopulmonary dysplasia at 36 weeks of postmenstrual age, the need for systemic glucocorticoid therapy, the need for bronchodilator therapy, the duration of respiratory support, and death.\n One hundred twenty-three infants received beclomethasone, and 130 received placebo. The frequency of bronchopulmonary dysplasia was similar in the two groups: 43 percent in the beclomethasone group and 45 percent in the placebo group at 28 days of age, and 18 percent in the beclomethasone group and 20 percent in the placebo group at 36 weeks of postmenstrual age. At 28 days of age, fewer infants in the beclomethasone group than in the placebo group were receiving systemic glucocorticoid therapy (relative risk, 0.6; 95 percent confidence interval, 0.4 to 1.0) and mechanical ventilation (relative risk, 0.8; 95 percent confidence interval, 0.6 to 1.0).\n Early beclomethasone therapy did not prevent bronchopulmonary dysplasia but was associated with lower rates of use of systemic glucocorticoid therapy and mechanical ventilation." ]

[ "8079448" ]

[ "No beneficial effect of low-dose fetal intravenous gammaglobulin administration in combination with intravascular transfusions in severe Rh D haemolytic disease." ]

[ "Recent observations have shown that treatment with high-dose intravenous gammaglobulin (IVIgG) given to the mother may improve fetal outcome in cases of severe Rh D alloimmunization. Unfortunately, the costs of this new method of treatment are too high for routine use. Therefore, we decided to apply this treatment to the fetus and to investigate whether the effect of IVIgG might be attributable to blockade of the fetal mononuclear phagocyte system. We have performed a randomized study in which 20 fetuses with severe Rh D-haemolytic disease (HDN) were treated with intrauterine intravascular red cell transfusions (IUT). In 10 of these 20 cases transfusions were followed by administration to the fetus of low-dose IVIgG (85.7 +/- 11.6 mg/kg by ultrasound-estimated fetal weight because of fetal vascular volume considerations). We compared the number of IUTs, postnatal exchange transfusions, haematocrit (Ht) and haemoglobulin (Hb) values before and after transfusion (s) needed by the newborns of the two groups. No significant differences in the transfusion requirements of the fetuses and in the clinical outcome could be demonstrated. However, the 95% confidence interval for the difference in the improvement of cord blood Ht was too wide for any conclusions. The 95% confidence interval for the difference in the improvement of Hb levels suggests that any clinically relevant advantage of IVIgG on Hb is unlikely." ]

[ "9386685", "9237594", "10509987", "12869172" ]

[ "Preoperative intraaortic balloon pump enhances cardiac performance and improves the outcome of redo CABG.", "Evaluation of preoperative intra-aortic balloon pump support in high risk coronary patients.", "Optimal timing of preoperative intraaortic balloon pump support in high-risk coronary patients.", "The role of intra-aortic counterpulsation in high-risk OPCAB surgery: a prospective randomized study." ]

[ "Reoperative coronary artery bypass grafting (redo CABG) is associated with an increased operative risk compared with primary CABG. Because the hospital mortality in redo CABG is known to be influenced by poor left ventricular function (left ventricular ejection fraction < or = 0.40), unstable angina, and left main stem stenosis greater than or equal to 70%, a preoperative intraaortic balloon pump (IABP) support could be beneficial to improve the outcome in high-risk redo CABG.\n Between June 1994 and October 1996, 48 high-risk patients underwent redo CABG and were randomized into the following groups: group 1 (24 patients) who received preoperative IABP treatment on average 2 hours before cardiopulmonary bypass, and group 2 (24 patients) who received no preoperative IABP and served as controls. Mean age was 65 years and 90% (43 patients) were men. Forty-one patients had preoperative left ventricular ejection fraction less than or equal to 0.40 (85%), 38% (18 patients) had left main stem stenosis greater than or equal to 70%, and 54% (26 patients) had unstable angina preoperatively. Preoperative patient characteristics did not differ between the groups.\n The time on cardiopulmonary bypass was shorter in group 1, 86 versus 110 minutes (p = 0.006). There were no hospital deaths in group 1, but four deaths occurred in the control group (p = 0.049). Cardiac index rose significantly preoperatively after introduction of the IABP in group 1. Cardiac index was significantly higher postoperatively in group 1 compared with group 2 and remained significantly higher during the first 24 hours after cardiopulmonary bypass. Significantly fewer patients in the IABP group had postoperative low cardiac output (4 versus 13 patients). Nine patients in group 2 required IABP support postoperatively for 4.1 +/- 1.7 days. Only 2 patients in group 1 needed IABP postoperatively, and their IABPs were successfully removed on the first postoperative day. The preoperative IABP-supported patients had a shorter intensive care unit stay, 2.4 +/- 0.8 days compared with group 2, 4.5 +/- 2.2 days (p = 0.007), as well as a shorter hospital stay. The preoperative IABP treatment was found to be cost-effective.\n Preoperative treatment with IABP in high-risk redo CABG patients is an effective modality to prepare these patients to have their myocardial revascularization in an as nonischemic situation as possible, which resulted in a significantly lower hospital mortality, fewer instances of postoperative low cardiac output, and shorter stays in both the intensive care unit and the hospital.", "The intra-aortic balloon pump (IABP) is an established additional support to pharmacological treatment of the failing heart after myocardial infarction, unstable angina and cardiac surgery. The effect of preoperative IABP in high risk patients was evaluated.\n Between June 1994 and March 1996 all high risk patients for CABG (two or more of these criteria: Left ventricular ejection fraction (LVEF) < or = 40%, left main stem stenosis > or = 70%, REDO-CABG, unstable angina) were randomized into either of 3 groups: (1) IABP 1 day prior to surgery, (2) IABP 1-2 h prior to CPB and (3) no preoperative IABP, controls. Exclusion criteria: cardiogenic shock preoperatively. Fifty-two patients have entered the study-group 1 (13 patients), group 2 (19 patients) and group 3 (20 patients). Preoperative patient characteristics and operative data revealed no group differences. There were 56% REDO's, unstable angina 59%, LVEF < or = 40%, 87% (34.0 +/- 11.6%) and left main stem stenosis in 35%.\n The CPB-time was shorter in groups 1 and 2 88.7 +/- 20.3 min than in group 3 105.5 +/- 26.8 min, P < 0.001, while ischemia time did not differ. Hospital mortality was higher in group 3, 25% vs. 6% (groups 1 and 2). Postoperative low cardiac output was seen in 12 patients (60%) in group 3 vs. 6 patients (19%) in groups 1 and 2, P < 0.05. Cardiac index increased significantly prior to CPB in groups 1 and 2. After CPB cardiac index was significantly higher in groups 1 and 2 compared to Group 3 and continued to increase. The IABP was removed after 3.1 +/- 1.0 days in group 3 vs. 1.3 +/- 0.6 days in groups 1 and 2, P < 0.001. In group 3, 11 patients required IABP postoperatively compared to only 4 patients in groups 1 and 2. ICU stay was shorter in groups 1 and 2--2.3 +/- 0.9 days vs. 3.5 +/- 1.1 days for group 3, P = 0.004. All patients received dopamin postoperatively, however in a lower dose in groups 1 and 2, 4.5 vs. 13.5 microg/kg/min. Dobutamine was added in 23% of the patients (group 1), 32% (group 2) and 95% (group 3). Adrenalin/amrinonum was required in 40% of the patients in group 3, 5% in group 2 and none in group 1. Group 1 patients had a better improvement of cardiac performance than group 2, while other parameters did not differ. Three months follow up of hospital survivors showed no group differences.\n The use of preoperative IABP in high risk patients lowers hospital mortality and shortens the stay in ICU, due to improved cardiac performance, compared to a controls. The procedure was cost-beneficial. One day preoperative IABP treatment improves cardiac performance more than 1-2 h preoperative IABP treatment, but does not significantly affect the outcome in terms of hospital mortality or postoperative morbidity.", "Beneficial effects of preoperative intraaortic balloon pump (IABP) treatment, on outcome and cost, in high-risk patients who have coronary artery bypass grafting have been demonstrated. We conducted a prospective, randomized study to determine the optimal timing for preoperative IABP support in a cohort of high-risk patients.\n Sixty consecutive high-risk patients who had coronary artery bypass grafting (presenting with two or more of the following criteria: left ventricular ejection fraction less than 0.30, unstable angina, reoperation, or left main stenosis greater than 70%) entered the study. Thirty patients did not receive preoperative IABP (controls), 30 patients had preoperative IABP therapy starting 2 hours (T2), 12 hours (T12), or 24 hours (T24), by random assignment, before the operation. Fifty patients had preoperative left ventricular ejection fraction mean, less than 0.30 (less than 0.26+/-0.08), (n = 40) unstable angina, 28% (n = 17) left main stenosis, and 32% (n = 19) were reoperations.\n Cardiopulmonary bypass was shorter in the IABP groups. There was one death in the IABP group and six in the control group. The complication rate for IABP was 8.3% (n = 5) without group differences. Cardiac index was significantly higher postoperatively (p<0.001) in patients with preoperative IABP treatment compared with controls. There were no significant differences between the three IABP subgroups at any time. The incidence of postoperative low cardiac output was significantly lower in the IABP groups (p<0.001). Intubation time, length of stay in the intensive care unit and the hospital was shorter in the IABP groups (p = 0.211, p<0.001, and p = 0.002, respectively). There were no differences between the IABP subgroups in any of the studied variables.\n The beneficial effect of preoperative IABP in high-risk patients who have coronary artery bypass grafting was confirmed. There were no differences in outcome between the subgroups; therefore, at 2 hours preoperatively, IABP therapy can be started.", "High-risk patients would benefit the most of OPCAB revascularization. This prospective and randomized study evaluates the efficacy and safety of pre- and perioperative IABC in high-risk OPCAB.\n Group A-IABC started prior to induction of anesthesia (n = 15); group B-no preoperative IABC (n = 15). Adult high-risk coronary patients to undergo OPCAB. High risk = (minimum 2) EF < 0.30, left main stenosis, unstable angina, redo. Bailout if hemodynamic instability CPB or IABC in group B. Study endpoints (a) cardiac protection (troponin 1, cardiac index (CI), ECG), (b) inflammatory response (lactate, IL-6), (c) clinical outcome (mortality, morbidity). Emergency operations 33%, re-operation 13%, unstable angina 100%, left main 60% and EF 0.29, without group differences.\n No bailout group A, 10 in group B, p < 0.0001. Postoperative IABC six (group A) and seven patients (group B), during 6.8 +/- 5.1 hours (group A) versus 41.2 +/- 25.5 hours (group B), p = 0.0110. Myocardial protection without group differences, but CI significantly better in group A. Inflammatory response significantly less in group A. CLINICAL OUTCOMES: one death, one MI and two renal failure in group B, none in group A. Intensive care unit (ICU) stay 27 +/- 3 hours (group A) versus 65 +/- 28 hours (group B), p = 0.0017. LOS 8 +/- 2 days (group A) versus 15 +/- 10 (group B), p = 0.0351. No IABC related complications.\n Pre- and perioperative IABC therapy offers efficient hemodynamic support during high-risk OPCAB surgery, lowers the risk of hemodynamic instability, is safe and shortens both ICU and hospital length of stay significantly, and is a cost-effective therapy." ]

[ "2086672", "2965154", "8750152", "7747370", "11359657", "10944130", "11118461", "11759643", "8171738", "15961764", "3543247", "16136045", "2412262", "9703284", "10023944", "7841054", "9562580", "2667326", "10859453", "9579838", "3881175", "2016626", "8729953", "12915604", "8558634", "11710825", "15625368", "3145964", "14981107", "8468720", "10561363", "9562581", "4056843", "11583750", "2185803", "8625167", "7003883", "1732429", "1390305", "1970108", "9862512", "11942956", "1960551", "10954911", "10561318", "9181906", "9677460", "3330126", "8625186" ]

[ "Biological and clinical effects of interferon-beta ser at two doses.", "Treatment of advanced renal cell cancer with recombinant interferon alpha as a single agent and in combination with medroxyprogesterone acetate. A randomized multicenter trial.", "Randomised study using IFN-alpha versus IFN-alpha plus coumarin and cimetidine for treatment of advanced renal cell cancer.", "Interferon alfa and vinblastine versus medroxyprogesterone acetate in the treatment of metastatic renal cell carcinoma.", "Randomized multicenter phase II trial of subcutaneous recombinant human interleukin-12 versus interferon-alpha 2a for patients with advanced renal cell carcinoma.", "Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma.", "Treatment of patients with metastatic renal carcinoma with a combination of subcutaneous interleukin-2 and interferon alfa with or without fluorouracil. Groupe Français d'Immunothérapie, Fédération Nationale des Centres de Lutte Contre le Cancer.", "Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer.", "A randomized study of low-dose interleukin-2 subcutaneous immunotherapy versus interleukin-2 plus interferon-alpha as first line therapy for metastatic renal cell carcinoma.", "Randomized phase II/III trial of interferon Alfa-2a with and without 13-cis-retinoic acid in patients with progressive metastatic renal cell Carcinoma: the European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951).", "Recombinant alfa interferon in renal cell carcinoma: a randomized trial of two routes of administration.", "Two randomised phase II trials of subcutaneous interleukin-2 and histamine dihydrochloride in patients with metastatic renal cell carcinoma.", "Interferon therapy in disseminated renal cell carcinoma.", "A randomized phase II trial of interleukin 2 and interleukin 2-interferon alpha in advanced renal cancer.", "Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators.", "EORTC (30885) randomised phase III study with recombinant interferon alpha and recombinant interferon alpha and gamma in patients with advanced renal cell carcinoma. The EORTC Genitourinary Group.", "Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. Canadian Urologic Oncology Group.", "Interferon alternating with chemotherapy for patients with metastatic renal cell carcinoma.", "Abrogation of the negative influence of opioids on IL-2 immunotherapy of renal cell cancer by melatonin.", "Survival in renal cell carcinoma-a randomized evaluation of tamoxifen vs interleukin 2, alpha-interferon (leucocyte) and tamoxifen.", "A randomized study of low and high doses of leukocyte alpha-interferon in metastatic renal cell carcinoma: the American Cancer Society collaborative trial.", "Vinblastine fails to improve response of renal cancer to interferon alfa-n1: high response rate in patients with pulmonary metastases.", "A phase II study of interleukin-2 with and without beta-interferon in the treatment of advanced renal cell carcinoma.", "Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer.", "Phase II study of interferon-gamma versus interleukin-2 and interferon-alpha 2b in metastatic renal cell carcinoma.", "IL-2 in combination with IFN- alpha and 5-FU versus tamoxifen in metastatic renal cell carcinoma: long-term results of a controlled randomized clinical trial.", "Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma.", "A prospective randomized trial of alpha 2B-interferon/gamma-interferon or the combination in advanced metastatic renal cell carcinoma.", "Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).", "Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer.", "Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer.", "Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Français d'Immunothérapie.", "Antitumor activity of recombinant-derived interferon alpha in metastatic renal cell carcinoma.", "Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial.", "Recombinant leukocyte interferon alpha-2a and medroxyprogesterone in advanced renal cell carcinoma. A randomized trial.", "The use of polyethylene glycol-modified interleukin-2 (PEG-IL-2) in the treatment of patients with metastatic renal cell carcinoma and melanoma. A phase I study and a randomized prospective study comparing IL-2 alone versus IL-2 combined with PEG-IL-2.", "[Treatment of metastasizing renal adenocarcinoma with specific plasma transfusion. A controlled trial of the effects on metastases and survival time].", "A randomized phase II trial of continuous infusion interleukin-2 or bolus injection interleukin-2 plus lymphokine-activated killer cells for advanced renal cell carcinoma.", "Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study.", "Effect of autolymphocyte therapy on survival and quality of life in patients with metastatic renal-cell carcinoma.", "Interleukin-2, interferon-alpha and interleukin-2 plus interferon-alpha in renal cell carcinoma. A randomized phase II trial.", "Cytoreductive nephrectomy: is it a realistic option in patients with renal cancer?", "A randomized prospective assessment of recombinant leukocyte A human interferon with or without aspirin in advanced renal adenocarcinoma.", "Combined treatment with low-dose interferon plus vinblastine is associated with less toxicity than conventional interferon monotherapy in patients with metastatic renal cell carcinoma.", "Multicenter, randomized, phase III trial of CD8(+) tumor-infiltrating lymphocytes in combination with recombinant interleukin-2 in metastatic renal cell carcinoma.", "[Preoperative subcutaneous immunotherapy with interleukin-2 in renal carcinoma with synchronous metastasis: randomized clinico-biological study. Preoperative use of Il-2 in renal carcinoma].", "Standard interleukin-2 (IL-2) and interferon-alpha immunotherapy versus an IL-2 and 4-epirubicin immuno-chemotherapeutic association in metastatic renal cell carcinoma.", "Active specific immunotherapy of renal cell carcinoma patients: a prospective randomized study of hormono-immuno-versus hormonotherapy. Preliminary report of immunological and clinical aspects.", "Phase III randomized trial of interleukin-2 with or without lymphokine-activated killer cells in the treatment of patients with advanced renal cell carcinoma." ]

[ "To assess biological response, therapeutic activity, and side effects, a randomized, double-blind trial of two doses of interferon-beta ser (IFN-beta ser), differing by 20-fold 4.5 and 90 x 10(6) units), was undertaken in 64 patients with metastatic renal carcinoma. Patients were treated intravenously with injections daily for 10 days with an 11-day rest before treatment was reinitiated. The trial confirmed the relatively good toleration of IFN-beta ser; in the first cycle only 4/63 patients had anorexia of moderate or greater severity. Median weight change over the duration on study was -1.5 kg; in the first cycle only 7% of patients had performance status decline greater than 1 level. Statistically significant changes (p less than 0.05) occurred in granulocytes, lymphocytes, calcium, cholesterol, alkaline phosphatase, and aspartate transferase (AST); however, except for AST, overall clinical differences in the two doses were not great. Of 60 patients evaluated, 1 developed neutralizing antibody. When assessed 24 h after IFN-beta ser at 4.5 x 10(6) units, significant (p less than 0.05) augmentation had occurred in beta 2-microglobulin, HLA-DR, and HLA-DQ expression on monocytes, 2',5'-oligoadenylate (2-5A) synthetase in peripheral mononuclear cells, and natural killer (NK) and K cells functional activity. Although the 90 x 10(6) unit dose also resulted in stimulation of these responses, little additional augmentation of biological response occurred at the higher dose. Except for a decline in monocyte HLA-DR expression, biological responses remained increased at both doses over the 10-day period of treatment. However, no objective regressions of metastatic disease occurred. In view of objective responses in metastatic renal carcinoma in other trials with IFN-beta ser, consideration should be given to alternative schedules.", "The response rates in metastatic renal cell cancer (RCC) after chemotherapy, hormonal treatment, or immunotherapy rarely exceed 15%. Recently, interferon alpha (IFN alpha) was used for treatment of this disease in several studies which also demonstrated response rates of 15%. In order to test whether IFN therapy combined with hormones would result in higher response rates we compared single agent IFN therapy with a combined therapy of rIFN alpha 2C plus medroxyprogesterone acetate (MPA) in a randomized multicenter trial. The rIFN alpha 2C (2MU) was given s.c. 5 times per week for 8-12 weeks and subsequently once weekly until week 48. In the combined treatment, 750 mg MPA was given p.o. daily until week 48 in addition to the IFN as described. The overall response rate in 93 evaluable patients was 5.4% corresponding to 2 complete and 3 partial responses. Median survival was 7 months in both treatment groups. These data confirm the ineffectivity of low IFN doses for treatment of RCC. The low response rate is not increased by addition of MPA to IFN. The analysis of other IFN studies suggests that not only IFN doses but also IFN sources may influence response rates in metastatic RCC.", "Treatment results in patients with metastatic renal cell cancer (RCC) are still extremely unsatisfactory. Rates of response to IFN-alpha monotherapy and/or IL-2 mono/combination therapy vary between 10% and 20%. Coumarin (Cum) together with cimetidine (Cim) has yielded objective responses in 20%-33% of patients with RCC, according to two recent phase II studies.\n In the present study 148 patients with metastatic RCC were randomised to receive either IFN-alpha (5 MU 5 x weekly s.c.) + coumarin (100 mg/d p.o.) + cimetidine (3 x 400 mg/d p.o.), or IFN-alpha-monotherapy (5 MU 5 x weekly s.c.).\n Of the 148 patients in the study 137 were evaluable for response. No differences in remission rates (RR IFN-alpha + Cum + Cim 17.1% and IFN-alpha 20.8%) or survival times (median survival 9 months and 8 months, respectively) were found between these two treatment arms.\n This study confirms that INFN-alpha has antitumoral activity in RCC. Adding coumarin + cimetidine to IFN-alpha in the dose and regimen prescribed in this study did not increase response rates or survival.", "Since the beginning of the 1980s, when gene technology provided sufficient amounts of cytokines, numerous Phase II studies in metastatic renal cell carcinoma were carried out mostly with interferon alfa (IFN-alpha) and interleukin-2 (IL-2). So far, no randomized prospective trials including untreated control groups have been reported. We present a prospective study comparing IFN-alpha and vinblastine (VBL) versus medroxyprogesterone acetate (MPA).\n Immunochemotherapy schedule consists of IFN-alpha 8 million U/day subcutaneously for 3 days per week and VBL 0.1 mg/kg body weight intravenously at 3-week intervals. MPA was administrated intramuscularly at a dosage of 500 mg/week. The response rates, toxicities, and actuarial overall survival were analyzed.\n The overall response rate in 41 patients receiving IFN-alpha and VBL treatment was 20.5% (95% confidence interval, 9% to 33%). Four patients reached a complete and 5 patients reached a partial remission. No remissions were observed in 35 patients of the control group. A statistically significant survival benefit for the IFN-alpha and VBL group could not be demonstrated. Excluding fever, mild to moderate toxicities were observed. About one third of patients refused the proposed schedule due to general malaise and fatigue.\n A survival benefit or a favorable outcome of patients with metastatic renal cell carcinoma, treated with IFN-alpha and VBL, could not be demonstrated. As judged from this analysis, IFN-alpha and VBL therapy does not sufficiently meet the requirements of a palliative treatment of renal cell carcinoma.", "Recombinant human interleukin-12 (rHuIL-12) is a pleiotropic cytokine with anticancer activity against renal cell carcinoma (RCC) in preclinical models and in a phase I trial. A randomized phase II study of rHuIL-12 compared with interferon-alpha (IFN-alpha) evaluated clinical response for patients with previously untreated, advanced RCC. Patients were randomly assigned 2:1 to receive either rHuIL-12 or IFN-alpha2a. rHuIL-12 was administered by subcutaneous (s.c.) injection on days 1, 8, and 15 of each 28-day cycle. The dose of IL-12 was escalated during cycle 1 to a maintenance dose of 1.25 microg/kg. IFN was administered at 9 million units by s.c. injection three times per week. Serum concentrations of IL-12, IFN-gamma, IL-10, and neopterin were obtained in 10 patients treated with rHuIL-12 after the first full dose of 1.25 microg/kg given on day 15 (dose 3) of cycle 1 and again after multiple doses on day 15 (dose 6) of cycle 2. Thirty patients were treated with rHuIL-12, and 16 patients were treated with IFN-alpha. Two (7%) of 30 patients treated with rHuIL-12 achieved a partial response, and the trial was closed to accrual based on the low response proportion. IL-12 was absorbed rapidly after s.c. drug administration, with the peak serum concentration appearing at approximately 12 h in both cycles. Serum IL-12 concentrations remained stable on multiple dosing. Levels of IFN-gamma, IL-10, and neopterin increased with rHuIL-12 and were maintained in cycle 2. rHuIL-12 is a novel cytokine with unique pharmacologic and pharmacodynamic features under study for the treatment of malignancy and other medical conditions. The low response proportion associated with rHuIL-12 single-agent therapy against metastatic RCC was disappointing, given the preclinical data. Further study of rHuIL-12 for other medical conditions is underway. For RCC, the study of new cytokines is of the highest priority.", "A randomized phase III trial was conducted to determine whether combination therapy with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFNalpha2a) is superior to IFNalpha2a alone in patients with advanced renal cell carcinoma (RCC).\n Two hundred eighty-four patients were randomized to treatment with IFNalpha2a plus 13-CRA or treatment with IFNalpha2a alone. IFNalpha2a was given daily subcutaneously, starting at a dose of 3 million units (MU). The dose was escalated every 7 days from 3 to 9 MU (by increments of 3 MU), unless >/= grade 2 toxicity occurred, in which case dose escalation was stopped. Patients randomized to combination therapy were given oral 13-CRA 1 mg/kg/d plus IFNalpha2a. Quality of life (QOL) was assessed.\n Complete or partial responses were achieved by 12% of patients treated with IFNalpha2a plus 13-CRA and 6% of patients treated with IFNalpha2a (P =.14). Median duration of response (complete and partial combined) in the group treated with the combination was 33 months (range, 9 to 50 months), versus 22 months (range, 5 to 38 months) for the second group (P =.03). Nineteen percent of patients treated with IFNalpha2a plus 13-CRA were progression-free at 24 months, compared with 10% of patients treated with IFNalpha2a alone (P =.05). Median survival time for all patients was 15 months, with no difference in survival between the two treatment arms (P =.26). QOL decreased during the first 8 weeks of treatment, and a partial recovery followed. Lower scores were associated with the combination therapy.\n Response proportion and survival did not improve significantly with the addition of 13-CRA to IFNalpha2a therapy in patients with advanced RCC. 13-CRA may lengthen response to IFNalpha2a therapy in patients with IFNalpha2a-sensitive tumors. Treatment, particularly the combination therapy, was associated with a decrease in QOL.", "Subcutaneous recombinant interleukin-2 (rIL-2) and recombinant interferon alfa-2a (rIFNalpha-2a) have been used extensively in the treatment of metastatic renal cancer. Most results, coming from noncontrolled phase II trials, showed inconsistent rates of response. More recently, the addition of fluorouracil (FU) was proposed to improve the efficacy of these regimens.\n The role of a subcutaneous combination of rIL-2 and rIFNalpha-2a with or without FU was investigated. Patients were randomly assigned to receive a combination of rIL-2 and rIFNalpha-2a at weeks 1, 3, 5, and 7 or the same combination together with a continuous infusion of FU at weeks 1 and 5. The major end points of this multicenter, randomized trial were progression-free survival, response rate, and toxicity. Overall survival was a secondary end point. Tumor responses were reviewed by an independent committee. Analysis of the results was performed on an intention-to-treat basis.\n One hundred thirty-one patients were enrolled. There was no difference in toxicity between the arms, and no toxic death was observed. One partial response was observed in arm A and five in arm B. Progression-free survival did not differ between the arms, and rates at 1 year were 12% and 15% in arms A and B, respectively. No statistically significant differences were detected in any end point.\n The subcutaneous combination of rIL-2 and rIFNalpha-2a with or without FU does not benefit patients with metastatic renal carcinoma. Neither of these regimens can be recommended as standard treatment. The results of the subcutaneous cytokine regimen seem disappointing.", "The value of nephrectomy in metastatic renal-cell cancer has long been debated. Several nonrandomized studies suggest a higher rate of response to systemic therapy and longer survival in patients who have undergone nephrectomy.\n We randomly assigned patients with metastatic renal-cell cancer who were acceptable candidates for nephrectomy to undergo radical nephrectomy followed by therapy with interferon alfa-2b or to receive interferon alfa-2b therapy alone. The primary end point was survival, and the secondary end point was a response of the tumor to treatment.\n The median survival of 120 eligible patients assigned to surgery followed by interferon was 11.1 months, and among the 121 eligible patients assigned to interferon alone it was 8.1 months (P=0.05). The difference in median survival between the two groups was independent of performance status, metastatic site, and the presence or absence of a measurable metastatic lesion.\n Nephrectomy followed by interferon therapy results in longer survival among patients with metastatic renal-cell cancer than does interferon therapy alone.", "IL-2 given subcutaneously in combination with interferon-alpha 2b (IFN) appears to induce a response rate comparable to that obtained with IL-2 intravenous injection in patients with metastatic renal cell carcinoma (RCC) but with lower toxicity. The role of IFN when combined with IL-2 has however still to be defined. The present study was performed to draw some preliminary conclusions about the effect of IFN in combination with IL-2 in metastatic RCC.\n The study included 30 consecutive patients with metastatic RCC who were randomized to treatment with IL-2 subcutaneous therapy (3 million IU twice/daily for 5 days/week for 6 weeks) or with IL-2 plus IFN (5 million U/m2 subcutaneously thrice weekly). In patients without progressive disease, a second cycle was repeated after a 28-day rest period.\n No significant difference in partial response rate was found between patients treated with IL-2 alone and those given IL-2 plus IFN (5/15 vs 4/15). Similarly, no difference was seen in the percentage of stable disease (7/15 vs 7/15). Toxicity was higher in patients who received IL-2 plus IFN. Lymphocyte and eosinophil mean increase was higher in patients treated with IL-2 alone than in those treated with IL-2 plus IFN, without however any significant difference.\n The present results, which require confirmation in a larger series, indicate that combination with IFN does not increase the efficacy of IL-2 subcutaneous immunotherapy in metastatic RCC but only the toxicity of treatment.", "A randomized phase II/III trial was conducted to determine whether combination treatment with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFN-alpha-2a) was superior to IFN-alpha-2a alone in patients with progressive metastatic renal cell carcinoma.\n Three hundred twenty patients were randomly assigned to treatment with IFN-alpha-2a plus 13-CRA or to IFN-alpha-2a alone. IFN-alpha-2a was given daily subcutaneously, starting at a dose of 3 million units (MU). The dose was escalated every 7 days from 3 to 9 MU by increments of 3 MU. Patients randomly assigned to combination therapy received oral 13-CRA 1 mg/kg/d plus IFN-alpha-2a.\n Median time to progression was 5.1 months for patients treated with the combination and 3.4 months for patients on IFN-alpha-2a alone (P = .008). Progression-free survival rates at 6 months were 43% for patients receiving combined therapy and 30% for patients on IFN-alpha-2a, and at 12 months, 27% and 17%, respectively. Median overall survival was 17.3 months for patients on IFN-alpha-2a and 13-CRA, and 13.2 months for patients treated with IFN-alpha-2a (P = .048). Twenty-two percent of the patients receiving the combination stopped treatment due to toxicity, as compared with 16% on IFN-alpha-2a.\n Progression-free and overall survival for patients with progressive metastatic renal cell carcinoma treated with IFN-alpha-2a plus 13-CRA were significantly longer compared with patients on IFN-alpha-2a alone (P = .007 and P = .048, respectively). Improvement in efficacy in the combination arm was accompanied by increased, though not serious, toxicity.", "Ninety-seven patients with recurrent or metastatic renal cell carcinoma were randomized to receive recombinant interferon (IFN) alfa-2b (Intron A; Schering-Plough, Kenilworth, NJ) by either the subcutaneous (SC) or intravenous (IV) route. The SC dosage was 2 X 10(6) IU/m2 three times weekly, and the IV dose 30 X 10(6) IU/m2 for five consecutive days every 3 weeks. Dose escalation to a maximum of 10 X 10(6) IU/m2 SC and 50 X 10(6) IU/m2 IV was allowed for patients with minimal or absent toxicity. Five of 51 of the SC-treated patients (10%) and three of 46 of the IV-treated patients (7%) had a partial response (PR) or complete response (CR). Patients with prior nephrectomy, no prior treatment, and lack of bone metastases were most likely to respond, and a retrospective analysis of this subgroup revealed a 23% response rate. Achievement of response took from 3 weeks to 11 months, while response duration lasted from 3 to 31+ months. All responders had prior nephrectomy; six of eight had no prior chemotherapy or hormonal therapy; five had lung metastases, and none had bone metastases. Regardless of route, almost all patients developed a flu-like syndrome; however, grade 3 or greater toxicity was much more common for IV-treated patients. This trial demonstrates modest, but definite antitumor activity for recombinant interferon in advanced renal cell carcinoma. SC administration with lower dose and toxicity is as effective as treatment administered IV.", "Histamine inhibits formation and release of phagocyte-derived reactive oxygen species, and thereby protects natural killer and T cells against oxidative damage. Thus, the addition of histamine may potentially improve the efficacy of interleukin-2 (IL-2). Two randomised phase II trials of IL-2 with or without histamine dihydrochloride (HDC) in patients with metastatic renal cell carcinoma (mRCC) were run in parallel. A total of 41 patients were included in Manchester, UK and 63 in Aarhus, Denmark. The self-administered, outpatient regimen included IL-2 as a fixed dose, 18 MIU s.c. once daily, 5 days per week for 3 weeks followed by 2 weeks rest. Histamine dihydrochloride was added twice daily, 1.0 mg s.c., concomitantly with IL-2. A maximum of four cycles were given. The Danish study showed a statistically significant 1-year survival benefit (76 vs 47%, P = 0.03), a trend towards benefit in both median survival (18.3 vs 11.4 months, P = 0.07), time to PD (4.5 vs 2.2 months, P = 0.13) and clinical benefit (CR + PR + SD) (58 vs 37%, P = 0.10) in favour of IL-2/HDC, whereas the UK study was negative for all end points. Only three patients had grade 4 toxicity; however, two were fatal. A randomised phase III trial is warranted to clarify the potential role of adding histamine to IL-2 in mRCC.", "Twenty patients with pulmonary metastases of renal cell carcinomas have been treated in a randomized study with either leucocyte interferon in daily doses of 3 x 10(6) I.U.i.m or irradiation of both lungs in a calculated mean central dose of 10 Gy in 4 weeks in combination with bleomycin and vincristine. Most patients had a short time to progression of their disease. Three patients in the interferon group had complete response (CR) and partial response (PR) and one patient in the other group had PR. The numbers of patients in both arms of the study are too small to allow any conclusions whether beneficial effects are more frequent in one group than in the other, but there is a more favourable tendency in the interferon group.", "A randomized phase II trial was performed to compare the efficacy and toxicity of interleukin 2 (IL-2) with an IL-2 and interferon alpha (IFN-alpha) regimen for the treatment of metastatic renal carcinoma. Sixty patients with recurrent renal cell carcinoma (RCC) who had previously undergone a nephrectomy were randomized to receive three cycles of IL-2 or IL-2 with IFN-alpha2b. Eighteen MU of IL-2 were administered subcutaneously on Mondays-Fridays for 3 weeks out of 4. Those patients randomized to receive the combination received the same regimen of IL-2 with 9 MU of IFN-alpha2b subcutaneously on Mondays, Wednesdays and Fridays for 3 weeks out of 4. Thirty patients were randomized to receive each arm. Twenty-nine were evaluable in each arm. Twenty-two patients received three cycles of IL-2 but only 14 patients received three cycles of IL-2/IFN-alpha because of the greater toxicity of the combination. The principal toxicities included nausea, fatigue and fever. There were no complete responses in either arm and only two patients who were treated with IL-2 attained a partial response. Twelve patients in each arm had stable disease and 15 patients in the IL-2 arm and 16 patients in the IL-2/IFN-alpha arm progressed through treatment. There were no significant differences in survival. Ten patients who received IL-2 are alive with a median follow-up of 266 days, whereas six patients who received IL-2/IFN-alpha are alive after a median of 278 days. The median survival from the time of identification of metastatic disease is 444 days in the IL-2 arm and 381 days in the IL-2/IFN-alpha arm. The IL-2/IFN-alpha combination is more toxic than IL-2 alone and this resulted in a reduced number of cycles of treatment. However, the median survival of the two groups was the same, suggesting that further evaluation of the IL-2/IFN-alpha combination should be confined to large prospective randomized clinical trials.", "Metastatic renal carcinoma has a 2-year survival of around 20% and is largely resistant to chemotherapy. The use of interferons in the treatment of metastatic renal carcinoma remains controversial. Although non-randomised studies suggest that biological therapy with interferons produces a small number of tumour responses, most clinicians judge such treatment to be ineffective. We have investigated the effect of treatment with interferon-alpha on survival in patients with metastatic renal carcinoma.\n In a multicentre, randomised trial, patients with metastatic renal carcinoma were randomly assigned subcutaneous interferon-alpha (three doses--5 MU, 5 MU, 10 MU--for the first week, then 10 MU three times per week for a further 11 weeks; n=174) or oral medroxyprogesterone acetate (MPA; 300 mg once daily for 12 weeks; n=176). The primary endpoint was overall survival. Analysis was by intention to treat. The trial used a triangular sequential design for early termination as soon as results were conclusive. The trial was stopped in November, 1997, when data were available for 335 patients (167 interferon-alpha, 168 MPA).\n A total of 111 patients have died in the interferon-alpha group, and 125 patients have died in the MPA group. There was a 28% reduction in the risk of death in the interferon-alpha group (hazard ratio 0.72 [95% CI 0.55-0.94], p=0.017). Interferon-alpha gave an improvement in 1-year survival of 12% (MPA 31% survival, interferon-alpha 43%), and an improvement in median survival of 2.5 months (MPA 6 months, interferon-alpha 8.5 months).\n The benefit of treatment with interferon-alpha should be weighed against the drug's toxic effects. Combination regimens of biological therapy and chemotherapy should now be compared with interferon-alpha monotherapy in randomised controlled trials.", "In the treatment of renal cell carcinoma both complete (CRs) and partial remissions (PRs) have been obtained using recombinant (r) interferon alpha (IFN-alpha), with response rates ranging from 0 to 31% (mean 16%). rIFN-gamma is a potent immunostimulating agent, but the clinical experience of its use is limited and results are conflicting. In a phase II study with the combination of rIFN-alpha 2c (Boehringer Ingelheim) and rIFN-gamma (Genentech, supplied by Boehringer Ingelheim) in 31 eligible patients, a response rate of 25% was recorded. Based on this observation a randomised phase III study was initiated to investigate the possible advantage of the addition rIFN-gamma to rIFN-alpha 2c treatment. Treatment consisted of rIFN-alpha 2c 30 micrograms m-2 = 10 x 10(6) IU m-2 s.c. twice weekly in arm A and the same dose of rIFN-alpha combined with rIFN-gamma 100 micrograms m-2 = 2 x 10(6) IU m-2 in arm B. Eligibility criteria included documented progression of disease; patients with bone lesions only and overt central nervous system metastases were excluded. Between November 1988 and September 1990, 102 patients were entered into the study. An interim analysis showed a response in 7/53 (13%) patients (two CRs and five PRs) in the rIFN-alpha 2c monotherapy arm and in 2/45 (4%) (one CR and one PR) patients in the combination arm. This difference was not statistically significant (P = 0.17). The probability of missing an eventual 10% advantage for the combination is 0.001. The numbers are insufficient to rule out a negative effect of the addition of rIFN-gamma. The dose intensity of IFN-alpha 2c for the two treatment arms was the same. The addition of rIFN-gamma does not improve the response rate of rIFN-alpha 2c monotherapy. A possible detrimental effect cannot be excluded.", "Most trials of immunomodulators in metastatic renal-cell carcinoma have been uncontrolled and subject to selection bias. The objective of this blinded, placebo-controlled study was to compare overall response rates, time to disease progression, and survival of patients with metastatic renal-cell carcinoma treated with recombinant human interferon gamma-1b or placebo.\n Patients with biopsy-proved metastatic renal-cell carcinoma were randomly assigned to receive interferon gamma-1b (60 microg per square meter of body-surface area subcutaneously once weekly) or placebo. The primary tumor had been treated by nephrectomy or angioinfarction at least three weeks previously. Patients were evaluated for radiologic evidence of progression, and all responses were independently reviewed by a committee that was unaware of the treatment.\n A total of 197 patients with metastatic renal-cell carcinoma were enrolled at 17 centers in Canada. One hundred eighty-one patients could be evaluated; of these, 91 were assigned to receive interferon gamma-1b and 90 were given placebo. The groups were well balanced in terms of prognostic factors. Two thirds of all patients had Karnofsky scores of 90 or 100, and more than half had two or more metastatic sites. Grade I and II toxicity, mostly chills, fever, asthenia, or headaches, was reported in 91 percent and 61 percent, respectively, of the patients in the interferon group, as compared with 76 percent and 63 percent in the placebo group. Life-threatening drug-related events were rare, occurring in 1 percent of patients in the interferon group. No significant differences between groups were observed in overall response rates, time to disease progression, or survival. The overall response rate was 4.4 percent (3.3 percent complete response and 1.1 percent partial response) in the interferon group and 6.6 percent (3.3 percent complete response and 3.3 percent partial response) in the placebo group (P=0.54), with a rate of durable complete response of 1 percent in both groups. The median time to disease progression was 1.9 months in both groups (P=0.49), and there was no significant difference in median survival (12.2 months with interferon vs. 15.7 months with placebo, P=0.52).\n No difference in outcome was observed in patients with metastatic renal-cell carcinoma who were treated with interferon gamma-1b as compared with placebo. These results emphasize the necessity of testing the efficacy of immunomodulators in randomized studies.", "A prospective randomized trial tested the hypothesis that interferon and cytotoxic chemotherapy delivered sequentially would be synergistic and would increase the response rate in metastatic renal cell carcinoma. Thirty-six patients were entered and randomized to chemotherapy only (5-fluorouracil, doxorubicin, mitomycin, and cis-platin) vs. interferon alternating with the same chemotherapy. Only 4 of 32 evaluable patients (13%), 2 in each arm, had a major response. Three patients in the alternating arm had minor responses. Complete, partial, and minor responses totaled 7 (22%). All four patients whose only disease was lung metastasis had some evidence of response (p = 0.001). Interferon alternating with chemotherapy did not appear to improve the major response rate over chemotherapy alone. Responses in metastatic renal cell carcinoma appear confined to a favorable subset of patients.", "IL-2 immunotherapy has been proven to be effective in the treatment of metastatic renal cell cancer (RCC). However, several drugs commonly used in the palliative therapy of cancer may potentially influence IL-2 efficacy, since the anticancer immunity has appeared to depend on complex interactions between immune system and psychoneuroimmunomodulation. In particular, experimental studies and preliminary clinical investigations have shown that the opioid substances, namely morphine, may suppress the anticancer immunity and the efficacy of IL-2 itself. In contrast, other neuroactive substances, in particular the pineal hormone melatonin (MLT), have been proven to stimulate the immune response, including the anticancer immunity, and to abrogate opioid-induced immunosuppression. On this basis, a study was planned to evaluate the effect of a concomitant MLT administration on the efficacy of IL-2 immunotherapy in advanced cancer patients chronically treated with morphine for cancer-related pain. The study was carried out in 30 metastatic RCC patients under chronic therapy with morphine at oral doses ranging from 60 to 120 mg/day. Patients were randomized to receive morphine alone or morphine plus MLT (20 mg/day orally in the evening). The immunotherapeutic cycle consisted of IL-2 subcutaneous administration at a dose of 6 million IU/day for 6 days/week for 4 consecutive weeks. In nonprogressing patients, a second cycle was planned after a 21-day rest period. The percent of partial responses achieved in patients treated with morphine alone was significantly lower than that observed in patients concomitantly treated with MLT (1/16 vs. 4/14, p<0.05). Moreover, the 3-year percent of survival was significantly higher in patients concomitantly treated with MLT (p<0.01). In contrast, no diminished analgesic efficacy of morphine occurred in patients concomitantly treated with MLT. This preliminary study seems to suggest that the negative influence of morphine therapy for cancer-related pain on the clinical efficacy of IL-2 cancer immunotherapy may be abrogated by the concomitant administration of the immunomodulating pineal neurohormone MLT.", "Metastatic renal cell carcinoma (RCC) has a poor prognosis. Conventional treatment strategies, including chemotherapy and hormonal therapy, have limited value. Although encouraging results have been achieved in terms of objective response using immunological manipulations, no conclusive studies yet exist with a controlled comparative evaluation of survival. Therefore, the present study was undertaken, which compared one of the present (and presumed best) treatments, interleukin 2/interferon-alpha (IL-2/IFN-alpha) and tamoxifen, with a control arm of tamoxifen only. Tamoxifen has been shown to potentiate in vivo anti-tumour activity of IL-2, and because of its non-toxic behaviour it was included in both groups. The study was open, randomized and included seven institutions in Sweden. The patients were stratified according to the different centres involved. An interim analysis was planned when a minimum of 100 patients were evaluable. The 128 patients finally included had a histologically documented metastatic RCC, with a life expectancy of more than 3 months, a performance status WHO 0-2 and no prior chemo- or immunotherapy. Informed consent was obtained from each patient. The patients randomized to the control arm (n = 63) received only tamoxifen 40 mg p.o. daily for at least 1 year or until progression. The patients (n = 65) randomized to biotherapy received subcutaneous recombinant IL-2, leucocyte IFN-alpha in a treatment cycle of 42 days, as well as tamoxifen p.o. In the absence of undue toxicity or disease progression, these patients received one additional treatment cycle of 42 days followed by maintenance treatment, consisting of 5 days therapy every 4 weeks, for 1 year, or until proven progression. Only two patients in the tamoxifen-only group received immunotherapy when the disease progressed, but without any beneficial effect. All patients received appropriate local treatment when indicated. The interim analysis demonstrated no survival advantage for either group, and therefore further inclusion of patients was stopped. The median follow-up was 11 months (range 0.4-48 months). The final survival analysis showed no significant differences between the two treatment arms in so far as comparison from the day of diagnosis of primary disease, from the day of first evidence of metastatic spread, or from the onset of treatment. This was valid both when the evaluation was performed with regard to intention to treat and when the analysis was directed only to patients that managed at least one treatment cycle (42 days) of IL-2/IFN-alpha. The adverse effects were more pronounced in the IL-2/IFN-alpha group. Although the number of patients is limited, the results raise doubt concerning immunotherapy with IL-2 and IFN-alpha as a routine treatment in the management of advanced RCC. The difference in cost of drugs and health care (drug costs per patient: IL-2/IFN-alpha $27000 vs tamoxifen $360) as well as adverse effects caused by IL-2/IFN-alpha are also factors of importance. The study emphasizes the need for more effort to find the 'optimal schedule' of immunotherapy, as well as the need for randomized controlled studies before approval of a new treatment in the routine setting.", "A prospective randomized trial of low versus high doses of human leukocyte alpha-interferon (1 X 10(6) units/day for 28 days versus 10 X 10(6) units/day for 28 days) was carried out in 30 patients with metastatic renal cell carcinoma, to test the tolerance and relative antitumor effects of these interferon doses. Both doses were tolerated well, and responses to the human leukocyte alpha-interferon were observed overall in seven individuals, including complete, partial, and minimal tumor regressions. Six of the seven responses occurred in patients who received the high dosage, and three of these responses were major responses. While not statistically significant, this result suggested a dose-response relationship. One minimal response was observed in a patient treated at low dosage. Nine individuals who were stable after 1 month of therapy at low dosage were randomized to a further month of therapy at low or high dosage, during which one of four at high dosage had a partial response, and none of five at low dosage manifested response. Regression of pulmonary disease in one individual was delayed, occurring 3 months after therapy at the high dose and enduring for a period of 28 months. Major objective responses in other patients were of 4 and 15 months duration. Human leukocyte alpha-interferon is an active agent in renal cell carcinoma at the dosage of 10 million units daily. No relationship of toxicity to response was evident in this trial. Optimum dosage and duration of treatment have yet to be established.", "One hundred sixty-five patients were randomized to receive either interferon alfa-n1 (Wellferon; Burroughs Wellcome Co, Research Triangle Park, NC) alone or with vinblastine. An initial six-cycle induction treatment consisted of interferon given at daily doses of 3, 5, 20, 20, and 20 x 10(6) U/m2 every 2 weeks. Vinblastine at a dose of 10 mg/m2 (later decreased to 5 mg/m2) was given on day 1 of alternate cycles. Toxicities were generally well tolerated. The overall response rate was 10% with no significant difference between treatment arms. Survival was also not significantly different for the arms. A small subset of patients (16) with metastases only to the lungs had a high complete response (CR) and partial response (PR) rate of 44%. Responses were durable, and overall survival of this group was much better than that of the other patients.", "Biologic response modifiers have activity in renal cell carcinoma. The combination of interleukin-2 (IL-2) and beta-interferon (B-IFN) is synergistic in vitro. This trial was initiated to determine the efficacy of IL-2 alone and with B-IFN in advanced RCC.\n Ambulatory patients with advanced RCC were randomly allocated to either IL-2 6 x 10(6) units/M2 intravenously (IV) three days a week for four weeks or IL-2 5 x 10(6) units/M2 IV plus B-IFN 6 x 10(6) units/M2 IV three days a week for 4 weeks. This induction phase was followed by a maintenance phase of the same drugs and doses administered for two weeks out of every four.\n 84 patients were entered onto this phase II trial with 75 considered eligible for response and survival. Toxicity is reported for the 81 patients on whom data was received, irrespective of eligibility. The overall response rate (RR) was 9.3% (7/75). Of the 3 responses in the IL-2 arm (RR = 8.3%), one was a complete response. 4 patients in the IL-2 + B-IFN arm (RR = 10.3%) achieved a partial response. Median survival was estimated to be 8.4 months for patients given IL-2 and 8.0 months for patients given the IL-2 and B-IFN combination. Multivariate analysis of survival data identified initial performance status, metastases of > 1 site, and weight loss as being important prognostic factors for survival. There were 2 lethal and 3 life threatening toxicities with the IL-2 treatment. While there were no lethal toxicities on the combination arm, there were 4 life threatening toxicities.\n The results of this study indicate that further investigation of IL-2 with or without B-IFN at this dose and schedule as treatments for renal cell carcinoma is probably not warranted.", "This three-arm randomized study compares response rates and overall survival of patients with metastatic renal cell cancer (RCC) receiving high-dose or one of two low-dose interleukin-2 (IL-2) regimens.\n Patients with measurable metastatic RCC and a good performance status were randomized to receive either 720,000 U/kg (high-dose [HD]) or 72,000 U/kg (low-dose [LD]), both given by intravenous (IV) bolus every 8 hours. After randomly assigning 117 patients, a third arm of low-dose daily subcutaneous IL-2 was added, and an additional 283 patients were randomly assigned.\n A total of 156 patients were randomly assigned to HD IV IL-2, and 150 patients to LD IV IL-2. Toxicities were less frequent with LD IV IL-2 (especially hypotension), but there were no IL-2-related deaths in any arm. There was a higher response proportion with HD IV IL-2 (21%) versus LD IV IL-2 (13%; P =.048) but no overall survival difference. The response rate of subcutaneous IL-2 (10%, partial response and complete response) was similar to that of LD IV IL-2, differing from HD IV (P =.033). Response durability and survival in completely responding patients was superior with HD IV compared with LD IV therapy (P =.04).\n Major tumor regressions, as well as complete responses, were seen with all regimens tested. IL-2 was more clinically active at maximal doses, although this did not produce an overall survival benefit. The immunological factors which constrain the curative potential of IL-2 to only a small percentage of patients need to be further elucidated.", "In a randomized phase II study we evaluated response, survival and side effects of low dose recombinant interferon-gamma in 30 patients (group 1) versus recombinant interleukin-2 and interferon-alpha 2b in 30 (group 2) with metastatic renal cell carcinoma.\n Group 1 received 200 micrograms interferon-gamma subcutaneously once a week. Group 2 received 4 x 4.8 x 10(6) IU/m.2 interleukin-2 subcutaneously on days 1 and 22, 2 x 4.8 x 10(6) IU/m.2 on days 2 and 23, and 2 x 2.4 x 10(6) IU/m.2 combined with interferon-alpha 2b subcutaneously at 3 x 10(6) IU/m.2 on days 3, 5, 24 and 26, and 6 x 10(6) IU/m.2 3 times weekly for 6 weeks.\n Toxicity grades 2 and 3 (World Health Organization) were observed in group 2 only. After followup of 13 months there was no remission in group 1 compared to 7 remissions in group 2, with 23 cases of progressive disease detected.\n Combination therapy showed an objective response rate of 23% (p = 0.01). Although survival was not a primary aim of the study, there was a tendency toward no significant difference in survival when evaluating these relatively small groups (p = 0.49).", "We conducted a prospectively randomized clinical trial to compare the efficacy and safety of subcutaneous interferon-alpha2a, subcutaneous interleukin-2 and intravenous 5-fluorouracil as home therapy against oral tamoxifen in 78 patients with progressive metastatic renal cell carcinoma. Treatment courses consisted of interferon-alpha2a 5 x 10(6) IU m(-2), day 1 weeks 1 + 4; days 1, 3, 5 weeks 2 + 3; 10 x 10(6) IU m(-2), days 1, 3, 5 weeks 5-8; interleukin-2 10 x 10(6) IU m(-2), twice daily days 3-5 weeks 1 + 4; 5 x 10(6) IU m(-2), days 1, 3, 5 weeks 2 + 3; and 5-fluorouracil 1000 mg m(-2), day 1 weeks 5-8. The tamoxifen group received tamoxifen 80 mg twice daily over 8 weeks. Among 41 patients treated with interleukin-2, interferon-alpha2a and 5-fluorouracil there were 7 complete (17.1%) and 9 partial responders (21.9%), with an overall objective response rate of 39.1% (95% CI, 24.2-55.5). An additional 15 patients (36.6%) were stable throughout therapy. The overall survival was 24 months (range 5-76+). In 37 patients receiving tamoxifen no objective remissions occurred. 13 patients (35.1%) had stable disease and 24 patients (64.9%) showed continued disease progression. The overall survival was 13 months (range 3-73+). In summary, this home-based therapy regimen of interferon-alpha2a, interleukin-2 and 5-fluorouracil demonstrated significant therapeutic efficacy in patients with progressive renal cell carcinoma when compared to hormonal therapy.\n Copyright 2001 Cancer Research Campaign http://www.bjcancer.com.", "The Cytokine Working Group conducted a randomized phase III trial to determine the value of outpatient interleukin-2 (IL-2) and interferon alfa-2b (IFN) relative to high-dose (HD) IL-2 in patients with metastatic renal cell carcinoma.\n Patients were stratified for bone and liver metastases, primary tumor in place, and Eastern Cooperative Oncology Group performance status 0 or 1 and then randomly assigned to receive either IL-2 (5 MIU/m(2) subcutaneously every 8 hours for three doses on day 1, then daily 5 days/wk for 4 weeks) and IFN (5 MIU/m(2) subcutaneously three times per week for 4 weeks) every 6 weeks or HD IL-2 (600,000 U/kg/dose intravenously every 8 hours on days 1 through 5 and 15 to 19 [maximum 28 doses]) every 12 weeks.\n One hundred ninety-two patients were enrolled between April 1997 and July 2000. Toxicities were as anticipated for these regimens. The response rate was 23.2% (22 of 95 patients) for HD IL-2 versus 9.9% (nine of 91 patients) for IL-2/IFN (P = .018). Ten patients receiving HD IL-2 were progression-free at 3 years versus three patients receiving IL-2 and IFN (P = .082). The median response durations were 24 and 15 [corrected] months (P = .18) [corrected] and median survivals were 17.5 and 13 months (P = .24). For patients with bone or liver metastases (P = .001) or a primary tumor in place (P = .040), survival was superior with HD IL-2.\n This randomized phase III trial provides additional evidence that HD IL-2 should remain the preferred therapy for selected patients with metastatic renal cell carcinoma.", "Eighty-nine patients with advanced measurable metastatic renal cell carcinoma were entered into a prospective randomized trial comparing alpha-interferon to gamma-interferon and to the combination. The trial was performed in order to confirm the activity of gamma-interferon and assess the potential clinical synergism. Response rates were 5, 10, and 5%, respectively. The low response rate may have been due to the inability to raise the doses of the interferons to higher levels. Clinical synergy at this dose, route, and schedule of administration in renal cell carcinoma does not exist.", "We conducted a prospectively randomized clinical trial to compare the efficacy of three outpatient therapy regimens in 341 patients with progressive metastatic renal cell carcinoma.\n Patients were stratified according to known clinical predictors and were subsequently randomly assigned. Treatment arms were: arm A (n = 132), subcutaneous interferon alfa-2a (sc-IFN-alpha-2a), subcutaneous interleukin-2 (sc-IL-2), and intravenous (IV) fluorouracil; arm B (n = 146): arm A treatment combined with per oral 13-cis-retinoic acid; and arm C (n = 63), sc-IFN-alpha-2a and IV vinblastine.\n Treatment (according to the standard 8-week Hannover Atzpodien regimen) arms A, B, and C yielded objective response rates of 31%, 26%, and 20%, respectively. Arm B, but not arm A, showed a significantly improved progression-free survival (PFS) compared with arm C (P =.0248). Both arm A (median overall survival, 25 months; P =.0440) and arm B (median overall survival, 27 months; P =.0227) led to significantly improved overall survival (OS) compared with arm C (median OS, 16 months). All three sc-IFN-alpha-2a-based therapies were moderately or well tolerated.\n Our results established the safety and improved long-term therapeutic efficacy of sc-IL-2 plus sc-INF-alpha-2a-based outpatient immunochemotherapies, compared with sc-INF-alpha-2a/IV vinblastine.", "Treatment using interleukin-2 (IL-2) alone or in conjunction with lymphokine-activated killer (LAK) cells has been shown to mediate disease regression in selected patients with advanced cancer.\n This prospective randomized trial was designed to determine whether the administration of LAK cells in conjunction with high-dose IL-2 alters response and survival rates, compared with those for IL-2 alone, in patients with advanced cancer.\n The 181 patients who had metastatic cancer that had failed to respond to standard therapy or who had disease for which no effective therapy existed received treatment with high-dose IL-2 alone or with LAK cells plus IL-2. Both treatment groups were to receive the same dose of IL-2 administered according to the same schedule. IL-2 doses were omitted depending on the tolerance of the patient. Of the 181 patients, 97 had renal cell cancer and 54 had melanoma.\n Median potential follow-up was 63.2 months. There were 10 complete responses among the 85 assessable patients who received IL-2 plus LAK cells, compared with four among the 79 who received IL-2 alone. There were 14 and 12 partial responses, respectively. Complete response continues in seven patients at 50-66 months. The 36-month actuarial survival with IL-2 plus LAK cells was 31%, compared with 17% with IL-2 alone (two-sided P value [P2] = .089). A trend toward improved survival was seen for patients with melanoma who received IL-2 plus LAK cells, compared with those who received IL-2 alone (24-month survival: 32% versus 15%; 48-month survival: 18% versus 4%; P2 = .064 [corrected]). None of 26 patients with melanoma who received IL-2 alone are alive; five of 28 who received IL-2 plus LAK cells are alive, and three continue in complete response. No difference in survival was seen in patients with renal cell cancer in the two treatment groups. There were six treatment-related deaths (3.3%); three were due to myocardial infarction. Other toxic effects resolved by discontinuation of IL-2. Many toxic effects were related to increased vascular permeability induced by IL-2.\n Some patients with metastatic cancer have prolonged remission when they are treated with high-dose IL-2 alone or in conjunction with LAK cells. Our results suggest a trend toward increased survival when IL-2 is given with LAK cells in patients with melanoma, but no trend was observed for patients with renal cell cancer.\n As these studies continue, efforts are underway to develop improved immunotherapies using tumor-infiltrating lymphocytes (TIL) and gene-modified TIL.", "The combination of interferon alfa-2a (IFNalpha2a) plus vinblastine (VLB) induces objective tumor responses in patients with advanced renal cell cancer. However, no prospective randomized trial has shown that this treatment prolongs overall survival. We compared overall survival after treatment with IFNalpha2a plus VLB versus VLB alone in patients with advanced renal cell cancer.\n We prospectively randomized 160 patients with locally advanced or metastatic renal cell cancer to receive either VLB alone or IFNalpha2a plus VLB for 12 months or until progression of disease. In both groups, VLB was administered intravenously at 0.1 mg/kg every 3 weeks, and in the combination group IFNalpha2a was administered subcutaneously at 3 million units three times a week for 1 week, and 18 million units three times a week thereafter for the second and subsequent weeks. For patients unable totolerate IFNalpha2a at 18 million units per injection, the dose was reduced to 9 million units.\n Median survival was 67.6 weeks for the 79 patients receiving IFNalpha2a plus VLB and 37.8 weeks for the 81 patients treated with VLB (P =.0049). Overall response rates were 16. 5% for patients treated with IFNalpha2a plus VLB and 2.5% for patients treated with VLB alone (P =.0025). Treatment with the combination was associated with constitutional symptoms and abnormalities in laboratory parameters, but no toxic deaths were reported.\n The combination of IFNalpha2a plus VLB is superior to VLB alone in the treatment of patients with locally advanced or metastatic renal cell carcinoma. This is the first study to demonstrate that survival can be prolonged by using IFNalpha2a for these patients.", "Recombinant human interleukin-2 (aldesleukin) and recombinant human interferon alfa can induce notable tumor regression in a limited number of patients with metastatic renal-cell carcinoma. We conducted a multicenter, randomized trial to determine the effect of each cytokine independently and in combination, and to identify patients who are best suited for this treatment.\n Four hundred twenty-five patients with metastatic renal-cell carcinoma were randomly assigned to receive either a continuous intravenous infusion of interleukin-2, subcutaneous injections of interferon alfa-2a, or both. The main outcome measure was the response rate; secondary outcomes were the rates of event-free and overall survival. Predictive factors for response and rapid progression were identified by multivariate analysis.\n Response rates were 6.5 percent, 7.5 percent, and 18.6 percent (P<0.01) for the groups receiving interleukin-2, interferon alfa-2a, and interleukin-2 plus interferon alfa-2a, respectively. At one year, the event-free survival rates were 15 percent, 12 percent, and 20 percent, respectively (P=0.01). There was no significant difference in overall survival among the three groups. Toxic effects of therapy were more common in patients receiving interleukin-2 than in those receiving interferon alfa-2a. Response to treatment was associated with having metastasis to a single organ and with receiving the combined treatment. The probability of rapid progression of disease was at least 70 percent for patients with at least two metastatic sites, liver metastases, and a period of less than one year between the diagnosis of the primary tumor and the appearance of metastases.\n Cytokines are active in a few patients with metastatic renal-cell carcinoma. The higher response rate and longer event-free survival obtained with a combination of cytokines must be balanced against the toxicity of such treatment.", "Fifty-six patients with metastatic renal cell carcinoma (RCC) were treated with recombinant DNA-derived interferon alpha (rIFN alpha A). The first 30 patients were randomized between doses of 2 X 10(6) U/m2 and 20 X 10(6) U/m2 intramuscularly daily. No complete (CR) or partial (PR) remissions were achieved in 15 patients receiving the low dose. In contrast, 27% of those receiving the high dose achieved CR or PR. Subsequently, 26 additional patients were given the high dose and achieved a 31% response rate. Remissions lasted from 1 to more than 12 months (median, 3 months). Responses occurred predominantly in lung parenchyma or mediastinal node metastases. Toxicity of the high dose required dose reduction in 50% of the patients. Neutralizing antibodies to rIFN alpha A developed in seven of 12 responsive (58%) and nine of 29 (31%) nonresponsive patients (P = greater than .5). The median duration of remission among the antibody-positive and antibody-negative patients were 2 and 10 months, respectively (P = .009). The clinical significance of the antibodies to rIFN alpha A remains unclear, but the coincidence between the detection of antibodies and the early relapse of the disease in some responsive patients suggests that these antibodies may abrogate the biologic activity of rIFN alpha A. This effect, however, was not associated with adverse clinical sequelae.", "Surgery is the main treatment for localised renal cell carcinoma, but use of radical nephrectomy for metastatic disease is highly controversial. We aimed to establish whether radical nephrectomy done before interferon-alfa-based immunotherapy improved time to progression and overall survival (primary endpoints) compared with interferon alfa alone.\n We included 85 patients from June, 1995, to July, 1998: two (one per group) were ineligible. 42 of the 83 participants were randomly assigned combined treatment (study group) and 43 immunotherapy alone (controls). All patients had metastatic renal-cell carcinoma that had been histologically confirmed and was progressive at entry. In study patients, surgery was done within 4 weeks of randomisation, and immunotherapy (5x10(6) IU/m(2) subcutaneously three times per week) started 2-4 weeks later. In controls, immunotherapy was started within 1 working day of randomisation. Follow-up visits were monthly. All analyses were by intention to treat.\n 40 (53%) of 75 patients received at least 16 weeks of interferon-alfa treatment, which was also the median duration of treatment. Time to progression (5 vs 3 months, hazard ratio 0.60, 95% CI 0.36-0.97) and median duration of survival were significantly better in study patients than in controls (17 vs 7 months, 0.54, 0.31-0.94). Five patients responded completely to combined treatment, and one to interferon alfa alone. Dose modification was necessary in 32% of patients, most commonly because of non-haematological side-effects.\n Radical nephrectomy before interferon-based immunotherapy might substantially delay time to progression and improve survival of patients with metastatic renal cell carcinoma who present with good performance status.", "In a randomized study of advanced renal cell carcinoma 60 patients were allocated to treatment with either recombinant interferon alpha-2a or medroxyprogesterone acetate. Correlation between the dose of interferon alpha-2a and plasma-concentration indicated linear kinetics. Survival was similar in the two treatment groups. Only one complete and one partial response were seen in the interferon group and only one complete response in the medroxyprogesterone group, indicating a low therapeutic potential of both interferon and medroxyprogesterone. Interferon influenced the serum liver enzyme levels; increased transaminases were seen in 17 patients treated with interferon but in only four patients in the medroxyprogesterone group. Two patients had very high serum liver-enzyme levels concomitant with intolerable tiredness, in both patients the symptoms disappeared and the enzymes normalized after discontinuation of the interferon treatment. Antibodies to interferon developed frequently in patients receiving high dose oligomeric interferon therapy but rarely in patients receiving low dose monomeric interferon treatment.", "Conjugation of polyethylene glycol to recombinant human interleukin-2 (IL-2) results in a compound, polyethylene glycol-modified IL-2 (PEG-IL-2) that retains the in vitro and in vivo activity of IL-2, but exhibits a markedly prolonged circulating half-life. In mice, one dose of PEG-IL-2 results in tumor regression comparable to that achieved with multiple bolus doses of IL-2. Based on these preclinical studies, a Phase I study with PEG-IL-2 was undertaken in patients with metastatic renal cell carcinoma (RCC) and melanoma. Then, to exploit the higher peak levels attained with IL-2 and the improved trough levels of PEG-IL-2, a combination regimen beginning with bolus IL-2 followed by low dose maintenance PEG-IL-2 was devised and tested for efficacy.\n Patients with measurable metastatic melanoma or RCC were entered in a Phase I dose escalation trial of PEG-IL-2 given once a week by intravenous bolus. This trial then was repeated using a twice-a-week schedule. After determining the maximum tolerated dose (MTD) and a safe outpatient regimen for PEG-IL-2, a hybrid regimen combining an initial high dose IL-2 cycle followed by chronic maintenance with weekly PEG-IL-2 was devised. This regimen was compared with a standard regimen consisting of two cycles of high dose unconjugated IL-2 in a randomized prospective clinical trial.\n When given by intravenous bolus once a week, the MTD of PEG-IL-2 was 12 million IU/m2, with toxicities similar to those of unconjugated IL-2. A twice-a-week schedule was less well tolerated. Of 28 patients given 32 treatment courses at varied dose levels, there were two partial responses and one minor response. A total of 124 patients with metastatic melanoma or RCC were randomized to either standard unconjugated IL-2 therapy or the hybrid regimen. There was no treatment-related mortality in either arm, and the use of PEG-IL-2 resulted in a significant decrease in the need for intensive-care-unit care. The response rates (partial response and complete response) for patients with RCC and melanoma were 19% and 15%, respectively, for IL-2 alone and 17% and 11%, respectively, for the IL-2 and PEG-IL-2 combination.\n The combination of high dose IL-2 followed by PEG-IL-2 is a well tolerated regimen with significant activity against RCC and melanoma, but it shows no significant increase in antitumor activity compared with high dose IL-2 alone.", "nan", "Since 1985, multiple centers have demonstrated that interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells produce durable anticancer responses in patients with metastatic renal cell carcinoma. High-dose recombinant IL-2 (rIL-2) has been administered by intravenous bolus injection (Rosenberg SA, et al: N Engl J Med 313:1485-1492, 1985) and by continuous intravenous infusion (West WH, et al: N Engl J Med 316:898-905, 1987) combined with lymphokine-activated killer (LAK) cells, with both methods producing responses in patients with advanced renal cell carcinoma. The Extramural IL-2/LAK Working Group has conducted a randomized phase II trial of two intravenous high-dose rIL-2 regimens (bolus three times daily or 24-hour continuous infusion) to determine if either one manifests greater anticancer activity or a more acceptable toxicity profile.\n Ninety-four patients with measurable advanced renal cell carcinoma were enrolled on this study: 46 to the bolus injection arm and 48 to the continuous infusion arm. On both arms, patients underwent a priming phase of rIL-2 administration, four daily lymphocytaphereses to harvest mononuclear cells that were placed in 3- to 4-day culture for generation of LAK cells, and an rIL-2/LAK coadministration phase. Patients were then observed monthly for evidence of response to this therapy and were offered up to two additional courses of treatment every 3 months if evidence of response was detected.\n Twenty percent of patients on the bolus injection arm experienced objective responses (three complete responses and six partial responses); 15% of patients on the continuous infusion arm responded (two complete responses and five partial responses). Complete responses were durable, persisting for 310+ to 700+ days. The incidence of severe life-threatening toxicities typical of high-dose rIL-2 therapy was similar in both arms (eg, patients with hypotension requiring pressors: bolus 71%, continuous 63%; oliguria less than or equal to 200 mL/8 hours: bolus 65%, continuous 71%). More episodes of fever, infection, and serum alkaline phosphatase elevation were associated with the continuous infusion arm, while more thrombocytopenia occurred on the bolus injection arm. Four patients (three bolus injection, one continuous infusion) died of respiratory and circulatory failure while under treatment. No clinical or laboratory parameter accompanying treatment on either arm was, by univariate or multivariate analysis, associated with an increased likelihood of response.\n Both methods of high-dose rIL-2/LAK cell administration produce nearly equivalent anticancer activity and toxicity in the treatment of renal cell carcinoma. The ability to predict responding patients based on patient or treatment characteristics is not possible.", "A total of 178 patients with metastatic renal cell cancer were randomized to receive interferon alfa-2a (rIFN alfa-2a) or interferon alfa-2a+vinblastine (VLB). IFN alfa-2a was injected intramuscularly at a dose of 18 MIU 3 times a week and VLB was given intravenously at a dose of 0.1 mg/kg once every 3 weeks. The response rate was 11% for patients on monotherapy and 24% for those on combination treatment. The 5-year survival for 145 eligible patients was 9%, independently from the treatment arm. The performance status was significantly related to long-term prognosis, and 13% of the patients with performance status 0 were alive at 5 years, as compared to 6% and 0% for patients with a WHO grade of 1 and 2, respectively. The most frequent adverse events in both treatment arms were flu-like symptoms (95%), fatigue (70%) and gastrointestinal disturbances (68%). Leukopenia was observed more frequently with combination treatment (53%) than with IFN alfa-2a alone (30%). In conclusion, rIFN alfa-2a monotherapy at this dose and schedule has modest antitumor activity in metastatic renal cell cancer. The combination of rIFN alfa-2a+VLB results in a doubling of the response rate, but this does not translate into prolonged survival. Toxicity (except leukopenia) and tolerance were similar in both treatment arms.", "To assess the value of autolymphocyte therapy (ALT) in the treatment of metastatic renal-cell carcinoma, 90 patients were randomised to receive every month for six months oral cimetidine plus an infusion of autologous peripheral blood lymphocytes activated in vitro by a previously generated autologous lymphokine mixture, or cimetidine alone. The median follow-up was 15 months. Survival time for the autolymphocyte group was approximately 2.5 times that for the cimetidine group (p = 0.008). Patients who had greater than 500 pg interleukin-1 (IL-1) per ml autologous lymphokine mixture had a six-fold survival advantage over those with less than 500 pg/ml (p less than 0.00005). Men treated with ALT had a four-fold survival advantage (p = 0.001) over men who received cimetidine only. Infusion of the cultured autolymphocytes was accompanied by mild, self-limited fever in 11 of the 45 ALT patients, and by only one instance in which fever was accompanied by tachypnoea and hypotension.", "The purpose of the present study was to investigate the therapeutic effectiveness of interleukin-2 (IL-2) and interferon (IFN), either alone or in combination, in comparable groups of patients affected by advanced renal cell carcinoma (RCC).\n In order to limit selection biases, treatment was allocated on a random basis. Patients randomized to IL-2 alone were scheduled to receive eight rlL-2 24-hour i.v. infusion cycles, days 1 to 4, at a daily dose of 18 x 10(6) lU/m2 for a total of 25 weeks. Patients randomized to IFN alone were scheduled to receive rIFN-alpha at a daily dose of 6 x 10(6) IU/m2, days 1, 3 and 5, every week for a total of 52 weeks. Patients randomized to the combination of IFN and IL-2 were given the same drugs at the same daily doses for a total of 24 weeks. Drug dose was modified according to toxicity.\n Twenty-three percent (95% CI:+/-17.5) of patients treated with IL-2 alone showed an objective response to treatment (9% CR). The corresponding figures in patients treated with IFN alone or IFN plus IL-2 were 9% (95% CI:+/-11.9) and 9% (95% CI:+/-11.9), respectively. Complete responses were observed only in patients treated with IL-2. The median duration of response in the IL-2 arm was 18 months (range, 9.5-24). The duration of the two responses achieved by IFN alone was seven and nine months, respectively. The corresponding figures in the two patients responding to the combination of IFN with IL-2 were 19 and 27 months, respectively. Total IL-2 dose appeared to be a major predictor of response. Only a minority of patients experienced grade 3-4 toxicity, the incidence being higher in those treated with IL-2 or IL-2 plus IFN.\n Neither IFN nor IL-2 or the combination of the two appear to be very active in patients with advanced RCC, even when trial entry was restricted to patients with relatively indolent disease. This stresses the need for the development of new approaches.", "To evaluate the role of cytoreductive nephrectomy (CRN) in improving survival in patients with renal cell cancer.\n The case-notes of 268 consecutive patients who presented to our specialized renal cancer clinic between 1998 and 2001 were reviewed. All patients with metastatic disease were assessed for CRN. If their primary tumour was considered operable, they were assessed further using the European Cooperative Oncology Group performance score; only patients with a performance score of 0 or 1 were considered for surgery.\n In all, 168 patients underwent nephrectomy with curative intent for M0 disease and 11 were treated conservatively. Ninety-four patients with M+ disease (mean age 65 years, range 38-80) were considered for CRN. Thirty-eight patients had an inoperable primary. Of the remaining 56 patients, 20 had a performance status of 0 or 1 and were offered CRN.\n Metastatic disease at presentation occurred in 34% of all patients referred; 40% patients had an inoperable primary and 38% had a performance score of > or =2. With an active policy of considering all patients for CRN, only 7% of those with renal cancer were suitable for this procedure. CRN is unlikely to have a significant effect on overall survival within a population of patients with renal cancer.", "We performed a prospective, controlled trial of recombinant leukocyte A interferon (IFN-alpha 2A) with or without aspirin (ASA) in 176 patients with assessable advanced renal cell cancer in light of a 34% response rate (10 of 29 patients) from the two-agent regimen in an earlier nonrandomized trial. This encouraging result was substantially higher than the 15% response rate typically achieved with IFN therapy alone. Eighty-seven patients received IFN-alpha 2A 20 x 10(6) U/m2 intramuscularly three times a week, and 89 received the same IFN therapy with ASA 600 mg orally four times each day. Each group was balanced as to relevant prognostic discriminants. Response rates were 8% for the group receiving ASA in addition to IFN, and 13% for the group receiving IFN alone (P = .30). The median times to progression were 1.9 months for the group receiving IFN with ASA and 2.7 months for the group receiving IFN alone (log-rank P = .36). The median survival durations were 8.8 months for the IFN and ASA group and 8.0 months for the IFN-only group (log-rank P = .60). These figures are also inferior to those typically reported from other studies. Our findings reemphasize the crucial role of randomized trials, admittedly cumbersome and time-consuming, to determine accurately the value of apparently promising therapies. Although some patients may derive benefit from IFN therapy, our findings raise disturbing questions regarding the potential IFN-alpha 2A according to the dose and schedule used in this trial to have any substantive impact on the ultimate outcome of disseminated renal cell cancer.", "The outcome of treatment of advanced renal cell carcinoma is disappointing. In interferon (IFN)-treated patients, the high incidence of adverse effects causes many patients to withdraw from treatment. This 12-week randomized study compared the incidence of toxicity associated with high-dose IFN monotherapy (15 x 10(6) U thrice weekly) and treatment with the combination of low-dose IFN (5 x 10(6) U thrice weekly) and 6 mg/m2 vinblastine (VBL) every 14 days in 100 consecutive patients. There was no significant difference in response rate between treatment arms (42% IFN vs. 34% IFN + VBL) or between subgroups (by tumor location). Combined treatment was associated with a significantly lower incidence of fever, fatigue, and weight loss but with a higher incidence of leukopenia. There was no significant difference in the incidence of other events. More patients treated with IFN monotherapy required bed rest, and overall treatment costs were 60% higher than for combined treatment. It is concluded that combined treatment with low-dose IFN and VBL, without loss of short-term efficacy, is better tolerated and less expensive than high-dose IFN monotherapy.", "To prospectively evaluate in a multicenter randomized trial the antitumor activity of CD8(+) tumor-infiltrating lymphocytes (TILs) in combination with low-dose recombinant interleukin-2 (rIL-2), compared with rIL-2 alone, after radical nephrectomy in metastatic renal cell carcinoma patients.\n Between December 1994 and March 1997, 178 patients with resectable primary tumors were enrolled at 29 centers in the United States and Europe. Patients underwent total nephrectomy, recovered, and were randomized to receive either CD8(+) TILs (5 x 10(7) to 3 x 10(10) cells intravenously, day 1) plus rIL-2 (one to four cycles: 5 x 10(6) IU/m(2) by continuous infusion daily for 4 days per week for 4 weeks) (TIL/rIL-2 group) or placebo cell infusion plus rIL-2 (identical regimen) (rIL-2 control group). Primary tumor specimens were cultured at a central cell-processing center in serum-free medium containing rIL-2 to generate TILs.\n Of 178 enrolled patients, 160 were randomized (TIL/rIL-2 group, n = 81; rIL-2 control group, n = 79). Twenty randomized patients received no treatment after nephrectomy because of surgical complications (four patients), operative mortality (two patients), or ineligibility for rIL-2 therapy (14 patients). Among 72 patients eligible for TIL/rIL-2 therapy, 33 (41%) received no TIL therapy because of an insufficient number of viable cells. Intent-to-treat analysis demonstrated objective response rates of 9.9% v 11.4% and 1-year survival rates of 55% v 47% in the TIL/rIL-2 and rIL-2 control groups, respectively. The study was terminated early for lack of efficacy as determined by the Data Safety Monitoring Board.\n Treatment with CD8(+) TILs did not improve response rate or survival in patients treated with low-dose rIL-2 after nephrectomy.", "Despite the efficacy of IL-2 in the treatment of metastatic renal cell carcinoma (RCC), the prognosis of patients with synchronous metastases still remains poor. Nephrectomy itself, as well as other surgical operations, may further suppress the antitumor immune response. Previous studies suggested that the preoperative injection of IL-2 may neutralize surgery-induced lymphocytopenia in advanced colon cancer. On this basis, a pilot randomized study was performed in an attempt to evaluate the effects of a preoperative administration of IL-2 on postoperative lymphocyte numbers and on the survival in advanced RVV patients with more than 3 synchronous metastases. The study included 20 consecutive patients, who were randomized to receive nephrectomy alone or nephrectomy plus preoperative subcutaneous immunotherapy with IL-2 (18 million IU/day for 3 days). Then, all patients underwent postoperative immunotherapy with IL-2 (6 million IU/day for 5 days/week for 6 weeks). Surgery-induced lymphocytopenia was completely abolished by IL-2 preoperative injection. The frequency of postoperative complications was significantly higher in controls than in patients preoperatively treated with IL-2. On the contrary, significant differences between control and patients preoperatively treated with IL-2 were observed neither in the clinical response to IL-2 immunotherapy, nor in the percent of 1-year survival. The results of this preliminary pilot study would suggest that IL-2 preoperative immunotherapy may neutralize surgery-induced lymphocytopenia and reduce the postoperative complications in RCC patients with synchronous metastases, without, however, influencing their prognosis in terms of survival time.", "Recombinant human interleukin-2 (IL-2) has a well-documented anti-tumor activity against RCC and has demonstrated a synergistic anti-tumor activity between doxorubicin and IL-2, thus providing better survival. This study investigated the toxicity and efficacy of the association between doxorubicin and IL-2, and interferon-alpha, and the immuno-chemotherapeutic association with IL-2 and 4-Epirubicin.\n Patients with histologic evidence of metastatic or advanced RCC were randomized to receive either IL-2 + IFN-alpha (Arm A) or IL-2 + 4-Epi (Arm B). Arm A patients received IFN-alpha subcutaneously at doses of 3 million UI on days 1, 3 and 5 for 6 weeks. Arm B patients received 4-EPI at doses of 25 mg/m2 on days 1, 8, 15, 22, 29 and 36. Treatment cycles were repeated at 10 week intervals.\n Of 38 evaluable patients, we observed 2 complete responses, 2 partial responses, 1 minimal response, 1 mixed response, 21 stationary disease and 11 disease progressions. There was no significant difference in overall survival between the two groups. However in arm B, the median overall survival for responding patients was better than that of patients who experienced a disease progression. Performance status was the only predictive prognostic factor.\n Our analysis confirms the low response rate associated with IL-2 treatments but seems to indicate a role of anthracycline in improving the survival of responding patients with an acceptable toxicity.", "Early results of a prospective, randomized trial of active, specific immunotherapy adjunctive to nephrectomy in all stages of RCC are presented. Forty-three patients with median followup of 30 m, who were randomly allocated to either immuno-hormonotherapy arm (IMT), or hormonotherapy alone (HT), are evaluated in terms of progression-free interval (PFI) and overall survival by life table method. Immunotherapy consisted of autologous irradiated tumor cells (AITC), admixed with bacillus Calmette-Guérin (Glaxo) administered by the intradermal and endolymphatic route. Clinical results of this study show only a trend for advantage of the experimental (IMT) arm over the control (HT) arm, this trend did not reach statistical significance level: prolongation of disease free period in stages I-III with localized disease (p less than 0.1) and prolongation of survival in patients with metastatic disease (p less than 0.07). A correlation was established between induction of cutaneous delayed hypersensitivity (DTH) to AITC and prolonged PFI and survival: patients with positive DTH had a significantly better course of disease than those who could not be converted to positivity after repeated immunizations. Positive in vitro leukocyte migration inhibition against autologous tumor preparations correlates well with positive in vivo cutaneous DTH. Some immunological aspects of active immunization with autologous tumor cells are discussed.", "Treatment with interleukin-2 (IL-2) and lymphokine-activated killer cells (LAK) resulted in responses in some patients with advanced renal cell carcinoma (RCC). However, the relative therapeutic benefit of the addition of LAK to IL-2 was unknown.\n A randomized Phase III trial was conducted in patients with RCC comparing continuous intravenous infusion (CI) IL-2 alone with CI IL-2 plus LAK. Interleukin-2 was administered at 3 x 10(6) U/m2/day on days 1-5, 13-17, 21-24, and 28-31. Patients on the LAK treatment arm underwent leukapheresis on days 8-10 and LAK cell reinfusion on days 13-15. The results are reported with long-term follow-up. The published experience with IL-2 alone or with the addition of LAK was investigated in a quantitative literature survey. The response proportions were studied by schedule (high dose bolus, moderate dose, low dose) and by concomitant administration of LAK.\n Seventy-one patients were treated, 36 on the IL-2 arm and 35 on the IL-2 plus LAK arm. Four patients (6%) had major responses (two complete, two partial). The median survival of all patients was 13 months (95% confidence interval [CI], 9-18 months). There were no differences between treatment arms with regard to response (P = 0.61) and survival (P = 0.67). More patients on the LAK arm experienced pulmonary toxicity (P = 0.008). The overall weighted response proportion was 16% (95% CI, 8%-24%) for the 39 published series of 1291 patients treated with IL-2. The 95% confidence intervals for response proportion overlapped when compared by schedule and by administration of LAK.\n The dose and schedule of IL-2 used in this study resulted in a low level of antitumor activity and the addition of LAK did not improve the response rate against RCC. Given the infrequent, but reproducible, responses with IL-2 and interferon-based regimens, continued investigation of these agents is warranted as is the study of new cytokines. Alternative treatment strategies should be studied in RCC and new agents and treatment regimens that appear promising in Phase II studies must be studied in randomized trials." ]

[ "12033074", "11399136", "15208209" ]

[ "Cup or bottle for preterm infants: effects on oxygen saturation, weight gain, and breastfeeding.", "A pilot study to assess the viability of a randomised controlled trial of methods of supplementary feeding of breast-fed pre-term babies.", "Effect of bottles, cups, and dummies on breast feeding in preterm infants: a randomised controlled trial." ]

[ "The impact of cup-feeding or bottle-feeding on weight gain, oxygen saturation, and breastfeeding rates of preterm infants was studied in 34 bottle-fed and 44 cup-fed preterm infants. At initiation of oral feeding, postconceptional age and weight were 37.2 +/- 2.2 weeks and 1676 +/- 83 g for the bottle-fed group (BF) and 37.0 +/- 1.6 weeks and 1637 +/- 40 g for the cup-fed (CF) group, respectively. No significant differences between groups were found with regard to time spent feeding, feeding problems, weight gain, or breastfeeding prevalence at discharge or at 3-month follow-up. Possible beneficial effects of cup-feeding were lower incidence of desaturation episodes (13.6% vs 35.3%, CF vs BF, P = .024) and a higher prevalence of breastfeeding at 3 months among those still breastfeeding at the first follow-up visit (68.4% vs 33.3%, CF vs BF, P = .04).", "to compare the impact of two methods of supplementary feeding of pre-term babies (bottle vs cup) on subsequent breast feeding and to assess the feasibility of using a randomised controlled trial (RCT) to investigate the topic.\n small scale prospective RCT. Data on breast feeding, as defined as the exclusive method of feeding, were collected. A range of relevant bio-data was also collected and their impact on breast feeding assessed.\n a special care baby unit in a District General Hospital in the UK.\n over a three-month period, all pre-term babies (32-37 weeks' gestation) who fulfilled the inclusion criteria and has been born to mothers who had expressed a pre-partum desire to breast feed, who had consented to take part, were included (n=14).\n the eligible babies were randomly allocated to supplementary feeding of breast milk, via either a cup or a bottle. Whether or not the baby was being breast fed at discharge was noted.\n the study suggested that this RCT framework is a viable method of investigating baby feeding. Because of the small-scale nature of the project, the actual database must be treated with extreme caution. No significant differences were found between the two groups in terms of breast feeding. However, the mothers reported high levels of support and also the breast-feeding rates were above the national averages. These two findings could have contributed to the non-significant results observed in this analysis.\n if the present findings could be supported by further research, then the non-significant results relating method of supplementary feeds to subsequent breast feeding could be explained by reference to three factors. Firstly, there is, in fact, no real effect of method of supplementary feeding and subsequent breast feeding; secondly, the method adopted differed from existing research and thus may be expected to produce non-corroborative results; and finally, the overall levels of breast feeding within the Unit generally were higher than the national average. The relevance of the RCT for investigating this subject is also discussed with reference to the present data set. Further experimental work to develop these ideas and to identify causal links is required.\n Copyright 2001 Harcourt Publishers Ltd.", "To determine the effect of artificial teats (bottle and dummy) and cups on breast feeding in preterm infants.\n Randomised controlled trial.\n Two large tertiary hospitals, 54 peripheral hospitals.\n 319 preterm infants (born at 23-33 weeks' gestation) randomly assigned to one of four groups: cup/no dummy (n = 89), cup/dummy (n = 72), bottle/no dummy (n = 73), bottle/dummy (n = 85). Women with singleton or twin infants < 34 weeks' gestation who wanted to breastfeed were eligible to participate.\n Cup or bottle feeding occurred when the mother was unable to be present to breast feed. Infants randomised to the dummy groups received a dummy on entry into the trial.\n Full breast feeding (compared with partial and none) and any breast feeding (compared with none) on discharge home. Secondary outcomes: prevalence of breast feeding at three and six months after discharge and length of hospital stay.\n 303 infants (and 278 mothers) were included in the intention to treat analysis. There were no significant differences for any of the study outcomes according to use of a dummy. Infants randomised to cup feeds were more likely to be fully breast fed on discharge home (odds ratio 1.73, 95% confidence interval 1.04 to 2.88, P = 0.03), but had a longer length of stay (hazard ratio 0.71, 0.55 to 0.92, P = 0.01).\n Dummies do not affect breast feeding in preterm infants. Cup feeding significantly increases the likelihood that the baby will be fully breast fed at discharge home, but has no effect on any breast feeding and increases the length of hospital stay." ]

[ "8498878", "11476129", "12858327" ]

[ "A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder.", "Clomipramine versus haloperidol in the treatment of autistic disorder: a double-blind, placebo-controlled, crossover study.", "Tianeptine: a novel strategy of psychopharmacological treatment of children with autistic disorder." ]

[ "To determine whether clomipramine hydrochloride, a serotonin reuptake blocker with unique anti-obsessional properties, is differentially effective for obsessive-compulsive and stereotyped motor behaviors in autistic disorder compared with placebo and with the noradrenergic tricyclic antidepressant agent, desipramine hydrochloride.\n Following a 2-week, single-blind placebo washout phase, 12 autistic subjects completed a 10-week, double-blind, crossover comparison of clomipramine and placebo, and 12 different subjects completed a similar comparison of clomipramine and desipramine.\n Outpatient clinic.\n A referral sample of 30 male and female autistic patients were enrolled, and 24 completed the study.\n Key outcome measures were the Autism Relevant Subscale of the Children's Psychiatric Rating Scale, the Modified Comprehensive Psychopathological Rating Scale-Obsessive-Compulsive Disorder Subscale, and the Clinical Global Impressions Scale.\n Clomipramine was superior to both placebo and desipramine on ratings of autistic symptoms (including stereotypies), anger, and compulsive, ritualized behaviors (P < .05), with no differences between desipramine and placebo. Clomipramine was equal to desipramine and both tricyclic agents were superior to placebo for amelioration of hyperactivity.\n Biological links between compulsions and stereotyped, repetitive behaviors in autistic disorder should be explored.", "Clomipramine, haloperidol, and placebo were compared with baseline in the treatment of autism, and overall outcome, specific symptoms, and side effects were examined. It was hypothesized that clomipramine would be better tolerated than haloperidol and prove superior on a measure of stereotypy. Individuals with a DSM-IV diagnosis of autistic disorder (mean age, 16.3 years; range, 10-36 years) were randomly assigned, by using a Latin square design, to the following 7-week trials: placebo, clomipramine (mean daily dose, 128.4 mg; range, 100-150 mg), or haloperidol (mean daily dose, 1.3 mg; range, 1-1.5 mg). Data on 36 subjects were analyzed and taken together; the results favored haloperidol. In those patients who were able to complete a full therapeutic trial, clomipramine proved comparable to haloperidol in terms of improvement compared with baseline. However, significantly fewer individuals receiving clomipramine versus haloperidol were able to complete the trial (37.5% vs. 69.7%, respectively) for reasons related to both side effects and efficacy or behavior problems. In the intent-to-treat sample, which is perhaps more clinically relevant, only haloperidol proved superior to baseline on a global measure of autistic symptom severity, as well as specific measures for irritability and hyperactivity. Clomipramine did not seem more effective on a measure of stereotypy, nor was it better tolerated.", "Many autistic children have problems of eye contact and expressive language that limit the effectiveness of educational and behavioural interventions. Few controlled psychopharmacological trials have been conducted in autistic children to determine which agents may be effective for these associated features.\n Twelve male children (7.3 +/- 3.3 years) with autistic disorder, diagnosed by ICD-10 criteria, completed a placebo-controlled, double-blind crossover trial of tianeptine, which lasted for 12 weeks. Subjects were included in the study if their eye contact and expressive language was inadaequate for their developmental level. Subjects had not tolerated or responded to other psychopharmacological treatments (neuroleptics, methylphenidate, clonidine or desipramine).\n Teacher ratings on the aberrant behaviour checklist irritability, stereotypy and inappropriate speech factors were lower during treatment with tianeptine than during treatment with placebo. Clinician ratings (children's psychiatric rating scale autism, anger and speech deviance factors; children's global assessment scale; clinical global impressions efficacy) of videotaped sessions were not significantly different between tianeptine and placebo.\n Tianeptine were modestly effective in the short-term treatment of irritability in some children with autistic disorder.\n Copyright 2003 John Wiley & Sons, Ltd." ]

[ "20833591", "18456558" ]

[ "Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, double-blind, randomised non-inferiority trial.", "Cilostazol as an alternative to aspirin after ischaemic stroke: a randomised, double-blind, pilot study." ]

[ "The antiplatelet drug cilostazol is efficacious for prevention of stroke recurrence compared with placebo. We designed the second Cilostazol Stroke Prevention Study (CSPS 2) to establish non-inferiority of cilostazol versus aspirin for prevention of stroke, and to compare the efficacy and safety of cilostazol and aspirin in patients with non-cardioembolic ischaemic stroke.\n Patients aged 20-79 years who had had a cerebral infarction within the previous 26 weeks were enrolled at 278 sites in Japan and allocated to receive 100 mg cilostazol twice daily or 81 mg aspirin once daily for 1-5 years. Patients were allocated according to a computer-generated randomisation sequence by means of a dynamic balancing method using patient information obtained at registration. All patients, study personnel, investigators, and the sponsor were masked to treatment allocation. The primary endpoint was the first occurrence of stroke (cerebral infarction, cerebral haemorrhage, or subarachnoid haemorrhage). The predefined margin of non-inferiority was an upper 95% CI limit for the hazard ratio of 1·33. Analyses were by full-analysis set. This trial is registered with ClinicalTrials.gov, number NCT00234065.\n Between December, 2003, and October, 2006, 2757 patients were enrolled and randomly allocated to receive cilostazol (n=1379) or aspirin (n=1378), of whom 1337 on cilostazol and 1335 on aspirin were included in analyses; mean follow-up was 29 months (SD 16). The primary endpoint occurred at yearly rates of 2·76% (n=82) in the cilostazol group and 3·71% (n=119) in the aspirin group (hazard ratio 0·743, 95% CI 0·564-0·981; p=0·0357). Haemorrhagic events (cerebral haemorrhage, subarachnoid haemorrhage, or haemorrhage requiring hospital admission) occurred in fewer patients on cilostazol (0·77%, n=23) than on aspirin (1·78%, n=57; 0·458, 0·296-0·711; p=0·0004), but headache, diarrhoea, palpitation, dizziness, and tachycardia were more frequent in the cilostazol group than in the aspirin group.\n Cilostazol seems to be non-inferior, and might be superior, to aspirin for prevention of stroke after an ischaemic stroke, and was associated with fewer haemorrhagic events. Therefore, cilostazol could be used for prevention of stroke in patients with non-cardioembolic stroke.\n Otsuka Pharmaceutical.\n Copyright © 2010 Elsevier Ltd. All rights reserved.", "Most patients who have had a stroke are given aspirin; however, aspirin-related cerebral haemorrhage is a complication that is currently of concern, particularly in China where there is a high incidence of cerebral haemorrhage in secondary prevention programmes and within the community. Cilostazol, a phosphodiesterase 3 (PDE3) inhibitor, is an alternative to aspirin that works through a different mechanism. This trial aimed to compare the efficacy and safety of cilostazol with that of aspirin for the long-term prevention of the recurrence of ischaemic stroke.\n 720 patients (mean age 60.2 years, SD 9.86) who had had an ischaemic stroke within the previous 1-6 months were enrolled consecutively in a prospective, multicentre, double-blind, randomised trial. 360 patients were randomly assigned to receive cilostazol and 360 patients to receive aspirin. Analysis was by intention to treat. Patients in both groups took the medication for 12-18 months. The primary endpoint was any recurrence of stroke (ischaemic stroke, haemorrhagic stroke, or subarachnoid haemorrhage) during the trial period. All patients had MRI with T1 MRI, T2 MRI, diffusion-weighted imaging (DWI), T2 fluid-attenuated inversion recovery (FLAIR), and T2 gradient echo imaging (T2*) at the beginning and the end of the study. This trial is registered with ClinicalTrials.gov, number NCT00202020.\n The average duration of treatment was 740 person-years, and 719 patients were analysed (360 in the cilostazol group and 359 in the aspirin group). The primary endpoint was reported in 12 patients in the cilostazol group and in 20 patients in the aspirin group. The estimated hazard ratio, calculated with Kaplan-Meier curves (risk of primary endpoint in cilostazol group vs aspirin group), was 0.62 (95% CI 0.30-1.26; p=0.185). Symptomatic cerebral haemorrhage was reported in six patients: one in the cilostazol group and five in the aspirin group. Asymptomatic cerebral haematoma was found in four patients in the aspirin group and one patient in the cilostazol group. Brain bleeding events were significantly more common in the aspirin group than in the cilostazol group (7 vs 1, p=0.034). All of the six patients with symptomatic haemorrhage had previous cerebral microbleeds in the area where the haematoma was located.\n The results of this pilot study showed no significant difference in the rate of recurrence of stroke between patients with ischaemic stroke who were randomly assigned to take either cilostazol or aspirin. The lower rates of ischaemic and haemorrhagic stroke in the cilostazol group suggest that cilostazol might be a more effective and safer alternative to aspirin for Chinese patients with ischaemic stroke; however, a larger phase III trial is required to confirm this.\n National Health Ministry of the People's Republic of China; Otsuka Pharmaceutical." ]

[ "17023707", "6315514" ]

[ "Effect of a low-glycemic-index diet during pregnancy on obstetric outcomes.", "A controlled trial of a high dietary fibre intake in pregnancy--effects on plasma glucose and insulin levels." ]

[ "Pregnancy is a condition in which the glycemic index (GI) may be of particular relevance because maternal glucose is the main energy substrate for intrauterine growth.\n The aim was to compare the effects of low-GI and conventional dietary strategies on pregnancy outcomes in healthy women. Compliance and acceptability were also investigated.\n The subjects were assigned alternately to receive dietary counseling that encouraged either low-GI (LGI) carbohydrate foods or high-fiber, moderate-to-high GI (HGI) foods and were studied 5 times between <16 wk gestation and delivery. Of the 70 women who met the inclusion criteria, 62 completed the study (32 in the LGI and 30 in the HGI groups). Primary outcomes were measures of fetal size.\n The mean diet GI fell significantly in the LGI group but not in the HGI group. Compared with the LGI group, women in the HGI group gave birth to infants who were heavier (3408 +/- 78 compared with 3644 +/- 90 g; P = 0.051) and had a higher birth centile (48 +/- 5 compared with 69 +/- 5; P = 0.005), a higher ponderal index (2.62 +/- 0.04 compared with 2.74 +/- 0.04; P = 0.03), and a higher prevalence of large-for-gestational age (3.1% compared with 33.3%; P = 0.01). Women in the LGI group found the diet easier to follow.\n Because birth weight and ponderal index may predict chronic disease in later life, a low-GI diet may favorably influence long-term outcomes.", "Non-obese women in the second half of pregnancy were randomised into a control group receiving standard dietary advice and a group advised to make high fibre whole-food substitutions in their diets at every opportunity. Glucose and insulin profiles were performed over 24-h periods at 29 and 35 weeks gestation when the diets were equivalent in available carbohydrate, protein and fat, but the control group ingested 12.4 g dietary fibre/24 h and the high fibre group 51.4 g/24 h. Glucose homeostasis was similar in both groups but there was a significant attenuation of post-prandial insulin secretion in the high fibre group. It is suggested that the characteristic post-prandial peaks of plasma insulin observed in Western pregnant women are an unphysiological response to dietary fibre depletion." ]

[ "11515714", "15917266" ]

[ "Double-blind, placebo-controlled, randomised cross-over clinical trial of NIPRISAN in patients with Sickle Cell Disorder.", "Clinical evaluation of extract of Cajanus cajan (Ciklavit) in sickle cell anaemia." ]

[ "The study was undertaken to determine the safety and efficacy of NIPRISAN, a phytomedicine, developed for the management of patients with Sickle Cell Disorder (SCD). The study design is a placebo-controlled double blind cross-over trial. Eighty-two (82) patients with SCD were recruited and randomised into two groups. An initial 4 month pre-trial study was undertaken to determine the similarity of the groups. The main study was conducted over a twelve-month period with crossover at six months. Safety of the drug was assessed clinically and biochemically. NIPRISAN significantly (P < 0.01) reduced the frequency of SCD crisis associated with severe pains. Acute toxicity to the liver assessed by the activities of liver enzymes, indicate that NIPRISAN is safe. Renal function assessed by the serum levels of creatinine and blood urea nitrogen remained normal. Both the clinical and laboratory results of the present phase IIB (pivot) clinical study suggest that NIPRISAN is a safe and efficacious phytomedicine for the management of patients with Sickle Cell Disorder.", "The major pathology in sickle cell anaemia (SCA) is sickling of red cells due to the precipitation of reduced haemoglobin. We report our experience with extract of Cajanus cajan as a possible antisickling agent by determining changes, if any, in clinical and laboratory features of the disease in patients given the extract in a single-blind placebo-controlled study. One hundred patients with steady-state SCA were randomized into treatment and placebo arms. The extract/placebo were administered twice daily to the subjects. Weight, hepatosplenomegaly, blood levels of biliurubin, urea, creatinine, and packed cell volume (PCV) were monitored over a 6-month period. Recall episodes of pain 6 months before enrolment were compared with episodes of pains recorded during the treatment period. Twenty-six cases (55.3 per cent) had hepatomegaly on enrolment. This significantly reduced to 33.3 per cent at 6 months (p = 0.03); but increased in the placebo arm (p > 0.05). The total number of recall painful episodes in cases was 207 (mean 4.4 +/- 10.3 (SD), range 0-60) and fell to 191 (mean 4.2 +/- 4.4 (SD), range 0-16); p = 0.03. Episodes of pain increased from 109 in controls (mean 2.6 +/- 5.0 (SD), range 0-26) to 164 (mean 3.9 +/- 4.3 (SD), range 0-22); p = 0.01. Mean PCV in the cases showed no appreciable changes (p = 0.1) but there was a significant increase in the controls (p = 0.02). In conclusion, the extract may cause a reduction of painful crises and may ameliorate the adverse effects of sickle cell anaemia on the liver. The mechanism of action remains to be determined." ]

[ "16101608", "19833454", "16934269", "11002954", "19757270", "7977546", "10519433", "21130446", "18001447", "19628206", "19277690", "18338474", "10432138", "12389002", "12738151", "11336714", "16343498", "16195287", "16271721", "15464767", "21130990", "11883025", "12738159", "16940738", "11002953", "12623474", "9512323", "15225189", "9790395", "15572491", "15902121", "21176086", "19902675", "7901080", "7732799", "18834340", "17321529", "12196880", "11577783", "11787915", "19249048", "16764879", "20043525", "20420283", "19249659", "16126208", "17825135", "2403792", "1873241", "11728483", "11641670", "17027730", "11551574", "10687755", "10426235", "8717567", "11455810", "16762355", "9763047" ]

[ "Misoprostol in the management of the third stage of labour in the home delivery setting in rural Gambia: a randomised controlled trial.", "[Benefit of misoprostol for prevention of postpartum hemorrhage in cesarean section: a randomized controlled trial].", "Oral misoprostol vs. intravenous oxytocin in reducing blood loss after emergency cesarean delivery.", "A double-blind placebo controlled randomised trial of misoprostol and oxytocin in the management of the third stage of labour.", "The effect of sublingual misoprostol versus intravenous oxytocin in reducing bleeding after caesarean section.", "A prospective, double-blind, randomized comparison of prophylactic intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, and intravenous oxytocin, 20 units, for the control of blood loss at elective cesarean section.", "Misoprostol compared with methylergometrine for the prevention of postpartum haemorrhage: a double-blind randomised trial.", "A double-blind, randomized, placebo-controlled trial of misoprostol and routine uterotonics for the prevention of postpartum hemorrhage.", "Oral misoprostol for the prevention of primary post-partum hemorrhage during third stage of labor.", "Comparison of sublingual misoprostol, intravenous oxytocin, and intravenous methylergometrine in active management of the third stage of labor.", "A randomized controlled trial of prophylactic sublingual misoprostol versus intramuscular methyl-ergometrine versus intramuscular 15-methyl PGF2alpha in active management of third stage of labor.", "A study of prophylactic use of 15-methyl prostalglandin F2alpha in the active management of third stage of labour.", "Oral misoprostol for third stage of labor: a randomized placebo-controlled trial.", "Is rectal misoprostol really effective in the treatment of third stage of labor? A randomized controlled trial.", "Oral misoprostol for the third stage of labor: a randomized controlled trial.", "Misoprostol for prevention of postpartum hemorrhage.", "Sublingual misoprostol versus oxytocin infusion to reduce blood loss at cesarean section.", "Effect of sublingual misoprostol on severe postpartum haemorrhage in a primary health centre in Guinea-Bissau: randomised double blind clinical trial.", "Oral misoprostol in the third stage of labor.", "Sublingual misoprostol versus methylergometrine for active management of the third stage of labor.", "Administration of 400 μg of misoprostol to augment routine active management of the third stage of labor.", "[Role of misoprostol in the delivery outcome].", "Pharmacokinetics and adverse-effect profile of rectally administered misoprostol in the third stage of labor.", "A double-blind randomized controlled trial of oral misoprostol and intramuscular syntometrine in the management of the third stage of labor.", "The misoprostol third stage of labour study: a randomised controlled comparison between orally administered misoprostol and standard management.", "A randomised controlled trial of misoprostol versus oxytocin in the active management of the third stage of labour.", "Randomized comparison of rectal misoprostol with Syntometrine for management of third stage of labor.", "A pilot-randomized comparison of sublingual misoprostol with syntometrine on the blood loss in third stage of labor.", "Rectal misoprostol in the prevention of postpartum hemorrhage: a placebo-controlled trial.", "Buccal misoprostol to decrease blood loss after vaginal delivery: a randomized trial.", "Buccal misoprostol to prevent hemorrhage at cesarean delivery: a randomized study.", "Administration of misoprostol by trained traditional birth attendants to prevent postpartum haemorrhage in homebirths in Pakistan: a randomised placebo-controlled trial.", "[Intrauterine misoprostol for the prevention of bleeding cesarean].", "Carboprost trometamol in the management of the third stage of labor.", "Preventing the recurrence of atonic postpartum hemorrhage: a double-blind trial.", "Low-dose sublingual misoprostol versus methylergometrine for active management of the third stage of labor.", "Misoprostol versus oxytocin for the reduction of postpartum blood loss.", "Randomized controlled trial of rectal misoprostol versus oxytocin in third stage management.", "A prospective randomised trial to compare the efficacy and safety of hemabate and syntometrine for the prevention of primary postpartum haemorrhage.", "Active management of the third stage at caesarean section: a randomised controlled trial of misoprostol versus syntocinon.", "Rectal misoprostol versus intravenous oxytocin for prevention of postpartum hemorrhage.", "Rectal misoprostol vs. 15-methyl prostaglandin F2alpha for the prevention of postpartum hemorrhage.", "A randomized comparison of rectal misoprostol with syntometrine on blood loss in the third stage of labour.", "Dinoprostone vaginal insert versus intravenous oxytocin to reduce postpartum blood loss following vaginal or cesarean delivery.", "Randomized double masked trial of Zhi Byed 11, a Tibetan traditional medicine, versus misoprostol to prevent postpartum hemorrhage in Lhasa, Tibet.", "Oral misoprostol versus injectable methylergometrine in management of the third stage of labor.", "Rectal misoprostol versus oxytocin in the management of the third stage of labour.", "Prophylactic intramyometrial carboprost tromethamine does not substantially reduce blood loss relative to intramyometrial oxytocin at routine cesarean section.", "A randomized comparison of oxytocin, sulprostone and placebo in the management of the third stage of labour.", "Misoprostol versus oxytocin in the third stage of labor.", "Rectal misoprostol versus intravenous oxytocin for the prevention of postpartum hemorrhage after vaginal delivery.", "Oral misoprostol in preventing postpartum haemorrhage in resource-poor communities: a randomised controlled trial.", "WHO multicentre randomised trial of misoprostol in the management of the third stage of labour.", "A randomized clinical trial comparing oral misoprostol with synthetic oxytocin or syntometrine in the third stage of labour.", "Misoprostol dose-related shivering and pyrexia in the third stage of labour. WHO Collaborative Trial of Misoprostol in the Management of the Third Stage of Labour.", "A randomized controlled study of prostaglandin 15-methyl F2 alpha compared with syntometrine for prophylactic use in the third stage of labour.", "Side-effects of oral misoprostol in the third stage of labour--a randomised placebo-controlled trial.", "Evaluation of two uterotonic medications for the management of the third stage of labor.", "A randomised placebo controlled trial of oral misoprostol in the third stage of labour." ]

[ "To assess the effectiveness of 600 microg oral misoprostol on postpartum haemorrhage (PPH) and postpartum anaemia in a low income country home birth situation.\n Double blind randomised controlled trial.\n Twenty-six villages in rural Gambia with 52 traditional birth attendants (TBAs).\n One thousand, two hundred and twenty-nine women delivering at home under the guidance of a trained TBA.\n Active management of the third stage of labour using three 200-microg misoprostol tablets and placebo or four 0.5-mg ergometrine tablets (standard treatment) and placebo. Tablets were taken orally immediately after delivery.\n Measured blood loss, postpartum haemoglobin (Hb), difference between Hb at the last antenatal care visit and three to five days postpartum.\n The misoprostol group experienced lower incidence of measured blood loss > or =500 mL and postpartum Hb <8 g/dL, but the differences were not statistically significant. The reduction in postpartum (compared with pre-delivery) Hb > or = 2 g/dL was 16.4% with misoprostol and 21.2% with ergometrine [relative risk 0.77; 95% confidence interval (CI) 0.60-0.98; P= 0.02]. Shivering was significantly more common with misoprostol, while vomiting was more common with ergometrine. Only transient side effects were observed.\n Six hundred micrograms of oral misoprostol is a promising drug to prevent life-threatening PPH in this setting.", "To assess the benefit of sublingual misoprostol in addition to standard oxytocin in the prevention of post-partum hemorrhage at caesarean section.\n This was a prospective randomized controlled clinical trial conducted from March to June 2007 at our department of obstetrics-Sousse-Tunisia, including 250 single low risk pregnant women undergoing caesarean section at gestational age>32 weeks gestation. Patients were randomly assigned to receive at cord clamping either sublingual 200microg misoprostol (Cytotec) with 20UI intravenous oxytocin (Oxytocin): bolus 10UI and infusion 10UI in 500ml Ringer Lactate): Group I, or only oxytocin at the same dose: Group II. The main outcome was total blood loss assessed by decrease in perioperative hematocrit. Secondary outcomes included measured collected blood loss, drop in hemoglobin level, additional oxytocin, side-effects and postoperative complications.\n The two groups were similar in demographic and obstetrical patient characteristics. Drop in hematocrit was more important in group II than in group I: 4.30%+/-3.14 versus. 1.10%+/-3.25; P=0.013. Drop in hemoglobin level was also more important in group II than in group I: 1.03g/dl+/-1.19 versus 0.54g/dl+/-1.17; P<0.01. Collected blood loss was less important in group I than in group II: 669.68cc+/-333.01 versus 852.52cc+/-295.08 ; P<0.01. Need for additional oxytocin and postoperative complications rate were more frequent in group II than in group I but the differences weren't significant. The rate of transient shivering, nausea and fever was significantly higher among women receiving misoprostol.\n Sublingual misoprostol (in addition to oxytocin) is effective in prevention of post-partum hemorrhage at caesarean sections when compared to oxytocin alone, without major side-effects. Larger studies are needed to confirm our results.", "To compare the effectiveness of oral misoprostol and intravenous oxytocin in reducing blood loss in women undergoing indicated or elective cesarean delivery (CD) under spinal anesthesia.\n In this prospective, double-blind pilot study, 56 parturients who received 5 IU of intravenous oxytocin after cord clamping were randomized to further receive either misoprostol orally and a placebo infusion intravenously or placebo orally and an oxytocin infusion intravenously.\n After adjustment was made for the sonographically estimated amniotic fluid volume, there was no statistical difference in blood loss between the 2 groups (mean+/-S.D., 1083+/-920 mL in the oxytocin group vs. 970+/-560 mL in the misoprostol group; P=.59).\n Oxytocin followed by oral misoprostol is as effective as an oxytocin injection followed by an oxytocin infusion in reducing postoperative blood loss after CD, and the protocol may be a safe, valuable, and cost-effective alternative to oxytocin alone. Visual estimation of intraoperative blood loss undervalues the effective value of misoprostol use by 30%.", "To compare oral misoprostol 400 microg with intramuscular oxytocin 10 IU in the routine management of the third stage.\n Double-blind placebo controlled trial.\n Main referral hospital and its associated polyclinics in Accra, Ghana.\n Four hundred and one low risk women, in the second stage of labour with anticipated vaginal delivery, who entered labour spontaneously.\n After delivery of the anterior shoulder of the baby, the women were randomised to receive either: 1. misoprostol 400 microg powder in water orally and 1 mL normal saline intramuscular injection (placebo); or 2. powdered cellulose in water orally (placebo) and 1 mL oxytocin 10 IU intramuscular injection.\n Change in haemoglobin concentration from before delivery to 12 hours postpartum. Secondary outcomes included need for additional oxytocics, blood loss > 500 mL and > 1,000 mL, operative intervention for postpartum haemorrhage, and side effects, including nausea, vomiting, diarrhoea, shivering and elevated temperature.\n Demographic characteristics were similar. There was no significant difference in change in haemoglobin concentration between the two groups (0.60 g/dL for misoprostol and 0.55 g/dL for oxytocin; relative difference 9.6%; 95% CI 20.5-39.6%; P = 0.54). There were no significant differences in secondary outcomes with the exception of shivering, which occurred more frequently in the misoprostol group (22.2% vs 5.7%; relative risk 4.73; 95% CI 2.31-9.68; P < 0.0001).\n In low risk women oral misoprostol appears to be as effective in minimising blood loss in the third stage of labour as intramuscular oxytocin. Shivering was noted more frequently with misoprostol use, but no other side effects were noted. Misoprostol has great potential for use in the third stage of labour especially in developing countries.", "In this study, 100 singleton pregnant women underwent a caesarean delivery under general anaesthesia and were studied in terms of postpartum bleeding using oxytocin or misoprostol. Patients were randomly divided into two equal groups. One group received two tabs of misoprostol 200 microg sublingually and the second group took intravenous infusion of 20 units of oxytocin at the rate of 10 cc/min immediately after delivery until full contraction of the uterine. The amount of blood loss was lower in misoprostol group comparing with oxytocin group (608.91 ml vs 673.9 ml) (p = 0.048) and this difference was statistically significant. The need to give additional oxytocin therapy in oxytocin group (36%) was significantly higher than misoprostol group (14%) (p = 0.032). It seems that the efficacy of sublingual misoprostol is equivalent to that of low dose intravenous oxytocin in reducing postpartum haemorrhage at caesarean section. Misoprostol has some other advantages like long shelf -life, stability at room temperature and oral use.", "Our purpose was to compare intramyometrial 15-methyl prostaglandin F2 alpha with intravenous oxytocin for controlling blood loss at elective cesarean section.\n A double-blind, randomized trial was performed with intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, or intravenous oxytocin, 20 U, in 60 women undergoing elective lower segment cesarean section at 36 to 41 weeks' gestation. Subjective assessment of the operative blood loss and early lochial discharge and objective change in hemoglobin and hematocrit before and 24 hours after delivery and the incidence of side effects were compared by nonparametric statistical tests.\n The mean estimated blood loss was similar in both groups, with 645 ml (SD 278, range 400 to 1500) in the 15-methyl prostaglandin F2 alpha group compared with 605 ml (SD 303, range 200 to 1750) in the oxytocin group. The mean fall in hemoglobin and hematocrit was greater in the 15-methyl prostaglandin F2 alpha group than in the oxytocin group, 0.98 gm/dl (SD 0.95) versus 0.65 gm/dl (SD 0.79) for hemoglobin and 2.58% (SD 2.96) versus 2% (SD 2.96) for hematocrit. None of these differences reached statistical significance. There were no differences in side effects and lochial discharge between the treatment groups. In both groups there was a decrease of approximately 1% in maternal arterial oxygen saturation.\n Routine intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, does not offer any obvious advantage over intravenous oxytocin, 20 U, in reducing operative blood loss at elective lower-segment cesarean section.", "To compare the efficacy and side effects of misoprostol, compared with methylergometrine, for the prevention of postpartum haemorrhage.\n A double-blind, randomised clinical trial of 200 women with apparently normal pregnancies.\n University teaching hospital.\n Two hundred women with apparently normal pregnancies.\n After the baby had been born, all women received two capsules by mouth and the contents of an ampule by intravenous injection. Each woman only received one active product. The capsules contained either a total of 600 microg misoprostol or placebo, and the ampule 200 microg of methylergometrine or placebo.\n Need for further oxytocic drugs, blood pressure, the presence of side effects, mean haemoglobin and haematocrit three days after delivery.\n Two hundred women completed the study (100 received methylergometrine and 100 misoprostol). Postpartum haemorrhage occurred in 4.3% of the methylergometrine group and 8.3% of the misoprostol group (P = 0.57). The need for further oxytocic drugs was 4.4% and 12.8% after methylergometrine and misoprostol, respectively (P = 0.065). One hour after the birth of the baby there was no difference in the mean systolic blood pressure (117 +/- 12 mmHg versus 115 +/- 11 mmHg) (P = 0.26) or the mean diastolic blood pressure (72 +/- 10 mmHg versus 71 +/- 11 mmHg for the groups receiving methylergometrine or misoprostol, respectively) (P = 0.97). The mean temperature in the misoprostol group rose to 37.4 degrees C, compared with 37 degrees C in the methylergometrine group (P < 0.0001). In the misoprostol group 34% developed fever (> 38 degrees C) compared with 3% in the methylergometrine group (P < 0.0001). Shivering (visual analogue score > or = 8) also occurred more often after misoprostol (42%) than after methylergometrine (8.5%) (P < 0.0001). The haemoglobin level (g/dL) on the third postpartum day was similar for both groups ( 11.0 and 11.2 for methylergometrine and misoprostol, respectively) (P = 0.39).\n This study suggests that although protection from postpartum haemorrhage using parenteral methylergometrine and oral misoprostol is nearly equal, misoprostol is associated with more side effects.", "To assess the effects of 400-μg sublingual misoprostol plus routine uterotonics on postpartum hemorrhage.\n A double-blind, placebo-controlled, randomized study was performed. After delivery of the child, eligible women received routine uterotonics and were randomly allocated to receive 400-μg misoprostol or placebo sublingually. The primary outcome measure was blood loss of at least 500 mL within 1 hour of taking the trial tablets.\n In total, 672 women received misoprostol and 673 received placebo. The baseline data were similar for both groups. Misoprostol plus routine uterotonics reduced postpartum blood loss, but the effect was not significant for blood loss of at least 500 mL (relative risk [RR] 0.96; 95% confidence interval [CI], 0.63-1.45) or blood loss of at least 1000 mL (RR 0.50; 95% CI, 0.15-1.66). Misoprostol also reduced the need for non-routine oxytocin, manual removal of the placenta, and hysterectomy, but these differences were not significant either. Misoprostol was associated with pyrexia and moderate/severe shivering. There was no death in either group.\n Misoprostol plus routine uterotonics resulted in modest reductions of blood loss in the third stage of labor, but the effects did not reach statistical significance. Larger studies are recommended.\n Copyright © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.", "To assess the effectiveness of oral misoprostol compared with methylergometrine in the prevention of primary post-partum hemorrhage during the third stage of labor.\n This was a randomized controlled trial of 864 singleton low-risk pregnant women. The outcomes were total blood loss, duration of the third stage of labor and peripartal change in hematocrit. Comparisons were by the chi2-test and Student t-test. Relative risks were calculated for side-effects profile. A P-value of less than 0.05 was statistically significant.\n The biodata of all the participants were similar. The mean blood loss for the misoprostol and methylergometrine groups was 191.6 +/- 134.5 mL and 246.0 +/- 175.5 mL, respectively (95% CI: -79.3 to -39.5 mL). The mean duration of the third stage of labor was 19.6 +/- 2.4 min and 9.4 +/- 3.3 min in the misoprostol and methylergometrine groups, respectively (95% CI: 9.82-10.58 min). More subjects had blood loss >500 mL, 42 (9.7%) versus 6 (1.4%), and peripartal hematocrit change greater than 10%, 38 (8.8%) versus 5 (1.2%), in the methylergometrine group than in the misoprostol group, respectively. Also, more subjects received additional oxytocic in the methylergometrine group, compared to the misoprostol group (80 [18.5%] versus 33 [7.6%] patients, respectively).\n Orally administered misoprostol was more effective in reducing blood loss during the third stage of labor than intramuscular methylergometrine. However, there were more subjects in the misoprostol group in whom duration of the third stage of labor was greater than 15 min and who also had manual placental removal than in the methylergometrine group.", "To compare the efficacy and adverse effects of sublingual misoprostol, intravenous oxytocin, and intravenous methylergometrine in active management of the third stage of labor (AMTSL).\n A double-blind randomized trial of 300 women with a healthy singleton pregnancy allocated into 4 groups to receive either: 400 microg or 600 microg of sublingual misoprostol, 5 IU of intravenous oxytocin, or 200 microg of intravenous methylergometrine. The primary outcome measure was blood loss in the third and fourth stage of labor; secondary measures were duration of the third stage of labor, changes in hemoglobin levels, and adverse effects.\n Patients who received 600 microg of misoprostol had the lowest blood loss (96.05+/-21.1 mL), followed by 400 microg of misoprostol (126.24+/-49.3 mL), oxytocin (154.7+/-45.7 mL), and methylergometrine (223.4+/-73.7 mL) (P<0.01). Shortest mean duration of the third stage of labor (5.74 minutes) was with 600 microg of misoprostol, while methylergometrine had the longest (6.83 minutes) (P<0.05). Pyrexia was observed in the misoprostol groups, and raised blood pressure in the methylergometrine group (P<0.001). The 24-hour postpartum hemoglobin level was similar among the groups (P>0.05).\n Administration of 600 microg of sublingual misoprostol was more effective than 400 microg of misoprostol, intravenous oxytocin, and intravenous methylergometrine for AMTSL.", "To compare the efficacy and side effects of 0.2 mg methyl-ergometrine IM, 400 microg misoprostol sublingual and 125 microg 15 methyl PGF2alpha IM in active management of third stage of labor.\n Two hundred low risk pregnant women with induced or spontaneous labor were randomized to receive either 400 microg misoprostol sublingually or 0.2 mg methyl-ergometrine intramuscularly or 125 microg 15-methyl PGF2alpha intramuscularly, after the delivery of anterior shoulder of baby. The main outcome measures were: blood loss more than 500 ml, need for additional oxytoxic drug, change in hemoglobin level and side effects due to drugs.\n The median estimated blood loss, blood loss more than 500 ml, need for additional oxytocic drug and change in hemoglobin levels were similar in all three groups. The significant side effects in the misoprostol group were shivering, pyrexia (temperature > 38 degrees C) and vomiting, which were self-limiting. Diarrhea was significantly more in the 15 methyl PGF2alpha group. Three women in methyl-ergometrine group underwent manual removal of placenta. One woman in misoprostol group received blood transfusion.\n Sublingual misoprostol appears to be as effective as intramuscular methyl-ergometrine and intramuscular 15-methyl PGF2alpha in the prevention of postpartum hemorrhage. It can be a good alternative in resource poor setting.", "To compare active management of third stage of labour with 15-methyl prostaglandin F2alpha (PGF2alpha) and conventional management with methylergometrine as prophylaxis for postpartum hemorrhage, a randomised comparative study was carried out at Calcutta National Medical College and Hospital, Kolkata on 100 women. They were randomly allotted to one of the two groups. Group A included 50 women who received 15-methyl PGF2alpha (125 microg) intramusculary at the time of delivery of the anterior shoulder and group B included 50 women who underwent conventional management of the third stage of labour where methylergometrine 0.2 mg was given after delivery of placenta. Main outcome measured were duration of third stage, amount of bleeding and side-effects. The present study showed that there were significent reduction of the duration of third stage as well as reduction of amount of bleeding particularly when 125 microg of 15-methyl PGF2alpha was given intramuscularly at the time of delivery of the anterior shoulder in comparison to coventional method of management of third stage of labour with methylergometrine. Placental expulsion occurred within 4 minutes in group A and 16.5 minutes in group B. The amount of bleeding following delivery was 95.6 ml in average in group A and 249.6 ml in average in group B. 15-methyl PGF2alpha (125 microg) is certainly effective in prevention of postpartum haemorrhage particularly in developing country like India where this complication contributes a major factor for maternal mortality.", "To investigate whether orally administered misoprostol during the third stage of labor is efficient in reducing postpartum blood loss.\n In a double-masked trial, during vaginal delivery women were randomly assigned to receive a single oral dose of misoprostol (600 microg) or placebo in third stage of labor, immediately after cord clamping. The third stage of labor was managed routinely by early cord clamping and controlled cord traction; oxytocin was administered only if blood loss seemed more than usual. Blood loss was estimated by the delivering physician and differences in hematocrit were measured before and after delivery.\n Mean (+/- standard error of the mean) estimated blood loss (345 +/- 19.5 mL versus 417 +/- 25.9 mL, P = .031) and hematocrit difference (4.5 +/- 0.9% versus 7.9 +/- 1.2%, P = .014) were significantly lower in women who received misoprostol than those who received placebo. Fewer women in the misoprostol group had postpartum hemorrhage (blood loss of at least 500 mL), but that difference was not statistically significant (7% versus 15%, P = .43). Additional oxytocin before or after placental separation was used less often in the misoprostol group (16% versus 38%, P = .047). There were no differences in the length of third stage of labor (8 +/- 0.9 minutes versus 9 +/- 1 minutes, P = .947). There were no differences in pain during third stage of labor, postpartum fever, or diarrhea, but shivering was more frequent in the misoprostol group.\n Oral misoprostol administered in the third stage of labor reduced postpartum blood loss and might be effective in reducing incidence of postpartum hemorrhage.", "The purpose of this study was to compare misoprostol 600 microg intrarectally with conventional oxytocics in the treatment of third stage of labor.\n In a controlled trial, 1606 women were randomly grouped to receive (1) oxytocin 10 IU plus rectal misoprostol, (2) rectal misoprostol, (3) oxytocin 10 IU, and (4) oxytocin 10 IU plus methylergometrine. The main outcome measures were the incidence of postpartum hemorrhage and a drop in hemoglobin concentration from before delivery to 24 hours after delivery.\n The incidence of postpartum hemorrhage was 9.8% in the group that received only rectal misoprostol therapy compared with 3.5% in the group that received oxytocin and methylergometrine therapy (P =.001). There were no significant differences among the 4 groups with regard to a drop in hemoglobin concentrations. Significantly more women needed additional oxytocin in the group that received only rectal misoprostol therapy, when compared with the group that received oxytocin and methylergometrine therapy (8.3% vs 2.2%; P <.001). The primary outcome measures were similar in the group that received only rectal misoprostol therapy and the group that received only oxytocin therapy.\n Rectal misoprostol is significantly less effective than oxytocin plus methylergometrine for the prevention of postpartum hemorrhage.", "To compare oral misoprostol with conventional oxytocics in the management of the third stage of labor. In a controlled trial, 1574 women were randomized into four groups, as follows: Group 1 received intravenous infusion of oxytocin 10 IU plus oral misoprostol 400 micro g, followed by two doses of oral misoprostol 100 micro g 4 hours apart; group 2 received oral misoprostol 400 micro g, followed by two doses of oral misoprostol 100 micro g 4 hours apart; group 3 received intravenous infusion of oxytocin 10 IU; and group 4 received intravenous infusion of oxytocin 10 IU plus intramuscular administration of methylergonovine maleate (Methergine) 0.2 mg. The incidence of postpartum hemorrhage and decrease in hemoglobin concentration from before delivery to 24 hours postpartum were the main outcome measures.\n The primary outcome measures were similar in groups 2 and 3. The incidence of postpartum hemorrhage was 9% in group 2, compared with 3.2% in group 1 and 3.5% in group 4 (P <.01, and P =.01, respectively). There were no significant differences among the four groups regarding hemoglobin concentrations. Significantly more women needed additional oxytocin in group 2, when compared with group 4 (5.9% versus 2.2%; P =.01). The proportion of women requiring additional methylergonovine maleate was 4.8% in group 2, compared with 0.7% in group 1 and 1% in group 4 (P <.01 and P =.01, respectively).\n Oral misoprostol alone is as effective as oxytocin alone for the prevention of postpartum hemorrhage; it is less effective than oxytocin plus methylergonovine maleate and oral misoprostol plus oxytocin.", "To compare the effectiveness of 400 microg rectal misoprostol in 5 cm(3) of saline with oxytocin 10 IU, i.m., in reducing bleeding during the third stage of labor.\n A double blind, randomized, clinical trial including 663 women with uncomplicated vaginal delivery who received misoprostol (n=324) or oxytocin (n=339).\n Changes in hemoglobin and hematocrit from before to 72 h postpartum; blood loss during the third stage; duration of the third stage of labor; need for additional oxytocic drug; frequency of requisition and of administration of blood; changes in blood pressure; and occurrence of side effects.\n No significant differences were observed between groups, before and 72 h postpartum, in mean hemoglobin and hematocrit, on volume of blood loss and duration of third stage of labor. The incidence of shivering and mean temperature (P<0.01) was significantly greater among women receiving misoprostol than oxytocin.\n Misoprostol administered as a micro-enema, 400 microg in 5 ml of saline during the third stage of labor, appears to be as effective as oxytocin 10 IU, i.m., but misoprostol produced more side effects than oxytocin.", "To compare the effectiveness of sublingual misoprostol administered immediately after delivery of the neonate at cesarean section, with intravenous oxytocin infusion in prevention of uterine atony and thereby reducing blood loss at cesarean section.\n One hundred women with singleton term pregnancy undergoing elective or emergency lower segment cesarean section under spinal anesthesia were included in this study. They were randomly allocated to receive either misoprostol 400 mug sublingually or intravenous infusion of 20 units of oxytocin soon after delivery of the neonate. The main outcome measures were blood loss at cesarean section, change in hemoglobin levels, need for additional oxytocics and drug related side effects.\n The mean blood loss estimated was significantly lower in misoprostol group compared to oxytocin group (819 ml versus 974 ml; p = 0.004). The number of women who had blood loss exceeding 500 ml and the change in hemoglobin, however, was comparable between the two groups. There was a need for additional oxytocic therapy in 16% and 18% after use of misoprostol and oxytocin respectively (p = 0.673). The incidence of side effects such as pyrexia, shivering and metallic taste was significantly higher in misoprostol group compared to oxytocin group.\n Sublingual misoprostol appears to be as effective as intravenous infusion of oxytocin in reducing blood loss at cesarean section. However, occurrence of transient side effects such as shivering and pyrexia were noted more frequently with the use of misoprostol.", "To evaluate whether routine administration of sublingual misoprostol 600 microg after delivery reduces postpartum haemorrhage.\n Randomised double blind placebo controlled trial.\n Primary health centre in Bissau, Guinea-Bissau, West Africa.\n 661 women undergoing vaginal delivery.\n Misoprostol 600 mug or placebo administered sublingually immediately after delivery.\n Postpartum haemorrhage, defined as a loss of > or = 500 ml and decrease in haemoglobin concentration after delivery.\n The incidence of postpartum haemorrhage was not significantly different between the two groups, the relative risk being 0.89 (95% confidence interval 0.76 to 1.04) in the misoprostol group compared with the placebo group. Mean blood loss was 10.5% (-0.5% to 20.4%) lower in the misoprostol group than in the control group. Severe postpartum haemorrhage of > or = 1000 ml or > or = 1500 ml occurred in 17% (56) and 8% (25) in the placebo group and 11% (37) and 2% (7) in the misoprostol group. Significantly fewer women in the misoprostol group experienced a loss of > or = 1000 ml (0.66, 0.45 to 0.98) or > or = 1500 ml (0.28, 0.12 to 0.64). The decrease in haemoglobin concentration tended to be less in the misoprostol group, the mean difference between the two groups being 0.16 mmol/l (-0.01 mmol/l to 0.32 mmol/l).\n Sublingual misoprostol reduces the frequency of severe postpartum haemorrhage.", "To compare the efficacy of intravenous ergometrine, intramuscular oxytocin, and oral misoprostol in the control of postpartum hemorrhage.\n Mean blood loss, rates of blood loss between 500 and 1000 ml, hematocrit fall greater than 10%, and need for additional oxytocic agents and nature and rates of adverse effects were assessed in this prospective, randomized, controlled study.\n All outcomes were similar in the 3 groups. The main adverse effects in the misoprostol group were temperatures higher than 99 degrees F, which normalized within 2 h and shivering, which was mild and self-limiting.\n Oral misoprostol is as effective as conventional oxytocic agents in preventing postpartum hemorrhage and can be recommended for use in low-resource settings.", "To compare the efficacy and side effects of sublingual misoprostol and intravenous methylergometrine for active management of third stage of labor.\n One hundred twenty low risk pregnant women at term with spontaneous onset of labor were included in the study. The women were randomized to receive either two tablets of misoprostol (200 microg/tablet) sublingually or 1 ml of methylergometrine (200 microg) intravenous injection, after the delivery of the anterior shoulder of the baby. The main outcome measures were: need for additional oxytocic drugs, blood loss >or=500 ml, change in hemoglobin levels and side effects.\n Postpartum hemorrhage as defined by hemorrhage >or=500 ml occurred in 3.1% of the women in the sublingual misoprostol group but none of the women in the methylergometrine group (P > 0.05). There was a need for additional oxytocic drugs in 5.0% and 8.3% after methylergometrine and misoprostol, respectively (P > 0.05). The change in hemoglobin levels at 24 h postpartum were 0.8 and 0.7 gm% in methylergometrine and misoprostol group, respectively(P > 0.05). In the misoprostol group, 6.6% women developed fever >or=38 degrees C and 21.6% had shivering while in methylergometrine group none experienced these side effects. However, the incidence of other side effects like nausea, vomiting, headache and giddiness were similar in both groups.\n Sublingual misoprostol appears to be as effective as intravenous methylergometrine in the prevention of postpartum hemorrhage. However, larger randomized studies are needed to advocate its routine use.", "To assess the effectiveness and safety of the administration of misoprostol, an orally active prostaglandin, in addition to routine uterotonic therapy as part of the active management of the third stage of labor.\n The present study was a hospital-based, decentralized, multi-center, randomized, placebo-controlled, double-blind trial. We enrolled 1103 women (out of a target sample size of 1180) at 4 hospitals in South Africa, Uganda, and Nigeria. Participants received a sublingual dose of 400 μg of misoprostol or a placebo, in addition to standard active management of the third stage of labor, after vaginal birth.\n The baseline characteristics of the participants were comparable. The difference in the primary outcome of blood loss of 500 mL or more within 1 hour of randomization was not significant between the 2 groups (misoprostol 22/546 [4.0%] versus placebo 35/553 [6.3%]; relative risk, 0.64; 95% confidence interval, 0.38-1.07). Shivering and pyrexia occurred more frequently in the misoprostol group. No maternal deaths occurred.\n The present study did not confirm a beneficial effect of administering 400 μg of misoprostol, in addition to routine uterotonic therapy, during the third stage of labor, but was consistent with other trials showing a cumulative modest benefit. Where routine uterotonics are available for prophylactic use, any potential benefit of misoprostol might not outweigh the likelihood of adverse effects.\n Copyright © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.", "Delivery-induced hemorrhage is defined as a blood loss greater than 500 ml within the first 24 hours after delivery. Loss of more than 1000 ml is a sign of gravity. For certain authors, 40% of these hemorrhages could be avoided with systematic preventive measures using uterotonic agents to control the third phase of labor. The aim of our work was to assess the preventive efficacy of active management measures during the third phase of labor and to determine which agents are most effective.\n We compared two protocols for controlled deliver: a conventional method using ocytocin (2.5 IU i.v. bolus), and a more recent method using a prostaglandin E1 analog: misoprostol (Cytotec, 3 tablets per os). We compared the two methods with a control group where no preventive measures were used, the standard procedure in our maternity unit.\n Six hundred two women participated in the study. They were divided into 3 homogeneous groups (ocytocin group misoprostol group, control group). There was a 46% reduction in delivery-induced hemorrhage in the ocytocin group but only a minimal preventive effect against severe hemorrhage. Misoprostol did not demonstrate any efficacy in our study.\n It would appear appropriate to take preventive measures against delivery-induced hemorrhage for all deliveries. A bolus intravenous injection of ocytocin immediately after delivery should bed used. The dose should be greater than that used in this study in order to prevent the development of severe hemorrhage. The most satisfactory results can be obtained with 5 IU (1 ampoule of Syntocinon). It is important to obtain a precise quantification of excessive blood loss in order to institute appropriate care rapidly. Misoprostol should be assessed with other prospective studies because of its easy administration, its low cost and easy storage, important advantages in countries with limited resources.", "To characterize the pharmacokinetics and adverse-effect profile of rectally administered misoprostol.\n To assess absorption of rectally administered misoprostol, 20 women were randomized to receive misoprostol 600 microg by either oral or rectal administration after delivery. Blood samples were obtained at 0, 7.5, 15, 30, 45, 60, 90, 120, and 240 minutes and analyzed for serum concentrations of misoprostol free acid by enzyme-linked immunosorbent assay. Additionally, 275 women were randomized to receive rectal 400 microg, rectal 600 microg, or oral 600 microg misoprostol after delivery. Self-assessment questionnaires were used to ascertain the adverse-effect profiles.\n Misoprostol tablets are absorbed rectally even though they are formulated for oral use. The area under the curve (integral of concentration and time graph) for rectal misoprostol was higher by 121 pg.h/mL (95% confidence interval [CI] -4.2, 246.2) than for oral misoprostol. The rectal route group had a mean maximum serum concentration 144 pg/mL lower than that for the oral route (95% CI 63, 225). This maximum was achieved on average 23 minutes later than in the oral group (95% CI 10, 35). Shivering was reported by 76% of the patients in the oral 600-microg arm, 56% of the patients in the rectal 400-microg arm, and 54% of the patients in the rectal 600-microg arm. The relative risk of shivering in the combined rectal groups is 73% that of the oral group (95% CI 61%, 86%). Severe shivering reported by patients was significantly reduced, by 72%, in rectal groups compared with the oral group (95% CI 60%, 81%).\n Misoprostol administered rectally is associated with lower peak levels and a reduction in adverse effects compared with the oral route. Increasing rectal doses may achieve higher efficacy without reducing the acceptability of the treatment.", "The aim of this study was to compare the efficacy and safety of oral misoprostol 400 mug with intramuscular syntometrine in the management of the third stage of labor.\n This was a double-blind randomized controlled trial conducted in a tertiary care hospital. Three hundred and fifty-five women randomized to receive either oral misoprostol 400 mug or intramuscular syntometrine in the third stage of labor were studied. The change in hemoglobin level from before to 48 h after delivery, use of additional oxytocics and treatment related side effects were the main outcome measures.\n There were no significant differences between the two groups in terms of the change in hemoglobin level and mean blood loss. The incidence of shivering was significantly higher in the misoprostol group whilst that of vomiting was significantly higher in the syntometrine group. There were no differences in the incidence of nausea, headache, diarrhea and pyrexia between the two groups.\n Orally administered misoprostol at a dose of 400 mug is an acceptable alternative in preventing post-partum blood loss, as measured by the peri-partum change in hemoglobin level and was not associated with an increased incidence of side effects.", "To compare misoprostol with standard oxytocic regimens in the prevention of postpartum haemorrhage.\n Randomised controlled trial.\n Obstetric unit in a large teaching hospital.\n One thousand women randomised to 500 microg misoprostol given orally or to standard oxytocic regimens of oxytocin, oxytocin with ergometrine, or ergometrine.\n Incidence of postpartum haemorrhage and the incidence and severity of side effects.\n Postpartum haemorrhage occurred in 12% of women given misoprostol and in 11% of women given standard oxytocic drugs (relative risk (RR) 1.10, 95% confidence interval (CI) 0.79, 1.55). Blood loss of 1000 mL or more occurred in 2% of women in each group. Nausea, headache, dizziness and tiredness were less frequent with misoprostol (RR (95% CI) 0.71 (0.59, 0.84); 0.53 (0.38, 0.74); 0.73 (0.61, 0.87) and 0.88 (0.83, 0.94) respectively). The main side effects of misoprostol were shivering (RR 1.95, 95% CI 1.69, 2.25) and a rise in temperature (difference in mean rise 0.34 degrees C, 95% CI 0.26, 0.42).\n Oral misoprostol for the prevention of postpartum haemorrhage was comparable to standard oxytocics. Many side effects were less common with misoprostol but shivering and pyrexia were more common. Larger randomised trials are needed before establishing the equivalence between misoprostol and standard oxytocic drugs in the prevention of postpartum haemorrhage.", "Our objective was to compare oral misoprostol with intramuscular oxytocin in the prevention of postpartum haemorrhage. Four hundred and ninety-six women were randomised to receive either 600 microg misoprostol orally or 10 IU oxytocin intramuscularly after delivery. There were no significant differences between the misoprostol and oxytocin groups with regard to the incidence of postpartum haemorrhage (1% vs. 0% respectively, relative risk (RR) 3.02, 95% confidence interval (CI) 0.32-28.88) or drop in haemoglobin concentration (0.71 g/dl vs. 0.68 g/dl, respectively, P = 0.699). The length of the third stage of labour and the percentage of women requiring manual removal of placenta, further oxytocics or blood transfusion were also similar. Shivering was significantly higher with misoprostol (57% vs. 14%; RR 4.06, CI 2.93-5.62), but there were no differences in other side effects. We conclude that oral misoprostol can replace intramuscular oxytocin in reducing postpartum haemorrhage in low-risk women, in developing countries, especially as it is administered orally and it is thermostable in tropical conditions.", "The search for an effective, easily stored, affordable uterotonic agent in preventing postpartum hemorrhage is of importance, especially in the developing world. The objective of this study was to randomly compare the effectiveness of rectal misoprostol with Syntometrine in the management of the third stage of labor.\n Four hundred and ninety-one low risk women in labor were randomly allocated to receive either misoprostol 400 microgram rectally or Syntometrine 1 ampuole intramuscularly, and postpartum blood loss was estimated as the principal end point. Comparisons were by the chi-square test or Fisher's test and relative risks with 95% confidence intervals for categorical data, and the Mann-Whitney test for ranked continuous variables.\n The baseline characteristics in terms of hemoglobin estimation in antenatal clinic, mean age, parity, and duration of labor in the 250 patients who received Syntometrine and 241 patients who received misoprostol were similar. However, there was a significant difference in the pre-delivery blood pressure of the two groups because of the non-protocol exclusion of women with elevated blood pressure allocated to receive Syntometrine. Duration of third stage of labor, blood loss postpartum and hemoglobin estimation post partum were all similar. Postpartum diastolic hypertension was more common in the Syntometrine group (p= 0.002). No other apparent side effect was noted in either group.\n Misoprostol rectally for management of the third stage of labor merits further investigation.", "To compare sublingual misoprostol with intravenous syntometrine use during third stage of labor by measuring the blood loss.\n Sixty women were randomized to receive either 600 micro g misoprostol sublingually or 1 ml syntometrine intravenously during the third stage of labor after spontaneous vaginal delivery. For those with risk factors of postpartum hemorrhage such as medical induction or augmentation of labor, previous third stage complications were excluded. The blood loss in labor was measured by the alkaline-hematin method, and differences in hemoglobin before and after delivery were compared.\n There was no significant difference in the median measured blood loss between the misoprostol group and the syntometrine group (280 versus 226 ml, p = 0.45). The change in hemoglobin was comparable between the two groups. There were more women in the misoprostol group who required additional oxytocics, but the difference was not statistically significant. A major complication occurred in one patient in the misoprostol group with blood loss in excess of 1000 ml. The incidence of side effects such as shivering and pyrexia in women receiving misoprostol was significantly higher than that in the syntometrine group.\n The use of sublingual misoprostol or intravenous syntometrine in spontaneous vaginal delivery resulted in a comparable amount of blood loss. Transient side effect such as fever and shivering which resolved within a day occurred more frequent to those who received sublingual misoprostol.", "This study investigated the effectiveness of rectal misoprostol in preventing postpartum hemorrhage.\n In a randomized, placebo-controlled study, 550 women were randomly allocated to rectally receive 400 microg misoprostol or nonidentical placebo after normal vaginal delivery. Any excessive bleeding was actively managed with conventional oxytocic agents. Blood loss was measured directly.\n The baseline variables were similar. Blood loss of > or = 1000 mL occurred in 4.8% (13/270) of the misoprostol group and 7% (19/272) of the placebo group. Additional oxytocic therapy was required by 3.3% and 4.7%, respectively. No predominance of side effects, particularly shivering, was noted in the misoprostol group.\n Postpartum use of 400 microg rectal misoprostol was well tolerated and associated with a statistically nonsignificant trend toward less postpartum hemorrhage. The early active management of excessive bleeding with conventional oxytocic agents may have reduced the potential of the study to detect differences between the groups.", "To assess the efficacy of buccal misoprostol to decrease bleeding after vaginal delivery.\n This was a randomized study of patients between 22 weeks and 42 weeks of gestation with anticipated vaginal delivery. Patients were given either a 200-mug misoprostol tablet or placebo in the buccal space at the time of cord clamping. A continuous dilute intravenous oxytocin infusion was given to all patients at delivery of the placenta. Postpartum hemorrhage was defined as blood loss exceeding 500 mL. Sample size calculations based on previous studies assumed a 13% incidence of postpartum hemorrhage in the control group. To show a statistically significant reduction of postpartum hemorrhage a total of 1,604 patients would be required in each group.\n A total of 848 patients were enrolled and 756 randomly assigned, 377 in the misoprostol group and 379 in the placebo group. Demographic, antepartum, and intrapartum characteristics were similar between the groups. The incidence of postpartum hemorrhage, 3% compared with 5%, (relative risk 0.65, 95% confidence interval 0.33-1.29, P = .22), mean estimated blood loss, 322 compared with 329 mL, (P = .45), and mean minutes of the third stage of labor, 6.7 compared with 6.9 (P = .52) were similar between the groups, misoprostol and placebo, respectively. Hemoglobin difference before and after delivery, need for second or third uterotonic agent, and all measured neonatal variables including birth weights, and umbilical cord pH were similar between the groups.\n Buccal misoprostol at cord clamping is no more effective than placebo in reducing postpartum hemorrhage.", "The purpose of this study was to assess the efficacy of buccal misoprostol to decrease uterine atony, hemorrhage, and the need for additional uterotonic agents during cesarean delivery.\n Patients who underwent cesarean delivery were assigned randomly to either 200-microg misoprostol or placebo placed in the buccal space. A dilute intravenous oxytocin infusion was given to all patients at delivery of the placenta. The primary outcome variable was the need for additional uterotonic agents.\n A total of 352 women received random assignments. Demographic and intrapartum characteristics were similar between the groups. More women in the placebo group required 1 additional uterotonic agent (43% vs 26%; P < .01; relative risk, 1.3; 95% CI, 1.10, 1.50). There was not a difference between the groups in the incidence of postpartum hemorrhage or a difference in preoperative and postoperative hemoglobin level.\n Buccal misoprostol reduces the need for additional uterotonic agents during cesarean delivery.", "to determine if misoprostol is safe and efficacious in preventing postpartum haemorrhage (PPH) when administered by trained traditional birth attendants (TBA) at home deliveries.\n a randomised, double-blind, placebo-controlled trial.\n Chitral, Khyber Pakhtunkhwa Province, Pakistan.\n a total of 1119 women giving birth at home.\n from June 2006 to June 2008, consenting women were randomised to receive 600 microg oral misoprostol (n = 534) or placebo (n = 585) after delivery to determine whether misoprostol reduced the incidence of PPH (≥ 500 ml).\n the primary outcomes were measured blood loss ≥ 500 ml after delivery and drop in haemoglobin >2 g/dl from before to after delivery.\n oral misoprostol was associated with a significant reduction in the rate of PPH (≥ 500 ml) (16.5 versus 21.9%; relative risk 0.76, 95% CI 0.59-0.97). There were no measurable differences between study groups for drop in haemoglobin >2 g/dl (relative risk 0.79, 95% CI 0.62-1.02); but significantly fewer women receiving misoprostol had a drop in haemoglobin >3 g/dl, compared with placebo (5.1 versus 9.6%; relative risk 0.53, 95% CI 0.34-0.83). Shivering and chills were significantly more common with misoprostol. There were no maternal deaths among participants.\n postpartum administration of 600 microg oral misoprostol by trained TBAs at home deliveries reduces the rate of PPH by 24%. Given its ease of use and low cost, misoprostol could reduce the burden of PPH in community settings where universal oxytocin prophylaxis is not feasible. Continual training and skill-building for TBAs, along with monitoring and evaluation of programme effectiveness, should accompany any widespread introduction of this drug.", "To evaluate efficacy of misoprostol by intrauterine route for the prevention of the obstetrical hemorrhage and to know its effects collaterals.\n Clinical and randomized test with 200 patients to those who one took place to them Caesarean. The Group A was applied placebo and the group B misoprostol (group B; 800 microg) intrauterine, after the birth of its newborns. The necessity of additional uterotonics was compared, loss of hemoglobin and hematocrit, and the effects collaterals.\n In group B it diminished the necessity of additional uterotonics to 50% and the loss of hemoglobin in 39.6%. In the group greater loss of 3 was registered g of hemoglobin in 13 versus 3% of the patients. With respect to the hematocrit, its loss was reduced in 40.6%. The patients in those who the hematocrit in more fell than 10%, registered themselves in 7 versus 1% cases. The effects collaterals were few and not so serious.\n The intrauterine combination of misoprostol and oxitocin diminishes the postcaesarean sanguineous loss and has brings about few effects collaterals.", "To compare carboprost trometamol with methylergometrine in managing the third stage of labor.\n One hundred and fifty parturient women were randomly assigned to use carboprost trometamol or methylergometrine immediately after delivery.\n Both the duration of the third stage and the mean blood loss were significantly less in the carboprost group than the methergine group (P < 0.001).\n Carboprost trometamol is a more potent uterotonic drug than methylergometrine. Reducing blood loss in parturient women is very important especially in cases where there is the likelihood of anemia.", "We conducted a double-blind randomized controlled trial to compare a conventional regimen of oxytocin and ergometrine with administration of the prostaglandin E2 analogue, sulprostone, for prophylaxis of postpartum hemorrhage in high-risk women.\n Women with a history of postpartum hemorrhage > or = 1000 were assigned to two coded prophylactic regimens. Drugs, given respectively at delivery of the anterior shoulder and after delivery of the placenta, were oxytocin and ergometrine in the control group, and sulprostone and placebo in the experimental group. Eighty-one women, 69 of whom actually participated in the trial, were investigated. Both the women and the caregivers were unaware of treatment allocation.\n Although the trial was terminated prematurely there was a slight, but not statistically significant, preference for the sulprostone regimen in terms of blood loss and use of blood transfusion. No serious adverse effects were noted with either of the two regimens.\n Prostaglandins may be more effective for preventing recurrence of severe postpartum hemorrhage than the oxytocin and ergometrine combination, but they do not eliminate the risk entirely.", "To compare the efficacy and side-effects of low-dose sublingual misoprostol and i.v. methylergometrine for active management of the third stage of labor.\n The study subjects were three hundred low-risk women with term pregnancy and spontaneous onset of labor. These women received either one (100 microg/tablet) or two tablets of misoprostol (200 microg) sublingually or 1 mL (200 microg) of methylergometrine, i.v. injection, after the delivery of the anterior shoulder of the baby. The main outcome measures were the need for additional oxytocic drugs, blood loss >or=500 mL, change in hemoglobin levels and side-effects.\n Post-partum hemorrhage (>or=500 mL blood loss) did not occur in any of the women, but above-average bleeding occurred in 2.0% of cases in groups I, II (sublingual misoprostol 100 microg and 200 microg respectively) and III (methylergometrine), despite additional oxytocics used in 5.0%, 4.0% and 3.0% cases in groups I, II and III respectively (P>0.05). The change in hemoglobin levels at 24 h post-partum were 0.8%, 0.7% and 0.8% in groups I, II and III respectively (P>0.05).\n A low dose of sublingual misoprostol appears to be as effective as a low dose of i.v. methylergometrine in the prevention of post-partum hemorrhage in low-risk cases. So given the advantages of its stability at room temperature, low cost and easy route of administration, misoprostol appears to be a better choice, and a low dose is enough. However, larger studies in low-risk as well as high-risk cases are needed to advocate routine use of a low dose at the primary level.", "To compare the effect of 400 mug of oral misoprostol with 5 U of intravenous oxytocin in the reduction of postpartum blood loss and prevention of postpartum hemorrhage.\n In a prospective, double-blind, randomized controlled trial conducted in a tertiary maternity hospital 622 women received either 400 mug of oral misoprostol or 5 U of intravenous oxytocin after delivery of the anterior shoulder or within 1 min of delivery. The primary outcome was a hematocrit drop of 10% or greater 24 h postpartum. The secondary outcomes were a hemoglobin drop of 30 mg/L or greater, the use of additional oxytocin, an estimated blood loss greater than 1000 mL, manual removal of the placenta, a blood transfusion, and shivering and fever (>or=38 degrees C) as adverse effects of misoprostol.\n There was no difference between the 2 groups regarding the primary outcome (a >or=10% hematocrit drop occurred in 3.4% and 3.7% of the participants in the oxytocin and misoprostol groups, P=0.98). The rate of use of additional oxytocin was higher in the misoprostol group (51% versus 40.5%, P=0.01). Shivering was confined to the misoprostol group (6.8%), and fever occurred in 12.5% of the women in the misoprostol group and 0.3% of the women in the oxytocin group.\n The routine use of 400 microg of oral misoprostol was no less effective than 5 U of intravenous oxytocin in reducing blood loss after delivery, as assessed by change in postpartum hematocrit. The adverse effects of misoprostol were mild and self-limiting.", "To compare rectal misoprostol with oxytocin for routine management of the third stage of labour.\n A total of 240 parturient women were randomized, at three University of Toronto teaching hospitals, to receive either rectal misoprostol (400 microg) after delivery of the infant or parenteral oxytocin (5 units i.v. or 10 units i.m.) with the delivery of the anterior shoulder, when possible, or 5 units i.v. or i.m after the delivery of the placenta. The primary outcome measure was change in hemoglobin (Delta[Hgb]) from admission in early labour to day one postpartum.\n The labour ward of three University of Toronto teaching hospitals: St. Michael's, Toronto General, and Mount Sinai.\n Labouring women either nulliparous or multiparous with no known risk for excessive third stage blood loss; vertex presentation; no previous Caesarean delivery; induced, spontaneous, or augmented labour.\n No difference in Delta[Hgb] was observed between the two groups; the Delta[Hgb] in the oxytocin and misoprostol groups were 1.43 g/L (95% confidence interval [CI], 1.2-1.6 g/L) and 1.59 g/L (95% CI, 1.4-1.8 g/L) respectively (p = 0.35). Secondary outcome measures (excessive third stage bleeding, duration of third stage of labour, need for manual removal of the placenta or the need for additional oxytocics) did not differ between the two groups.\n Rectal misoprostol is of equivalent efficacy to parenteral oxytocin for the prevention of primary postpartum hemorrhage. Rectal misoprostol is an appropriate uterotonic agent for routine management of the third stage of labour.", "In a prospective, open-label, assessor-blind, randomised parallel group study the efficacy and safety of Hemabate (Pharmacia-Upjohn Pharmaceuticals, Milton Keynes, Buckinghamshire) an analogue of 15-methyl-prostaglandin (PGF2alpha) analogue was compared with Syntometrine (Alliance Pharmaceuticals, Chippenham, Wilts) the standard combination of ergometrine and syntocinon used for the active management of the third stage of labour and the prevention of primary postpartum haemorrhage (PPH). The study was set in a district general hospital with approximately 4,000 deliveries annually. The study was discontinued at the time of the interim analysis because of unacceptable gastrointestinal side effects. At the time of the interim analysis, a total of 529 women had completed the study with 263 randomised to receive PGF2alpha and 266 to receive ergometrine and syntocinon. In a pre-specified subgroup analysis, women delivered vaginally were further subdivided into those considered to be at high or low risk of primary PPH. The measured blood loss and incidence of PPH was similar in both treatment groups whether delivered by caesarean section or vaginally independent of whether women were considered to be at high or low risk. Adverse gastrointestinal events were recorded more often in the Hemabate group. The most common symptom was diarrhoea which occurred in 21% of women who received Hemabate compared to only 0.8% of Syntometrine users. PGF2alpha is as effective as Syntometrine in the prophylaxis of primary PPH in all groups studied but there was a statistically significantly increased risk of diarrhoea among users of PGF2alpha.", "The objective of this trial was to investigate whether 500 microg oral misoprostol given immediately after delivery of the neonate at Caesarean section is as effective as a bolus intravenous injection of 10 iu Syntocinon in stimulating uterine contractions and thereby reducing blood loss. Forty women undergoing elective or emergency Caesarean section were included in a placebo-controlled randomised trial. Group 1 received oral misoprostol and a placebo intravenous bolus and Group 2 received intravenous Syntocinon and oral placebo tablets. The main outcome measures were estimated blood loss at Caesarean section, drop in serum haemoglobin, and the need for additional uterotonic agents. We found that there was no significant difference (p = 0.75) in estimated blood loss between the two groups. No differences were observed in the decrease in haemoglobin, requirement for additional oxytocics, the need for blood transfusion or the degree of shivering in each group (p > 0.05 in each case). We concluded that oral misoprostol could be used as an alternative oxytocic agent for the third stage at Caesarean section. However, there is an obvious need for a larger randomised controlled trial to be undertaken. Previous published studies have concentrated on vaginal births and further studies should be extended to Caesarean deliveries.", "To assess the effectiveness of 800 microg of rectal misoprostol compared with an intravenous infusion of 5 IU of oxytocin as prophylaxis against postpartum hemorrhage (PPH).\n A total of 514 women in labor were randomized into two groups (257 women in each). Within 1 minute of delivery of the anterior shoulder participants in group 1 received 800 microg of rectal misoprostol and 1 ampoule of normal saline in 5 mL lactated Ringer solution intravenously; group 2 received a rectal placebo tablet and 5 IU of oxytocin in 5 mL lactated Ringer solution intravenously.\n Both groups were comparable regarding the need for uterotonics, blood transfusion, and hematocrit drop of 10% or greater, 24 hours post partum (P=0.54, P=0.25, and P=0.85, respectively). Fever was significantly higher among misoprostol patients (18.7% vs 0.8%, P<0.001).\n Routine use of 800 microg of rectal misoprostol was effective in reducing blood loss after delivery. We recommend the regimen for low-resource, busy obstetric settings.", "nan", "a) To compare the clinical effect of rectal misoprostol with intramuscular syntometrine in reducing blood loss in the third stage of labour b) to determine the severity and incidence of side effects of both drugs and c) to measure blood loss, patient tolerance and acceptance of rectal misoprostol.\n One hundred and forty parturients were randomly allocated to receive intramuscular syntometrine (syntocinon 10 IU + ergometrine 0.5 mg) or rectal misoprostol 400 microg within five minutes of the delivery of the anterior shoulder Blood loss was measured by the use of a plastic collection drape. Additional oxytocic therapy was instituted for uterine atony or if blood loss was in excess of one litre.\n There was no significant difference in patient demographics of each treatment group (Table 1). There was no difference in mean duration of the third stage of labour (8.4 +/- 14 min vs 7.8 +/- 6.6 min). The mean blood loss from those parturients receiving misoprostol (180.1 +/- 120 mls) was not significantly different (p = 0.5) from those receiving syntometrine (197 +/- 176.97 mls) for the active management of the third stage of labour Treatment with syntometrine was associated with a significant elevation of post-partum systolic blood pressure compared with misoprostol treatment (mean increase 0.57 +/- 18.79 mmHg vs -1.43 +/- 14.17 mmHg, (mean +/- SD), p < 0.04). Rectal misoprostol was well tolerated in 88.5% of participants, 11.4% reported that insertion was uncomfortable, of which 2.8% reported that they would have preferred parenteral drug administration.\n The clinical effect of rectal misoprostol and intramuscular syntometrine were not different at the doses used in the active management of the third stage of labour in this study. Rectal misoprostol was well tolerated by the patients and had a low side effect profile. Blood loss assessment using the blood collection drape is of invaluable benefit in resource-poor settings.", "To compare the impact of a dinoprostone vaginal insert and intravenous oxytocin in reducing blood loss of women undergoing vaginal or cesarean delivery.\n This study was conducted among term singleton pregnancies delivered vaginally or by elective cesarean section. In the vaginally delivered cases, active management of the third stage of labor was conducted. During cesarean delivery, 20 IU of intravenous oxytocin was administered. Women, who either delivered via the vaginal or abdominal route, were then randomly allocated to receive 10 mg vaginal dinoprostone insert for 12 hours (group I, n: 100) or intravenous oxytocin (group II, n: 100), respectively.\n Mean blood loss and need for additional uterotonics and postpartum hemoglobin and hematocrit levels at 24 and 36 hours after delivery did not differ between the two groups. Women allocated to the dinoprostone vaginal insert arm experienced more nausea and vomiting.\n Dinoprostone vaginal insert was as effective as intravenous oxytocin in the prevention of postpartum blood loss.", "The objective of this study was to compare a Tibetan traditional medicine (the uterotonic Zhi Byed 11 [ZB11]) to oral misoprostol for prophylaxis of postpartum hemorrhage (PPH). We conducted a double-blind randomized controlled trial at three hospitals in Lhasa, Tibet, People's Republic of China. Women (N = 967) were randomized to either ZB11 or misoprostol groups. Postpartum blood loss was measured in a calibrated blood collection drape. The primary combined outcome was incidence of PPH, defined as measured blood loss (MBL) > or = 500 mL, administration of open label uterotonics, or maternal death. We found that the rate of the combined outcome was lower among the misoprostol group (16.1% versus 21.8% for ZB11; P = .02). Frequency of PPH was lower with misoprostol (12.4% versus 17.4%; P = .02). There were no significant differences in MBL > 1000 mL or mean or median MBL. Fever was significantly more common in the misoprostol group (P = .03). The rate of combined outcome was significantly lower among women receiving misoprostol. However, other indices of obstetric hemorrhage were not significantly different.", "nan", "To compare the effect of rectal misoprostol with intramuscular oxytocin in the routine management of the third stage in a rural developing country.\n A randomized controlled trial was performed at two district hospitals in Ghana, West Africa. Four hundred fifty women in advanced labour were enrolled. The only exclusion criterion was a known medical contraindication to prostaglandin administration. Women were randomized to receive rectal misoprostol 800 microg or intramuscular oxytocin 10 IU with delivery of the anterior shoulder. The main outcome measure was change in hemoglobin concentration from before to after delivery. Secondary outcomes included the need for additional uterotonics, estimated blood loss, transfusion, and medication side effects.\n Demographic characteristics were similar in each treatment group. There was no significant difference between treatment groups in change in hemoglobin (misoprostol 1.19 g/dL and oxytocin 1.16 g/dL; relative difference 2.6%; 95% confidence intervals [CI]-16.8% to 19.4%; P = 0.80). The only significant secondary outcome was shivering, which was more common in the misoprostol group (misoprostol 7.5% vs. oxytocin 0.9%; relative risk 8.0; 95% CI 1.86-34.36; P = 0.001).\n Rectal misoprostol 800 microg is as effective as 10 IU intramuscular oxytocin in minimizing blood loss in the third stage of labour. Rectal misoprostol has a lower incidence of side effects than the equivalent oral dose. This confirms the utility of misoprostol as a safe and effective uterotonic for use in the rural and remote areas of developing nations where other pharmacologic agents may be less feasible.", "The influence of intramyometrial injection of 125 micrograms of 15-s-15-methyl prostaglandin F2 alpha (carboprost tromethamine, Prostin/15M) versus 20 U of oxytocin immediately after delivery of placenta on blood loss at cesarean section was investigated by means of a double-blinded, randomized trial. Hematocrit decrease from the day before operation to the third postoperative day was used as an index of blood loss. Decreases in hematocrit were comparable for the oxytocin and carboprost tromethamine groups. Excess blood loss (hematocrit decrease more than 6 vol. %) was significantly associated with the indication for cesarean section (three of four for cephalopelvic disproportion versus 9 of 42 others, p less than 0.01), but not with age, parity, number of prior cesarean sections, or birthweight. Carboprost tromethamine does not appear to be more effective than oxytocin when given by intramyometrial injection at this dose for routine cesarean section; its prophylactic utility in higher doses or in cases at risk for hemorrhage from uterine atony remains to be investigated.", "To compare the effect on post partum bloodloss of the postpartum prophylactic administration of oxytocin or sulprostone in low risk women having an expectant management of the third stage.\n Randomized, placebo controlled, double-blind trial.\n Radboud University Hospital, Nijmegen (67 women) and Lievensberg Hospital, Bergen op Zoom (10 women).\n 77 women entered the trial (three were excluded).\n The intramuscular injection, immediately after the birth of the baby, of either oxytocin 5 IU, sulprostone 500 micrograms or 0.9% saline.\n Quantitative postpartum blood loss and length of third stage.\n Postpartum blood loss was reduced almost equally, by about 35%, by oxytocin (P = 0.02), or sulprostone (P = 0.05). The mean length of the third stage was shorter in both groups receiving the active treatment, this effect was significant in the sulprostone group (P = 0.01).\n Prophylactic administration of oxytocin or sulprostone directly after delivery followed by expectant management of the third stage reduces post partum blood loss and shortens the third stage.", "A double blind randomized controlled trial was performed at the tertiary hospital in Harare, Zimbabwe to compare oral misoprostol with intramuscular oxytocin in the management of third stage of labor.\n A total of 499 women were randomized to receive either 400 microg misoprostol orally or 10 IU oxytocin intramuscularly. The incidences of postpartum hemorrhage and side effects were examined.\n The demographic and labor characteristics were comparable. Postpartum hemorrhage occurred in 15.2% of women given misoprostol and in 13.3% of those given oxytocin (P=0.534). Measured blood loss of more than 1000 ml occurred in 3.7% of the misoprostol group compared with 2% in the oxytocin group (P=0.237). There was no significant difference in the need for additional oxytocic drugs or blood transfusion in women given misoprostol (P values 0.137 and 0.600, respectively). Significant side effects of misoprostol were shivering [RR=1.32 (95% CI 1.11-1.58); P=0.002) and a rise in temperature [RR=2.02 (95% CI 1.75-2.33); P<0.001].\n Oral misoprostol is as effective as intramuscular oxytocin in the prevention of PPH. Shivering and transient pyrexia were specific side effects of misoprostol. Misoprostol has potential in reducing the high incidence of PPH in developing countries.", "To compare rectally administered misoprostol to intravenously administered oxytocin for the management of third-stage labor.\n Subjects were randomized to receive two, 200-microg misoprostol tablets rectally (study medication) plus 2 mL saline in Ringer's lactate intravenously or two lactose tablets rectally plus 20 units oxytocin in Ringer's lactate intravenously (control medication). Blood loss was determined by estimation, measurement, and change in hematocrit values from admission to postpartum day 1. Subjects were excluded if cesarean delivery was required.\n A total of 325 women underwent analysis. By estimation, 21% of subjects and 15% of controls had postpartum hemorrhage (P =.17). By using measured blood loss, we determined that 70 of 154 (46%) study subjects and 61 of 161 (38%) control subjects had postpartum hemorrhage (P =.17). For 36 (23%) misoprostol subjects and 18 (11%) oxytocin subjects at least one additional agent was required to control bleeding (P =.004).\n Rectal misoprostol (400 microg) was no more effective than intravenous oxytocin in preventing postpartum hemorrhage.", "Postpartum haemorrhage is a major cause of maternal mortality in the developing world. Although effective methods for prevention and treatment of such haemorrhage exist--such as the uterotonic drug oxytocin--most are not feasible in resource-poor settings where many births occur at home. We aimed to investigate whether oral misoprostol, a potential alternative to oxytocin, could prevent postpartum haemorrhage in a community home-birth setting.\n In a placebo-controlled trial undertaken between September, 2002, and December, 2005, 1620 women in rural India were randomised to receive oral misoprostol (n=812) or placebo (n=808) after delivery. 25 auxiliary nurse midwives undertook the deliveries, administered the study drug, and measured blood loss. The primary outcome was the incidence of acute postpartum haemorrhage (defined as > or =500 mL bleeding) within 2 h of delivery. Analysis was by intention-to-treat. The trial was registered with the US clinical trials database (http://www. clinicaltrials.gov) as number NCT00097123.\n Oral misoprostol was associated with a significant reduction in the rate of acute postpartum haemorrhage (12.0% to 6.4%, p<0.0001; relative risk 0.53 [95% CI 0.39-0.74]) and acute severe postpartum haemorrhage (1.2% to 0.2%, p<0.0001; 0.20 [0.04-0.91]. One case of postpartum haemorrhage was prevented for every 18 women treated. Misoprostol was also associated with a decrease in mean postpartum blood loss (262.3 mL to 214.3 mL, p<0.0001). Postpartum haemorrhage rates fell over time in both groups but remained significantly higher in the placebo group. Women taking misoprostol had a higher rate of transitory symptoms of chills and fever than the control.\n Oral misoprostol was associated with significant decreases in the rate of acute postpartum haemorrhage and mean blood loss. The drug's low cost, ease of administration, stability, and a positive safety profile make it a good option in resource-poor settings.", "Postpartum haemorrhage is a leading cause of maternal morbidity and mortality. Active management of the third stage of labour, including use of a uterotonic agent, has been shown to reduce blood loss. Misoprostol (a prostaglandin E1 analogue) has been suggested for this purpose because it has strong uterotonic effects, can be given orally, is inexpensive, and does not need refrigeration for storage. We did a multicentre, double-blind, randomised controlled trial to determine whether oral misoprostol is as effective as oxytocin during the third stage of labour.\n In hospitals in Argentina, China, Egypt, Ireland, Nigeria, South Africa, Switzerland, Thailand, and Vietnam, we randomly assigned women about to deliver vaginally to receive 600 microg misoprostol orally or 10 IU oxytocin intravenously or intramuscularly, according to routine practice, plus corresponding identical placebos. The medications were administered immediately after delivery as part of the active management of the third stage of labour. The primary outcomes were measured postpartum blood loss of 1000 mL or more, and the use of additional uterotonics without an unacceptable level of side-effects. We chose an upper limit of a 35% increase in the risk of blood loss of 1000 mL or more as the margin of clinical equivalence, which was assessed by the confidence interval of the relative risk. Analysis was by intention to treat.\n 9264 women were assigned misoprostol and 9266 oxytocin. 37 women in the misoprostol group and 34 in the oxytocin group had emergency caesarean sections and were excluded. 366 (4%) of women on misoprostol had a measured blood loss of 1000 mL or more, compared with 263 (3%) of those on oxytocin (relative risk 1.39 [95% CI 1.19-1.63], p<0.0001). 1398 (15%) women in the misoprostol group and 1002 (11%) in the oxytocin group required additional uterotonics (1.40 [1.29-1.51], p<0.0001). Misoprostol use was also associated with a significantly higher incidence of shivering (3.48 [3.15-3.84]) and raised body temperature (7.17 [5.67-9.07]) in the first hour after delivery.\n 10 IU oxytocin (intravenous or intramuscular) is preferable to 600 microg oral misoprostol in the active management of the third stage of labour in hospital settings where active management is the norm.", "This is a multicentre, blocked, randomized trial to compare the efficacy of oral misoprostol 400 microg with current injectable uterotonic agents (oxytocin/ Syntometrine) used prophylactically in the third stage of labour. Main outcome measures were blood loss, use of a second uterotonic agent and difference in haemoglobin level from antepartum to postpartum. Data analysis from 863 women showed a statistically significant increase in both the mean blood loss (p < 0.001) and the rate of postpartum haemorrhage > 500 mL, (RR 2.72: 95% C1 1.73-4.27) in the misoprostol group compared to the oxytocin/Syntometrine group. The use of a second uterotonic agent was higher in the misoprostol group (RR 2.89: 95% Cl 2.00-4.18) as well as a greater decrease in postpartum haemoglobin (p = 0.015). Oral misoprostol 400 microg is significantly less effective than the traditional intramuscular uterotonic agents currently used and therefore cannot be considered as a viable option to these agents in the management of the third stage of labour.", "To select the misoprostol dose to be used in a large multicentre randomised trial comparing misoprostol with oxytocin in the routine management of the third stage of labour.\n Randomised pilot trial, double-blinded with the use of double placebos.\n Two of the nine hospitals that will participate in the main multicentre trial. The hospitals were located in Johannesburg, South Africa and Khon Kaen, Thailand.\n Women during second stage of labour about to be delivered vaginally.\n The trial had three arms: misoprostol 400 microg versus misoprostol 600 microg versus intramuscular oxytocin 10 IU. Each group received an injection and three tablets immediately after the birth of the baby.\n Shivering and pyrexia rates were the main outcome measures. Data on other side effects and characteristics of the third stage of labour were also collected. Side effects were noted as none, mild, moderate or severe.\n Both shivering and pyrexia (temperature > 38 degrees C) were most common in the 600 microg misoprostol group (28% and 7.5% for shivering and pyrexia, respectively) compared with 400 microg misoprostol (19% and 2%), and the oxytocin group (12.5% and 3%). The increase in shivering in the misoprostol 600 microg group was due primarily to a higher rate of moderate shivering. None of the women had a temperature > 40 degrees C. There were no increases in severe side effects and other adverse events in the misoprostol 600 microg group.\n When used in the management of the third stage of labour oral misoprostol is associated with an increase in the rate of moderate shivering and pyrexia which seems to be dose-related. Based on the results of this pilot trial, the Steering Committee has decided to use 600 microg misoprostol in the main trial, comparing it with oxytocin, in order to achieve higher effectiveness.", "A randomized controlled study of 112 women with singleton pregnancies at term, and no antenatal complications, admitted in spontaneous labour were randomized to receive either an intramuscular injection of 0.5 mg of Syntometrine or an intramuscular injection of 125 ug of prostaglandin 15-methyl F2 alpha at delivery of the anterior shoulder of the baby. Blood lost in the first 2 hours, and subsequent 22 hours postdelivery were collected separately and measured by colourimetric measurement of haemoglobin content. Other parameters in the third stage were measured, including need for transfusion of blood or blood products, length of the third stage, and change in haemoglobin concentration before and 24 hours after delivery. The incidence of side-effects with administration of either prostaglandin 15-methyl F2 alpha or Syntometrine were documented. The prophylactic use of intramuscular prostaglandin 15-methyl F2 alpha (Carboprost) in the active management of the third stage of labour gave similar results to prophylactic intramuscular Syntometrine in terms of length of the third stage of labour, incidence of postpartum haemorrhage and total blood loss in the first 2 hours and subsequent 22 hours after delivery. However it has the disadvantage of higher cost, as well as statistically significant increase in the incidence of profuse and frequent diarrhoea. Based on these results intramuscular injection of prostaglandin 15-methyl F2 alpha offers no advantage over intramuscular Syntometrine for routine prophylactic use to reduce blood loss in the third stage of labour.", "Misoprostol, an inexpensive, stable, orally active prostaglandin analogue, has been suggested for use in the prevention of postpartum haemorrhage. Potential side-effects, however, need to be quantified.\n To compare the rate of postpartum shivering and pyrexia following oral misoprostol 600 micrograms and placebo.\n A double-blind placebo-controlled trial. Women in labour were randomly allocated to receive either misoprostol 600 micrograms orally or placebo after delivery. Conventional oxytocics were given immediately if blood loss was thought to be more than usual. Side-effects were recorded. Postpartum blood loss in the first hour was measured by collection in a special flat plastic bedpan.\n The labour ward of an academic hospital in Johannesburg, with 7,000 deliveries per annum.\n Shivering and pyrexia.\n The groups were well matched. Misoprostol use was associated with more shivering (44% versus 11%, relative risk (RR) 4.03, 95% confidence interval (CI) 2.85-5.70), pyrexia > or = 37.8 degrees C (38% v. 6%, RR 6.23, CI 3.89-9.97), 1-hour systolic blood pressure > or = 140 mmHg (33% v. 25%, RR 1.32, CI 1.03-1.70), and diastolic blood pressure > or = 90 mmHg (10.5% v. 3.0%, RR 3.44, CI 1.67-7.11). There were no other significant differences. The study was not designed to be large enough to assess a difference in blood loss > or = 1,000 ml (9% v. 9.7%, RR 0.93, CI 0.56-1.53). Possible effects on blood loss may have been obscured by the lesser use of additional oxytocics in the misoprostol group (14% v. 18%, RR 0.78, CI 0.54-1.13).\n This study has shown the association of postpartum oral misoprostol 600 micrograms with shivering, pyrexia and hypertension. The increased blood pressure, as for the trend towards increased abdominal pain, may be secondary to the uterotonic effect of misoprostol. Large randomised trials are needed to assess the effectiveness of misoprostol in the prevention of postpartum haemorrhage, against which the disadvantages demonstrated here can be weighed.", "nan", "To compare oral misoprostol 400 microg with placebo in the routine management of the third stage of labour.\n A double-blind placebo controlled trial. Setting The labour ward of an academic hospital in Johannesburg, South Africa with 7000 deliveries per annum.\n Low-risk women expected to deliver vaginally.\n Women in labour were randomly allocated to receive either misoprostol 400 microg orally or placebo after the birth. Conventional oxytocics were given immediately if blood loss was thought to be more than usual. Postpartum blood loss in the first hour was measured by collection in a special flat plastic bedpan. Side effects were recorded.\n Measured blood loss > or = 1000 ml within the first hour after birth. Use of additional oxytocics.\n The groups were well matched. Measured blood loss > or = 1000 ml occurred in 15/250 (6%) after misoprostol and 23/250 (9%) after placebo (relative risk 0.65; 95% confidence interval 0.35-1.22). The difference may have been reduced by the greater use of conventional oxytocics in the placebo group, which was statistically significant for intravenous oxytocin infusion (2.8% vs 8.4%, relative risk 0.33, 95% confidence interval 0.14-0.77). Shivering was more common in the misoprostol group (19% vs 5%, relative risk 3.69; 95% confidence interval 2.05-6.64).\n Shivering has been shown in this study to be a specific side effect of misoprostol administered orally in the puerperium. No serious side effects were noted. Misoprostol shows promise as a method of preventing postpartum haemorrhage. Because of the potential benefits for childbearing women, particularly those in developing countries, further research to determine its effects with greater certainty should be expedited." ]

[ "12028259", "15337331" ]

[ "A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations.", "No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study." ]

[ "To determine the effect of small doses of oral cyanocobalamin supplements in older patients with low or borderline serum vitamin B12 concentrations but no other evidence of pernicious anemia (PA).\n Randomized, double-blind, placebo-controlled study assessing the efficacy of oral cyanocobalamin 10 microg and 50 microg daily for 1 month.\n Two geriatric hospitals in the North Western Health Care Network, Melbourne, Australia.\n Thirty-one inpatients with serum vitamin B12 levels between 100 and 150 pmol/L, without PA, other malabsorption disorders, or progressive neurological or terminal illness. The mean age was 81.4 years.\n After informed consent, a medical and drug history was taken and the Mini-Mental State Examination (MMSE) completed. A dietitian made assessment of oral cobalamin intake. Blood was taken for serum vitamin B12, serum and red cell folate assay, full blood examination, fasting serum gastrin, parietal and intrinsic factor antibodies, fasting serum homocysteine, and creatinine. Patients were then randomized to receive 10 microg oral cyanocobalamin, 50 microg oral cyanocobalamin, or placebo treatment for 1 month, after which the investigations and clinical examinations were repeated.\n Percentage change in the level of vitamin B12, homocysteine, folate, and red cell parameters and absolute changes in MMSE were calculated and compared between groups. The groups were compared on the number of responders who improved their level of B12 by 20%. Chi-square calculations on changes in serum vitamin B12 concentration were also performed.\n Mean serum vitamin B12 +/- standard deviation improved by 51.7 +/- 47.1% in the 50-microg group, 40.2 +/- 34.4% in the 10-microg group, and 11.7 +/- 24.5% in the placebo group. The change in the 50-microg cyanocobalamin group was significantly greater than that in the placebo group (P=.044). The change in the 10-microg cyanocobalamin group was not significantly different from that in the placebo group (P=.186). Eight of 10 subjects in each treatment group were classified as responders, compared with two of 11 in the placebo group (P=.004). Homocysteine levels fell in patients receiving cyanocobalamin, but this fall failed to reach statistical significance. There were no significant changes in the other parameters measured.\n Cyanocobalamin supplementation of 50 microg but not 10 microg daily produced a significant increase in serum vitamin B12. This result has implications for the management of patients with subnormal or borderline serum vitamin B12 concentrations and for food fortification with vitamin B12.", "Associations between vitamin B-12 deficiency and impaired cognitive function and depression have been reported.\n A randomized placebo controlled study including 140 individuals with an increased plasma methylmalonic acid (0.40-2.00 micromol/l) not previously treated with vitamin B-12. Cognitive function was assessed by the Cambridge Cognitive Examination (CAMCOG), Mini-Mental State Examination (MMSE), and a 12-words learning test. Symptoms of depression were evaluated by the Major Depression Inventory. The main outcome measure was change in cognitive function and depression score from baseline to follow-up 3 months later.\n At baseline 78 (56%) individuals had cognitive impairment judged from the CAMCOG score and 40 (29%) according to the MMSE; 18 (13%) individuals had symptoms of depression. No improvement was found in cognitive function comparing the treatment and placebo group (total CAMCOG score: P = 0.43), nor among individuals with only slightly impaired cognitive function (n = 44, total CAMCOG score: P = 0.42). The treatment group did not improve in depression score as compared to the placebo group (P = 0.18).\n The duration of impaired cognitive function was unknown.\n A high proportion of individuals with an increased plasma methylmalonic acid had impaired cognitive function, and a rather high prevalence of depression was observed. However, vitamin B-12 treatment did not improve cognitive function or symptoms of depression within the 3-months study period." ]

[ "773416", "320230", "17687129", "1251139", "21255253" ]

[ "Prophylaxis in haemophilia: a double-blind controlled trial.", "Twice weekly prophylactic therapy in haemophilia A.", "Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia.", "Evaluation of prophylactic replacement therapy in haemophilia B.", "A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study)." ]

[ "A double-blind controlled trial of prophylactic factor VIII therapy has been carried out on nine severe haemophiliacs at the Lord Mayor Treloar College. Infusions were given once weekly and calculated to give a post-infusion plasma concentration of at least 0.25 I.U./ml of factor VIII. This regime reduced the overall bleeding frequency by 15%. The bleeding frequency in the first 3 days post-infusion was reduced by 66%. A moderate overall reduction in morbidity was also achieved. It is calculated that to reduce the incidence of bleeding in severe haemophiliacs by 15% would require a 73% increased usage of therapeutic materials. More than twice this amount of material is likely to be needed to reduce the bleeding frequency of the same group by 66%.", "Factor VIII-containing materials were administered to four severely affected haemophiliacs twice weekly in doses calculated to raise the factor VIII level to either 15% or 30% of average normal. The pooled results from those patients with statistically similar baseline bleeding frequencies showed a significant reduction in bleeding frequency on both doses in the first 48 hours. The 30% dose produced a more significant reduction than the 15% dose in the first 24 hours, but there was no significant difference between the two doses in the second 24 hours. It appears that to reduce the bleeding frequency of severely affected haemophiliacs by 60% would require a two-and-a-half-fold increase in therapeutic materials. A 90% reduction would need nine times the amount of material currently in use.", "Effective ways to prevent arthropathy in severe hemophilia are unknown.\n We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI).\n Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P=0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups.\n Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597 [ClinicalTrials.gov].).\n Copyright 2007 Massachusetts Medical Society.", "Prophylaxis replacement therapy has been assessed for a period of 12 months in 10 patients with severe haemophilia B showing a high incidence of spontaneous bleeding episodes. Two different schedules of administration of a freeze-dried factor IX concentrate were randomly evaluated: according to scheme A, 7.5 U/kg were administrated biweekly, whereas scheme B was based on the weekly infusion of 15 U/kg. On prophylaxis the frequency of bleeding episodes was significantly reduced (P less than 0.005) when compared with that observed in one-year period preceding the trial. Biweekly infusions were superior to weekly infusion (P less than 0.01), and the benefit appeared to be related to the higher number of days in which measurable levels of factor IX were attained in plasma. Range of motion, which was redeced at the start of the trial in 26 joints, was found to have improved in 23. Favourable changes of the joint radiological picture were observed in 6 cases. Hepatitis and factor IX inhibitors did not develop during the trial period. Side effects were rare and mild.", "Prevention of arthropathy is a major goal of hemophilia treatment. While studies in adults have demonstrated an impact of prophylaxis on the incidence of joint bleeds and patients' well-being in terms of improved quality of life (QoL), it is unclear whether or not prophylaxis influences the outcome and perception of well- of children with hemophilia.\n This randomized controlled study compared the efficacy of prophylaxis with episodic therapy in preventing hemarthroses and image-proven joint damage in children with severe hemophilia A (factor VIII <1%) over a 10-year time period.\n Forty-five children with severe hemophilia A, aged 1-7 years (median 4), with negative clinical-radiologic joint score at entry and at least one bleed during the previous 6 months, were consecutively randomized to prophylaxis with recombinant factor VIII (25 IU kg(-1) 3 × week) or episodic therapy with ≥25 IU kg(-1) every 12-24 h until complete clinical bleeding resolution. Safety, feasibility, direct costs and QoL were also evaluated.\n Twenty-one children were assigned to prophylaxis, 19 to episodic treatment. Children on prophylaxis had fewer hemarthroses than children on episodic therapy: 0.20 vs. 0.52 events per patient per month (P < 0.02). Plain-film radiology showed signs of arthropathy in six patients on prophylaxis (29%) vs. 14 on episodic treatment (74%) (P < 0.05). Prophylaxis was more effective when started early (≤36 months), with patients having fewer joint bleeds (0.12 joint bleeds per patient per month) and no radiologic signs of arthropathy.\n This randomized trial confirms the efficacy of prophylaxis in preventing bleeds and arthropathy in children with hemophilia, particularly when it is initiated early in life.\n © 2011 International Society on Thrombosis and Haemostasis." ]

[ "2374076", "9672959", "2212181", "6537445", "11519371", "3688597", "2621541", "3262219", "14600049", "8138869", "6526547", "6611026", "1862062", "2180065", "1625111", "11394955", "12206062", "6706454", "1787697" ]

[ "A primary preventive approach to children's drug refusal behavior: the impact of rehearsal-plus.", "One-year outcomes of Project Towards No Drug Abuse.", "Preventing adolescent drug abuse through a multimodal cognitive-behavioral approach: results of a 3-year study.", "An experimental evaluation of a drug education course.", "Drug abuse prevention among minority adolescents: posttest and one-year follow-up of a school-based preventive intervention.", "Changing perceptions of riskiness in drinking, drugs, and driving: an emergency department-based alcohol and substance abuse prevention program.", "An outcome evaluation of refusal skills program as a drug abuse prevention strategy.", "Affective and social influences approaches to the prevention of multiple substance abuse among seventh grade students: results from project SMART.", "New inroads in preventing adolescent drug use: results from a large-scale trial of project ALERT in middle schools.", "Drug refusal behavior: the relative efficacy of skills-based and information-based treatment.", "An evaluation of the alternatives approach to drug abuse prevention.", "A cognitive-behavioral approach to substance abuse prevention.", "Preventing alcohol, marijuana, and cigarette use among adolescents: peer pressure resistance training versus establishing conservative norms.", "Drug prevention in junior high: a multi-site longitudinal test.", "Two-year follow-up of a social-cognitive intervention to prevent substance use.", "Project Towards No Drug Abuse: generalizability to a general high school sample.", "Development and immediate impact of a self-instruction curriculum for an adolescent indicated drug abuse prevention trial.", "Substance abuse: assessment of the outcomes of activities and activity clusters in school-based prevention.", "Effects of a take-home drug prevention program on drug-related communication and beliefs of parents and children." ]

[ "The effectiveness of a short-term prevention program to increase drug refusal behavior in a school-age population was assessed. Forty-two third-grade children were randomly assigned to one of three groups: rehearsal-plus, traditional, or attention control. Children in the rehearsal-plus group were taught specific drug refusal techniques and appropriate social skills, and were provided a rationale for each response. This procedure included behavioral training and elaborative rehearsal. Training occurred in four socially validated situations corresponding to settings where children were likely to be offered drugs. The traditional procedure consisted of instructions derived from a \"Just Say No\" drug program. Assessment focused on specific refusal behaviors, procedural knowledge, and self-efficacy. Significant gains in desired functioning and appropriate behavioral and social skills were found. The effectiveness of the rehearsal-plus procedure as a method of increasing adaptive responding in dangerous and/or anxiety-arousing situations is discussed.", "This paper presents the 1-year outcomes evaluation of Project Towards No Drug Abuse (Project TND), a large-scale indicated drug abuse prevention program in southern California applied to continuation high school youth, who are at high risk for drug abuse.\n The efficacy of nine-lesson health motivation--social skills--decision-making curriculum was evaluated in a three-condition experimental design. Twenty-one schools were randomly assigned by block to one of three conditions--standard care (control), classroom program, and classroom program plus a semester-long school-as-community component. A pretest was followed by a 3-week-long drug abuse prevention program and then a posttest at 14 continuation high schools. The 7 standard care schools received only the pretest followed by the posttest (same time duration). Subjects were followed up 1 year later.\n Changes in use of cigarettes, alcohol, marijuana, and hard drugs were assessed in a pretest-1-year follow-up time interval. The follow-up rate was 67% (analysis n = 1,074). Indicated preventive effects were found on alcohol and hard drug use. No differences were found across the two program conditions.\n Project TND is the first program to demonstrate 1-year self-reported behavioral effects on alcohol use and hard drug use among older, high-risk youth by using a school-based, limited-session model.", "Students (N = 4,466) attending 56 schools in New York State were involved in a 3-year study testing the effectiveness of a cognitive-behavioral approach to substance abuse prevention. In a randomized block design, schools were assigned to receive (a) the prevention program with formal provider training and implementation feedback, (b) the prevention program with videotaped provider training and no feedback, or (c) no treatment. After pretest equivalence and comparability of conditions with respect to attrition were established, students who received at least 60% of the prevention program (N = 3,684) were included in analyses of program effectiveness. Significant prevention effects were found for cigarette smoking, marijuana use, and immoderate alcohol use. Prevention effects were also found for normative expectations and knowledge concerning substance use, interpersonal skills, and communication skills.", "nan", "Most drug abuse prevention research has been conducted with predominantly White middle-class adolescent populations. The present study tested a school-based drug abuse preventive intervention in a sample of predominantly minority students (N = 3,621) in 29 New York City schools. The prevention program taught drug refusal skills, antidrug norms, personal self-management skills, and general social skills in an effort to provide students with skills and information for resisting drug offers, to decrease motivations to use drugs, and decrease vulnerability to drug use social influences. Results indicated that those who received the program (n = 2,144) reported less smoking, drinking, drunkenness, inhalant use, and polydrug use relative to controls (n = 1,477). The program also had a direct positive effect on several cognitive, attitudinal, and personality variables believed to play a role in adolescent substance use. Mediational analyses showed that prevention effects on some drug use outcomes were mediated in part by risk-taking, behavioral intentions, and peer normative expectations regarding drug use. The findings from this study show that a drug abuse prevention program originally designed for White middle-class adolescent populations is effective in a sample of minority, economically disadvantaged, inner-city adolescents.", "For the last three years, the University of New Mexico School of Medicine/Division of Emergency Medicine has sponsored an Alcohol and Substance Abuse Prevention Program (ASAP). The program's objectives were to expose youth to the \"real-life\" social and medical consequences of alcohol and substance abuse through visits and interviews with patients and their families at the University of New Mexico Emergency Department and Trauma Center. A pretest, post-test, and eight-month follow-up evaluation design was used to assess the program's effects. Questionnaires were administered to randomly selected experimental and control groups of seventh grade students (n = 27). Repeated-measures analysis of variance detected a significant experimental/control condition x time crossover interaction effect for stated perception of riskiness, F (2, 31) = 3.20, P = .049. The data indicated that, over time, the experimental group perceived the riskiness of driving under the influence of drugs or alcohol to be greater, while the control group perceived such behavior to be less risky.", "In recent years successful strategies developed in the antismoking campaign became the basis for widely publicized and federally endorsed antidrug \"Just Say No\" programs. Similarly, many refusal skills programs have been introduced as a new strategy in adolescent drug abuse prevention. However, none of these programs have been evaluated. While employing a typical refusal skills program entitled \"WHOA! A Great Way To Say NO,\" the effectiveness of the program was examined. Through this outcome evaluation, it has been learned that the program was not able to impact on the \"high-risk\" attitudinal syndromes that are closely related to student drug involvement. Unexpectedly, a significantly larger proportion of students in the program felt it was more difficult to say \"No\" at the time of the posttest than during the time of the pretest. This seems to suggest that the program participants became more attentive to the issues surrounding saying \"No\" or, perhaps, were more sensitized to the whole issue involving saying \"No,\" thereby making it more difficult for them to say \"No\" during the posttest period.", "Two drug abuse prevention curricula were tested to determine their efficacy in preventing the onset of tobacco, alcohol, and marijuana use among adolescents. The first program focused on prevention through social pressure resistance training. The second featured affective education approaches to prevention. Curricula were tested on seventh grade students. Subjects were pretested just prior to the program and were post-tested at 12 and 24 months. Post-test analyses indicated that the social program delivered to seventh grade subjects was effective in delaying the onset of tobacco, alcohol, and marijuana use. No preventive effect of the affective education program was observed. By the final post-test, classrooms that had received the affective program had significantly more drug use than controls.", "We evaluated the revised Project ALERT drug prevention program across a wide variety of Midwestern schools and communities.\n Fifty-five South Dakota middle schools were randomly assigned to program or control conditions. Treatment group students received 11 lessons in 7th grade and 3 more in 8th grade. Program effects for 4276 8th-graders were assessed 18 months after baseline.\n The revised Project ALERT curriculum curbed cigarette and marijuana use initiation, current and regular cigarette use, and alcohol misuse. Reductions ranged from 19% to 39%. Program effects were not significant for initial and current drinking or for current and regular marijuana use.\n School-based drug prevention programs can prevent occasional and more serious drug use, help low- to high-risk adolescents, and be effective in diverse school environments.", "Examined the impact of two treatment strategies on children's drug refusal skills and drug-related information. Fifty-seven third graders were randomly assigned to one of three groups: rehearsal-plus, general information, and control. Children in the rehearsal-plus group were taught drug knowledge, assertiveness skills, decision-making skills, rationale and specific drug refusal skills in the context of a skills-based strategy. At a more global level, the general information group targeted all of the same components with the exception of rationale. Results indicated that children in the skills-based strategy (rehearsal-plus) showed significant improvement in behavioral skills, decision-making, and rationale, while children in the information/education-based strategy (general information) improved most on the measure of general knowledge. At follow-up, gains were generally maintained.", "An alternatives-oriented, school-based drug abuse prevention program, Positive Alternatives for Youth (PAY), was evaluated over a 2-year period. Using a random-assignment, pretest-posttest control group design, 135 PAY students and 106 control group students were assessed on several attitudinal and behavioral measures of drug use. During the first year significant differences were detected between PAY and control students. Fewer differences were found in the second year, although a special analysis showed evidence of impact on PAY students rated as more involved in program activities. Reasons for specific results are discussed and implications are drawn for the alternatives approach and the field of drug abuse prevention.", "The effectiveness of a 20 session cognitive-behavioral approach to substance abuse prevention was tested on seventh grade students (n = 1,311) from 10 suburban New York junior high schools. The prevention strategy attempted to reduce intrapersonal pressure to smoke, drink excessively, or use marijuana by fostering the development of general life skills as well as teaching students tactics for resisting direct interpersonal pressure to use these substances. Additionally, this study was designed to compare the relative effectiveness of this type of prevention program when implemented by either older peer leaders or regular classroom teachers. Results indicated that the prevention program had a significant impact on cigarette smoking, excessive drinking, and marijuana use when implemented by peer leaders. Furthermore, significant changes were also evident with respect to selected cognitive, attitudinal, and personality predisposing variables in a direction consistent with non-substance use. These results provide further support for the efficacy of a broad-spectrum smoking prevention strategy and tentative support for its applicability to the prevention of other forms of substance abuse.", "Two strategies for preventing the onset of alcohol abuse, and marijuana and cigarette use were tested in junior high schools in Los Angeles and Orange Counties, California. The first strategy taught skills to refuse substance use offers. The second strategy corrected erroneous normative perceptions about prevalence and acceptability of use among peers and established conservative groups norms regarding use.\n Four experimental conditions were created by randomly assigning schools to receive (a) neither of the experimental curricula (placebo comparison), (b) resistance skill training alone, (c) normative education alone, or (d) both resistance skill training and normative education. Students were pretested prior to the program and post-tested 1 year following delivery of the program.\n There were main effects of normative education for summary measures of alcohol (P = 0.0011), marijuana (P = 0.0096), and cigarette smoking (P = 0.0311). All individual dichotomous measures of alcohol, marijuana, and tobacco use indicated significant reductions in onset attributable to normative education. There were no significant main effects of resistance skill training.\n These results suggest that establishing conservative norms is an effective strategy for preventing substance use.", "Results from a longitudinal experiment to curb drug use during junior high indicate that education programs based on a social-influence model can prevent or reduce young adolescents' use of cigarettes and marijuana. This multi-site experiment involved the entire seventh-grade cohort of 30 junior high schools drawn from eight urban, suburban, and rural communities in California and Oregon. Implemented between 1984 and 1986, the curriculum's impact was assessed at 3-, 12-, and 15-month follow-ups. The program, which had positive results for both low- and high-risk students, was equally successful in schools with high and low minority enrollment. However, the program did not help previously confirmed smokers and its effects on adolescent drinking were short-lived.", "This study presents two-year follow-up results of the Adolescent Decision-Making Program initially implemented when students were in their sixth grade. The intervention was found to maintain a positive effect on mean tobacco use, but no differences were observed for mean alcohol, marijuana, or hard drug use. In a test of the differential effectiveness of the intervention, program students living with married parents reported lower mean tobacco use than control students living with married parents and program and control students living with single parents. Logistic regression analyses examining the proportion of users at follow-up revealed a negative program effect for alcohol and no differences for the other substances. Subsequent attrition analyses strongly suggested that the positive effect for tobacco use at follow-up was most likely even stronger, and that the negative effect for alcohol was spurious. The importance of examining both program and attrition effects when evaluating the impact of longitudinal preventive interventions was emphasized, and the need to consider alternative models to guide the conceptualization and evaluation of adolescent substance use prevention programs was discussed.", "We examined the generalizability of a successful classroom-based prevention program developed for youth at alternative high schools (high risk) to youth at general high schools.\n A replication of a previously tested prevention program in a general high school population was conducted with 1-year follow-up data. Classrooms within each of three schools were randomly assigned to two conditions, classroom education or standard care control.\n Statistically significant effects on alcohol and illicit drug use were achieved in this population through a 1-year period following the program, although effects were not achieved on cigarette smoking and marijuana use.\n These results suggest that this program (Project Towards No Drug Abuse) has applicability to a wide range of older teens.\n Copyright 2001 American Health Foundation and Academic Press.", "This article describes the development and immediate impact of a self-instruction indicated drug abuse prevention program, Project Towards No Drug Abuse (TND). Self-instruction programming often is used to help youth that are at high risk for dropout and drug abuse to complete their high school education, and is a method of choice among educators at alternative high schools. This article describes the justification for the self-instruction program, keys to good programmed self-learning, and how a 12-session health educator delivered program was converted to a self-instruction format. In addition, the immediate impact of a 3-group experimental trial is presented. Health educator led, self-instruction, and standard care control conditions are compared on knowledge change, and the two program conditions are compared on process ratings. Self-instruction programming can be successfully adapted from a health educator-led format, though the lack of student group interaction in this modality may limit its receptivity among students.", "The purpose of the research reported herein was to associate prevention activities in the schools with abusing behaviors of the students, after statistically controlling relevant variables. Discrete activities and clusters of activities (\"programs\" or \"models\") were studied with a randomly assigned control group design. This approach was selected so that effective activities could be identified even against an overall background of increasing abuse during and after the prevention experience.", "Five hundred and eleven fourth, fifth, and sixth grade students and their parents from six schools in northwest Arkansas participated in this study. Students were blocked on school and grade level, then assigned randomly by class to either the intervention Keep A Clear Mind (KACM) program or a waiting list control. KACM students received four weekly correspondence lessons designed to be completed at home with a parent. KACM students reported significantly less perceived peer use of alcohol, tobacco, and marijuana, as well as significantly less peer pressure susceptibility to experiment with cigarettes. Mothers in the KACM program reported significantly more recent and frequent communication with their children about refusing drugs, and significantly greater discussions with their children regarding how to resist peer pressure to use alcohol, tobacco, and marijuana. Intervention program fathers reported significantly more communication with their children concerning how to resist peer pressure to drink alcohol and use tobacco, and significantly greater motivation to help their children avoid drug use. No significant differences were found between groups on student intentions to use drugs. These data suggest a print medium that emphasizes parent-child activities holds promise for accessing families and enhancing drug prevention communication." ]

[ "2753302", "3542496", "7890905", "8574231", "3287167", "2199290", "11069317", "11943949" ]

[ "Treatment of alcoholic hepatitis with colchicine. Results of a randomized double blind trial.", "[Colchicine therapy of fibrosing liver diseases--report of a randomized double-blind study].", "A double-blind randomized controlled trial of colchicine in patients with hepatitis B virus-related postnecrotic cirrhosis.", "[Colchicine in chronic liver disease of alcoholic etiology. Double-blind, randomized study of its effects on blood levels of plasma proteins and clinical course in patients].", "Colchicine in the treatment of cirrhosis of the liver.", "Failure of colchicine to improve short-term survival in patients with alcoholic hepatitis.", "Unfavourable effects of colchicine in combination with interferon-alpha in the treatment of chronic hepatitis C.", "Lack of effect of colchicine in alcoholic cirrhosis: final results of a double blind randomized trial." ]

[ "A randomized double-blind trial of colchicine vs placebo was conducted in 67 patients with histologically proven alcoholic hepatitis, 33 of whom had cirrhosis. Patients with hepatic encephalopathy, ascites, protracted prothrombin time, severe thrombocytopenia, hepatocellular carcinoma, evident lack of discipline or refusal to participate in the trial were not included. Thirty-three patients received colchicine (1 mg/day) and 34 received placebo for 6 months. Blood parameters including N-terminal peptide of type III procollagen were assessed in the serum, and a percutaneous liver biopsy was performed at the start of the trial and after 3 and 6 months. Alcoholic hepatitis and fibrosis scores were established for each biopsy specimen. Twenty-eight percent of patients were lost to follow-up at 3 months, and fifty-two percent at 6 months. One patient died of liver failure. Fifty-eight percent of patients were abstaining from alcohol at 3 months and fifty percent at 6 months. No significant effect of treatment was noted. Nevertheless, improvement in alcoholic hepatitis core at 3 months was more important in the colchicine group than in the placebo group. No side-effects were noted except transient diarrhea. Our results suggest that colchicine has no important effect on the course of alcoholic hepatitis. A trial including of at least 260 patients might be necessary for the observed alcoholic hepatitis score difference at 3 months, favoring colchicine, to be statistically significant.", "It is reported on results of a double blind study of colchicine therapy in fibrotic liver diseases over a period of three years. The study includes 74 probands; 37 of them had been treated after randomization for five days a week with 4 X 0,25 mg/d colchicine, 37 with placebo. 53 probands attained the 12th month of treatment, 43 of them 24th, 24 probands were in the study for 36 months. 3 diagnoses groups had been formed with regard to the histological grades of fibrosis: chronic hepatitis (without structural transformation); structural liver transformation/moderate liver cirrhosis; severe liver cirrhosis. In 38 cases the disease was caused by alcohol. 45 data had been studied (clinical results, paraclinical data concerning hepatological diagnostic and connective tissue metabolism and morphologic data). The biometric evaluation was carried out with the stage variant analysis by Friedman. Rebiopsies have been carried out in 40 probands after 1 year, in 4 probands after 2 years. 4 data (Serumalbumine, Gamma-GT, ALAT, KP) showed significant changes in the colchicine-group as well as in the placebo-group. In both therapy groups the morphologic supervisions of the fibrosis grades (rebiopsies) showed improvements, no changes, and deterioration about in the same frequency. In this study there was no effectiveness of colchicine on the course of fibrotic liver diseases to be stated. Concerning the contradictions in the recent literature and probable the insufficient colchicine dose, the authors recommend further studies on colchicine therapy in liver diseases with incipient i.e. reversible fibrosis.", "The preliminary results of a prospective double-blind controlled trial of colchicine in 100 patients with hepatitis B virus-related cirrhosis are reported. The patients, 94 males and 6 females, aged 32-80, were assigned to receive either 1 mg of colchicine or an identical placebo orally on a daily basis. The duration of the follow up ranged from 15 to 51 months (median 26 months). Seventy percent had histological proof of cirrhosis. On entry, 80 patients were in Child-Pugh class A, 19 were in class B, and one was in class C. Compared to the placebo group, there was no improvement in the colchicine group after a 24-month follow up in any of the biochemistry data, for example, serum albumin, alkaline phosphatase, alanine and aspartate aminotransferase, bilirubin, and prothrombin time. The difference in the cumulative survival rates at 51 months did not reach statistical significance (p = 0.8) in either group. There was no histological improvement in 30 patients who were willing to undergo repeated liver biopsies. No trend toward improvement of the hepatic pressure gradient was observed in these patients. The serum levels of aminopropeptide of type III procollagen increased significantly in patients in both groups after 24 months of therapy (1.07 +/- 0.06 vs. 1.36 +/- 0.06 U/ml in the colchicine group, 0.93 +/- 0.09 vs. 1.25 +/- 0.07 U/ml in the placebo group; p < 0.05). In addition, neither the clinical deterioration of cirrhosis nor death was prevented in patients receiving colchicine therapy. This report indicates that colchicine has no effect in the treatment of HBV-related postnecrotic cirrhosis.", "Patients with alcoholic chronic liver disease when treated with colchicine during a 12 month-period improved significantly the plasmatic levels of albumin and prothrombin when compared with a similar group of patients who took placebo. No differences in the mortality rate and in number of patients admitted at the hospital could be detected among those groups during this period.\n To evaluate the clinical outcome and the plasmatic levels of albumin, pre-albumin, prothrombin and transferrin in patients presenting alcoholic chronic liver disease taking colchicine or placebo, during a 12-month period.\n In a double-blind, randomized, controlled trial, 41 patients with alcoholic chronic liver disease were assigned to either placebo (20 patients) or a colchicine (21 patients) treatment group, assessing their clinical course (mortality rate and hospital admission) and plasmatic protein levels during a 12-month period. Albumin, pre-albumin and transferrin plasmatic levels were assessed through a immunodiffusion radial method and prothrombin time and activity was assessed by a one stage Quick modified method.\n At the end of the trial, only 7.3% of the patients were lost during follow-up. No statistical differences could be found in mortality and number of patients admitted at the hospital among placebo and colchicine groups. Comparatively to the placebo group, a significant increase in the mean of percentage variation was found in patients of the colchicine group for serum albumin levels (17.9% colchicine x 3.6% placebo, p < 0.05) and for prothrombin activity (19.2% colchicine x 2.1% placebo, p < 0.05). A similar pattern of response was found in pre-albumin serum levels, but such differences were not statistically different. No differences were found in serum transferrin levels among both groups.\n These results suggest that colchicine intake has a positive effect on plasmatic protein levels in patients with alcoholic chronic liver disease.", "There is preliminary evidence that colchicine, an inhibitor of collagen synthesis, may be beneficial in the treatment of cirrhosis of the liver. To evaluate the use of colchicine (1 mg per day, five days per week) in the treatment of hepatic cirrhosis, we performed a randomized, double-blind, placebo-controlled trial in which 100 patients were followed for up to 14 years. Forty-five patients had alcoholic cirrhosis, 41 had posthepatitic cirrhosis, and the remaining 14 had cirrhosis with various other causes. Histologic studies were available for 92 percent of patients. Seventy-three patients were in Child-Turcotte class A, 26 were in class B, and one was in class C. Fifty-four patients received colchicine, and 46 received placebo. The overall survival in the colchicine group was markedly better than in the placebo group (median survival, 11 and 3.5 years, respectively; P less than 0.001). The cumulative 5-year survival rates were 75 percent in the colchicine group and 34 percent in the placebo group; the corresponding 10-year survival rates were 56 percent and 20 percent. Among the 30 patients treated with colchicine who underwent repeated liver biopsies, histologic improvement was seen in 9; the liver appeared normal in 2, and 7 had minimal portal fibrosis. No histologic improvement was observed in the 14 members of the placebo group who had two or more biopsies. Few side effects were observed in either group.", "Colchicine treatment was used in this randomized placebo-controlled trial in patients with severe acute alcoholic hepatitis [serum bilirubin greater than or equal to 5 mg/dL (85.5 mumol/L) mean, 17.5 +/- 7.5 mg/dL (299.25 +/- 128.25 mumol/L)]. Hospitalization mortality and morbidity and the effect on biochemical test results were the end points of the treatment. Patients in the two groups were evenly matched by demographics and laboratory test results. Mean time to study entry was less than 7 days from admission. The duration of the trial was 30 days. Thirty-six patients (24 men, 12 women) received colchicine (1 mg orally every morning) and 36 (25 men, 11 women) received an identical placebo. Seven (19%) colchicine-treated and six (17%) control patients died during the index hospitalization after a mean of 17.4 +/- 10.8 and 17.8 +/- 5.3 days, respectively (NS). During a 4-month follow-up period from entry into the trial, there were two additional deaths in each group. No differences between placebo- and colchicine-treated patients were observed in any of the laboratory parameters (serum bilirubin, aspartate transaminase, alanine transaminase, prothrombin activity, albumin, white blood cell count, hemoglobin, and creatinine) that were followed up over the 30-day treatment period. The frequency of complications did not differ statistically between the two groups. This study showed no effect of colchicine treatment on mortality and morbidity of severe alcoholic hepatitis. Colchicine cannot be recommended for the treatment of patients with alcoholic hepatitis.", "The prognosis of chronic hepatitis depends on the progression of hepatic fibrosis.\n To investigate whether the antifibrotic drug colchicine, in combination with interferon-alpha has a role in the treatment of chronic hepatitis C.\n Sixty-five HCV-RNA positive patients with chronic hepatitis were randomized to receive interferon-alpha, 6 MU t.i.w. for 6 months followed by 3 MU t.i.w. for further 6 months, with or without the adjunct of colchicine, 1 mg o.d., 6 days a week, for 3 years. We report an interim analysis after the first 18 months.\n Thirty-four patients received interferon-alpha and 31 received interferon-alpha and colchicine. The two groups were comparable for baseline data, including HCV-RNA levels, genotypes and histological grading/staging. Drop-outs and side-effects were similar. The proportion of patients who achieved alanine transaminase normalization or undetectable HCV-RNA at month 6 was higher in the interferon-alpha (68% and 47%, respectively) than in the interferon-alpha plus colchicine group (32% and 23%, P=0.004 and P=0. 04, respectively). End-of-treatment biochemical and virological response occurred in 41% and 29% of the interferon-alpha and 19% and 10% of the combination group, respectively (P=0.05 and P=0.05). Sustained biochemical response occurred in 26% of the interferon-alpha and 6% of the interferon-alpha plus colchicine group (P=0.03), corresponding percentages of sustained HCV-RNA loss being 21% and 3% (P=0.04).\n The combination of colchicine and interferon-alpha worsens the effectiveness of interferon-alpha alone in HCV chronic hepatitis. These alarming findings prompted us to interrupt the trial at this stage.", "Colchicine, an inhibitor of collagen synthesis, has been suggested as potentially beneficial in cirrhosis.\n This long-term, randomized, double blind, placebo controlled trial was conducted in order to evaluate the efficacy of colchicine in alcoholic cirrhosis.\n Ambulatory patients with biopsy proven alcoholic cirrhosis, presenting from 1989 to 1997, with no exclusion criteria (e.g. Child-Pugh C, bilirubin > 10 mg/dl and gastrointestinal bleeding in the previous 15 days), were randomized to receive orally, 5 days/week, 1 mg/day of colchicine or placebo.\n Results were analysed on an intention to treat basis, for survival, incidence of complications, biochemical liver tests and safety.\n Twenty-nine patients received colchicine and 26 placebo; characteristics of both groups were similar. The median follow-up was 40.6 (1.4-126.3) months in the colchicine versus 42.4 (5.7-118.2) months in the placebo group (NS). No significant side effects were reported. During follow-up, there were no significant differences in compliance and alcohol abstinence (86% vs 85%). Overall survival was not statistically different (P = 0.38). Cumulative 3-year survival rates were 74.9% in the colchicine versus 91.4% in placebo group (NS). The annual incidence rate of complications was similar with colchicine or placebo: gastrointestinal bleeding, 1.5% vs 1.2%; ascites, 3.7% vs 3.7%; and encephalopathy, 1.0% vs 0.9%. The comparison of changes in biochemical parameters between groups did not show any significant difference.\n Although well tolerated, colchicine does not appear to overcome the progression and natural history of long-established alcoholic cirrhosis." ]

[ "15171968", "7192170", "8608288", "10522767", "10920832" ]

[ "Nurse-led follow-up on demand or by a physician after breast cancer surgery: a randomised study.", "Effect of counselling on the psychiatric morbidity associated with mastectomy.", "Psychological support for patients undergoing breast cancer surgery: a randomised study.", "Effects of a nursing intervention on subjective distress, side effects and quality of life of breast cancer patients receiving curative radiation therapy--a randomized study.", "Effects of advanced nursing care on quality of life and cost outcomes of women diagnosed with breast cancer." ]

[ "The value of routine follow-up with frequent visits to a breast cancer specialist-both in terms of detection of recurrence and patient satisfaction-has been questioned. The aim of this study was to compare nurse-led follow-up on demand versus physician follow-up after breast cancer treatment with regards to patients' well-being, satisfaction, access to medical care and medical safety. Two hundred and sixty-four consecutively selected women with newly diagnosed breast cancer, classified as UICC stage I or stage II, were randomised to follow-up at two hospitals in Sweden, either by routine medical follow-up, the physician group (PG, n=131), or on demand by a specialist nurse, the nurse group (NG, n=133). Measures were done at baseline and twice a year over a period of 5 years by means of a questionnaire containing the Hospital Anxiety and Depression Scale (HAD), and the Satisfaction and Accessibility (SaaC) scale. Number of contacts with the health care services, number of diagnostic procedures, and time to recurrence or death were monitored. The ratings of HAD and SaaC did not show any statistically significant differences between the groups. The levels of anxiety and depression were generally low and levels of patient satisfaction high. There were no differences between the groups concerning time to recurrence or death. This study indicates that women with breast cancer in stages I to II can be followed up by a specialist nurse with high patient satisfaction and good medical safety.", "A controlled trial was conducted to determine whether counselling by a specialist nurse prevented the psychiatric morbidity associated with mastectomy and breast cancer. Seventy-five patients were counselled by the nurse and monitored during follow-up, while 77 patients received only the care normally given by the surgical unit. Counselling failed to prevent morbidity, but the nurse's regular monitoring of the women's progress led her to recognise and refer 76% of those who needed psychiatric help. Only 15% of the control group whose condition warranted help were recognised and referred. Consequently, 12 to 18 months after mastectomy there was much less psychiatric morbidity in the counselled group (12%) than in the control group (39%). These findings highlight the high degree of psychiatric morbidity in patients who have undergone mastectomy and indicate the need to find ways of reducing this morbidity.", "To evaluate the effect of support from a nurse specialising in breast care and a voluntary support organisation on prevalence of psychological morbidity after surgery for breast cancer.\n Prospective randomised study.\n Three teaching hospitals in Glasgow with established breast clinics.\n 272 women aged less than 70 years undergoing surgery for breast cancer.\n Patients were randomly allocated to receive routine care from ward staff, routine care plus support from breast care nurse, routine care plus support from voluntary organisation, or routine care plus support from nurse and organisation.\n Prevalence of psychological morbidity as assessed by self rating scales: 28 item general health questionnaire and its subscales, and hospital anxiety and depression scale. Measurements were made at first postoperative clinic visit and at three, six, and 12 months after surgery.\n On each self rating scale, psychological morbidity tended to fall over the 12 month period. For each scale, scores were consistently lower in patients offered support from breast care nurse alone compared with the other groups, which were similar to each other. Differences were significant or nearly so: P values were 0.015 (28 item general health questionnaire), 0.027 (anxiety and insomnia), 0.072 (severe depression), 0.053 (somatic symptoms), 0.031 (social dysfunction), 0.093 (hospital anxiety), and 0.003 (hospital depression).\n Support from breast care nurse can significantly reduce psychological morbidity, as measured by self rating scales, in women undergoing breast cancer surgery.", "The purpose of this randomized study was to investigate whether a nursing intervention using Orem's self-care theory as a framework would affect subjective distress, side effects and quality of life as perceived by breast cancer patients receiving curative radiation therapy. The intervention consisted of five 30-min sessions once a week during the treatment period and two follow-up sessions after completion of treatment. The experimental group consisted of 67 patients, as did the control group. Measurements were collected five times: at baseline before commencement of treatment, at weeks 3 and 5 (completion of treatment) and follow-up periods of 2 weeks and 3 months. No measurable effect of the nursing intervention was found for side effects or quality of life but nursing intervention proved to have a positive effect in minimizing stress reactions (p = < 0.05). It is suggested that a nursing intervention should be implemented for breast cancer patients receiving curative radiation therapy.", "To evaluate quality of life (QOL) and cost outcomes of advanced practice nurses' (APNs') interventions with women diagnosed with breast cancer.\n Randomized clinical trial.\n Integrated healthcare system in a midwestern suburban community.\n 210 women with newly diagnosed breast cancer with an age range of 30-85 years.\n The control group (n = 104) received standard medical care. The intervention group (n = 106) received standard care plus APN interventions based on Brooten's cost-quality model and the Oncology Nursing Society's standards of advanced practice in oncology nursing QOL was measured using the Functional Assessment of Cancer Therapy, Mishel Uncertainty in Illness Scale and Profile of Mood States at seven intervals over two years. Information about costs (charges and reimbursement) was collected through billing systems.\n Uncertainty, mood states, well-being, charges, and reimbursement.\n Uncertainty decreased significantly more from baseline in the intervention versus control group at one, three, and six months after diagnosis (p = 0.001, 0.026, and 0.011, respectively), with the strongest effect on subscales of complexity, inconsistency, and unpredictability. Unmarried women and women with no family history of breast cancer benefited from nurse interventions in mood states and well-being. No significant cost differences were found.\n APN interventions improved some QOL indicators but did not raise or lower costs.\n The first six months after breast cancer diagnosis is a critical time during which APN interventions can improve QOL outcomes. More research is necessary to define cost-effective interventions." ]

[ "11832576", "7039663", "1547164" ]

[ "Is in-patient management of diastolic blood pressure between 90 and 100 mm Hg during pregnancy necessary?", "A randomized controlled trial of complete bed rest versus ambulation in the management of proteinuric hypertension during pregnancy.", "Does admission to hospital for bed rest prevent disease progression or improve fetal outcome in pregnancy complicated by non-proteinuric hypertension?" ]

[ "A randomised controlled trial was performed at the Queen Elizabeth Hospital to compare the effects and acceptance of routine in-patient versus out-patient management of diastolic blood pressure between 90 and 100 mm Hg in pregnant women. There were no significant differences in the establishment of the diagnosis of hypertension, development of severe hypertension or proteinuric hypertension, the number of women requiring obstetric interventions, or the neonatal outcome between the two groups. Antenatal hospital stay for the in-patient group, however, was more than twice as long as for the out-patient group (difference in mean stay, 3.7 days; 95% confidence interval, 1.3-6.2). The number of hospitalisations in the in-patient group was almost four times greater than that in the out-patient group (difference in mean number of hospitalisations, 1.7; 95% confidence interval, 1.2-2.2). The two groups did not differ in their levels of satisfaction of the overall management of blood pressure. Nevertheless, a greater proportion of women preferred to choose the same type of care among the out-patient group than among the in-patient group if they had hypertension in a future pregnancy (83.7% versus 51.2%; P<0.001). More women were dissatisfied about the number of admissions than on the frequency of out-patient care (40.5% versus 16.3%; P<0.001). We conclude that in-patient care, day care, or home monitoring should be individualised.", "Forty patients participated in a randomized controlled trial of complete bed rest versus ambulation as desired in the management of proteinuric hypertension during pregnancy. Daily increases in serum human placental lactogen and oestriol concentrations were greater in the rested group. An especially 'at risk' group of 10 patients with both hyperuricaemia and severe fetal growth retardation was identified. Strict confinement to bed in these cases seemed to encourage the development of the premonitory symptoms of eclampsia, but was associated with a better prognosis for the fetus.", "To test whether a policy of admission to hospital for rest is of value in the management of women with non-proteinuric hypertension during pregnancy.\n A randomized controlled trial.\n Harare Maternity Hospital, Zimbabwe.\n 218 (28 first pregnancies) women with non-proteinuric hypertension and a singleton pregnancy at between 28 and 38 weeks gestation allocated to rest in hospital or routine outpatient care.\n Admission to hospital for rest. Encouraged to rest in bed although voluntary ambulation around the ward was allowed. The women in the control group were encouraged to continue normal activity at home, to check urine each day for proteinuria. All the women were reviewed weekly.\n Disease progression was assessed by the development of severe hypertension (greater than or equal to 160/110 mmHg), development of proteinuria, need for induction of labour and number of infants born preterm (less than 37 weeks). Fetal outcome was assessed by birthweight, number of infants small-for-gestational age (SGA), and the number of infants requiring admission to the neonatal unit and their length of stay.\n The hospital rest group had a decreased risk of developing severe hypertension (blood pressure greater than or equal to 160/110 mmHg [odds ratio 0.47, 95% CI 0.26-0.83]). No differences were found in fetal growth or neonatal morbidity. The mean antenatal stay in hospital was 22.2 (SD 16.5), and 6.5 (SD 7.9) days in the rest and control groups, respectively.\n Hospital admission for bed rest decreased the risk of developing severe hypertension but no improvement in fetal growth or neonatal morbidity was observed. Fetal monitoring at home and continued outpatient antenatal care provided a safe, alternative policy to hospital admission." ]

[ "8829299", "7672141", "9262927", "1755466", "1348806", "1855380", "7796764", "3168444", "16183590", "3168445", "8876092" ]

[ "An assessment of the nine-month lactational amenorrhea method (MAMA-9) in Rwanda.", "Effectiveness of the lactational amenorrhea method in Pakistan.", "Multicenter study of the Lactational Amenorrhea Method (LAM): I. Efficacy, duration, and implications for clinical application.", "Santiago Breastfeeding Promotion Program: preliminary results of an intervention study.", "Clinical study of the lactational amenorrhoea method for family planning.", "Contraceptive efficacy of lactational amenorrhea in urban Chilean women.", "A study of breastfeeding and the return of menses in Hoima District, Uganda.", "Breastfeeding pattern and the duration of lactational amenorrhea in urban Chilean women.", "Breast-feeding, return of menses, sexual activity and contraceptive practices among mothers in the first six months of lactation in Onitsha, South Eastern Nigeria.", "Lactational amenorrhea and the recovery of ovulation and fertility in fully nursing Chilean women.", "Effectiveness of lactational amenorrhoea in prevention of pregnancy in Manila, the Philippines: non-comparative prospective trail." ]

[ "This report presents a secondary data analysis based on prospectively collected records gathered during a field assessment that was carried out in Rwanda in August 1993. The assessment used service statistics and follow-up interviews to evaluate the efficacy of a modified lactational amenorrhea method (LAM) as a nine-month introductory postpartum natural family planning method. The program, carried out by Action Familiale Rwandaise (AFR), reflects high efficacy of the method in a compliant sample that sought this method followed by another form of family planning. These results are promising and provide guidance for the extended use of LAM past six months. Programmatic findings suggest that studies be conducted of the contribution of extended LAM to improved weaning practices, the high efficacy of continued reliance on substantial lactation and amenorrhea beyond nine months, and male involvement in LAM and breastfeeding.", "To determine the efficacy of the lactational amenorrhea method of family planning (amenorrhea during full or nearly full breastfeeding for 6 months postpartum).\n Prospective noncomparative study.\n Normal breastfeeding women in Karachi and Multan, Pakistan, most delivered at home by a midwife.\n Three hundred ninety-nine newly delivered mothers who successfully had breastfed a previous child and chose the lactational amenorrhea method to prevent a subsequent pregnancy, 391 of whom were followed for a full year.\n Mothers were taught, before or shortly after delivery, to use the method and were interviewed in their homes each month by a Lady Health Visitor.\n Life-table pregnancy rates. Periods of postpartum or lactational abstinence were excluded in the calculation of the pregnancy rates.\n During full or nearly full breastfeeding, while the women were amenorrheic and not otherwise contracepting, the rate of pregnancy was 0.6%. The pregnancy rate during lactational amenorrhea alone was 1.1% at 1 year postpartum.\n The lactational amenorrhea method was found to be highly effective for 6 months. A high degree of contraceptive protection endures for a full year during lactational amenorrhea, but not after the return of menses during breastfeeding.", "A multicenter study of the Lactational Amenorrhea Method (LAM) was carried out to test the acceptability and efficacy of the method. Additionally, the data are used to test new constructs for improvement of method criteria. A protocol was designed at the Institute for Reproductive Health (IRH), Department of Obstetrics and Gynecology, Georgetown University Medical Center, a World Health Organization (WHO) Collaborating Center, and was reviewed and modified in collaboration with the co-sponsors, the World Health Organization and the South to South Cooperation for Reproductive Health, and the principal investigators from each site. Data were gathered prospectively on LAM acceptors at 11 sites. Data were entered and cleaned on-site and further cleaned and analyzed at IRH, using country-level and pooled data to produce descriptive statistics and life tables. The 98+% efficacy of LAM is confirmed in a wide variety of settings. In addition, the results yield insight on the possibility of continued use beyond 6 months. LAM is found to be highly effective as an introductory postpartum method when offered in a variety of cultures, health care settings, socio-economic strata, and industrial and developing country locales. In addition, LAM acceptance complements breastfeeding behaviors without ongoing breastfeeding support services. The parameters studied yield high efficacy and method continuation. Therefore, the basic tenets of the 1995 Bellagio consensus on LAM is reconfirmed and it is recommended that LAM be reconfirmed and it is recommended that LAM be incorporated into hospital, maternity, family planning, maternal and child health, and other primary health care settings.", "A prospective intervention study was undertaken in Santiago, Chile, to assess the impact of a breastfeeding promotion program and the acceptance and use of the lactational amenorrhea method for natural child spacing. The intervention study significantly increased the duration of exclusive breastfeeding and amenorrhea. In addition, the use of the lactational amenorrhea method proved highly efficacious, with an unplanned pregnancy rate of less than 0.5% by 6-month cumulative life table. Total family planning coverage at 6 months was increased in the intervention group.", "The effect of breastfeeding on fertility is well known; however, its use as a method of family planning was, until recently, untested. In 1988, the Bellagio Consensus Conference proposed guidelines that became the basis for a method of family planning called the lactational amenorrhoea method (LAM). The principle of LAM is that a woman who continues to fully or nearly fully breastfeed her infant and who remains amenorrhoeic during the first 6 months postpartum is protected from pregnancy during that time. We have assessed this method in the context of a breastfeeding support intervention study of 422 middle-class women in urban Santiago, Chile. The cumulative 6-month life-table pregnancy rate was 0.45% among women who relied on LAM as their only family planning method (1 woman pregnant in month 6). The findings indicate that LAM, with its high acceptance and efficacy, is a viable method of family planning and can safely serve as an introductory method for breastfeeding women.", "The contraceptive efficacy of breastfeeding was assessed in 236 healthy urban women who were followed at monthly intervals during the first postpartum year. Proportional hazard models were used to evaluate the influence of time postpartum, menstrual status and breastfeeding pattern upon the risk of pregnancy. Time and menstrual status had a highly significant effect on this risk. Those women who remained in amenorrhea had cumulative probabilities of pregnancy of 0.9% and 17% at 6 and 12 months postpartum, respectively. In those who recovered menstrual cycles, the risk rose to 36% and 55% at 6 and 12 months, respectively. Milk supplementation also increased significantly the risk when considered alone but not when time and/or menstrual status were included in the analysis. However, amenorrheic women who introduced bottle feeding, had a higher risk of pregnancy after 6 months postpartum than those who remained fully nursing. The analysis was unable to detect a significant influence of the nursing frequency. The results confirm that lactational amenorrhea is an effective contraceptive during the first six months postpartum. The first postpartum bleeding marks a great increase in the risk of pregnancy. Supplementation also increases the risk, particularly in amenorrheic women.", "The effect of breastfeeding on reestablishment of ovulation and fertility and on birth spacing are now well known. A study was conducted on lactational amenorrhoea (LAM) at 180 days in Hoima District, Uganda in order to understand whether and how LAM could be applied in fertility control and birth spacing. Since the introduction of supplementary food by Ugandan women does not replace or substitute for breastfeeding, a study was designed to determine if LAM was effective irrespective of supplementation of infant's diet. One hundred and fifty four mother/child pairs were entered into the study and 134 women completed the sixth month of the study. At the end of the period, eighty four women (62.7%) were amenorrhoeic of whom only 33 (39.3%) were exclusively breastfeeding and no woman had dropped out of the study because of pregnancy or the use of other family planning methods other than LAM. The study confirmed that LAM could be applicable in Uganda to the majority of the breastfeeding women (62.7%). It is expected that if health workers increase the intensity of breastfeeding support as well as the women's knowledge and motivation to use LAM for family planning, this would contribute to children's health as well as to birth spacing that is one of the major factors related to infant deaths. According to data from this study, the return of menses is irrespective of whether supplements have been introduced and their frequency.", "The influence of the breastfeeding pattern and several clinical variables upon the duration of postpartum amenorrhea was assessed in a group of healthy women selected for having had a normal pregnancy and delivery and being highly motivated for prolonged breastfeeding on demand. 676 women who were fully nursing at the second month postpartum entered the study. Supplements were administered to 11% and 48% of the infants by the end of the 3rd and 6th month, respectively. The first bleeding was experienced before the end of the sixth month postpartum by 57% of the cases. Supplementation had a strong negative influence while nursing frequency had a significant positive influence upon the length of amenorrhea. Notwithstanding, a frequency of 8+ suckling episodes per 24 h could not maintain amenorrhea in around half of the subjects. Age and parity had a moderate negative influence upon the risk of experiencing the first postpartum bleeding. Maternal weight and ponderal index, infant sex, birth weight and growth rate showed no significant influence upon the length of amenorrhea. In this urban population selected for having the highest motivation and best breastfeeding performance, the association of breastfeeding with amenorrhea was weak in comparison with what has been described for other populations. The risk of experiencing the first bleeding was reduced while fully breastfeeding with a high number of nursing episodes per day and night, particularly in older women with higher parity. But even in such situation 25% and 50% of the women had started to cycle by the end of the fifth and eight postpartum month.", "The objective of this study was to determine the exclusive breast-feeding practices, return of menstruation, sexual activity and contraceptive practices among breast-feeding mothers in the first six months of lactation. The study was based in Onitsha, South Eastern Nigeria. A structured questionnaire was used to obtain data from breast-feeding mothers on their age, educational attainment, breast-feeding practices, return of menstruation, sexual activity and contraceptive practices within the first six months of lactation at intervals of 6 weeks, 10 weeks 14 weeks and 6 months post delivery. Analysis of the information obtained showed that out of the 178 mothers who participated in the study 81% of the mothers were within the ages of 20 - 34 years. While all the mothers had formal education, the majority (59%) had secondary education. Seventy-three percent initiated breast-feeding within one hour of delivery. On discharge from hospital, all of them had already established breast-feeding which continued up to six weeks and dropped to 97.8% at six months. Exclusive breast-feeding which was practised by 100% on discharge dropped to 3.9% at six months. The feeding regimen was on demand as practised by 98.9% of the mothers. Menstrual flow had returned in 33.8% of the mothers by 6 weeks of lactation, and had risen to 70.2% at six months. There was more prolonged lactational amenorrheoa in exclusively breast-feeding mothers than in those who were not. By 6 weeks post delivery 31.6% of the mothers had resumed sexual activity and this rose to 93.6% at six months. With the resumption of sexual activity only 5% of the mothers resorted to contraceptive practices other than lactational amenorrhea and this increased to 54% at six months. There was no pregnancy in any of these women during the six months period. While appreciating the role of lactational amenorrhea in child spacing and considering the early return of sexual activity among the mothers the practice of introducing contraceptive practices needs to be encouraged especially in women whose menstruation has returned.", "The probability of experiencing the first postpartum bleeding, the first ovulation and the risk of pregnancy during exclusive breastfeeding was assessed in a selected group of urban Chilean women. Admission criteria included having had a normal pregnancy and a vaginal term delivery of a healthy infant and the desire to maintain breastfeeding for as long as possible. The risk of bleeding and the recovery of ovulation was assessed in 48 women selected for being amenorrheic and fully nursing at day 75 postpartum and their willingness to participate in the blood sampling protocol. The first bleeding and ovulation was experienced while fully nursing by 28% and 26% of these subjects, respectively, at day 180 postpartum. The probability of experiencing the first bleeding and the probability of pregnancy during full nursing were calculated for 236 women not contracepting who were enrolled during the first month postpartum. The cumulative probability of bleeding and of pregnancy was 52% and 9.4% at day 180 postpartum, respectively. The risk of pregnancy was less than 2% in the subset of amenorrheic cases. In this urban population selected for having the highest motivation and best breastfeeding performance, the association of breastfeeding with infertility was too weak to serve as an effective birth spacer, except for the period of lactational amenorrhea. When the first postpartum bleeding took place before the sixth postpartum month in fully nursing women, it had a good predictive value to indicate the onset of a higher risk period.", "To determine the contraceptive efficacy of the lactational amenorrhoea method.\n Non-comparative prospective trial.\n Urban Manila, the Philippines.\n 485 lower income, educated women with extensive experience of breast feeding.\n Women were offered all available contraceptives for use after birth. Those who chose the lactational amenorrhoea method were taught the method, screened for the study, and followed for 12 months to determine the risk of pregnancy when the method was used.\n Life table pregnancy rates during correct and incorrect use of the method, censored monthly in the event of sexual abstinence or the use of another contraceptive method.\n The lactational amenorrhoea method was 99% effective when used correctly (that is, during lactational amenorrhoea and full or nearly full breast feeding for up to six months). At 12 months the effectiveness during amenorrhoea dropped to 97%.\n The lactational amenorrhoea method provided as much protection from pregnancy as non-breast feeding women experience with non-medicated intrauterine devices and barrier methods. The contraceptive effect of lactation cannot be attributed to lactational or postpartum abstinence." ]

[ "16797162", "17194269", "7514366", "12860772", "7683702" ]

[ "A double-blind comparison of risperidone, quetiapine and placebo in patients with schizophrenia experiencing an acute exacerbation requiring hospitalization.", "A double-blind study of combination of clozapine with risperidone in patients with schizophrenia: effects on cognition.", "Risperidone in the treatment of schizophrenia.", "Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder.", "A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients." ]

[ "This study compared the effects of atypical antipsychotics (risperidone or quetiapine) with placebo and with each other in recently exacerbated patients with schizophrenia requiring hospitalization.\n This international, randomized, double-blind study included a 2-week monotherapy phase followed by a 4-week additive therapy phase. Recently exacerbated patients with schizophrenia or schizoaffective disorder (DSM-IV) were randomized (2:2:1) to risperidone (n = 153), quetiapine (n = 156), or placebo (n = 73). Target doses were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5, with the ability to increase to 600 or 800 mg/day of quetiapine on day 8. The main outcome measures were the total Positive and Negative Syndrome Scale (PANSS) and need for additional psychotropic medications.\n Monotherapy Phase: The combined atypical antipsychotic group (n = 308) reached borderline superiority to placebo (n = 71) at the 2-week endpoint on mean change in total PANSS score (-24.1 +/- 1.2 and -20.2 +/- 2.0, respectively; p = 0.067). The change in the atypical group was driven by the improvement with risperidone (-27.7 +/- 1.5 vs. -20.2 +/- 2.0 with placebo, p < 0.01; and vs. -20.5 +/- 1.5 with quetiapine, p < 0.01); the improvement with quetiapine was similar to placebo, p = 0.879. Results were similar on other efficacy endpoints. Additive Therapy Phase: Additional psychotropics were prescribed to fewer (p < 0.01) risperidone (36%) than quetiapine (53%) or placebo patients (59%). The overall discontinuation rate was 18%, 26%, and 38%, respectively. Risperidone, compared with placebo, was associated with more parkinsonism, akathisia, plasma prolactin changes, and weight gain; while quetiapine was associated with more somnolence, sedation, dizziness, constipation, tachycardia, thyroid dysregulation, and weight gain.\n While the combined atypical antipsychotic group did not experience greater improvements than the placebo group, risperidone, but not quetiapine, was significantly superior in all measured domains to placebo in the management of recently exacerbated hospitalized patients with schizophrenia or schizoaffective disorder, with no unexpected tolerability findings.", "Atypical antipsychotic drugs produce improvement in some domains of cognition as well as psychopathology in patients with schizophrenia. However, the effect of combinations of atypical antipsychotic drugs on cognitive function is unknown. The aim of this study was to compare the effect of risperidone or placebo on cognitive function in patients with schizophrenia who were previously treated with clozapine monotherapy.\n This prospective, randomized, double-blind, placebo-controlled, 6-week study included 30 patients with DSM-IV schizophrenia. Patients whose psychopathology was no more than partially responsive to clozapine treatment were randomly assigned to receive adjunctive treatment with risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Cognitive test scores for verbal learning and memory, verbal fluency, attention, executive function, verbal working memory, and motor function were the primary outcome measures. Secondary outcome measures included assessment of psychopathology, extrapyramidal side effects, and global functioning. Data were collected between November 2001 and July 2003.\n Significant improvement was found in both treatment groups in a variety of cognitive measures, but there was significantly greater improvement in the placebo-augmented group on measures of initial learning acquisition and attention. The improvement in cognition was not correlated with improvement in psychopathology. There were significant correlations between improvement in verbal working memory, verbal learning and memory, and attention and quality of life and global functioning in the placebo-augmented but not the risperidone-augmented group.\n Adjunctive treatment with risperidone for 6 weeks in patients with schizophrenia who had received chronic treatment with clozapine does not significantly improve cognitive function.", "The purpose of this study was to investigate the safety and efficacy of risperidone in the treatment of schizophrenic patients and determine its optimal dose.\n This double-blind study included 388 schizophrenic patients drawn from 20 sites in the United States. Patients were randomly assigned to 8 weeks' treatment with placebo, one of four doses of risperidone (2, 6, 10, or 16 mg), or 20 mg of haloperidol daily.\n Clinical improvement (20% reduction in total scores on the Positive and Negative Syndrome Scale for Schizophrenia) at the study end point was shown by 35% of the patients receiving 2 mg of risperidone, 57% receiving 6 mg, 40% receiving 10 mg, and 51% receiving 16 mg; and by 30% receiving haloperidol and 22% receiving placebo. Statistically significant differences in clinical improvement were found between 6 and 16 mg of risperidone versus placebo and versus haloperidol. Positive symptom scores were significantly lower after 6, 10, and 16 mg of risperidone and 20 mg of haloperidol than placebo; negative symptom scores, however, were reduced significantly, compared with placebo, only after 6 and 16 mg of risperidone. The incidence of extra-pyramidal side effects (measured by the Extrapyramidal Symptom Rating Scale) was significantly higher in patients treated with 16 mg of risperidone or 20 mg of haloperidol than placebo. The results indicate that the optimal daily dose of risperidone for most schizophrenic patients in this study was 6 mg; this dose was as effective as 16 mg, and the incidence of extrapyramidal symptoms in patients receiving 6 mg of risperidone was no higher than that in patients receiving placebo.\n Risperidone is a safe antipsychotic that is effective against both the positive and negative symptoms of schizophrenia.", "Aripiprazole is a dopamine D2 receptor partial agonist with partial agonist activity at serotonin 5HT1A receptors and antagonist activity at 5HT2A receptors. This multicenter trial examined the efficacy, safety, and tolerability of aripiprazole in patients with acute exacerbation of schizophrenia or schizoaffective disorder.\n In this 4-week double-blind study, 404 patients were randomized to 20 mg/d (n = 101) or 30 mg/d (n = 101) of aripiprazole, placebo (n = 103), or 6 mg/d of risperidone (n = 99). Efficacy assessments included Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression scores. Safety and tolerability evaluations included extrapyramidal symptoms and effects on weight, prolactin, and corrected QT (QTc) interval.\n Aripiprazole (20 and 30 mg/d) and risperidone (6 mg/d) were significantly better than placebo on all efficacy measures. Separation from placebo occurred at week 1 for PANSS total and positive scores with aripiprazole and risperidone and for PANSS negative scores with aripiprazole. There were no significant differences between aripiprazole and placebo in mean change from baseline in the extrapyramidal symptom rating scales. Mean prolactin levels decreased with aripiprazole but significantly increased 5-fold with risperidone. Mean change in QTc interval did not differ significantly from placebo with any active treatment group. Aripiprazole and risperidone groups showed a similar low incidence of clinically significant weight gain.\n Aripiprazole is effective, safe, and well tolerated for the positive and negative symptoms in schizophrenia and schizoaffective disorder. It is the first non-D2 receptor antagonist with clear antipsychotic effects and represents a novel treatment development for psychotic disorders.", "In a double-blind study, 135 inpatients with a diagnosis of chronic schizophrenia were randomly assigned to 8 weeks of treatment with one of six parallel treatments: risperidone (a new central 5-hydroxytryptamine2 and dopamine D2 antagonist), 2, 6, 10, 16 mg/day; haloperidol, 20 mg/day; or placebo, after a single-blind placebo washout period. Doses were increased in fixed increments up to a fixed maintenance dose reached after 1 week. On the Clinical Global Impression-Severity of Illness and Improvement, all active medications were superior to placebo except for risperidone (2 mg) on the Clinical Global Impression-Improvement. On the total Positive and Negative Syndrome Scale (PANSS) score and positive subscale, superiority to placebo was observed for all treatment groups except for haloperidol and risperidone (2 mg), which tended to be superior to placebo on total PANSS and the positive subscale, respectively. On the PANSS negative subscale, only risperidone (6 mg/day) was significantly better than placebo. Risperidone (6 mg) was superior to haloperidol on the total PANSS, General Psychopathology, and Brief Psychiatric Rating Scale subscales. Although there was a linear increase in parkinsonism with increasing risperidone dosage, there were no statistically significant differences between risperidone (2, 6, and 16 mg/day) and placebo. At doses of 6 to 16 mg, risperidone displayed a marked antidyskinetic effect compared with placebo. This effect was more pronounced in patients with severe dyskinesia. By contrast, haloperidol produced significantly more parkinsonism than placebo and risperidone (2, 6 and 16 mg), with no effect on tardive dyskinesia. These data suggest that risperidone, at the optimal therapeutic dose of 6 mg/day, produced significant improvement in both positive and negative symptoms without an increase in drug-induced parkinsonian symptoms and with a significant beneficial effect on tardive dyskinesia." ]

[ "1944900", "2178869", "2201660", "8797468", "10994000", "1444880" ]

[ "Long-term acetyl-L-carnitine treatment in Alzheimer's disease.", "Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer's dementia.", "Pharmaco-electroencephalographic and clinical effects of the cholinergic substance--acetyl-L-carnitine--in patients with organic brain syndrome.", "A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease.", "A 1-year controlled trial of acetyl-l-carnitine in early-onset AD.", "Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's disease." ]

[ "In a double-blind, placebo-controlled, parallel-group, randomized clinical trial, we studied the efficacy of long-term (1-year) oral treatment with acetyl-L-carnitine in 130 patients with a clinical diagnosis of Alzheimer's disease. We employed 14 outcome measures to assess functional and cognitive impairment. After 1 year, both the treated and placebo groups worsened, but the treated group showed a slower rate of deterioration in 13 of the 14 outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, ideomotor and buccofacial apraxia, and selective attention. Adjusting for initial scores with analysis of covariance, the treated group showed better scores on all outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, verbal critical abilities, long-term verbal memory, and selective attention. The analysis for patients with good treatment compliance showed a greater drug benefit than for the overall sample. Reported adverse events were relatively mild, and there was no significant difference between the treated and placebo groups either in incidence or severity.", "A randomized, double-blind, placebo-controlled, parallel-group clinical trial was carried out to compare 24-week periods of treatment with 1 g acetyl-l-carnitine twice daily and placebo in the treatment of patients with dementia of the Alzheimer type. A total of 36 patients entered the trial, of whom 20 patients (7 active, 13 placebo) completed the full 24 weeks. Whilst several of the efficacy indices showed little change in either group during the trial, there was an apparent trend for more improvement in the acetyl-l-carnitine group in relation to the Names Learning Test and a computerized Digit Recall Test, both related to aspects of short-term memory. Similarly, there was a trend for reaction time in the computerized classification test to show less deterioration in the active treatment group. Changes within groups, and changes between groups, failed to reach statistical significance, at least partially because of the small number of patients available for analysis. Two indices of overall therapeutic benefit showed a trend for less deterioration in the active-treatment group than in the placebo group. Nausea and/or vomiting occurred in 5 patients in the acetyl-l-carnitine group. Laboratory tests revealed no signs of drug toxicity. The results suggest that acetyl-l-carnitine may have a beneficial effect on some clinical features of Alzheimer-type dementia, particularly those related to short-term memory.", "In two double-blind, placebo-controlled clinical studies of the nootropic compound acetyl-L-carnitine on the electroencephalogram (EEG) and impaired brain functions of elderly outpatients with mild to moderate cognitive decline of the organic brain syndrome, statistically significant effects could be detected after eight weeks (on the EEG), and after 12 weeks of treatment (on the physician's clinical global impression and the patient-rated level of activities of daily living). Side-effects of acetyl-L-carnitine were generally minor and overall rare. Longer treatment periods and further specifications with regard to the aetiopathology and degree of cognitive impairment are recommended for further clinical studies of this promising compound.", "A 1-year, double-blind, placebo-controlled, randomized, parallel-group study compared the efficacy and safety of acetyl-L-carnitine hydrochloride (ALCAR) with placebo in patients with probable Alzheimer's disease (AD). Subjects with mild to moderate probable AD, aged 50 or older, were treated with 3 g/day of ALCAR or placebo (1 g tid) for 12 months. Four hundred thirty-one patients entered the study, and 83% completed 1 year of treatment. The Alzheimer's Disease Assessment Scale cognitive component and the Clinical Dementia Rating Scale were the primary outcome measures. Overall, both ALCAR- and placebo-treated patients declined at the same rate on all primary and most secondary measures during the trial. In a subanalysis by age that compared early-onset patients (aged 65 years or younger at study entry) with late-onset patients (older than 66 at study entry), we found a trend for early-onset patients on ALCAR to decline more slowly than early-onset AD patients on placebo on both primary endpoints. In addition, early-onset patients tended to decline more rapidly than older patients in the placebo groups. Conversely, late-onset AD patients on ALCAR tended to progress more rapidly than similarly treated early-onset patients. The drug was very well tolerated during the trial. The study suggests that a subgroup of AD patients aged 65 or younger may benefit from treatment with ALCAR whereas older individuals might do more poorly. However, these preliminary findings are based on past hoc analyses. A prospective trial of ALCAR in younger patients is underway to test the hypothesis that young, rapidly progressing subjects will benefit from ALCAR treatment.", "To determine the efficacy of acetyl-l-carnitine (ALCAR) on the rate of decline in early-onset AD patients.\n A 1-year, multicenter, double-blind, placebo-controlled, randomized trial was conducted. Subjects were 45 to 65 years old, with a diagnosis of probable AD according to National Institute of Neurological Communicative Disorders-Alzheimer's Disease and Related Disorders Association criteria and had a Mini-Mental State Examination (MMSE) score between 12 and 26. They were treated with ALCAR (1 g tid) or placebo. Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive Component and the Clinical Dementia Rating Scale. Secondary measures included the ADAS Non-Cognitive Subscale, the MMSE, an Activities of Daily Living Scale (ADL), and a Clinician-Based Impression of Change (CIBIC).\n Two-hundred twenty-nine patients were enrolled and randomized to drug treatment, with 117 taking placebo and 112 taking ALCAR. There were no significant differences between the two groups at baseline. For the primary outcome measures, there were no significant differences between the treatment groups on the change from baseline to endpoint in the intent-to-treat analysis. In the completer sample only, there was less deterioration in the MMSE for the ALCAR-treated subjects. There was no difference in rate of decline on the CIBIC and the ADL scale. There were no significant differences in the incidence of adverse events by treatment arm.\n Overall, in a prospectively performed study in young-onset AD patients, ALCAR failed to slow decline. Less decline was seen on the MMSE in the completer sample only, with the difference being mediated by reducing decline in attention. A combination of ALCAR and a cholinesterase inhibitor should be tested for additivity.", "Acetyl levocarnitine hydrochloride has been reported to retard dementia in patients with Alzheimer's disease. In a double-blind, parallel design, placebo-controlled pilot study of 30 mild to moderately demented patients with probable Alzheimer's disease, tests of memory, attention, language, visuospatial, and constructional abilities were administered, and the level of acetyl levocarnitine was measured in the cerebrospinal fluid. Patients were then randomly assigned to receive acetyl levocarnitine hydrochloride (2.5 g/d for 3 months followed by 3 g/d for 3 months) or placebo. After 6 months, the acetyl levocarnitine group demonstrated significantly less deterioration in timed cancellation tasks and Digit Span (forward) and a trend toward less deterioration in a timed verbal fluency task. No differences were found in any other neuropsychological test results. A subgroup with the lowest baseline scores, receiving acetyl levocarnitine, had significantly less deterioration on the verbal memory test and a significant increase in cerebrospinal fluid acetyl levocarnitine levels compared with those receiving placebo. These results suggest that acetyl levocarnitine may retard the deterioration in some cognitive areas in patients with Alzheimer's disease and stress the need for a larger study of this drug." ]

[ "3421279", "2587133", "3601288", "16519625", "8296850", "2585215" ]

[ "The use of antenatal vitamin K in the prevention of early neonatal intraventricular hemorrhage.", "Maternal administration of vitamin K does not improve the coagulation profile of preterm infants.", "Maternally administered antenatal vitamin K1: effect on neonatal prothrombin activity, partial thromboplastin time, and intraventricular hemorrhage.", "Maternal antenatal administration of vitamin K1 results in increasing the activities of vitamin K-dependent coagulation factors in umbilical blood and in decreasing the incidence rate of periventricular-intraventricular hemorrhage in premature infants.", "Antenatal vitamin K therapy of the low-birth-weight infant.", "Maternal-fetal transport of vitamin K1 and its effects on coagulation in premature infants." ]

[ "To establish the effect of antenatal vitamin K on the incidence and severity of intraventricular hemorrhage, 92 patients destined to deliver infants less than 32 weeks' gestation were, in a prospective fashion, randomly assigned to two groups. Group I received 10 mg of vitamin K1 intramuscularly every 5 days until delivery. Group II received no antenatal vitamin K1 therapy. There were 100 neonates less than 1500 gm, equally divided between groups I and II with respect to gestational age, birth weight, race, sex, presentation, route of delivery, duration of labor, Apgar scores, and arterial umbilical cord acid-base balance. The antenatal use of vitamin K resulted in significant reduction in the prothrombin time (12.7 versus 15.2 seconds) and partial thromboplastin time (42.6 versus 58.9 seconds; p less than 0.05). Furthermore, group I experienced a lower incidence of total (16% versus 36%) and severe (0% versus 11%) grades of intraventricular hemorrhage (p less than 0.05). This study suggests that the antenatal use of vitamin K may result in a reduction and severity of intraventricular hemorrhage in the neonate less than 1500 gm.", "The effect of maternal administration of vitamin K1 on cord blood prothrombin time, activated partial thromboplastin time, activity of factors II, VII, and X, and antigen levels of factors II and X in infants less than 35 weeks' gestation was evaluated. Pregnant women in preterm labor were randomly assigned to receive 10 mg of vitamin K1 intramuscularly or no injection. If delivery did not occur in 4 days, the dose of vitamin K1 was repeated. Women who continued their pregnancy 4 days beyond the second dose received 20 mg of vitamin K1 orally daily until the end of the 34th week of gestation. The birth weights of infants ranged from 370 to 2550 g and gestational age ranged from 22 to 34 weeks. The prothrombin time, activated partial thromboplastin time, factors II, VII, and X activity, and factors II and X antigen levels were not statistically different in either group of infants. Intraventricular hemorrhage occurred in 25 of 51 control infants and 25 of 47 vitamin K-treated infants. More control infants had grade III intraventricular hemorrhage on day 1 (P = .032), but on day 3 and 14 of life, the severity of intraventricular hemorrhage was comparable in both groups. Infants in whom an intraventricular hemorrhage developed were significantly smaller, younger, and more critically ill than infants without intraventricular hemorrhage. Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation does not improve the hemostatic defects nor does it reduce the incidence or severity of intraventricular hemorrhage in their infants.", "Infants weighing 1500 g or less at birth are susceptible to intraventricular hemorrhage. This may be due in part to low concentrations of vitamin K-dependent clotting factors. Women in labor between 24-34 weeks' gestation were selected, according to their hospital registration number, to receive 10 mg vitamin K1 intramuscularly at least four hours before delivery. Control women received no vitamin K. The study included only infants born of mothers who were in hospital more than four hours before delivery, who weighed 1500 g or less at birth, and were less than 34 weeks' gestation. Twenty vitamin K1 and 33 control infants qualified for the study. Infants in both groups received routine postnatal vitamin K1. On admission, the infant's prothrombin activity and partial thromboplastin time (PTT) were measured. A head ultrasound was done between days 2 and 4 of life. Results demonstrated significantly improved prothrombin activity, a nonsignificant trend toward improved PTT, and a significantly decreased frequency of intraventricular hemorrhage in infants whose mothers had received vitamin K1. The effect of antenatal vitamin K1 on prothrombin activity and PTT appeared to be more pronounced in female infants.", "Infants less than 35 weeks' gestation age are susceptible to periventricular-intraventricular hemorrhage (PIVH). This may be partially attributable to low concentrations of vitamin K-dependent coagulation factors. The purposes of this study were: (1) to determine the umbilical blood activity levels of vitamin K-dependent coagulation factors II, VII, IX and X; (2) to investigate the change in activities of these factors in premature infants' umbilical blood after prenatal administration of vitamin K1 to the mothers; and (3) to study the prophylactic effects on PIVH after maternal antenatal supplemental vitamin K1.\n Pregnant women in preterm labor at less than 35 weeks of gestation were randomly selected to receive antenatal vitamin K1 10 mg per day injection intramuscularly or intravenously for 2-7 days (vitamin K1 group, n = 40), or no such treatment (control group, n = 50). At the same period, cord blood samples were collected from thirty full-term neonates to compare the factor levels with those of premature infants. Intracranial ultrasound was performed by the same sonographer to determine the presence and severity of PIVH.\n The activities of vitamin K-dependent coagulation factors in umbilical blood in the control group were: factor II 25.64+/-9.49%, factor VII 59.00+/-17.66%, factor IX 24.67+/-8.88%, and factor X 30.16+/-5.02%. In full-term infants, the respective values were: factor II 36.70+/-4.88%, factor VII 64.54+/-10.62%, factor IX 30.18+/-5.69%, and factor X 34.32+/-12.63%. In vitamin K1 group these factors were: factor II 36.35+/-6.88%, factor VII 69.59+/-16.55%, factor IX 25.71+/-10.88%, and factor X 39.26+/-8.02%. The data suggest the absence of vitamin K-dependent coagulation factors in preterm infants, and antenatal supplement of vitamin K1 may increase the cord blood activity of factor II, VII and factor X (P < 0.001). In addition, the overall rates of PIVH in the vitamin K1 group and in controls were 32.4 and 52.0%, respectively (P = 0.036), and the frequency of severe PIVH was 5.0 and 20.0%, respectively (P = 0.038).\n Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation age may result in improved coagulation and may reduce the incidence as well as the severity degree of PIVH.", "The purpose of our study was to determine whether maternal vitamin K1 administered antenatally improved global coagulation parameters and the levels of specific vitamin K-dependent proteins in low-birth-weight infants.\n Thirty-three preterm mothers admitted in labor were assigned in a prospective, blinded fashion to receive either intramuscular vitamin K1 (17) or placebo (16). At delivery cord blood samples were tested for prothrombin time, activated partial thromboplastin time, factor II and protein C activity, and antigen levels. Statistical analysis was by Student t test.\n No statistically significant differences could be demonstrated with regard to group mean values for global tests (prothrombin time, activated partial thromboplastin time) or specific vitamin K-dependent protein levels (factor II, protein C) in newborns whose mothers received antenatal vitamin K compared with those who did not.\n These results would suggest that antenatal vitamin K1 therapy to mothers < 32 weeks' gestation has no significant effect on the level of vitamin K-dependent factors in the fetus.", "We conducted a prospective study to determine (1) the maternal-fetal vitamin K1 transport in premature infants after vitamin K1 was given to the mothers antenatally and (2) the vitamin K1 effects on blood coagulation in the babies. Women in labor at less than or equal to 34 weeks of gestation were randomly selected to receive antenatal vitamin K1, 5 mg given intramuscularly (vitamin K1 group), or no vitamin K1 (control group). Eight infants, including one set of twins, were in the vitamin K1 group and six in the control group. Vitamin K1 concentrations were higher in the vitamin K1 group than in the control group (p = 0.06). Activated partial thromboplastin time was prolonged, and factor II coagulation activity and factor II antigen were proportionately decreased in cord plasma in both groups. The average ratio of factor II coagulation activity to antigen was not decreased in either group. Protein induced by vitamin K absence-II (PIVKA-II) was not detectable in any cord plasma sample in either group. These findings support previous reports that the decreased vitamin K-dependent coagulation activity in premature infants is the result of reduced synthesis of precursor proteins, rather than the result of vitamin K deficiency, and suggest that additional vitamin K1 is not likely to improve coagulation activity. Among those infants who underwent cranial ultrasonography, all four in the vitamin K1 group and one of five in the control group had mild intraventricular hemorrhage. Studies of a larger number of patients are necessary before it can be established that maternal antenatal administration of vitamin K1 results in improvement of coagulation and the prevention of intraventricular hemorrhage in premature infants." ]

[ "10051255", "16236850", "14621090", "1926024", "9192927", "16327534", "12622605", "16281645", "9619472", "3731895", "2227172", "3101821", "15546454", "9782692" ]

[ "Quality of life assessment after patient education in a randomized controlled study on asthma and chronic obstructive pulmonary disease.", "A randomized trial of two types of nurse-assisted home care for patients with COPD.", "Effects of a comprehensive self-management programme in patients with chronic obstructive pulmonary disease.", "Randomised controlled trial of the effectiveness of a respiratory health worker in reducing impairment, disability, and handicap due to chronic airflow limitation.", "Evaluation of a self-management plan for chronic obstructive pulmonary disease.", "Managing chronic obstructive pulmonary disease in the community. A randomized controlled trial of home-based pulmonary rehabilitation for elderly housebound patients.", "Reduction of hospital utilization in patients with chronic obstructive pulmonary disease: a disease-specific self-management intervention.", "Care plans for acutely deteriorating COPD: a randomized controlled trial.", "Psychological and cognitive outcomes of a randomized trial of exercise among patients with chronic obstructive pulmonary disease.", "Chronic obstructive airway disease. Impact of health education.", "A randomized controlled evaluation of a psychosocial intervention in adults with chronic lung disease.", "Controlled trial of respiratory health worker visiting patients with chronic respiratory disability.", "A chronic disease management programme can reduce days in hospital for patients with chronic obstructive pulmonary disease.", "Humanistic outcomes in the hypertension and COPD arms of a multicenter outcomes study." ]

[ "The effect of patient education in patients with asthma and Chronic Obstructive Pulmonary Disease (COPD) on health-related quality of life (HRQoL) is not previously investigated using the St. George's Respiratory Questionnaire (SGRQ). We randomly allocated at our out-patient clinic 78 asthmatics and 62 patients with COPD to either a control or an intervention group. Intervention consisted of two 2-h group sessions and one to two individual sessions each by a nurse and a physiotherapist. A self-management plan was developed. Baseline quality of life assessment showed comparable scores independent of treatment groups among asthmatics and patients with COPD, but statistically significantly better scores (p < 0.05) for the educated asthma group after 12 mo compared with the control group. This aligned with the 12-mo SGRQ assessment, which revealed better symptoms, activity, impact, and total scores by 11 (p < 0.02), 15 (p < 0.01), 19 (p < 0.001), and 16 (p < 0.001) units, respectively. Patient education among asthmatics increased the FEV1 by a mean value of 6.1% (SD, 12) compared with the control group (p < 0.05). Education among patients with COPD did not indicate a significant increase in HRQoL as measured by the SGRQ or increased FEV1. We conclude that patient education increased HRQoL and FEV1 among asthmatics, but not among patients with COPD.", "Whereas pulmonary rehabilitation reduces symptoms and improves the quality of life of patients with COPD and is recommended in management guidelines, few patients have access to rehabilitation services. The purpose of this study was to investigate the effectiveness of increasing access to selected components of pulmonary rehabilitation by providing nurse-assisted home care that was composed of patient education, efforts to improve patient self-management skills, and enhanced follow-up.\n We conducted a 6-month, randomized, controlled trial.\n Primary care clinics associated with an urban academic health system.\n Patients were > or = 45 years of age with a physician diagnosis of COPD, and had a > or = 20-pack-year smoking history, had experienced at least one respiratory symptom during the past 12 months, and had airflow obstruction (ie, FEV1/FVC ratio, < 70%; FEV1, < 80%).\n Four nurses were trained in the use of the Global Initiative for Chronic Obstructive Lung Disease guidelines, and two of the four nurses received additional training in collaborative management. Patients were randomly assigned to usual care (UC), nurse-assisted medical management (MM), or nurse-assisted collaborative management (CM).\n The main outcome measures were of generic (Medical Outcome Study 36-item short form [SF-36], illness intrusiveness) and disease-specific (St. George's respiratory questionnaire [SGRQ]) quality of life and self-reported health-care utilization.\n Overall, 151 patients (UC group, 51 patients; MM group, 49 patients; and CM group, 51 patients) completed the study, their average age was 69 years, and 56.9% were women. The average change in the SF-36 general health domain for the MM group vs the UC group was 1.1 (95% confidence interval [CI], -7.9 to 11.2), and for the CM group vs the UC group the average change was 2.5 (95% CI, -7.0 to 12.3). The corresponding changes in SGRQ total domain were -2.9 (95% CI, -9.8 to 4.1) and -2.6 (95% CI, -9.5 to 4.3). There was no change in the number of self-reported emergency department visits or hospitalizations, but the utilization of these services was infrequent.\n The findings of our investigation and those from the published literature suggest that interventions to enhance patient education, self-management skills, and follow-up among patients with COPD do not result in clinically meaningful improvements in health status or self-reported health-care utilization. Moreover, future studies of disease management programs for patients with COPD need to evaluate interventions that address associated comorbidities, exercise, and social support.", "The aim of this study was to assess the effects of a comprehensive self-management intervention on health-related quality of life (HRQoL), symptoms and walking distance in patients with stable moderately severe chronic obstructive pulmonary disease (COPD). This study was part of the overall COPD study of the Dept of Pulmonary Medicine, Enschede, which consisted of an inhaled corticosteroid (ICS) trial and a self-management trial. After the ICS trial, all patients were randomised again to a self-management and a control group. The self-management intervention consisted of a skill-oriented patient education programme and a near-home fitness programme, on top of usual care. The control group received usual care by the treating chest physician. HRQoL was measured by the St George's Respiratory Questionnaire (SGRQ) and walking distance by the 6-min walking test. Patients recorded their symptoms in diaries and graded their health status from 1-10 in a weekly report. Altogether, 248 COPD patients were randomly allocated to either an intervention (127) or control (121) group. No differences in the SGRQ scores within and between both groups were observed over 1 yr. Similarly, no differences in symptom scores and 6-min walking distance were found within and between groups. The intervention group reported more exacerbations than the control group. The majority (69%) of the exacerbations in the intervention group were self-treated at home. This study failed to show positive effects of a self-management programme among moderately severe chronic obstructive pulmonary disease patients.", "A randomised controlled trial was undertaken to determine whether a respiratory health worker was effective in reducing the respiratory impairment, disability, and handicap experienced by patients with chronic airflow limitation attending a respiratory outpatient department. The 152 adults (aged 30-75 years) who participated had a prebronchodilator forced expiratory volume in one second (FEV1) below 60% predicted and no other disease. They were randomised to receive the care of a respiratory health worker or the normal services provided by the outpatient department. The respiratory health worker provided health education and symptom and treatment monitoring in liaison with primary care services. After one year there was little difference between the two groups in spirometric values (FEV1 and forced vital capacity before and after salbutamol 200 micrograms), disability (six minute walking distance and paced step test), and handicap (sickness impact profile, hospital anxiety and depression scale). Patients not looked after by the respiratory health worker were more likely to die (relative risk 2.9 (95% confidence limits 0.8, 10.2); when age and FEV1 were controlled for this risk increased to 5.5 (95% confidence limits 1.2, 24.5). Patients looked after by the respiratory health worker attended their general practitioner more frequently and were prescribed a greater range of drugs. This is the third study to have found limited measurable benefit in terms of morbidity from the intervention of a respiratory health worker. This may be due to the ability of such workers to keep frail patients alive.", "We hypothesized that the use of an Action Plan might assist self-management for patients with chronic obstructive pulmonary disease (COPD). A pilot process and randomized, controlled study were undertaken to evaluate an Action Plan that provided advice on management of usual care and exacerbations, together with a booklet on self-management. Fifty six subjects with COPD recruited through general practitioners (GPs) completed the 6 month study, 27 in the control group and 29 in the intervention group. The control group received usual care from their GP, and the intervention group received a booklet and Action Plan from their practice nurse plus a supply of prednisone and antibiotic from their GP. The two groups were demographically similar with a mean age of 68 yrs. The resources were well received by GPs, practice nurses and intervention group subjects. After 6 months, there were no differences in quality of life scores or pulmonary function. There were significant changes in self-management behaviour in the intervention group compared to controls. In response to deteriorating symptoms, 34 versus 7% (p=0.014) initiated prednisone treatment and 44 versus 7% (p=0.002) initiated antibiotics. Subjects in the intervention group readily adopted self-management skills but did not show any difference in quality of life or lung function parameters. A larger, prospective, controlled, clinical trial of this approach is warranted.", "Pulmonary rehabilitation is essential for managing chronic obstructive pulmonary disease (COPD). Housebound COPD patients are frequently excluded from this treatment because they are unable to access outpatient pulmonary rehabilitation programs because of the severity of their disease. This randomized controlled trial assesses the effects of a 12-week home-based pulmonary rehabilitation program for 60 housebound COPD patients older than 60 years.\n Intervention patients received an individually tailored supervised walking and arm exercise program as well as individual multidisciplinary education sessions on COPD and its management. Outcomes were assessed using the 6-minute walk test, St George's respiratory questionnaire, and Borg score of perceived breathlessness. Healthcare utilization was assessed using hospital admission rates with exacerbation of COPD and average length of stay at readmission.\n Complete data for 23 patients in each group were available for analysis. There was no significant difference between groups on baseline measures. Compared with the control group, intervention patients demonstrated a significant improvement in 6-minute walk test (P = .023), Borg score of perceived breathlessness (P = .024), St George's respiratory questionnaire total score (P = .020), and impact subscore (P = .024). At 6 months, the intervention group had a significantly shorter average length of stay at readmission to hospital with exacerbation (P = .035).\n A 12-week home-based pulmonary rehabilitation is effective in improving exercise tolerance, perception of breathlessness, and quality of life for housebound COPD patients. To manage COPD in the community more effectively, health services should focus on expanding home-based pulmonary rehabilitation.", "Self-management interventions improve various outcomes for many chronic diseases. The definite place of self-management in the care of chronic obstructive pulmonary disease (COPD) has not been established. We evaluated the effect of a continuum of self-management, specific to COPD, on the use of hospital services and health status among patients with moderate to severe disease.\n A multicenter, randomized clinical trial was carried out in 7 hospitals from February 1998 to July 1999. All patients had advanced COPD with at least 1 hospitalization for exacerbation in the previous year. Patients were assigned to a self-management program or to usual care. The intervention consisted of a comprehensive patient education program administered through weekly visits by trained health professionals over a 2-month period with monthly telephone follow-up. Over 12 months, data were collected regarding the primary outcome and number of hospitalizations; secondary outcomes included emergency visits and patient health status.\n Hospital admissions for exacerbation of COPD were reduced by 39.8% in the intervention group compared with the usual care group (P =.01), and admissions for other health problems were reduced by 57.1% (P =.01). Emergency department visits were reduced by 41.0% (P =.02) and unscheduled physician visits by 58.9% (P =.003). Greater improvements in the impact subscale and total quality-of-life scores were observed in the intervention group at 4 months, although some of the benefits were maintained only for the impact score at 12 months.\n A continuum of self-management for COPD patients provided by a trained health professional can significantly reduce the utilization of health care services and improve health status. This approach of care can be implemented within normal practice.", "Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a frequent reason for admission to hospital and are responsible for the majority of the direct economic costs of treating COPD.\n To test whether an individualized care plan for patients experiencing acute exacerbations of COPD result in reduced health care utilization and improved quality of life for patients.\n Ninety-two patients with confirmed COPD were selected by general practitioners or district nurses, and randomly assigned to care plan or usual care groups. The care plan was developed in collaboration with general practitioners, secondary care specialists, specialist nurses, ambulance service providers and the after hours clinic. Patients were followed for 12 months, and the primary end-points were frequency of use of primary care services and hospital admissions.\n There was no significant reduction in hospital admissions or improvement in quality of life in the group of patients who used the care plan compared to controls. The care plan group called out the ambulance service more frequently [2.8 (1.3, 4.3) versus 1.1 (0.7, 1.5) calls per 12 months; P = 0.03], and there was a trend towards greater use of oral prednisone [2.3 (1.4, 3.2) versus 1.3 (0.8, 1.8) courses per 12 months; P = 0.06].\n In contrast to asthma, the provision of individualized self-management plans, whose content was enhanced to provide guidance to carers and health care professionals, did not reduce health care utilization or improve overall quality of life during acute exacerbations of COPD. Other strategies are required.", "Exercise rehabilitation is recommended increasingly for patients with chronic obstructive pulmonary disease (COPD). This study examined the effect of exercise and education on 79 older adults (M age = 66.6 +/- 6.5 years; 53% female) with COPD, randomly assigned to 10 weeks of (a) exercise, education, and stress management (EXESM; n = 29); (b) education and stress management (ESM; n = 25); or (c) waiting list (WL; n = 25). EXESM included 37 sessions of exercise, 16 educational lectures, and 10 weekly stress management classes. ESM included only the 16 lectures and 10 stress management classes. Before and after the intervention, assessments were conducted of physiological functioning (pulmonary function, exercise endurance), psychological well-being (depression, anxiety, quality of life), and cognitive functioning (attention, motor speed, mental efficiency, verbal processing). Repeated measures multivariate analysis of variance indicated that EXESM participants experienced changes not observed among ESM and WL participants, including improved endurance, reduced anxiety, and improved cognitive performance (verbal fluency).", "We conducted a controlled study of the impact of an education program on the health outcomes and perceptions of patients with varying degrees of airway obstruction in two communities. In one community, patients with chronic obstructive airway disease (COAD) were identified, assessed and offered an educational program. In the other community, patients were identified, assessed and advised of the findings only. Patients at both sites were given the same pretest and, one year later, the same posttest. These tests measured physical and social function, and health outcomes (eg, respiratory symptoms, exercise tolerance, mental health), plus patients' health perceptions. Posttest results showed a significant difference between groups on a health perception measure and locus of control, but no difference on health outcomes. We conclude that education programs for COAD are unlikely to improve patients' health status unless they are part of a comprehensive medical program that includes physical reconditioning.", "The effect of a stress management program on morbidity and psychosocial and physical function in patients with chronic lung disease was assessed. Adults attending either a VA pulmonary clinic or university hospital pulmonary rehabilitation clinic who met criteria for obstructive or restrictive pulmonary disease were randomly assigned to receive the intervention or to a control group. The intervention was provided by a nurse and included one to three teaching sessions, reading material, audiotapes, and telephone follow-up. The program focused on stress management techniques such as cognitive restructuring, progressive relaxation, breathing exercises, and visual imagery. The 45 experimental subjects were similar to the 49 controls with respect to baseline characteristics. Experimental and control subjects had similar rates of mortality, hospital days, bed-disability days, restricted-activity days, and physician visits during the 12-month follow-up. There were no differences between the two groups in physical or psychosocial function at six months or in levels of stressful life changes, social supports, and self-esteem at six and 12 months. Intervention recipients had better function at 12 months, suggesting a possible benefit of the intervention.", "Seventy five patients with chronic respiratory disability were randomised to a group visited by a respiratory health worker (42) or control group (33). The first group was visited monthly by a respiratory nurse, who gave education and support. The effect of the intervention was assessed in terms of quality of life (by questionnaires), the number and duration of admissions to hospital, and the number of deaths. The questionnaires on quality of life showed no changes in either group during the study, but nearly all of the group visited by a respiratory health worker said that they valued the visits and wished them to continue. Their knowledge about their condition also improved compared with that of the controls. The duration of stay in hospital for respiratory reasons in the group visited by a respiratory health worker was longer than that of control patients. This was explained by their being scored as more ill than the controls on admission. Fewer patients died in the group visited by a respiratory health worker than in the control group (p = 0.11). The patients in the group visited by respiratory health workers may have survived longer because they sought help rather than dying at home. If confirmed this could have implications for the cost of their care.", "A steady increase in chronic obstructive pulmonary disease (COPD) admissions was addressed by enhancing primary care to provide intensive chronic disease management.\n To compare the effect of a disease management programme, including a COPD management guideline, a patient-specific care plan and collaboration between patients, general practitioners, practice nurses, hospital physicians and nurse specialists with conventional care, on hospital admissions and quality of life.\n One hundred and thirty-five patients with a clinical diagnosis of moderate to severe COPD were identified from hospital admission data and general practice records. General practices were randomized to either conventional care (CON), or the intervention (INT). Pre- and post-study assessment included spirometry, Shuttle Walk Test, Short Form-36, and the Chronic Respiratory Questionnaire (CRQ). Admission data were compared for 12 months prior to and during the trial.\n For respiratory conditions, mean hospital bed days per patient per year for the INT group were reduced from 2.8 to 1.1, whereas those for the CON group increased from 3.5 to 4.0 (group difference, P = 0.030) The INT group also showed an improvement for two dimensions of the CRQ, fatigue (P = 0.010) and mastery (P = 0.007).\n A chronic disease management programme for COPD patients that incorporated a variety of interventions, including pulmonary rehabilitation and implemented by primary care, reduced admissions and hospital bed days. Key elements were patient participation and information sharing among healthcare providers.", "To evaluate the effects of pharmaceutical care on selected humanistic outcomes in patients with hypertension or chronic obstructive pulmonary disease (COPD).\n Clinic patients with hypertension or COPD were randomly assigned to a treatment group (pharmaceutical care) or a control group (traditional pharmacy care) over a six-month period. Clinical pharmacists and pharmacy residents conducted the protocols. There were 133 evaluable patients (63 treatment, 70 control) in the hypertension study arm and 98 evaluable patients (43 treatment, 55 control) in the COPD study arm. The Pharmaceutical Care Questionnaire evaluated patient satisfaction with care. Tests specific to the disease states assessed disease and disease management knowledge. Quality of life (QOL) was evaluated using the Health Status Questionnaire 2.0 (HSQ 2.0) in the COPD arm; in the hypertension arm, the Hypertension/Lipid TyPE Specification Form 5.1 was used.\n Ambulatory care centers of 10 Department of Veterans Affairs (DVA) medical centers and 1 university medical center.\n Patient-centered pharmaceutical care model (employing standardized care) implemented by clinical pharmacy residents.\n Satisfaction with pharmaceutical care, disease and disease management knowledge, and QOL.\n Statistically significant differences in most satisfaction items were found, with treatment patients expressing greater satisfaction. Treatment groups in both arms strongly agreed that pharmacists helped them with confidence in use of their medication and understanding of their illness, gave complete explanations about their medications, made them feel that their care was a priority, and followed up on their questions and concerns. In the hypertension arm, treatment patients demonstrated significant increases in knowledge scores. Trends in QOL were positive for both hypertension groups, with a significant decrease found in number of treatment patients reporting problems with sexual function. In the COPD arm, improvement trends were significantly stronger for treatment patients.\n Although patients were not dissatisfied with traditional pharmacy care, they were more satisfied overall with the pharmaceutical care model." ]

[ "1960828", "1852179", "9593407" ]

[ "Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. Veterans Affairs Cooperative Studies Program 309 Trialist Group.", "Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis.", "Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST)" ]

[ "To determine whether carotid endarterectomy provides protection against subsequent cerebral ischemia in men with ischemic symptoms in the distribution of significant (greater than 50%) ipsilateral internal carotid artery stenosis.\n Prospective, randomized, multicenter trial.\n Sixteen university-affiliated Veterans Affairs medical centers.\n Men who presented within 120 days of onset of symptoms that were consistent with transient ischemic attacks, transient monocular blindness, or recent small completed strokes between July 1988 and February 1991. Among 5000 patients screened, 189 individuals were randomized with angiographic internal carotid artery stenosis greater than 50% ipsilateral to the presenting symptoms. Forty-eight eligible patients who refused entry were followed up outside of the trial.\n Cerebral infarction or crescendo transient ischemic attacks in the vascular distribution of the original symptoms or death within 30 days of randomization.\n Carotid endarterectomy plus the best medical care (n = 91) vs the best medical care alone (n = 98).\n At a mean follow-up of 11.9 months, there was a significant reduction in stroke or crescendo transient ischemic attacks in patients who received carotid endarterectomy (7.7%) compared with nonsurgical patients (19.4%), or an absolute risk reduction of 11.7% (P = .011). The benefit of surgery was more profound in patients with internal carotid artery stenosis greater than 70% (absolute risk reduction, 17.7%; P = .004). The benefit of surgery was apparent within 2 months after randomization, and only one stroke was noted in the surgical group beyond the 30-day perioperative period.\n For a selected cohort of men with symptoms of cerebral or retinal ischemia in the distribution of a high-grade internal carotid artery stenosis, carotid endarterectomy can effectively reduce the risk of subsequent ipsilateral cerebral ischemia. The risk of cerebral ischemia in this subgroup of patients is considerably higher than previously estimated.", "Without strong evidence of benefit, the use of carotid endarterectomy for prophylaxis against stroke rose dramatically until the mid-1980s, then declined. Our investigation sought to determine whether carotid endarterectomy reduces the risk of stroke among patients with a recent adverse cerebrovascular event and ipsilateral carotid stenosis.\n We conducted a randomized trial at 50 clinical centers throughout the United States and Canada, in patients in two predetermined strata based on the severity of carotid stenosis--30 to 69 percent and 70 to 99 percent. We report here the results in the 659 patients in the latter stratum, who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic carotid artery. All patients received optimal medical care, including antiplatelet therapy. Those assigned to surgical treatment underwent carotid endarterectomy performed by neurosurgeons or vascular surgeons. All patients were examined by neurologists 1, 3, 6, 9, and 12 months after entry and then every 4 months. End points were assessed by blinded, independent case review. No patient was lost to follow-up.\n Life-table estimates of the cumulative risk of any ipsilateral stroke at two years were 26 percent in the 331 medical patients and 9 percent in the 328 surgical patients--an absolute risk reduction (+/- SE) 17 +/- 3.5 percent (P less than 0.001). For a major or fatal ipsilateral stroke, the corresponding estimates were 13.1 percent and 2.5 percent--an absolute risk reduction of 10.6 +/- 2.6 percent (P less than 0.001). Carotid endarterectomy was still found to be beneficial when all strokes and deaths were included in the analysis (P less than 0.001).\n Carotid endarterectomy is highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or nondisabling strokes and ipsilateral high-grade stenosis (70 to 99 percent) of the internal carotid artery.", "Our objective was to assess the risks and benefits of carotid endarterectomy, primarily in terms of stroke prevention, in patients with recently symptomatic carotid stenosis.\n This multicentre, randomised controlled trial enrolled 3024 patients. We enrolled men and women of any age, with some degree of carotid stenosis, who within the previous 6 months had had at least one transient or mild symptomatic ischaemic vascular event in the distribution of one or both carotid arteries. Between 1981 and 1994, we allocated 1811 (60%) patients to surgery and 1213 (40%) to control (surgery to be avoided for as long as possible). Follow-up was until the end of 1995 (mean 6.1 years), and the main analyses were by intention to treat.\n The overall outcome (major stroke or death) occurred in 669 (37.0%) surgery-group patients and 442 (36.5%) control-group patients. The risk of major stroke or death complicating surgery (7.0%) did not vary substantially with severity of stenosis. On the other hand, the risk of major ischaemic stroke ipsilateral to the unoperated symptomatic carotid artery increased with severity of stenosis, particularly above about 70-80% of the original luminal diameter, but only for 2-3 years after randomisation. On average, the immediate risk of surgery was worth trading off against the long-term risk of stroke without surgery when the stenosis was greater than about 80% diameter; the Kaplan-Meier estimate of the frequency of a major stroke or death at 3 years was 26.5% for the control group and 14.9% for the surgery group, an absolute benefit from surgery of 11.6%. However, consideration of variations in risk with age and sex modified this simple rule based on stenosis severity. We present a graphical procedure that should improve the selection of patients for surgery.\n Carotid endarterectomy is indicated for most patients with a recent non-disabling carotid-territory ischaemic event when the symptomatic stenosis is greater than about 80%. Age and sex should also be taken into account in decisions on whether to operate." ]

[ "9625329", "8391042", "7540996", "9500717", "7908624", "1900254", "8200260", "9819446", "8509627", "1899852", "9097267", "1906028", "9138278", "9303508", "8792690", "1742400", "7657272", "9672169", "9493517", "9444445", "2127790", "8773908", "1912556", "9537453", "7843696", "10347132", "7639224", "9247476", "1742537", "8340603", "9328328", "2127787", "8172137", "7694894", "9722203", "7907073", "7489345", "9021962", "8654159", "8583134", "7564784", "8938163", "7739681", "7493300", "9261621", "8382646", "2127789", "9310931", "8895005", "2509916" ]

[ "A randomized controlled trial of interferon-alpha in patients with cirrhosis caused by 2a/2b genotype hepatitis C virus.", "Randomised trial of lymphoblastoid alpha-interferon in chronic hepatitis C. Effects on inflammation, fibrogenesis and viremia.", "Lack of benefit of escalating dosage of interferon alfa in patients with chronic hepatitis C.", "Interferon alfa treatment of HCV RNA carriers with persistently normal transaminase levels: a pilot randomized controlled study.", "Treatment of chronic sporadic-type non-A, non-B hepatitis with lymphoblastoid interferon: gamma GT levels predictive for response.", "Recombinant human alpha-interferon in patients with chronic non-A, non-B hepatitis: a multicenter randomized controlled trial from France.", "Viral and host factors that contribute to efficacy of interferon-alpha 2a therapy in patients with chronic hepatitis C.", "Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group.", "Treatment with interferon(s) of community-acquired chronic hepatitis and cirrhosis type C. The TVVH Study Group.", "High doses of recombinant alpha-interferon or gamma-interferon for chronic hepatitis C: a randomized, controlled trial.", "A double-blind controlled trial of recombinant interferon-alpha 2b in haemodialysis patients with chronic hepatitis C virus infection and abnormal aminotransferase levels. Nephrologists' Group for the Study of HCV infection.", "Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis.", "Recombinant interferon-alpha-2a for treatment of chronic hepatitis C: results of a multicenter randomized controlled dose study.", "Treatment of chronic hepatitis C with consensus interferon: a multicenter, randomized, controlled trial. Consensus Interferon Study Group.", "Comparative efficacy of a high or low dose of interferon alpha 2b in chronic hepatitis C: a randomized controlled trial.", "[Therapy of chronic non-A, non-B hepatitis with interferon alfa-2B. A controlled clinical study and long-term follow-up].", "Randomized trial comparing three different regimens of alpha-2a-interferon in chronic hepatitis C. The TriVeneto Viral Hepatitis Group.", "Efficacy of interferon dose and prediction of response in chronic hepatitis C: Benelux study in 336 patients.", "Comparison of high initial and fixed-dose regimens of interferon-alpha2a in chronic hepatitis C: a randomized controlled trial. French Multicenter Interferon Study Group.", "Human lymphoblastoid interferon treatment for patients with hepatitis C virus-related cirrhosis.", "Prolonged treatment (18 months) of chronic hepatitis C with recombinant alpha-interferon in comparison with a control group.", "Transfusion-associated chronic hepatitis C: alpha-n1 interferon for 6 vs. 12 months.", "A randomized controlled trial of recombinant interferon-alpha in chronic hepatitis C in hemophiliacs.", "Lymphoblastoid interferon alfa-n1 improves the long-term response to a 6-month course of treatment in chronic hepatitis C compared with recombinant interferon alfa-2b: results of an international randomized controlled trial. Clinical Advisory Group for the Hepatitis C Comparative Study.", "Ability of prolonged interferon treatment to suppress relapse after cessation of therapy in patients with chronic hepatitis C: a multicenter randomized controlled trial.", "Treatment of hepatitis C virus-related cirrhosis: a randomized, controlled trial of interferon alfa-2b versus no treatment.", "A controlled study to determine the optimal dose regimen of interferon-alpha 2b in chronic hepatitis C.", "Predictors of the efficacy of interferon therapy in chronic hepatitis C virus infection. Tokyo-Chiba Hepatitis Research Group.", "Treatment of chronic hepatitis C with recombinant interferon alfa.", "alpha-Interferon in the treatment of chronic viral hepatitis: effects on fibrogenesis serum markers.", "Virological response to interferon treatment in hepatitis C virus carriers with normal aminotransferase levels and chronic hepatitis.", "A randomized controlled trial of interferon alfa-2b as therapy for chronic non-A, non-B hepatitis.", "A randomized, controlled trial of human lymphoblastoid interferon in patients with compensated type C cirrhosis.", "Long-term follow-up of patients with chronic hepatitis C treated with different doses of interferon-alpha 2b.", "Reinforced regimen of interferon alfa-2a reduces the incidence of cirrhosis in patients with chronic hepatitis C: a multicentre randomised trial. Multicentre GER-CYT-04 Group.", "Comparative efficacy of interferon alfa in cirrhotic and noncirrhotic patients with non-A, non-B, C hepatitis. Le Groupe Français pour l'Etude du Traitement des Hépatites Chroniques NANB/C.", "Comparative study of two high doses of lymphoblastoid interferon in the treatment of chronic hepatitis C: influence on the levels of ALT, viraemia and histologic activity.", "Treatment of chronic hepatitis C with interferon alfa-n3: a multicenter, randomized, open-label trial.", "Alpha but not beta interferon is useful in chronic active hepatitis due to hepatitis C virus. A prospective, double-blind, randomized study.", "Interferon alfa-2b for chronic hepatitis C: effects of dose increment and duration of treatment on response rates. Results of the first multicentre Australian trial. Australia Hepatitis C Study Group.", "Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis.", "A prospective, randomized trial comparing lymphoblastoid to recombinant interferon alfa 2a as therapy for chronic hepatitis C.", "A comparison of three interferon alfa-2b regimens for the long-term treatment of chronic non-A, non-B hepatitis. Multicenter Study Group.", "Long-term titrated recombinant interferon-alpha 2a in chronic hepatitis C: a randomized controlled trial.", "Comparison of treatment with two different doses of leukocyte interferon alpha in patients with chronic hepatitis C.", "Quantitative analysis of hepatitis C virus RNA in serum during interferon alfa therapy.", "Therapy of chronic post-transfusion non-A, non-B hepatitis with interferon alfa-2b: Swedish experience.", "Virological, biochemical and histological effects of human lymphoblastoid interferon in Swedish patients with chronic hepatitis C.", "Fixed versus titrated interferon-alpha 2B in chronic hepatitis C. A randomized controlled multicenter trial. The Swiss Association for the Study of the Liver.", "Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group." ]

[ "nan", "Seventy-two patients with chronic hepatitis C were included in a randomised trial of lymphoblastoid interferon versus no treatment. Thirty-six patients entered each group. Interferon was given in a step-down schedule for 12 months. Aminotransferase activities became normal during treatment in 30 of 36 (83.3%) treated patients, but in only 1 out of 36 (2.7%) non-treated cases (p < 0.001). However, a reactivation of the disease during the interferon course was observed in 12 patients after a mean of 5.58 +/- 1.55 months of therapy, and a post-treatment relapse was observed in 5 additional cases. The remaining 13 patients (36%) had sustained normalization of the aminotransferase levels for 15.27 +/- 10.34 months (range 3-30) after discontinuation of interferon, thus representing a long-term sustained remission of the disease. Knodell's histological activity index decreased in all treatment patients, except for 3 non-responders (91.5%), but in only 9 of 36 non-treated cases (25%) (p < 0.001). Procollagen type III peptide levels normalized in most cases (83%) with a sustained response. A significant decrease in the detection of hepatitis C virus RNA was observed in patients with a sustained response (p < 0.05). Anti-interferon antibodies were only detected in one non-responder. Thus, interferon diminishes inflammatory and fibrogenic activity in the majority of patients with chronic hepatitis C and abolishes viremia in most of the patients with a sustained response.", "In patients with chronic hepatitis C treated with interferon alfa, sustained normalization of alanine aminotransferase was observed in about 20%, and no predictive factor of response could be clearly identified. The aims of this study were to assess the efficacy of an escalating dose of interferon and to determine the predictive factors of response.\n Seventy-five patients were randomly assigned to two groups. Twenty-five patients received a dosage of 3 million units of recombinant interferon alfa-2b three times weekly for 24 weeks, and 50 patients received a dose that was increased to 5 million units at 8 weeks in nonresponders and to 10 million units 8 weeks later in persistent nonresponders. Multivariate analysis was performed to determine the features associated with response.\n A sustained response was observed in 17% of the patients with constant dosage and in 19% of patients with an escalating dosage. Low pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotype were found to be independent predictive factors of sustained response.\n In patients with chronic hepatitis C, an escalating dosage of interferon did not improve the overall rate of response. Low pretreatment serum hepatitis C virus RNA levels and genotype other than 1b were the only predictive factors of sustained response.", "Most patients with serum hepatitis C virus (HCV) RNA and persistently normal alanine transaminase (ALT) levels show histological features of mild to moderately active chronic hepatitis. Some cirrhosis has also been reported. To assess whether interferon (IFN) treatment led to long-term HCV suppression in these patients, 31 previously untreated patients (15 men, 16 women; mean age, 44 years) with serum HCV RNA, persistently normal ALT levels on at least four consecutive occasions 2 months apart, and histological features of chronic hepatitis (21 mild activity, 10 moderate activity) were randomized to receive 1FN-alpha-2a, 3 MU three times a week for 6 months (n = 16), or no treatment (n = 15). All patients were followed up for at least 6 months after treatment ended. HCV RNA was tested by nested reverse-transcription polymerase chain reaction (RT-PCR) using 5'-untranslated region complementary primers, quantified by branched-DNA assay, and typed by nested RT-PCR testing for the HCV core region. Treated and untreated patients had similar epidemiological, virological, and histological characteristics. At the end of treatment, serum HCV RNA was still detected in 15 patients (94%) and 14 controls (93%). ALT levels flared up in 10 patients receiving IFN (62%) and in 1 control (62% vs. 7%; P < .005, chi2 test). In conclusion, 6 months' treatment with IFN-alpha-2a did not eradicate HCV RNA from serum in carriers with persistently normal ALT levels but caused ALT flare-ups in two thirds of them. Until more is known about the natural history of HCV RNA carriers with normal ALT levels, these patients should not be treated with IFN.", "The aim of this study was to evaluate the efficacy of human lymphoblastoid interferon-alpha treatment in chronic sporadic-type non-A, non-B hepatitis. We also aimed to determine if histological or liver function data could predict either response or relapse. Sixty patients with chronic sporadic-type non-A, non-B hepatitis were randomized in two groups of 30. One group was treated with interferon-alpha (3 MU thrice weekly) for one year; the other group was untreated controls. The treated group was followed for another year after interferon withdrawal. Liver function tests were performed during treatment. Liver biopsy was carried out before and a year after randomization. We evaluated rate of response [normalization of alanine aminotransferase (ALT) levels for at least three consecutive months] and rate of relapse (ALT rebound after therapy suspension). We also looked at possible predictive factors for response and relapse. In the treatment group the rate of response was 55% (16/29). No control patient exhibited ALT normalization. Among the responders, 31% (5/16) relapsed after interferon withdrawal. Low gamma GT and female sex are positive predictive factors of response (P < 0.01 and P < 0.02 respectively). Presence of portal and periportal inflammation at the second liver biopsy was correlated with relapse (P < 0.05). In conclusion, human lymphoblastoid interferon-alpha treatment for one year is beneficial in patients suffering from chronic sporadic-type non-A, non-B hepatitis. Low pretreatment gamma GT levels and female sex are positive predictors of response in this patient population.(ABSTRACT TRUNCATED AT 250 WORDS)", "We have conducted a multicenter randomized controlled trial comparing two doses of recombinant human alpha-interferon for efficacy in 60 patients with chronic non-A, non-B hepatitis. The source of infection appeared to be transfusion in 30 patients, intravenous drug abuse in 16 patients and was unknown in 14 patients. Patients were randomly assigned to no treatment or to treatment with either 1 or 3 MU of alpha-interferon given three times a week for 24 wk. Forty-five patients (75%) were positive for antibody to hepatitis C virus. During the 24-wk treatment period, mean serum ALT levels decreased in both treatment groups, but the decrease was statistically significant only in the 3 MU group. However, at 24 wk, the proportion of patients with normal ALT levels was similar in the 3 MU group (39%) and the 1 MU group (45%), and both were significantly higher than in controls (0%). Repeat liver biopsy specimens showed a significant decrease in the severity of histological changes in the 3 MU group but not in the 1 MU group or in controls. Responses to alpha-interferon did not correlate with patient's age, gender, source of infection, pretreatment serum ALT, presence of anti-hepatitis C virus or cirrhosis. After treatment, the mean ALT levels rose in both treated groups. The proportion of patients with normal ALT levels at wk 48 was 28% in the 3 MU group and 20% in the 1 MU group. In conclusion, a dose of 3 MU was superior to 1 MU of alpha-interferon given three times weekly for 24 wk in inducing improvements in serum ALT levels and liver histological examinations.(ABSTRACT TRUNCATED AT 250 WORDS)", "Using conventional statistical analysis and multiple regression analysis, we investigated the viral and host factors that influence the response to recombinant interferon-alpha 2a therapy in patients with chronic hepatitis C. A total of 36 patients was randomly assigned to three administration schedules, 12 patients in each. Response to treatment was set as the criterion variable. Four variables were statistically significant in the conventional method in predicting a good therapeutic outcome: HCV genotype III and IV, lower histology activity index (HAI) score for liver, higher total dose of interferon administration, and lower serum HCV RNA concentration. In multiple regression analysis, a combination of the above four variables resulted in a higher multiple correlation coefficient (R = 0.84, P < 0.0001) using a stepwise method. Of those four, HCV genotype had the highest absolute value of standard partial regression coefficient (0.51). The HCV RNA concentration was correlated with HCV genotype and HAI score, whereas HCV genotype and HAI score showed no correlation. Thus, HCV RNA concentration was not statistically significant in multiple regression analysis. These findings indicate that HCV genotype, HAI score, and schedule of administration can be important predictors of the response to interferon therapy.", "Only 15 to 20 percent of patients with chronic hepatitis C have a sustained virologic response to interferon therapy. We compared the efficacy and safety of recombinant interferon alfa-2b alone with those of a combination of interferon alfa-2b and ribavirin for the initial treatment of patients with chronic hepatitis C.\n We randomly assigned 912 patients with chronic hepatitis C to receive standard-dose interferon alfa-2b alone or in combination with ribavirin (1000 or 1200 mg orally per day, depending on body weight) for 24 or 48 weeks. Efficacy was assessed by measurements of serum hepatitis C virus (HCV) RNA and serum aminotransferases and by liver biopsy.\n The rate of sustained virologic response (defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed) was higher among patients who received combination therapy for either 24 weeks (70 of 228 patients, 31 percent) or 48 weeks (87 of 228 patients, 38 percent) than among patients who received interferon alone for either 24 weeks (13 of 231 patients, 6 percent) or 48 weeks (29 of 225 patients, 13 percent) (P<0.001 for the comparison of interferon alone with both 24 weeks and 48 weeks of combination treatment). Among patients with HCV genotype 1 infection, the best response occurred in those who were treated for 48 weeks with interferon and ribavirin. Histologic improvement was more common in patients who were treated with combination therapy for either 24 weeks (57 percent) or 48 weeks (61 percent) than in those who were treated with interferon alone for either 24 weeks (44 percent) or 48 weeks (41 percent). The drug doses had to be reduced and treatment discontinued more often in patients who were treated with combination therapy.\n In patients with chronic hepatitis C, initial therapy with interferon and ribavirin was more effective than treatment with interferon alone.", "Two hundred and thirty-four patients with chronic non-A, non-B hepatitis, 86% positive for anti-HCV by ELISA, were treated with recombinant interferon-alpha 2a or with natural (human-leukocytes-derived) interferon-alpha using different dosage and periods of administration. Interim analysis of follow-up data indicate that 65-70% of patients treated initially with 6 MU, thrice weekly, of recombinant interferon-alpha 2a achieved a complete biochemical response (normalization of alanine aminotransferase: ALT) during therapy compared to 56-58% of those treated with 3 MU, thrice weekly, of recombinant or natural interferon-alpha. A 12-month schedule of interferon administration appeared superior to a 6-month schedule in reducing the probability of reactivation of liver disease after therapy withdrawal, although further data are needed to confirm such a conclusion. The probability of response to interferon in terms of maintaining normal ALT after withdrawal did not appear to be influenced by sex, while it was significantly higher in patients aged below 45 years and in those without cirrhosis.", "Chronic hepatitis C is often a progressive liver disease for which there is no satisfactory treatment. We studied the efficacy of recombinant alpha-interferon or gamma-interferon in the treatment of this disease in comparison with a control group. Thirty patients were randomly assigned to three groups. Ten patients received 7.5 MU alpha-interferon/m2 body surface three times weekly for 3 mo, then 5 MU/m2 for 3 mo and 2.5 MU/m2 for 6 mo. Ten patients were treated with gamma-interferon at a dose of 2 MU/m2 for 6 mo and the other 10 served as controls without treatment. The mean serum ALT levels and liver histological findings improved significantly only in the patients treated with alpha-interferon. No changes were observed in patients treated with gamma-interferon or in controls. Five of 10 patients treated with alpha-interferon had complete responses (mean ALT normal during therapy). After treatment ALT returned to pretreatment levels in two of 5 patients. The long-term response rate after alpha-interferon therapy was 30% at 18 mo. We conclude that alpha-interferon is effective in controlling disease activity in a portion of patients with chronic hepatitis C. High doses of alpha-interferon do not appear to add further benefit in the response rate or relapse rate. gamma-Interferon therapy is ineffective.", "The efficacy and safety of recombinant interferon-alpha 2b (rIFN-alpha 2b) was evaluated in a double-blind controlled trial comprising 23 haemodialysis patients with antibodies to hepatitis C virus (anti-HCV), detectable serum HCV RNA by polymerase chain reaction and chronic alanine aminotransferase elevation. The patients were randomly assigned to receive rIFN-alpha 2b at a dose of 1.5 MU (increasing to 3 MU if no response was observed) (Group I: n = 14) or identical placebo (Group II: n = 9), for 6 months. A biochemical response (normal alanine aminotransferase) was observed in 10 patients (71.4%) from Group I and in one patient (11.1%) from Group II (P < 0.01) at the end of therapy, and in four patients from Group I (28.6%) and in none from Group II (NS) 12 months after therapy. Virological response (HCV RNA negative) was observed in four patients (28.6%) from Group I and in none from Group II (NS) at the end of therapy, and in two patients (14.2%) from Group I and in none from Group II (NS) 12 months after therapy. Interferon doses were 1.5 MU in 12 patients and 3 MU in two patients. Therapy interruption owing to severe side-effects was necessary in three patients (21.4%) from Group I and in two patients (22.2%) from Group II. Although long-term statistical differences were not observed, these results suggest that rIFN-alpha 2b at a low dose is a reasonable and well tolerated therapeutic approach for haemodialysis patients with chronic hepatitis C.", "Ninety patients with histologically documented chronic non-A, non-B hepatitis were randomly allocated to receive SC injections of placebo or of 1 or 3 MU of recombinant interferon alfa-2b three times weekly for 24 weeks. Complete normalization of alanine aminotransferase levels occurred posttreatment in 43.3% of patients receiving 3 MU, in 20% of those receiving 1 MU, and in 6.7% of untreated patients (P less than 0.0005 vs. those treated with 3 MU). Alanine aminotransferase normalization was sustained for 6 months after therapy in 13.3% of the patients treated with 3 MU and in 3.3% of those given 1 MU or placebo. The decline of alanine aminotransferase levels following interferon therapy showed independent, positive correlations with female sex (P less than 0.03) and younger age (P less than 0.05). The Knodell's fibrosis score was strongly positively correlated with age (P less than 0.0001). It is concluded that 3 MU of interferon is a more effective dose than 1 MU for controlling disease activity in non-A, non-B chronic hepatitis patients. Women and younger and noncirrhotic patients are more likely to respond.", "To compare the efficacy of low and relatively high dosages of recombinant interferon (IFN)-alpha-2a in Japanese patients with chronic hepatitis C, as well as to characterize the type of patients who will respond well to a low-dosage treatment, 88 patients with histologically proven chronic hepatitis C were randomly assigned to two treatment groups; one treated with IFN-alpha-2a 6 MU daily for 2 weeks followed by 6 MU three times weekly for 22 weeks (6-MU group), and another given the same initial treatment followed by 3 MU three times weekly for 22 weeks (3-MU group). The rate of sustained normalization of ALT 6 months after the cessation of treatment was 33% in the 3-MU group and 40% in the 6-MU group (p = 0.64). In addition, there was no difference in elimination of serum HCV-RNA 6 months after the cessation of treatment between the 3-MU group (26%) and 6-MU group (29%). Multivariate stepwise regression analysis revealed that serum HCV-RNA level (p = 0.0035) and platelet count (p = 0.0009) were independent variables useful in predicting a sustained response of ALT. The sustained response rate of ALT in patients with a serum HCV-RNA level less than 10(5) copies/ml and serum platelet level above 15 x 10(4)/microliter was 71%, whereas that in patients with a serum HCV-RNA level above 10(5) copies/ml and serum platelet level less than 15 x 10(4)/microliter was 12%. These results indicate that a high rate of sustained response to IFN therapy can be expected in chronic hepatitis C patients with a low serum level of HCV-RNA and a high level of platelets, even if treated with a low dose of IFN.", "This multicenter, randomized, controlled, double-blind, phase III study in 704 patients with chronic hepatitis C infection compared treatment with consensus interferon (CIFN), a non-natural recombinant type-1 interferon, with a standard regimen of recombinant interferon alfa-2b (IFN-alpha2b). Patients were randomized to receive CIFN at doses of 3 microg or 9 microg, or 15 microg IFN-alpha2b (3 million units), subcutaneously three times weekly for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum alanine transaminase (ALT) concentration and decrease in serum hepatitis C virus (HCV) RNA concentration below the limit of detection by reverse-transcription polymerase chain reaction (RT-PCR) (100 copies/mL). The beneficial effect of CIFN was greater with the 9-microg dose than the 3-microg dose. The sustained ALT and HCV RNA response rates were 20.3% and 12.1%, respectively, in the 9-microg CIFN cohort and 19.6% and 11.3%, respectively, in the 15-microg IFN-alpha2b cohort. However, patients receiving 9 microg of CIFN had a greater reduction in serum HCV RNA concentrations compared with patients receiving 15 microg IFN-alpha2b over the course of treatment (P < .01). Similarly, analysis of patients infected with HCV genotype 1 showed a greater reduction in serum HCV RNA concentration over the course of treatment for the 9-microg CIFN group when compared with the 15-microg IFN-alpha2b group (P < .01). In addition, a greater percentage of patients infected with HCV genotype 1 treated with 9 microg CIFN had undetectable HCV RNA concentrations when compared with patients in the 15-microg IFN-alpha2b cohort at the end of treatment (24% vs. 15%; P = .04). Improvements in liver histology were noted in all three treatment groups; 52% to 55% of the patients in the three cohorts had at least a 2-unit improvement in the Knodell score at the end of the posttreatment period. The adverse-events profiles were characteristic of treatment with type-1 interferon, and the incidences of anti-interferon antibody formation did not significantly differ among the three treatment groups. These results show that administration of 9 microg CIFN three times weekly for 6 months is safe and is effective in reducing serum HCV RNA concentration.", "Our objective was to determine the relative efficacy of 6 months of treatment with 10 MU versus 3 MU of interferon-alpha 2b (IFN-alpha), three times weekly, in chronic hepatitis C (HCV) in a randomized trial.\n Ten megaunits of IFN-alpha were given to 28 patients (group A), and 3 MU were given to 30 patients (group B). After treatment ended, follow-up was continued for 26 wk.\n Overall, the sustained response rate was higher in group A than in group B (16/26 or 61.5% vs. 12/28 or 42.9%, p = 0.17), but the difference did not reach statistical significance. However, it was higher in group A than in group B among patients with minimal or mild chronic hepatitis (15/20 or 75% vs. 9/24 or 37.5%, p = 0.013) and among those with mild or moderate fibrosis (15/17 or 88.2% vs. 11/19 or 57.9%, p = 0.042). IFN-alpha treatment significantly reduced histological activity index (HAI) scoring and all its parameters, except fibrosis, but the decrease was similar in the two groups. Sex, age, stage, and HCV genotype were statistically significant predictors of sustained response in univariate analysis. However, multiple logistic regression analysis revealed that advanced histological stage (severe fibrosis and cirrhosis) was the only significant prognostic factor of poor sustained response (RR = 31.0, 95% CI 2-460, p = 0.01), whereas the presence of genotype 1 had marginal statistical significance (RR = 5.0, 95% CI 0.9-28, p = 0.07).\n 1) A larger dose of IFN-alpha does not improve the sustained response rate; however, it may be of benefit in early stages of chronic hepatitis C. 2) Pretreatment, histological stage, and possibly HCV genotype appear to be the main prognostic factors of sustained response.", "In order to assess the efficacy of alpha-2b interferon (r-IFN) in the treatment of non-A non-B chronic hepatitis, 30 patients were randomised to receive r-IFN (3 MU subcutaneously three times a week for 24 weeks) or no therapy. A total of 21 males and 9 females, aged between 24-66 years old and who had had increased transaminase levels for at least one year, were included in the study. Three patients were ex-drug addicts and 6 had received blood transfusions whereas the cause of the infection in the remaining 21 patients was unknown. Hepatic biopsies performed prior to the study revealed persistent chronic hepatitis in 7 patients, active chronic hepatitis (ACH) in 19 patients and ACH with hepatic cirrhosis in 4 patients. Anti-HCV antibodies were present in 21 patients (70%). Transaminase values returned to normal in 11 (73%) of the 15 patients treated and remained unchanged in controls after 6 months of therapy. During the 18-month follow-up following the suspension of r-IFN treatment, transaminase values rose again to pre-treatment levels in 4 patients. Anti-HCV antibodies did not disappear in any of the patients who responded to therapy.", "Alpha-interferon (IFN-alpha) is an effective treatment for chronic hepatitis C, but only 20% to 30% of patients are apparently cured with the current recommended schedule of 3 MU given three times a week for 6 months. To evaluate the efficacy of more aggressive treatment regimens, we have conducted a randomized trial in 174 patients with chronic hepatitis C using three different schedules: (1) 12-month treatment starting with 6 MU/ three times a week and decreasing the dose on the basis of serum alanine transaminase (ALT) activities (group A: 59 cases); (2) fixed dose of 3 MU three times a week for 12 months (Group B: 61 cases), (3) fixed dose of 6 MU three times of week for 6 months (Group C: 54 cases). Patients were evaluated during therapy for biochemical and virological response and followed for at least 12 months after therapy to assess long-term efficacy and liver histological outcome. The genotype of infecting HCV was also analyzed in all patients, and predictors of response were determined by multivariate analysis. Serum ALT became normal during therapy in 76% of patients (95% confidence interval [CI]: 63 to 86), 65% (CI: 52 to 77), and 74% (CI: 60 to 85) in groups A, B, and C, respectively (P = NS). The corresponding figures for sustained response 12 months after therapy were 49% (CI: 36 to 62), 31% (CI: 20 to 44), and 28% (CI: 16 to 42)(A vs. B, P = .06; A vs. C, P = 0.03). Eighty-six percent of patients with sustained response cleared HCV-RNA from serum, and 72% improved histologically.(ABSTRACT TRUNCATED AT 250 WORDS)", "In an attempt to improve the limited efficacy of treatment of chronic hepatitis C with interferon-alpha 3 MU tiw, we studied the effects of double-dose therapy followed by downward titration, and analyzed the pre- and pertreatment factors associated with response or non-response.\n Three hundred and fifty-four consecutive patients in 19 centers were randomized to interferon-alpha 3 MU tiw for 6 months or 6 MU tiw for 8 weeks followed by down-titration (3,1 MU tiw) till alanine aminotransferase remained normal and plasma HCV RNA was repeatedly undetectable. The primary outcome measure was sustained alanine aminotransferase and HCV RNA response 6 months after treatment.\n Three hundred and thirty-six patients received treatment. The sustained response rate for patients receiving 3 MU tiw for 6 months was 14% (9-21%,) and for patients receiving double dose tiw for 8 weeks and thereafter titrated therapy 15% (10-21%) (p=0.8). Pretreatment factors associated with a sustained alanine aminotransferase plus HCV RNA response were the absence of cirrhosis, presence of genotype 2 or 3, a low viral load and, in addition, a low alanine aminotransferase/aspartate aminotransferase ratio; a model was developed to allow estimation of the chance of response for the individual patient. The most powerful predictor of sustained response, however, was plasma HCV RNA at week 4; a positive test virtually precluded a sustained response (1.7%, 0.4-5.0%). If week 4 HCV RNA was not detectable, the chance of a sustained response was 21% (12-34%) for genotype 1 versus 40% (28-54%) for the others (p=0.02). Six MU tiw led to a significantly higher week 4 HCV RNA response (47% not detectable) than 3 MU (37%) (p=0.02). During down-titration this difference in viral on-treatment response was lost.\n In the treatment of hepatitis C, an early HCV RNA response is a prerequisite for long-term efficacy. Doubling the initial interferon dose increases this early response, but subsequent downward titration negates this effect, especially in genotype 1.", "The efficacy of a high-dose de-escalating treatment regimen versus the standard, fixed-treatment regimen of interferon-alpha2a (IFN; Roferon-A) in chronic hepatitis C was evaluated in 291 patients who had elevated alanine aminotransferase (ALT) levels, for at least 6 months prior to the study, and histologically proven chronic hepatitis. Patients were randomized into two groups: 142 patients received IFN at a fixed dose (3 million international units (MIU) three times a week for 6 months) and 149 patients received 6 MIU three times a week for 3 months followed by 3 MIU three times a week for the next 3 months. The groups did not differ significantly with respect to age, gender or percentage of patients with cirrhosis. Response was evaluated by monitoring ALT levels monthly during treatment and during the 6 months post-treatment follow-up. Sixty-one per cent and 66% of the patients in the fixed and de-escalating treatment groups had a primary response (serum ALT normalization) during the treatment period; sustained-response rates at the end of follow-up were 20% and 29%, respectively (not significant). In non-cirrhotic patients, a primary response was recorded in 65% and 70% of the patients in the fixed and de-escalating groups; sustained-response rates were 22% and 33%, respectively. Overall, 62% of patients with a sustained response showed histological improvement. In univariate analysis, patients with sustained response tended to be non-cirrhotic and had lower initial serum gamma-glutamyl transpeptidase and ferritin levels. Multivariate analysis indicated that only ALT activity assessed at month 1 (P < 0.01) was a significant predictor of sustained response. These findings suggest that although the difference in the response rates between the de-escalating (6 MIU three times a week for 3 months; 3 MIU three times a week for 3 months) and fixed (3 MIU three times a week for 6 months) treatment regimens did not reach statistical significance, there was a clear trend towards higher response with the 6 MIU induction dose in patients without cirrhosis.", "To evaluate the efficacy and safety of human lymphoblastoid interferon treatment (interferon alfa) for patients with compensated cirrhosis caused by hepatitis C virus (HCV) infection, we randomly assigned 82 cirrhotic patients with chronic HCV infection (44 men, 38 women; mean age, 58.6 years) to two groups: 41 patients were treated with interferon alfa (480 million U over 6 months), and the other patients received no drug treatment. HCV RNA genotypes were determined by polymerase chain reaction (PCR) testing using type-specific primers. HCV RNA levels were measured by competitive PCR testing. No untreated patients eliminated HCV RNA from the serum or had a decrease in the level of alanine aminotransferase to normal during the observation period. Of the 34 patients who completed interferon alfa treatment, 6 (17.6%) who were considered complete responders eliminated HCV RNA from the serum by the end of treatment and sustained this elimination throughout a 6-month follow-up period. Complete responders constituted 6 (46.2%) of 13 patients with HCV RNA levels < or = 10(5) copies/50 microL, but none of the 21 patients with levels > 10(5) copies/50 microL were complete responders. Two (7.1%) of 28 patients with genotype 1b infection and 4 (66.7%) of 6 with genotype 2a were complete responders. Five patients withdrew because of interferon alfa-induced side effects (1 for thrombocytopenia, 3 for severe general malaise, and 1 for impotence), and 2 withdrew after being diagnosed with hepatocellular carcinoma. Hepatic failure did not occur in any treated patient in the present study. These findings indicate that interferon alfa treatment is useful for compensated cirrhosis caused by HCV infection if the HCV RNA levels are low and the infection is of genotype 2a.", "The effectiveness of recombinant alpha-interferon was evaluated in chronic non-A, non-B hepatitis of parenteral transmission. Thirty patients were randomly allocated two groups: control group (without treatment) and treatment group (alpha-interferon 5 mega units thrice weekly for 2 months, and then 1.5 mega units until the eighteenth month). Retrospectively, 26 patients had anti-hepatitis C antibodies. After the first month, 40% of the treated patients had normal serum alanine aminotransferase levels, and no one in the control group (p less than 0.05). After 18 months of treatment, 40% (6/15) of treated patients and 7% (1/14) of controls had normal serum transaminases (p less than 0.05). Interferon was well tolerated. A decrease in the Knodell Index score on final biopsy was found in treated patients (p less than 0.05), with no variations in the control group. Relapse within 7 months after the end of treatment occurred in two out of six complete responders. Thus, recombinant alpha-interferon therapy given for 18 months normalizes serum transaminases and improves histological lesions in chronic hepatitis C of parenteral epidemiology. This long-term interferon schedule is well tolerated.", "To compare the long-term effects of brief and prolonged therapy with alpha-n1 interferon for transfusion-associated chronic hepatitis C.\n One hundred and sixteen subjects (male/female 48/68, mean age 46.9 years) were studied. Sixty patients were randomised to brief treatment (group 1: interferon 5 Mu/msq. t.i.w. for 2 months, then 3 Mu/msq. t.i.w. for 4 months), and 56 to prolonged treatment (group 2: interferon 5 Mu/msq. t.i.w. for 2 months, then 3 Mu/msq. t.i.w. for 10 months). All were followed for 12 months after stopping interferon.\n The early response rate was 47.4% (Group 1 [45%], Group 2[50%]. No \"breakthrough\" reactivations were observed. The early response rate was 19% in patients with and 63% in patients without cirrhosis. Twenty-three (19.8%) subjects stopped therapy. Among 54 evaluable early responders, 21 had a sustained response. The rate of sustained response was comparable in group 1 (18.3%) and group 2 (18.2%). All sustained response subjects and some non-responders were HCV-RNA negative at the end of follow-up. Histological improvement was seen only after sustained response. Cirrhosis developed in 20% of non-responders. Overall, interferon induced a long-lasting remission of chronic hepatitis C in about one of every five patients.\n In a population predominantly infected by hepatitis C virus type 1, 12 months of therapy with high doses of interferon does not confer any additional benefit on the early response or sustained response rates as compared to a 6-month course.", "Chronic liver disease associated with hepatitis C virus (HCV) is an important cause of morbidity and mortality in hemophilia. We have used recombinant interferon alpha-2b (IFN alpha-2b) in a randomized controlled liver biopsy trial to treat hemophiliacs with chronic hepatitis. Eighteen patients entered the study, 16 of whom were subsequently shown to have antibodies to the HCV. All underwent liver biopsy at entry and were randomized to either treatment with self-administered IFN alpha-2b, 3 million units subcutaneously thrice weekly (n = 10) or no treatment (control group) (n = 8). Nine subjects had chronic active hepatitis, seven had chronic persistent hepatitis, and two had cirrhosis. Twelve months after entry into the study 17 patients underwent a second liver biopsy. All biopsies were coded, assessed, and scored according to the histologic severity of the liver disease. Ten patients were administered IFN for 1 year, and in four patients normalization of alanine aminotransferase (ALT) occurred compared with none in the untreated group. After the second liver biopsy, six of the eight initial no-treatment patients were treated with interferon 3 million units thrice weekly for 6 months, and normalization of ALT was seen in five patients. Biochemical relapse within 4 months of stopping IFN occurred in one of four patients treated for 1 year and in four of five patients treated for 6 months. IFN treatment was well tolerated. Although the histologic scores of the two groups were similar at entry into the study, after 12 months the biopsy appearances in the treated group were significantly improved compared with the controls (P less than .01). Histologic improvement was noted in the three interferon-treated human immunodeficiency virus antibody-positive patients and also in other patients who had no biochemical response. We conclude that low-dose recombinant IFN alpha is effective in normalizing transaminases and improving the histologic appearances in at least 50% of hemophiliacs with chronic hepatitis C.", "The aim of this study was to compare the short-term and long-term efficacy and safety of lymphoblastoid interferon with a recombinant interferon alfa (IFN-alpha) in a 24-week treatment course for chronic hepatitis C. One thousand seventy-one patients with chronic hepatitis C were randomized to receive lymphoblastoid IFN-alpha n1 or recombinant IFN-alpha2b at the same dosing regimen, 3 million units administered subcutaneously three times a week for 24 weeks. Hepatitis C viral (HCV) genotype (by line probe assay) was determined at baseline, and serum HCV RNA level (by quantitative reverse-transcriptase polymerase chain reaction) was measured at baseline and weeks 24, 48, and 72. Primary end points were normalization of serum alanine aminotransferase (ALT) levels at end of therapy (week 24) and sustained ALT normalization at weeks 48 and 72. Secondary end points were nondetectability of serum HCV RNA at 24, 48, and 72 weeks, and histological improvement at weeks 24 and 72. The two treatment groups were similar with respect to demographic, clinical, and histological variables (10% had cirrhosis at entry), baseline serum HCV RNA levels, and distribution of HCV genotypes. Intent-to-treat analysis showed that ALT response at end of treatment was 35.3% for IFN-alpha n1 and 37.9% for IFN-alpha2b (P = .38). Histological improvement and nondetectability of HCV RNA were also similar between the two treatment groups at the end of treatment, as were the type and frequency of reported adverse experiences. Among treatment responders, post-treatment relapse was significantly less frequent with IFN-alpha n1 than with IFN-alpha2b. Thus, sustained ALT responses (SR) to IFN-alpha n1 were significantly more frequent than SR to IFN-alpha2b (12.0% vs. 7.6% at 48 weeks, P = .02; 10.3% vs. 6.7% at 72 weeks, P = .04). SR were associated with viral loss and histological improvement, and more patients treated with IFN-alpha n1 were HCV RNA negative at week 72 compared with patients treated with IFN-alpha2b (P = .03). SR at week 72 were two- to sixfold better with other HCV genotypes relative to type 1, but the improved long-term efficacy of IFN-alpha n1 compared with IFN-alpha2b was evident for all major HCV genotypes. It is concluded that IFN-alpha n1 and IFN-alpha2b have similar end-of-treatment response rates and safety profiles but the sustained response rate is higher with IFN-alpha n1. SR to IFN-alpha treatment are associated with clearance of HCV RNA, and histological improvement was maximal in patients who exhibited sustained ALT normalization and clearance of HCV RNA.", "The aim of this study was to determine whether 12 months course of interferon alfa (IFN-alpha) therapy could improve the beneficial effect of IFN in chronic hepatitis C. Eighty-eight patients were treated with natural IFN-alpha for either 28 weeks (45 cases) or 52 weeks (43 cases). Sustained response was achieved in 15 (33.3%) of 45 cases treated for 28 weeks and in 23 (53.5%) of 43 cases treated for 52 weeks. Transient response with relapse of alanine transaminase (ALT) after completion of therapy was observed in 13 cases (28.9%) treated for 28 weeks and in 4 cases (9.3%) treated for 52 weeks. Thus, ALT relapse was suppressed by prolonged IFN treatment. No response was found in 17 cases (37.8%) treated for 28 weeks and in 16 cases (37.2%) treated for 52 weeks, indicating that approximately 38% of the patients with chronic hepatitis C were resistant to IFN therapy even with prolonged treatment. The rate of sustained response was significantly higher in patients with type 2a or 2b than in those with type 1b. Even in type 1b cases, it was higher in the 52-week treatment group than in the 28-week treatment group, and the rate of transient response was lower in the 52-week treatment group, indicating that relapse in type 1b cases was suppressed by prolonged IFN therapy. IFN therapy was not effective for patients with advanced liver fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)", "To examine the effects of interferon (IFN) therapy on clinical, biochemical, and histological features in patients with compensated hepatitis C virus (HCV)-related cirrhosis, we have conducted a randomized, controlled trial of IFN therapy versus observation. Eight centers included a total of 99 patients with biopsy-proven cirrhosis. IFN-alpha2b, 3 million units three times per week, or no antiviral therapy was given for 48 weeks. Twenty-three patients dropped out. End-of-treatment biochemical response was not observed in any of the 39 controls but was observed in 6 of the 47 treated patients (P <.02); sustained biochemical response was obtained in only 2 treated patients. Controls and treated patients did not significantly differ with regard to the changes in serum level of albumin, bilirubin, alpha-fetoprotein, in plasma prothrombin, in histological activity, or liver collagen content. During trial or follow-up (160 +/- 57 weeks), hepatocellular carcinoma developed in 9 controls and 5 treated patients (NS); decompensation of cirrhosis occurred in 5 controls and 7 treated patients. Seven controls and 10 treated patients died. In conclusion, in patients with compensated HCV-related cirrhosis, a 48-week course of IFN therapy is safe and is able to induce end-of-treatment biochemical response in a significant proportion of patients. However, a 48-week course of IFN therapy usually fails to achieve sustained response and, within the limit of this study, did not significantly improve the 3-year outcome. Therefore, a longer course of IFN therapy or combination therapy with ribavirin should be evaluated in patients with HCV-related cirrhosis.", "The efficacy of three different dose treatments of interferon (IFN) was evaluated in patients with chronic hepatitis C (HCV).\n Ninety-one patients with chronic hepatitis C were allocated to receive 3, 6, or 10 U of recombinant IFN-alpha 2b three times weekly for 24 wk. The number of patients was 26, 35, and 30 in the low, middle, and high dose groups, respectively. Treatment was discontinued, however, in four patients (one in the middle dose group and three in the high dose group) because of depression occurring 1-3 months after therapy began. A total of 87 patients, therefore, was analysed and was comprised of 26 patients in the low dose group, 34 in the middle dose group, and 27 in the high dose group.\n At the end of treatment, serum levels of ALT were normal in 50% (13/26) of patients in the low dose group, 70% (24/34) in the middle dose group, and 74% (20/27) in the high dose group. Patients with persistent normalization of ALT for 12 months of follow-up were defined as sustained responders. Twelve months after treatment cessation, the percentage of sustained responders was 23% (6/23) in the low dose group, 44% (15/34) in the middle dose group, and 41% (11/27) in the high dose group. Including the four patients who required discontinuation of IFN administration, the percentage of sustained responders was 43 and 37% in the middle and high dose groups, respectively. The clearance of HCV RNA was 40% in the middle dose group and 33% in the high dose group. This decrease in the clearance of HCV RNA was prominent in the high dose group. The percentage tended to be higher in the middle dose group, but the differences were not significant.\n The results suggest that a regimen of recombinant IFN-alpha 2b in a dose of 6 U three times weekly for 24 wk may be appropriate for the treatment of chronic HCV.", "The relative role of virus load and hepatitis C virus (HCV) subtype as predictor of the efficacy of interferon (IFN) therapy is still in dispute. To resolve this issue, a multicenter, randomized, prospective study of 272 patients with chronic hepatitis C but without cirrhosis was conducted.\n The patients were randomly assigned to two different dose groups: 6 million units (MU) or 9 MU IFN three times a week for 6 months. Serum HCV RNA levels and HCV subtypes were determined.\n HCV RNA negativity rate at the completion of treatment with 9 MU IFN was higher than that with 6 MU (75% vs. 44%; P < 0.05). Virus eradication at 12 months after completion of treatment was higher in the 9 MU group than in the 6 MU group (36% vs. 25%; P < 0.05), especially in patients who had an intermediate virus load (10(4)-10(5) copies/mL by Amplicor monitor assay) (52% vs. 19%; P = 0.029). Virus eradication rate in patients with serotype 2 was higher than in those with serotype 1 for both regimens (6 MU, 53% vs. 15%; 9 MU, 76% vs. 29%; each P < 0.05).\n This prospective study showed that virus load, HCV serotype, and IFN dose are important predictors of the virological response to IFN therapy but virus load is the most important factor influencing the efficacy of IFN.", "We studied the clinical course and the effect of alfa interferon treatment in sixty-six patients of Southern Italy suffering from chronic hepatitis C virus. The patients were randomly assigned to the control group (33 patients without treatment) or to the group treated with 3MU of interferon three times a week for six months. Alanine transaminase (ALT) levels normalized in 17 of the 33 treated subjects (52%) within two months of treatment. Seven of these \"responders\" relapsed at the end of the six-month treatment period, but ALT normalized in these patients after resumption of interferon at the same dosage. None of the non responders on 3MU for four months showed improvement even when the dose was increased to 6MU. Our results coincide with other reports on interferon treatment in hepatitis C virus. Further studies are required to clarify whether or not higher doses at the onset of treatment increase the number of responders and decrease the frequency of relapses.", "Forty patients with chronic viral hepatitis or active cirrhosis (33 anti-HCV positive) entered a recombinant human alpha 2A interferon randomized trial. Twenty-one subjects were treated with 6 million units (MU) three times per week for 6 months. Nineteen were not treated. Six months later in 12 patients of the treated group (60% of the evaluable 20) with normalized serum aminotransferases levels (responders), fibrogenesis serum markers (NPIIIP and laminin) were significantly lower than baseline. In the untreated patients and in non-responders NPIIIP and laminin were unchanged. Semi quantitative histological evaluation (allotting scores for inflammation, necrosis and fibrosis) confirmed a significant improvement of necro-inflammation in the responders. These data suggest that alpha-IFN treatment may decrease stimuli for fibrogenesis by reducing liver inflammation and necrosis, thus preventing evolution to cirrhosis.", "Hepatitis C virus (HCV) carriers with normal aminotransferase levels often show histological chronic hepatitis. This study was undertaken to determine the effect of interferon (IFN) in such patients. Nineteen HCV carriers with normal aminotransferase activities and chronic hepatitis were randomized to receive IFN-alpha2b (3 million units 3 times weekly for 12 months) or no treatment. Therapy was monitored by qualitative and quantitative determination of viral RNA. Patients who did not clear HCV RNA after 6 months discontinued therapy. In all, 9 patients constituted the control group, while 10 patients were treated. Five of these patients, still viremic after 6 months, stopped IFN. The remaining 5 patients, who cleared the viral RNA within 6 months, completed the 12-month course. Three of these patients relapsed off treatment, and 2 were still free of viremia 12 months after stopping therapy. A transient flare-up of aminotransferase activities was detected in 2 patients during treatment and in 3 patients after. None of the 9 control patients cleared the viral RNA during follow-up. A variable degree of sequence heterogeneity was detected in the hypervariable region before therapy, and IFN treatment decreased sequence diversity in all patients. These results indicate that IFN therapy can be effective in chronic HCV carriers with normal aminotransferase activities, inducing short-term virological response in 3 of 10 patients and sustained response in 2. The effects of treatment on viral load and quasispecies complexity were similar to those reported previously in patients with increased aminotransferase activities.", "Eighty patients with chronic non-A, non-B hepatitis completed a randomized controlled trial of the therapeutic efficacy of recombinant interferon alfa-2b. Twenty-nine received 1 million units and 26 received 3 million units of interferon subcutaneously thrice weekly for 6 months, and 25 were controls. Normalization or a significant decrease of alanine aminotransferase values was obtained in 19/29 (66%) patients treated with 1 million units, in 18/26 (69%) patients treated with 3 million units and in one control patient (4%, p less than 0.05). However, when control patients were randomized after the initial 24 weeks to receive 1 or 3 million units of interferon for 48 weeks, 12/14 (86%) patients receiving 3 million units responded to therapy versus 3/11 patients receiving 1 million units (27%, p less than 0.05). After a 1 to 6 months follow-up period post treatment, an alanine aminotransferase relapse was observed in 18/30 (60%) responders to 3 million units and in 17/22 (77%) responders to 1 million units. Cirrhotic patients responded less than patients with non-cirrhotic disease (47 vs. 78%, p less than 0.05). Only responders treated with 3 million units significantly ameliorated their histologic picture (pre-therapy Knodell's index = 8.9, post-therapy = 6.0, p less than 0.05). The data confirm that treatment with interferon is of benefit in patients with chronic non-A, non-B hepatitis.", "To determine the efficacy of human lymphoblastoid interferon (L-IFN) in the treatment of compensated type C cirrhosis, 30 patients were assigned randomly to three groups, consisting of 10 patients each, who were treated as follows.\n The 1- and 3-megaunit (MU) groups received 1 or 3 MU of L-IFN, respectively, daily for 2 wk, and three times weekly for 24 wk thereafter. The control group received no treatment. All of the patients had positive C100-3 hepatitis C virus antibody (anti-HCV) titers.\n The serum alanine aminotransferase (ALT) levels decreased 26 wk after L-IFN treatment was began, in both treatment groups. In the 3-MU group, the ALT levels became normal [complete response (CR)] in 40%, improved to less than twice the upper limit of the normal value [partial response (PR)] in 10%, and remained unchanged [no change (NC)] in 50%. In the 1-MU group, a PR occurred in 30%. There was NC in 70%, and NC occurred in the control group. Twenty-four weeks after stopping L-IFN, the CR and NC rates in the 3-MU group were 10% and 90%, respectively, and NC was observed in all of the 1-MU and control patients. 2',5'-Oligoadenylate synthetase activities increased in both treatment groups (p < 0.05), but not in the control group. The anti-HCV titers decreased in the 3-MU group (p < 0.05), but not in the 1-MU and control groups. Higher doses of L-IFN were more effective. No serious side effects occurred.\n These findings suggest that IFN administration can be effective and safe in patients with compensated type C cirrhosis, and that it would be worthwhile to evaluate IFN therapy for cirrhotic patients further.", "Eighty patients with chronic hepatitis C who completed a previously reported randomized controlled trial on the efficacy of interferon-alpha 2b were followed up for at least 36 mo after therapy discontinuation. Seventeen patients (21.2%) maintained normal ALT values throughout the follow-up; 63 (78.8%) either did not normalize the levels of ALT or relapsed during the follow-up. A significantly greater proportion of patients treated with 3 million units of interferon three times a week subcutaneously for 48 wk were long-term responders compared with patients treated for 24 wk. Sex, age, hepatitis C virus antibody status, source of infection and pretreatment levels of ALT were not predictive of long-term response. Cirrhosis was found to be an unfavorable predictive factor. After 3 yr of follow-up, clearance of viremia was observed in 58.9% of the 17 long-term responders but in none of the non-responders (p = 0.002). E2-NS1 antibody tested negative in 88.2% of long-term responders and in 14.3% of nonresponders (p = 0.001). Fifty-nine percent of long-term responders tested negative for C100-NS4 antibody compared with 14.3% of nonresponders (p = 0.031). No significant change was observed in other antibodies. Four long-term responders underwent liver biopsy 2 yr after discontinuation of therapy. All four patients had normal liver histology compared with baseline assessment of chronic active hepatitis in three and chronic persistent hepatitis in the other. Three of the four were negative for serum hepatitis C virus RNA.", "Our aim was to assess and compare the long-term effect of interferon at standard (6 months) and reinforced dose and duration regimens in chronic hepatitis C.\n A multicentre institutional trial included 244 previously untreated patients with chronic hepatitis C, without cirrhosis, who were randomly allocated to either standard (3 MU thrice a week for 24 weeks; n=120) or reinforced (6 MU daily for 12 days, 6 MU thrice a week for 22 weeks, 3 MU thrice a week for 24 weeks; n=124) regimens. The main endpoint was sustained ALT response at 72 weeks (18 months); secondary end-points were virological (branched DNA and PCR) and histological responses (incidence of cirrhosis) at month 18.\n Sustained ALT response was observed in five patients (4%, 95% confidence interval 0-8%) in the standard group and in 21 patients (18%, 95% confidence interval 11-25%), from the reinforced group (p=0.002), in agreement with virological response in 21 (81%) patients. Cirrhosis at month 18 was observed in ten (10%) patients in the standard group and one (1%) in the reinforced group (p=0.004).\n The standard regimen of interferon, in chronic hepatitis C, confers a minimal sustained response rate at 18 months and may not prevent the occurrence of cirrhosis. Reinforced regimens allow sustained response to be reached in a limited number of patients and reduce the risk of cirrhosis during 18 months of follow-up.", "Because the effects of interferon in the presence and absence of cirrhosis are still debated in chronic active hepatitis type non-A, non-B, C (NANB/C), the aim of this study was to determine to what extent the presence of cirrhosis influences the response to interferon.\n We compared the response to interferon alfa in 108 patients with chronic active hepatitis NANB/C with or without cirrhosis. The patients were randomly assigned to one of the two regimens: one group received 6 months of interferon 3 MU 3 times weekly, while the second group received a 12-month course, 3 MU three times weekly during the first 6 months, 2 MU for the following 3 months, and 1 MU for the last 3 months.\n In both regimens, the proportion of patients with normal alanine aminotransferase at the end of treatment was significantly lower in the cirrhotic than in the noncirrhotic patients. In males, abnormal serum alkaline phosphatase levels and gamma glutamyl transpeptidase were also related to a lesser response independent of cirrhosis. The response at the end of treatment was not significantly different between the two regimens in either the cirrhotic or the noncirrhotic patients. However, the 12-month regimen gave a significantly higher rate of sustained response 6 months after the end of treatment in patients without cirrhosis.\n It is suggested that the presence of cirrhosis markedly reduces the rate of response to interferon and that in noncirrhotic patients, a 1-year treatment regimen could improve the beneficial effect of interferon.", "Ninety consecutive patients with chronic hepatitis C were included in a randomized, uncontrolled trial to compare the efficacy of two treatment regimens, 10 MU (group A) vs 5 MU (group B), of lymphoblastoid interferon, in a step-down schedule for 24 weeks. All of the patients had antibodies against the hepatitis C virus, and all but one were HCV RNA positive in serum. The origin of the infection was attributed to blood transfusion in 30 patients and classified as sporadic in 60 patients. During treatment reduction in the ALT levels as well as the elimination of viraemia was observed in both treated groups, although these changes did not correlate significantly with the interferon dose. Nine months after the end of therapy, a sustained response was achieved in 13.6% (12/88) of the patients. Relapse in group B (87.5%) was significantly higher than in group A (59.1%). The percentage of cases which remained with undetectable HCV RNA was significantly higher for the sustained responders (66.7%) than for the non-responders (11.8%) and relapser patients (2.4%). Repeated liver biopsies showed an overall significant reduction of all the subindices of histological activity from patients with sustained response, except for fibrosis. In short: the 10 MU dosing regimen of lymphoblastoid interferon was as efficient as the 5 MU dose as it brought about a similar improvement in ALT levels, histological activity and elimination of viraemia, albeit 10 MU proved significantly more effective in the prevention of a relapse among the responders after 24 weeks therapy.", "We studied the antiviral effectiveness and safety of interferon alfa-n3, a natural alpha interferon which contains multiple interferon species, in the treatment of previously untreated patients with chronic hepatitis C. Seventy-seven patients were randomized to receive either 1.0, 2.5, 5.0, or 10.0 million units (MU) of interferon alfa-n3 three times a week for 24 weeks and were then followed for an additional 24 weeks. At the end of therapy, 67% of patients in the 10 MU group normalized serum alanine transaminase (ALT) levels and 59% had no hepatitis C virus (HCV) RNA detected by polymerase chain reaction. At the end of the follow-up period, 44% of patients in the 10 MU group maintained normal ALT, and 24% had nondetectable HCV RNA. Lower doses were much less effective. Interferon alfa-n3 was well tolerated and no patient developed neutralizing anti-interferon antibodies during or after the treatment period. Interferon alfa-n3 appears to be effective against hepatitis C virus and deserves further study in larger randomized controlled trials.", "Interferon-alpha has been widely used in chronic hepatitis C, but controlled studies with intramuscular interferon-beta are lacking. We therefore performed a prospective, double-blind, randomized study comparing intramuscular IFN-alpha and -beta in patients with chronic hepatitis C. Sixty patients were randomly assigned to receive 3 MU thrice weekly intramuscularly of either recombinant IFN-alpha or leukocyte IFN-alpha or fibroblast IFN-beta for six months. Nine of 20 patients (45.0%) in the recombinant IFN, 5/19 (26.3%) in the leukocyte IFN, and none in the IFN-beta group had a complete response during therapy (recombinant IFN vs IFN-beta: P < 0.01). Only in IFN-alpha-treated patients, was infection with a single HCV genotype (type 2a or 2b) associated with significantly better long-term outcome. IFN-alpha is useful in chronic hepatitis C while intramuscular IFN-beta interferon does not exert any beneficial effect. This is probably due to an insufficient bioavailability of IFN-beta when given intramuscularly.", "Two hundred and thirty patients with histologically proven chronic hepatitis C were randomized to receive one of the following treatment protocols: (a) 3 million units of interferon alfa-2b thrice weekly for 6 months, (b) 5 million units thrice weekly for 6 months, or (c) 3 million units thrice weekly for 2 years. The short-term response to treatment was defined by normal alanine aminotransferase for at least 3 months and until the end of treatment, and was confirmed by loss of hepatitis C viraemia in 42 (91%) of 46 cases as determined by reverse transcription-polymerase chain reaction. Short-term response to interferon alfa-2b was independent of the incremental dose, being 64% for 5 million units and 58% for 3 million units. Long-term response to interferon alfa-2b was defined by continued normality of alanine aminotransferase levels for at least 6 months after treatment withdrawal. The long-term response rates among responders treated for 6 months and those treated for 2 years were 29% and 54%, respectively (p < 0.001). Among all 18 patients tested, serum HCV-RNA was negative at both 6 and 12 months of follow-up in all long-term responders, and none have subsequently relapsed. Improvement in hepatic necroinflammatory changes was confirmed by quantitative histology (Scheuer score) in responders at the end of interferon alfa-2b treatment. The changes were significantly greater among those who had been treated for 2 years compared with those treated for 6 months (p < 0.05 and p < 0.02, respectively, for portal and lobular inflammation scores). Several pretreatment characteristics could be correlated with a favourable response to interferon alfa-2b. Thus, absence of cirrhosis was associated with a short-term response of 75%, while only 42% of patients with cirrhosis had a short-term response (p < 0.001). The frequency of short-term response to interferon alfa-2b also differed according to mode of disease acquisition, being best for injecting drug use (71%), less favourable for blood transfusion (56%) and worst for sporadic cases (43%) (p < 0.01). This observed difference, however, was not independent of histology on multivariate analysis. In summary, a 5 million unit dose of interferon alfa-2b failed to improve the short-term or long-term response to interferon alfa-2b treatment, but prolongation of interferon alfa-2b treatment to 2 years resulted in substantially improved long-term response rate.", "Patients with chronic active hepatitis C and cirrhosis often develop hepatocellular carcinoma. Interferon (IFN) seems to be effective in some patients but whether it prevents carcinogenesis is unknown. In a prospective randomised controlled trial, we evaluated the effects of IFN-alpha in cirrhotic patients with HCV infection because of their high risk of hepatocellular carcinoma. 90 patients with compensated chronic active hepatitis C with cirrhosis were randomly allocated to receive IFN-alpha (6 MU three times weekly for 12-24 weeks) (45 patients) or symptomatic treatment (45 controls), and were followed up for 2-7 years. In nine controls, alanine aminotransferase (ALT) decreased to less than 80 IU/L but did not stay in the normal range. In 19 patients given IFN-alpha, ALT decreased to less than 80 IU/L (in seven patients, it became and stayed normal; p = 0.011, Wilcoxon rank-sum test). However, the mean change in ALT was not significantly different between the two groups. The mean change in peak alpha-fetoprotein values was smaller in patients given IFN-alpha than in controls (p = 0.021). The mean change in the serum albumin level was higher in the IFN-alpha group (p < 0.001). The histological activity index in the 12 IFN-alpha patients undergoing a second biopsy after therapy was improved (p = 0.031). Hepatitis C viral RNA disappeared in seven (16%) of the 45 IFN-alpha patients (95% CI, 7-29%) and in none of the 45 controls (0-8%; p = 0.018). Hepatocellular carcinoma was detected in two (4%, 1-15%) IFN-alpha patients and 17 (38%, 24-54%) controls (p = 0.002, Wilcoxon signed-rank test). The risk ratio of IFN-alpha treatment versus symptomatic treatment was 0.067 (0.009-0.530; p = 0.010 Cox's proportional hazards). IFN-alpha improved liver function in chronic active hepatitis C with cirrhosis, and its use was associated with a decreased incidence of hepatocellular carcinoma.", "To compare the long-term effectiveness and tolerability of lymphoblastoid interferon (IFN-alphaN1) and recombinant interferon alfa 2a (IFN-alpha2a) in patients with chronic hepatitis caused by hepatitis C virus (HCV), 234 consecutive patients with HCV-related chronic hepatitis were randomized prospectively to receive titrated doses (starting dose = 6 million units [MU]) of IFN-alpha2a (n = 118) or IFN-alphaN1 (n = 116) for 12 months. HCV RNA was detected by reverse-transcription polymerase chain reaction (RT-PCR), quantified by branched-DNA (bDNA) assay, and genotyped by reverse hybridization assay. Thirty-one patients in the IFN-alpha2a group and 28 in the IFN-alphaN1 group (total, 59 [25%] had normal transaminases and undetectable HCV RNA by RT-PCR after 12 months of therapy, but only 19 in the first group and 20 in the second group (total, 39 [17%]) had biochemical and virological responses 12 months after treatment was discontinued. The two treatment groups differed in terms of prevalence of major drug-related adverse reactions (23% vs. 37%, P = .025). The mean total dose per patient was similar for the two groups, i.e., 502 MU IFN-alpha2a vs. 496 MU IFN-alphaN1, and the cost of each sustained response was $31,800 and $32,440, respectively. By multivariate analysis, pretreatment viremia higher than 0.2 MEq/mL and infection with genotype 1 were independently associated to treatment failure. The outcome of treatment in chronic hepatitis C patients was not improved by the administration of high cumulative doses of lymphoblastoid IFN.", "We studied the effects of long-term treatment with interferon on histologic features of the liver and serum alanine aminotransferase concentrations in patients with chronic non-A, non-B hepatitis.\n Consecutive patients who met the inclusion criteria were enrolled in the study. The diagnosis of chronic non-A, non-B hepatitis was established on the basis of the liver-biopsy findings and an abnormal serum alanine aminotransferase value (greater than 1.5 times the normal value) for at least one year. All patients were treated for six months with 3 million units of interferon alfa-2b given subcutaneously three times a week and were then randomly assigned to the same treatment for an additional 12 months (group 1), a regimen of 1 million units three times a week for 12 months (group 2), or no further treatment (group 3). Patients in group 3 who had elevated serum alanine aminotransferase concentrations for three consecutive months underwent the initial regimen once again. Follow-up continued for two years after the discontinuation of treatment. Histologic improvement was defined as a decrease of at least one grade in the score for necroinflammatory activity (0, no activity; 1, mild; 2, moderate; or 3, severe) between the first liver biopsy and a biopsy performed at 18 months.\n Of the 329 patients initially treated, 303 were randomized: 103 to group 1, 101 to group 2, and 99 to group 3. Of the 286 patients tested, 252 (88.1 percent) had antibodies to hepatitis C virus. In an intention-to-treat analysis, 46 of the patients in group 1 (44.7 percent) had normal serum alanine aminotransferase values at 18 months, as compared with 27 of the patients in group 2 (26.7 percent, P = 0.008) and 30 of those in group 3 (30.3 percent, P = 0.04). Between 19 and 42 months, 23 of the patients in group 1 (22.3 percent) continued to have normal serum alanine aminotransferase values (measured every six months), as compared with 10 of the patients in group 2 (9.9 percent, P = 0.02) and 8 of those in group 3 (8.1 percent, P = 0.005). Among the 176 patients with repeated liver biopsies at 18 months, more patients in group 1 had improved histologic-activity scores (69.6 percent) than in group 2 (47.6 percent, P = 0.02) or group 3 (38.6 percent, P < 0.001).\n Among patients with chronic non-A, non-B hepatitis, a regimen of 3 million units of interferon alfa-2b given three times a week for 18 months produced better histologic findings and serum alanine aminotransferase values than regimens involving a lower dose or a shorter duration of treatment.", "The efficacy and tolerability of 12-month treatment with titrated doses of recombinant interferon-alpha 2a (IFN-alpha 2a) in chronic hepatitis C were studied in 67 consecutively recruited patients randomly assigned either to a starting dose of IFN-alpha 2a 6 MU, subsequently adjusted to the serum alanine aminotransferase (ALT) response (n = 35), or to no therapy (n = 32; controls). End-of-treatment ALT levels were normal and hepatitis C virus (HCV) RNA was negative by nested polymerase chain reaction (PCR) in 17 (49%) treated patients compared to none of the controls (P < 0.001). During the 12 months after stopping treatment the number of patients who remained in remission was eight (23%) and one respectively (4%) (P = 0.031). Follow-up liver biopsy showed reduced hepatic inflammation in 80% of treated patients and in 29% of controls (P < 0.001). The eight sustained responders and 27 non-responders or relapsers received similar mean total doses of IFN (565 MU vs 545 MU) and had a similar incidence of anti-IFN neutralizing antibodys (13% vs 19%). Absence of cirrhosis was the only independent pretreatment parameter that predicted a sustained response. In conclusion, a mean cumulative dose of IFN 549 MU, titrated over 12 months, was well tolerated, and resulted in the long-term clearance of HCV RNA and normal ALT levels in 23% of patients.", "This study was carried in order to investigate whether human leukocyte interferon-alpha administered for 12 months at two different dosages, improves long-term responses in chronic hepatitis C and to see whether pre-treatment gamma-glutamyl transpeptidase values help to predict the clinical response to Interferon.\n Forty-five patients were treated for 12 months with natural Interferon-alpha: 3 MU (group A: 31 cases); 6 MU (group B: 14 cases). Biochemical and virological responses were monitored during treatment and follow-up.\n Alanine aminotransferase was normalized in 58.1% (Group A) and 54.5% (Group B) of patients by the end of the treatment. Due to side effects 3 patients had to discontinue treatment. During follow-up, remission was maintained in 30.8% and 45.4% of patients respectively (p = 0.046). After 12 months of therapy, respectively 46.7% and 45.4% of patients with complete biochemical response, cleared virus from serum, as did, among long-term responders, 3/8 and 3/4 evaluated patients. Independently of dosage, a complete response was found more often in patients with normal pre-treatment gamma-glutamyl transpeptidase than in those with pre-treatment abnormal values.\n High dosage of IFN alpha was associated with a significantly greater rate of sustained biochemical response and with a better chance of viremia becoming negative. Pre-treatment gamma-glutamyl transpeptidase was able to predict the outcome of the treatment.", "Interferon alfa is effective for controlling disease activity in chronic hepatitis C. However, many responders suffer relapse after cessation of therapy. In the present study, the serum concentration of hepatitis C virus RNA was correlated with a sustained response to interferon therapy.\n Fifty-three patients with chronic hepatitis C received a 26-week course of interferon alfa. Hepatitis C virus RNA was quantitated in serum at the beginning and end of treatment using a competitive assay that combined reverse transcription and polymerase chain reaction.\n In long-term responders, whose alanine aminotransferase levels remained within the normal range during the 24 weeks after therapy, the titer of viral RNA (logarithmic transformed copy numbers per milliliter of serum) before therapy (7.1 +/- 1.2) was significantly lower (P < 0.001) than that of short-term responders (8.3 +/- 0.5) who had a relapse within the 24 weeks after therapy and nonresponders (8.1 +/- 0.4). Multivariate multiple logistic regression showed that the titer of viral RNA before therapy was the strongest independent predictor of a sustained response to interferon-alfa therapy (P = 0.002).\n The titer of hepatitis C virus RNA is the most important factor influencing the sustained response to interferon treatment.", "Thirty-three Swedish patients with chronic post-transfusion non-A, non-B hepatitis entered a randomized trial of interferon alfa-2b treatment (INTRON A, Schering-Plough Corporation) (3 million units, three times weekly, subcutaneously for 36 weeks). Twenty-two patients (67%) were reactive for antibodies against hepatitis C virus. Nineteen patients completed the course of therapy; 11 (58%) had a complete response with normalization of serum alanine aminotransferase levels, compared to none of the 12 controls (p less than 0.001). Four treated patients with chronic active hepatitis were non-responders. Non-responders had a significantly higher mean body weight than responders (p less than 0.05) and tended to have a longer duration of prior disease. During the 10-month follow-up period post treatment, 4/11 (36%) complete responders had a sustained response and three (75%) of these four were reactive for antibodies against hepatitis C virus, whereas 7/11 (64%) relapsed, of whom four (57%) were reactive for antibodies against hepatitis C virus. All patients who were treated again responded but relapsed once more after retreatment was stopped. We conclude that the majority of patients with chronic post-transfusion non-A, non-B hepatitis will respond to 9 months' interferon alfa-2b treatment, but that only one of three responders will have a sustained response 10 months post treatment. Reactivity for antibodies against hepatitis C virus is not predictive of the outcome of therapy.", "Thirty-eight Swedish patients with chronic hepatitis C were randomly assigned to receive either 3 million units (MU) or 5 MU of human lymphoblastoid interferon-alpha-n1 (Wellferon) three times per week for either 6 or 12 months. The patients were monitored biochemically, histologically and by quantitative polymerase chain reaction for circulating HCV RNA, during therapy and for the following year. Overall, 22 (58%) of the patients lost detectable hepatitis C virus (HCV) viraemia during therapy but eight of these patients relapsed during follow-up, leaving 14 (37%) sustained responders. Patients infected with HCV non-type 1 genotypes were significantly more likely to achieve a sustained response than were those infected with HCV type 1 (63% vs 10.5%, P = 0.001). Sustained virological responses were also associated with lower pretreatment viraemia level, younger age, absence of cirrhosis and the higher interferon dosage regimens but these associations failed to reach statistical significance. In 97% of patients there was concordance between virological and biochemical responses, and a statistically significant (P = 0.005) improvement in the Knodell histological activity index was observed in the virological sustained responders.", "Interferon has become the mainstay of treatment of chronic hepatitis C; however, duration of treatment and dose remain unresolved questions. The present study aimed to compare standard dose interferon with a titrated dose regimen carried out for 1 year.\n This was a randomized, controlled multicenter trial. Patients with chronic hepatitis C were randomly allocated to a control group (n = 30), to a fixed dose group (n = 31) where interferon-alpha 2b 3 MU thrice weekly was given for 1 year or a titrated group (n = 34) where interferon was titrated starting at 5 MU thrice weekly to the lowest dose keeping the patient in remission as assessed by a normal ALT value. Liver biopsies were obtained before and at the end of treatment; in addition, galactose elimination capacity was measured as a measure of cytosolic function.\n In the control, fixed and titrated groups a complete response was achieved in 2/29, 10/28 and 15/31, respectively (p < 0.001 in favor of treatment, p = n.s. for the two treatments). The corresponding figure for sustained response was 1/29, 5/28 and 6/ 31 (p = n.s). In the titrated group, a complete (sustained) response was achieved with 5 MU in 2 (2), with 4 MU in 1 (0), with 3 MU in 4 (0), with 2 MU in 3 (0) and with 1 MU in 5 (4). Liver biopsy score and galactose elimination capacity improved significantly in responders but not in treatment failures.\n Both fixed and titrated dosing of interferon given for 1 year induced virus clearance in only a minority of treated patients. However, in a small number of patients, a complete and sustained response can be achieved with low doses of interferon. Dose titration could be an interesting approach to decreasing the cost and side effects in the treatment of chronic hepatitis C.", "Chronic hepatitis C (non-A, non-B hepatitis) is a common and often progressive viral liver disease. To assess the efficacy of therapy with the antiviral agent interferon alfa, we randomly assigned 166 patients with chronic hepatitis C to treatment with either 3 million or 1 million units of recombinant interferon alfa three times weekly for 24 weeks, or to no treatment. The probability of normalization or near normalization of the serum alanine aminotransferase levels after six months of interferon therapy was 46 percent in patients treated with 3 million units of interferon (P less than 0.001) and 28 percent in those treated with 1 million units (P less than 0.02), but only 8 percent in untreated patients. The serum alanine aminotransferase level became completely normal in 22 of the 26 patients (85 percent) who responded to treatment with 3 million units of interferon and 9 of the 16 patients (56 percent) who responded to treatment with 1 million units. The patients who received 3 million units of interferon had histologic improvement because of the regression of lobular and periportal inflammation. Relapse within six months after the completion of treatment occurred in 51 percent of the patients treated with 3 million units of interferon and 44 percent of those treated with 1 million units. We conclude that a 24-week course of interferon therapy is effective in controlling disease activity in many patients with hepatitis C, although relapse after the cessation of treatment is common." ]

[ "14736626", "2266221", "8492283", "2687306", "907011", "3143750", "2504794" ]

[ "The relative efficacy of two brief treatments for sleep problems in young learning disabled (mentally retarded) children: a randomised controlled trial.", "Enhancing the effectiveness of self-administered videotape parent training for families with conduct-problem children.", "Bibliotherapy as an adjunct to stimulant medication in the treatment of attention-deficit hyperactivity disorder.", "Reducing sleep disruptions in young children: evaluation of therapist-guided and written information approaches: a brief report.", "Behavioral training for parents of retarded children: alternative formats based on instructional manuals.", "Self-administered videotape therapy for families with conduct-problem children: comparison with two cost-effective treatments and a control group.", "The long-term effectiveness and clinical significance of three cost-effective training programs for families with conduct-problem children." ]

[ "Settling and night waking problems are particularly prevalent, persistent, and generally considered difficult to treat in children with a learning disability, although intervention trials are few. Scarce resources, however, limit access to proven behavioural treatments.\n To investigate the efficacy of a media based brief behavioural treatment of sleep problems in such children by comparing (1) face-to-face delivered treatment versus control and (2) booklet delivered treatment versus controls.\n The parents of 66 severely learning disabled children aged 2-8 years with settling and/or night waking problems took part in a randomised controlled trial with a wait-list control group. Behavioural treatments were presented either conventionally face-to-face or by means of a 14 page easy to read illustrated booklet. A composite sleep disturbance score was derived from sleep diaries kept by parents.\n Both forms of treatment were almost equally effective compared with controls. Two thirds of children who were taking over 30 minutes to settle five or more times per week and waking at night for over 30 minutes four or more times per week improved on average to having such settling or night waking problems for only a few minutes or only once or twice per week (H = 34.174, df = 2, p<0.001). These improvements were maintained after six months.\n Booklet delivered behavioural treatments for sleep problems were as effective as face-to-face treatment for most children in this population.", "Parents of 43 conduct-problem children, aged 3-8 years, were randomly assigned to one of two treatments: an individually self-administered video-tape modeling treatment (IVM) and IVM treatment plus therapist consultation (IVMC). Randomization also included a waiting-list control group (CON). Compared with the control group, both treatment groups of mothers reported significantly fewer child behavior problems, reduced stress levels, and less use of spanking. Home visit data indicated that both treatment groups exhibited significant behavioral changes. There were relatively few differences between the two treatment conditions. However, the IVMC children were significantly less deviant than the IVM children, suggesting that the IVMC (with therapist consultation) treatment was superior to self-administered treatment with no therapist involvement. The added benefits of therapist involvement are discussed.", "The effectiveness of bibliotherapy as an adjunct to stimulant medication in the treatment of children with attention-deficit hyperactivity disorder was investigated. Subjects were randomly assigned to the experimental group, or the control group. Parents in the experimental group received a written protocol (bibliotherapy) outlining behavioral techniques for managing oppositional child behavior. Results indicated significant differences favoring the experimental group on standardized measures of the intensity of behavior problems in the home, parental knowledge of behavioral principles, and teacher ratings of behavior. This bibliotherapy approach appears to offer an inexpensive adjunct to stimulant medication in the treatment of attention-deficit hyperactivity disorder when individual or group behavior management training is not feasible.", "Regular night waking of young children is one of the most common problems encountered by parents. This study compared a standardized night waking programme that involved organized bedtime routines, procedures for settling the child and for the handling of crying, calling out and getting out of bed, with a group which received written information only and a waiting list control group. The children receiving the standard programme and those receiving written information only showed significant improvement over children in the waiting list group. This result supports the use of written parent instructions with or without therapist support.", "A series of instructional manuals in behavior modification with retarded children was tested as a self-contained resource and as part of three larger training programs involving different amounts of professional assistance to parents: telephone consultations, training groups, training groups plus home visits. One hundred and sixty families were randomly assigned to the four training conditions or to a delayed-treatment control group. The 20-week treatment period emphasized the programming of self-help skills, but also provided an introduction to programming language skills and managing behavior problems. The manuals-alone format was as effective as the more expensive training formats in producing gains in children's self-help skills and fostering knowledge of behavioral principles in mothers. The two group-training formats produced more efforts at behavior-problem management, greater gains in knowledge of principles by fathers, and higher self-confidence as teachers. Telephone consultation was generally the least effective training format; the manuals-alone condition was surprisingly effective. Some implications of the results for future strategies of family intervention were discussed.", "nan", "We evaluated the long-term effectiveness of three cost-effective parent training programs for conduct-problem children. One year posttreatment, 93.1% of families (94 mothers and 60 fathers) were assessed on the basis of teacher and parent reports and home observations. Results indicated that all the significant improvement reported immediately posttreatment were maintained one year later. Moreover, approximately two thirds of the entire sample showed \"clinically significant\" improvements. There were very few differences between the three treatment conditions except for the \"consumer satisfaction\" measure indicating that the treatment combining group discussion and video-tape modeling was superior to treatments without both components." ]

[ "20156979", "21272713" ]

[ "Respiratory muscle training improves cardiopulmonary function and exercise tolerance in subjects with subacute stroke: a randomized controlled trial.", "Inspiratory muscular training in chronic stroke survivors: a randomized controlled trial." ]

[ "To determine whether two types of exercise--breathing retraining (BRT) and inspiratory muscle training (IMT)--improve on cardiopulmonary functions and exercise tolerance in patients with stroke.\n A randomized controlled trial.\n Education and research hospital.\n Forty-five inpatients with stroke (24 men, 21 women) were recruited for the study. The subjects were randomized into three groups: 15 assigned to receive inspiratory muscle training (IMT); 15 assigned to received breathing retraining, diaphragmatic breathing and pursed-lips breathing (BRT); 15 assigned to a control group.\n All study groups participated in a conventional stroke rehabilitation programme. For the same period, the IMT and BRT groups trained daily, six times a week, with each session consisting of one half-hour of training for six weeks.\n Each subject underwent pulmonary function and cardiopulmonary exercise tests. Subjects were also assessed for exertional dyspnoea, stages of motor recovery, ambulation status, activity of daily living and quality of life.\n After the training programme, the IMT group had significantly improved forced expiratory volume at 1 second (FEV(1)), forced vital capacity (FVC), vital capacity (VC), forced expiratory flow rate 25-75% (FEF 25-75%) and maximum voluntary ventilation (MVV) values compared with the BRT and control groups, although there were no significant differences between the BRT and control groups (P<0.01). Peak expiratory flow rate (PEF) value was increased significantly in the BTR group compared with the IMT and control groups. The IMT group also had significantly higher peak oxygen consumption (Vo(2peak)) than the BRT and control groups, although there were no significant differences between the BRT and control groups (P<0.001). There was a statistically significant increase in maximum inspiratory pressure (PI(max)) and maximum inspiratory and expiratory pressure (PE(max)) in the BRT group and, PI(max) in the IMT group compared with baseline and the control group. In the IMT group, this was associated with improvements in exercise capacity, sensation of dyspnoea and quality of life.\n Significant short-term effects of the respiratory muscle training programme on respiratory muscle function, exercise capacity and quality of life were recorded in this study.", "To assess the effectiveness of inspiratory muscular training (IMT) on measures of strength, resistance, functional performance, and quality of life (QOL) for chronic stroke survivors.\n Double-blinded randomized controlled trial.\n Research laboratory.\n Subjects (N=21) with stroke (11 men, 10 women; maximal inspiratory pressure [MIP] <90% of predicted values) were randomly assigned to the experimental (n=11) and control groups (n=10); 18 participants completed all testing and training.\n Interventions were based on home-based training, with resistance adjusted biweekly to 30% of MIP for the experimental group. The control group underwent the same protocol without the threshold resistance valve. Both groups received home training 30 minutes a day 5 times a week for 8 weeks.\n MIP, inspiratory muscular endurance (IME), functional performance, and QOL.\n There were significant between-group differences for the MIP and IME measures. Significant changes were observed for only the experimental group for MIP (67.8±14.6 at baseline to 102.2±26.0cmH(2)O at posttraining) and IME (31.8±19.3 to 49.2±21.1cmH(2)O). No statistically significant differences were observed for measures of functional performance and QOL.\n Significant short-term effects of the IMT program for inspiratory strength and endurance were observed in chronic stroke survivors. These findings gave some indications that IMT may benefit people with stroke, and it is feasible to be included in rehabilitation interventions with this population.\n Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved." ]

[ "3891264", "8364262", "10724098", "9640480", "3512926", "10868823", "10948785", "11280842", "6721016", "11023136", "3180635", "10957848", "8833557", "3769719", "12027926" ]

[ "Medication compliance in non-insulin-dependent diabetes: a randomized comparison of chlorpropamide and insulin.", "Pharmacists' interventions using an electronic medication-event monitoring device's adherence data versus pill counts.", "Assessment of the function and effect of diabetes education programs in Taiwan.", "Management of patients with type 2 diabetes by pharmacists in primary care clinics.", "Increasing prescribed office visits. A controlled trial in patients with diabetes mellitus.", "Can medication packaging improve glycemic control and blood pressure in type 2 diabetes? Results from a randomized controlled trial.", "Effect of a pharmacist-managed diabetes care program in a free medical clinic.", "Effect of diabetes education on glucose control.", "A randomized study of the impact of home health aides on diabetic control and utilization patterns.", "Intervention study for smoking cessation in diabetic patients: a randomized controlled trial in both clinical and primary care settings.", "Use of a pharmacologic indicator to compare compliance with tablets prescribed to be taken once, twice, or three times daily.", "Telemedicine improved diabetic management.", "Evaluation of a pharmaceutical care model on diabetes management.", "Management of obese patients with diabetes mellitus: comparison of advice education with group management.", "Teaching patients to monitor their risk factors retards the progression of vascular complications in high-risk patients with Type 2 diabetes mellitus--a randomized prospective study." ]

[ "Medication compliance may be a problem in the management of patients with diabetes. Some physicians initially treat patients having non-insulin-dependent diabetes with oral sulfonylureas because they fear greater compliance problems with insulin therapy. We compared compliance with insulin and chlorpropamide in patients newly beginning medication for NIDDM. Seventy-seven adults with hyperglycemia despite diet therapy were randomly assigned to chlorpropamide or insulin. Compliance was measured four times over 24 wk. Patients then crossed over to the other medication and were followed for 24 additional weeks. Overall, there were no differences in compliance with the two medications in terms of percent of prescription used, proportion taking at least 80% of prescribed medication, self-report of medication or diet compliance, or protocol dropout rates. However, treatment satisfaction was higher with chlorpropamide, and most patients preferred chlorpropamide to insulin (P less than 0.0001). While such differences in satisfaction may affect long-term compliance, physicians should not assume that their patients will be less compliant with insulin than with oral sulfonylureas.", "To compare adherence data from an electronic medication-event monitoring device (MEMS, Aprex) with pill counts in assisting pharmacists in making recommendations regarding diabetes therapy.\n Two-month, double-blind, randomized, controlled trial.\n Veterans Affairs Medical Center ambulatory care clinics.\n Forty-seven patients with poor to fair metabolic control of diabetes mellitus were enrolled. Patients were excluded if they were receiving insulin, had a concurrent infection, required child-resistant caps or medication remainder devices, or could not return for followup visits. Twenty patients were randomized to the MEMS and 27 to the control group (pill counts). Fasting plasma glucose concentrations were measured monthly and glycohemoglobin concentrations were measured at baseline and 60 days. Thirty-two patients were evaluable: 15 using MEMS and 17 using pill counts.\n Investigators made pharmacologic or educational recommendations to the patient's healthcare provider based on both laboratory data and MEMS readings in the treatment group or laboratory data and pill counts in the control group.\n Quantities and types of recommendations regarding diabetes therapy made by pharmacists using adherence data from the two methods were tabulated.\n In the MEMS group, 47 percent of the recommendations related to patient education compared with 12 percent in the control group (p = 0.028). MEMS data would have changed four recommendations in the control group to involve patient education.\n MEMS data resulted in different numbers and types of recommendations than pill counts. Pharmacists then could make specific recommendations regarding patient education before resorting to pharmacologic manipulations.", "A multi-center prospective study was conducted to assess the function and impact of diabetic education programs on diabetic control. A total of 208 subjects with type 2 diabetes were recruited. Diabetes self-care, assessed by questionnaire, was evaluated before, and 4 months after attending a diabetes education course. A total of 121 subjects who received advanced diabetes education courses were designated as the experimental group. A second group of 87 cases receiving a basic course served as controls. In addition to basic knowledge, the advanced education programs included dietary control, blood glucose monitoring, management of hypoglycemia, medication compliance, foot care and exercise. Diabetes self-care techniques were significantly improved in the experimental group. The overall score for diabetes self-care techniques improved in both groups at the 4th month over baseline values. The change was significant with the controls' (P < 0.001). Multiple regression analysis confirmed the intensity of diabetic education was the only significant variable correlated with the decrease of fasting blood glucose and systolic blood pressure. In conclusion, integrated and intensive diabetes education program in diabetes education centers provides an effective method for improving diabetes self-care techniques and metabolic outcome.", "To determine the impact of clinical pharmacists involved in direct patient care on the glycemic control of patients with type 2 diabetes mellitus.\n Eligible patients included those with type 2 diabetes who received insulin or were initiated on insulin therapy by the pharmacists and were willing to perform self-monitoring of blood glucose. The pharmacists provided diabetes education, medication counseling, monitoring, and insulin initiation and/or adjustments. All initial patient interactions with the pharmacists were face-to-face. Thereafter, patient-pharmacist interactions were either face-to-face or telephone contacts.\n Two primary care clinics in a university-affiliated Veterans Affairs Medical Center.\n Study subjects were patients with type 2 diabetes who were referred to the pharmacists by their primary care providers for better glycemic control.\n Primary outcome variables were changes from baseline in glycosylated hemoglobin, fasting blood glucose, and random blood glucose measurements. Secondary outcomes were the number and severity of symptomatic episodes of hypoglycemia, and the number of emergency room visits or hospitalizations related to diabetes. Twenty-three veterans aged 65-9.4 years completed the study. Fifteen (65%) patients were initiated on insulin by the pharmacists; 8 (35%) were already using insulin. Patients were followed for a mean-SD of 27-10 weeks. Glycosylated hemoglobin, fasting blood glucose concentrations, and random blood glucose concentrations significantly decreased from baseline by 2.2% (p = 0.00004), 65 mg/dL (p < 0.01), and 82 mg/dL (p = 0.00001), respectively. Symptomatic hypoglycemic episodes occurred in 35% of patients. None of these episodes required physician intervention.\n This study demonstrates that pharmacists working as members of interdisciplinary primary care teams can positively impact glycemic control in patients with type 2 diabetes requiring insulin.", "Patients who fail to show for scheduled visits or who fail to contact their provider when warning symptoms occur pose important problems for the primary care physician. A group of interventions was examined to determine the effectiveness in increasing the number of prescribed office visits in patients with diabetes mellitus. This group of interventions included mailed packets with information on how to use the clinic, providers' names and phone numbers, after-hours phone numbers, a list of early warning signs, and a booklet on managing diabetes mellitus; mailed appointment reminders; and intense follow-up of visit failures for prompt rescheduling. Eight hundred fifty-nine patients on drug therapy for diabetes mellitus were stratified by risk of hospitalization and randomly assigned within strata to control and intervention groups. The intervention group received all interventions. After 1 year, the intervention group averaged 12% more total contacts than the control group (5.8 vs. 5.2, P = 0.01), due largely to an increase in kept scheduled visits (4.1 vs. 3.6, P = 0.006). These effects were greatest in those patients at higher risk of hospitalization. Also, visit failures were reduced only in high-risk patients. The effect of the interventions did not diminish during the year of study. This systematic and repetitive intervention appears effective in increasing prescribed office visits and is especially effective in patients requiring more frequent care.", "To assess the impact of calendar blister pack (CBP) use on glycemic and blood pressure control.\n We conducted an 8-month randomized controlled double-blind study among diabetic patients with poor glucose control (HbA1c >9.0%) in an urban area of South Auckland, New Zealand, with a high proportion of Maori and Pacific Islands people. Subjects included 68 consecutive patients, of whom 50% were prescribed three or more medications per day\n HbA1c was reduced by 0.95+/-0.22% in the CBP group and 0.15+/-0.25% in the control group (P = 0.026). Diastolic blood pressure decreased 5.8+/-1.5 mm Hg in the CBP group and increased 0.1+/-1.9 mm Hg in the control group (P = 0.0041). Systolic blood pressure did not change significantly\n CBPs should be considered among diabetic patients with poor glycemic control receiving multiple medications.", "Diabetes care, morbidity, and mortality are usually worse in poor minority populations compared with non-minority ones. This report evaluates evidence-based process and outcome measures of diabetes care in diabetic patients followed in a free medical clinic and compares them to published results. The following process measures compared favorably with measures of the general population: dilated eye and foot exams and measurements of glycated hemoglobin levels; concentrations of total cholesterol; fasting triglycerides and low density lipoprotein (LDL) cholesterol; and proteinuria (by dipstick). Process and outcome measures in 89 diabetic patients referred to a Diabetes Management Program in which diabetes care was delivered by pharmacists following detailed algorithms (experimental group) were compared with measures in 92 diabetic patients who received diabetes care in the general clinic setting (control group). The patients in the experimental group had a slightly longer duration of diabetes and more microvascular and neuropathic complications, and more diabetic patients were taking insulin than were patients in the control group. All of the process measures listed above were more frequent in the experimental group. Compared with the control group, the initial glycated hemoglobin level (% +/- SE) in the experimental group was significantly (P < .001) higher (8.8 +/- 0.2 versus 7.9 +/- 0.2) but fell significantly (P < .03) more (-0.8 +/- 0.2 versus -0.05 +/- 0.3). The lack of a greater decrease in the glycated hemoglobin levels in the experimental group was not related to the inability of the pharmacists to follow the algorithms, the patients' refusal to follow the recommended medication adjustments, or the lack of appropriate self-monitoring of blood glucose in insulin-requiring patients. It was inversely related (r = -0.36, P < .03) to the number of missed visits, i.e., the greater the number of broken appointments, the less the glycated hemoglobin fell. In conclusion, diabetes care for a poor minority population in a free clinic setting can compare favorably to care in the general population. Pharmacists following detailed algorithms can enhance this care further. Administrative and support system changes that minimize the number of missed visits might further improve diabetes care in this population.", "After diabetes education, 39 adult diabetic patients were randomized to either an education group or control group. The two groups received identical medical care and follow-up, except that the education group met with their diabetes educator on at least a quarterly basis. Neither group showed any statistically significant change in their glycosylated hemoglobin values, although the education group did have a 4% drop after initial education compared to a 6% rise in the control group. The education group had a lower attrition rate and a better improvement in self-rated dietary compliance. Education remains the cornerstone of diabetes management. Our team identified some trends between the two groups as well as some ideas to improve motivating and developing a stronger and more effective relationship with our patients.", "Home health aides were offered to half of a group of 227 low-income diabetic clinic patients; in the group offered aides, fasting blood sugar (FBS) declined when compared to control group (10.1 mg/dl vs an increase of 5.1 mg/dl), and missed clinic appointments and emergency room use also decreased. The group of 44, who, upon offer of an aide actually accepted one, showed a significant increase in eye clinic appointments as well as the greatest decline in FBS (13.9 mg/dl).", "To evaluate the effectiveness of a nurse-managed smoking cessation intervention in diabetic patients.\n This randomized controlled clinical trial involved 280 diabetic smokers (age range 17-84 years) who were randomized either into control (n = 133) or intervention (n = 147) groups at 12 primary care centers and 2 hospitals located in Navarre, Spain. The intervention consisted of a 40-min nurse visit that included counseling, education, and contracting information (a negotiated cessation date). The follow-up consisted of telephone calls, letters, and visits. The control group received the usual care for diabetic smokers. Baseline and 6-month follow-up measurements included smoking status (self-reported cessation was verified by urine cotinine concentrations), mean number of cigarettes smoked per day, and stage of change.\n At the 6-month follow-up, the smoking cessation incidence was 17.0% in the intervention group compared with 2.3% in the usual care group, which was a 14.7% difference (95% CI 8.2-21.3%). Among participants who continued smoking, a significant reduction was evident in the average cigarette consumption at the 6-month follow-up. The mean number of cigarettes per day decreased from 20.0 at baseline to 15.5 at 6 months for the experimental group versus from 19.7 to 18.1 for the control group (P < 0.01).\n A structured intervention managed by a single nurse was shown to be effective in changing the smoking behavior of diabetic patients.", "By use of an interview, return tablet count, and a pharmacologic indicator (low-dose phenobarbital), we compared compliance with tablets prescribed to be taken once, twice, or three times daily. One hundred seventy-nine patients with type II diabetes were randomly allocated to take one 2 mg phenobarbital tablet once, twice, or three times daily for 28 days. Phenobarbital level/dose ratios indicated that compliance was similar with once- and twice-daily regimens, and both were better than thrice-daily dosing. Mean return tablet counts suggested that compliance was best with the once-daily regimen; both twice- and thrice-daily regimens were similarly inferior. This difference between the techniques may be explained by the inadequacies of the residual tablet count, which identified only 13% of cases identified by phenobarbital. We conclude that compliance with the once-daily regimen was best, but that compliance with a twice-daily regimen was very similar, and both were superior to dosing three times a day.", "Effective control of diabetes is known to delay or prevent the end-organ complications of this disease. Can telemedicine improve a patient's ability to self-manage diabetes? Twenty-eight patients entered a study comparing home telemedicine consultation with standard outpatient care. A nurse case manager contacted the telemedicine group once a week under the direction of a primary care physician, who contacted the telemedicine group once a month. Laboratory studies and total body weight were measured at the beginning and at the end of the 3-month study. The hemoglobin A1c (HbA1c) and total body weight improved significantly in the intervention (telemedicine) group, as shown by a 16% reduction in mean HbA1c level (from 9.5 to 8.2%) and a 4% mean weight reduction (from 214.3 to 206.7 pounds). Based on our experience, we present a functionally based telemedicine classification system to improve the application of electronic medicine in future studies.", "To assess the effectiveness of a pharmaceutical care model on the management of non-insulin-dependent diabetes mellitus (NIDDM) in urban African-American patients.\n Eligible patients were randomized to either a pharmacist intervention or control group and followed over a 4-month period. Patients in the intervention group received diabetes education, medication counseling, instructions on dietary regulation, exercise, and home blood glucose monitoring, and evaluation and adjustment of their hypoglycemic regimen. Patients in the control group continued to receive standard medical care provided by their physicians.\n A university-affiliated internal medicine outpatient clinic.\n The study population consisted of urban African American patients with NIDDM currently attending the clinic.\n Primary outcome measures included fasting plasma glucose and glycated hemoglobin concentrations. Secondary outcome endpoints included blood pressure, serum creatinine, creatinine clearance, microalbumin to creatinine ratio, total cholesterol, triglycerides, high-density lipoprotein, and low density lipoprotein concentrations. Quality-of-life assessments were performed in both groups at baseline and at the end of the study.\n Thirty-nine patients (17 intervention, 22 control) completed the study. The intervention group consisted of 12 women and 5 men with a mean +/- SD age of 59 +/- 12 years, total body weight (TBW) of 93 +/- 22 kg, body mass index (BMI) of 34 +/- 7 kg/m2, and duration of NIDDM 6.8 +/- 6.5 years. The control group consisted of 15 women and 7 men with a mean age of 65 +/- 12 years, TBW of 88 +/- 19 kg, BMI of 33 + 7 kg/m2, and a duration of NIDDM of 6.2 +/- 4.8 y. Significant improvement in glycated hemoglobin (p = 0.003) and fasting plasma glucose (p =0.015) was achieved in the intervention group. No change in glycemia was observed in the control subjects. Statistically significant differences in the final glycated hemoglobin (p = 0.003) and fasting plasma glucose (p = 0.022) concentrations were noted between groups. No significant changes in blood pressure control, lipid profile, renal function parameters, weight, or quality-of-life measures were noted within or between groups.\n Our data demonstrate the effectiveness of pharmaceutical care in the reduction of hyperglycemia associated with NIDDM in a group of urban African-American patients.", "The purpose of our study was to compare the effect on diabetes control of group management with the advice-educational technique traditionally used in managing obese outpatients with poorly controlled non-insulin-dependent diabetes mellitus (NIDDM). Forty-one patients were randomly assigned to these two treatment programs, and 32 patients completed the 6-mo study. Initially, patients were seen for 1-h sessions at 1- and 2-wk intervals and later at 1-mo intervals. Patients were asked to do home blood glucose monitoring, decrease caloric intake, increase exercise, and if they were taking insulin, to adjust the dose to attain approximate euglycemia and to stabilize food and exercise patterns. The combined groups reduced mean +/- SD glycohemoglobin from 10.9 +/- 3.1 to 9.4 +/- 2.4% (P less than .05). Internal Health Locus of Control Scale was negatively and significantly correlated with initial and subsequent glycohemoglobin values (the more internal, the lower the glycohemoglobin). At the end of the study the patients in the group management program had significantly lower blood glucose levels than those given advice and education, but no significant differences in glycohemoglobin values or percentage overweight were observed. One patient had a normal initial glycohemoglobin, and only 4 patients had values in the normal range of 4-6.8% at the end of the study. Better management programs need to be developed for treating obese outpatients with NIDDM.", "Intensive management of risk parameters in diabetic patients may retard the progression of both micro- and macrovascular complications. Intensified care requires expert staff and is expensive. The aim of the present study was to examine whether sharing the therapeutic responsibility with the patients will improve the outcome.\n A randomized prospective study of 165 patients with diabetes mellitus Type 2, hypertension (> 140/90 mmHg) and hyperlipidaemia (LDL-C > 120 mg/dl). Patients were randomly allocated to standard annual consultation (SC) or to a patient participation programme (PP). The medical care for both groups was administered by primary care physicians, who were unaware of the nature of the intervention.\n At 4 years the mean blood pressure was 148/88 (+/- 6.1/1.7) mmHg in the SC patients vs. 142/84 (+/- 5.8/1.8) mmHg in the PP group (P = 0.02). The mean LDL-C was 124 +/- 8 and 114 +/- 6 mg/dl (P = 0.01) and the mean HbA1c was 8.9 +/- 1.2% and 8.2 +/- 1.5% (P = 0.04) in the SC and PP groups, respectively. The average annual fall in estimated glomerular filtration rate was 3.5 ml/min per year in the SC group vs. 2.25 in the PP group (P < 0.05). Albumin/creatinine ratio > 300 mg/g developed in four SC patients vs. none of the PP patients. There was a total of 36 cardiovascular events in the SC group vs. 23 in the PP group (P = 0.04). All patients in the PP group received ACE inhibitors (or AII blockers) and statins vs. 52% and 43%, respectively, in the SC group. Glucose-lowering regimens were similar.\n Well-informed and motivated patients were more insistent to reach and maintain target values of the main risk factors of diabetic complications. The differences between the PP and SC groups were of the same order of magnitude as those between intensive and standard care groups in other studies albeit with, comparatively, a very modest cost." ]

[ "10742314", "16553931", "17556631", "3812435", "7971087", "7860156", "10230828", "16023513", "3354545", "17446290", "10487104", "7211827", "2603190", "2285172" ]

[ "Effect of infection control measures on the frequency of diarrheal episodes in child care: a randomized, controlled trial.", "Combining drinking water treatment and hand washing for diarrhoea prevention, a cluster randomised controlled trial.", "A cluster-randomized controlled trial evaluating the effect of a handwashing-promotion program in Chinese primary schools.", "An educational intervention for altering water-sanitation behaviors to reduce childhood diarrhea in urban Bangladesh. II. A randomized trial to assess the impact of the intervention on hygienic behaviors and rates of diarrhea.", "Evaluation of an hygienic intervention in child day-care centers.", "Community-based hygiene education to reduce diarrhoeal disease in rural Zaire: impact of the intervention on diarrhoeal morbidity.", "Effectiveness of a training program in reducing infections in toddlers attending day care centers.", "Effect of handwashing on child health: a randomised controlled trial.", "Diarrheal illness among infants and toddlers in day care centers: effects of active surveillance and staff training without subsequent monitoring.", "Effect of intensive handwashing in the prevention of diarrhoeal illness among patients with AIDS: a randomized controlled study.", "[Hand-hygiene and sickness among small children attending day care centers. An intervention study].", "Handwashing to prevent diarrhea in day-care centers.", "Prevention of diarrhoea and dysentery by hand washing.", "Occurrence of infectious symptoms in children in day care homes." ]

[ "Diarrheal infections are common in children who attend child care, and preventing transmission of disease in this setting depends on actions by child care staff. We set out to discover whether transmission of gastrointestinal infections in child care could be reduced by improved infection control procedures.\n We performed a cluster randomized, controlled trial of an infection control intervention conducted in child care centers for 1 city in Australia. The intervention was training of child care staff about transmission of infection and handwashing and focused on both staff and child behavior. Implementation of the intervention was recorded by an observer. Illness was measured by parent report in telephone interviews every 2 weeks.\n There were 311 child-years of surveillance for diarrheal episodes. The rate of episodes of diarrhea was 1.9 per child-year in intervention centers and 2.7 per child-year in control centers. Multivariable analysis showed that diarrheal episodes were significantly reduced in intervention center children by 50%. However, the impact of the intervention was confined to children over 24 months of age. For those centers in which children's compliance with handwashing was high, diarrheal episodes were reduced by 66%.\n This trial supports education about infection control, for staff and children in child care, as a means of reducing transmission of diarrhea. Reduction in episodes of diarrhea in children in child care was limited to children over 24 months of age.", "To evaluate the effectiveness of point of use water treatment with flocculent-disinfectant on reducing diarrhoea and the additional benefit of promoting hand washing with soap.\n The study was conducted in squatter settlements of Karachi, Pakistan, where diarrhoea is a leading cause of childhood death. Interventions were randomly assigned to 47 neighbourhoods. Households in 10 neighbourhoods received diluted bleach and a water vessel; nine neighbourhoods received soap and were encouraged to wash hands; nine neighbourhoods received flocculent-disinfectant water treatment and a water vessel; 10 neighbourhoods received disinfectant-disinfectant water treatment and soap and were encouraged to wash hands; and nine neighbourhoods were followed as controls. Field workers visited households at least once a week from April to December 2003 to promote use of the interventions and to collect data on diarrhoea.\n Study participants in control neighbourhoods had diarrhoea on 5.2% of days. Compared to controls, participants living in intervention neighbourhoods had a lower prevalence of diarrhoea: 55% (95% CI 17%, 80%) lower in bleach and water vessel neighbourhoods, 51% (95% CI 12%, 76%) lower in hand washing promotion with soap neighbourhoods, 64% lower (95% CI 29%, 90%) in disinfectant-disinfectant neighbourhoods, and 55% (95% CI 18%, 80%) lower in disinfectant-disinfectant plus hand washing with soap neighbourhoods.\n With an intense community-based intervention and supplies provided free of cost, each of the home-based interventions significantly reduced diarrhoea. There was no benefit by combining hand washing promotion with water treatment.", "Intensive handwashing promotion can reduce diarrheal and respiratory disease incidence. To determine whether less intensive, more scalable interventions can improve health, we evaluated a school-based handwashing program. We randomized 87 Chinese schools to usual practices: standard intervention (handwashing program) or expanded intervention (handwashing program, soap for school sinks, and peer hygiene monitors). We compared student absence rates, adjusting for cluster design. In control schools, children experienced a median 2.0 episodes (median 2.6 days) of absence per 100 student-weeks. In standard intervention schools, there were a median 1.2 episodes (P = 0.08) and 1.9 days (P = 0.14) of absence per 100 student-weeks. Children in expanded intervention schools experienced a median 1.2 episodes (P = 0.03) and 1.2 days (P = 0.03) of absence per 100 student-weeks. Provision of a large-scale handwashing promotion program and soap was associated with significantly reduced absenteeism. Similar programs could improve the health of children worldwide.", "An educational intervention was designed to improve three water-sanitation behaviors empirically shown to be associated with high rates of childhood diarrhea in Dhaka, Bangladesh: lack of handwashing before preparing food, open defecation by children in the family compound, and inattention to proper disposal of garbage and feces, increasing the opportunity for young children to place waste products in their mouth. Fifty-one communities, each comprising 38 families, were randomized either to receive (n = 25) or not to receive (n = 26) the intervention. During the six months after the intervention, the rate of diarrhea (per 100 person-weeks) in children under six years of age was 4.3 in the intervention communities and 5.8 in the control communities (26% protective efficacy; p less than 0.0001). A corresponding improvement in handwashing practices before preparing food was noted, although no improvement was observed for defecation and waste disposal practices. These data suggest that educational interventions for water-sanitation practices can have an important beneficial effect upon childhood diarrhea in developing countries, particularly when the interventions are designed in a simple way to promote naturally occurring salutory behaviors that are empirically associated with lower rates of childhood diarrhea.", "nan", "Diarrhoeal disease is a leading cause of morbidity in young children in rural Zaire. Few diarrhoea prevention programmes have been implemented in Bandundu Province, where available data suggest an annual prevalence rate of 10%. The urgent need to reduce diarrhoeal morbidity in Zaire, together with the potential effectiveness and feasibility of hygiene education as a diarrhoea prevention strategy, led to the development of the present research project.\n A randomized, controlled trial of an education intervention to reduce diarrhoea through improved personal and domestic hygiene behaviours was conducted in 18 geographically separate village clusters (sites) in rural Zaire. For 12 weeks baseline information on the diarrhoeal morbidity of 2082 children aged 3-35 months was collected at weekly home visits, and structured observations of hygiene practices related to diarrhoea were made on a subset of 300 families. Intervention messages addressed disposal of animal faeces from the yard, handwashing after defecation and before meal preparation and eating, and disposal of children's faeces. Three months after the start of the intervention and exactly 1 year after the baseline studies, a second diarrhoeal morbidity study and a second observational study were conducted in order to evaluate the intervention.\n Children in intervention communities experienced an 11% reduction in the risk of reporting diarrhoea during the peak diarrhoeal season, compared to controls (P < 0.025). The largest differences were seen among children aged 24-35 months, with those from intervention communities reporting significantly fewer episodes, shorter mean durations and hence fewer days of diarrhoea. There was some evidence that greater reductions in diarrhoea occurred in sites where the quality of the intervention, a scored measure of volunteer efficacy and community participation, was highest.\n The results of this study suggest that hygiene education may be an effective approach to reduce the incidence and duration of diarrhoeal episodes in rural Zaire. Children aged 2 years appear to benefit the most. A Hawthorne effect of the education may contribute to diarrhoeal reductions.", "The objective of this study was to assess the effectiveness of a hygiene program in reducing the incidence of respiratory and diarrheal diseases in toddlers attending day care centers. A randomized field trial was conducted in 52 day care centers in Quebec, Canada, between September 1, 1996 and November 30, 1997. Absences for any reasons and the daily occurrence of colds and/or diarrhea in toddlers were recorded on calendars by the educators. The number of fecal coliforms on children's hands and on educators' hands was measured during three unannounced visits. Overall, 1,729 children were followed in 47 day care centers for a total of 153,643 child-days. The incidence rate of diarrhea was considerably reduced by the effect of monitoring (IRR = 0.73, 95% CI = 0.54,0.97), and the intervention reduced the incidence rate of upper respiratory tract infections (IRR = 0.80, 95% CI = 0.68,0.93). Monitoring alone also had an important effect in reducing the level of bacterial contamination on children's and educators' hands. The results indicate that both an intervention program and monitoring alone play a role in reducing infections in children attending day care centers.", "More than 3.5 million children aged less than 5 years die from diarrhoea and acute lower respiratory-tract infection every year. We undertook a randomised controlled trial to assess the effect of handwashing promotion with soap on the incidence of acute respiratory infection, impetigo, and diarrhoea.\n In adjoining squatter settlements in Karachi, Pakistan, we randomly assigned 25 neighbourhoods to handwashing promotion; 11 neighbourhoods (306 households) were randomised as controls. In neighbourhoods with handwashing promotion, 300 households each were assigned to antibacterial soap containing 1.2% triclocarban and to plain soap. Fieldworkers visited households weekly for 1 year to encourage handwashing by residents in soap households and to record symptoms in all households. Primary study outcomes were diarrhoea, impetigo, and acute respiratory-tract infections (ie, the number of new episodes of illness per person-weeks at risk). Pneumonia was defined according to the WHO clinical case definition. Analysis was by intention to treat.\n Children younger than 5 years in households that received plain soap and handwashing promotion had a 50% lower incidence of pneumonia than controls (95% CI (-65% to -34%). Also compared with controls, children younger than 15 years in households with plain soap had a 53% lower incidence of diarrhoea (-65% to -41%) and a 34% lower incidence of impetigo (-52% to -16%). Incidence of disease did not differ significantly between households given plain soap compared with those given antibacterial soap.\n Handwashing with soap prevents the two clinical syndromes that cause the largest number of childhood deaths globally-namely, diarrhoea and acute lower respiratory infections. Handwashing with daily bathing also prevents impetigo.", "From October 1981 to September 1984, the authors conducted a three-year longitudinal study of diarrhea among infants and toddlers attending day care centers in Maricopa County, Arizona. In the third year of study, they evaluated the effects on diarrhea rates of staff training without external monitoring and of active surveillance conducted throughout the study. From 21 study day care centers, they randomly selected 10 (\"intervention day care centers\") to receive staff training in procedures to reduce transmission of infectious diarrhea. Continuing active surveillance in the 10 intervention and 11 control day care centers found no difference between diarrhea rates in intervention day care centers in the pre- and posttraining years and no difference between diarrhea rates in the two groups of centers either before or after the training intervention. Biweekly family-based surveys during the two months after training also demonstrated no difference between infant-toddler diarrhea rates in intervention and control day care centers. These surveys found the 21 study day care centers to have significantly higher diarrhea rates than did day care homes or households not using day care, but significantly lower rates than day care centers not included in the active surveillance. Continuous surveillance without training was associated with a significant decrease in diarrheal illness during the course of longitudinal study. One-time staff training without subsequent monitoring did not result in additional decreases and did not lower day care center diarrhea rates to the levels observed in day care homes and households not using day care.", "Patients with AIDS frequently develop diarrhoeal illness. In this randomized, controlled study, 260 patients were screened for those who had not had diarrhoea in the preceding 3 months and who had received a stable highly active antiretroviral therapy regimen for at least 6 weeks prior to the study enrollment. A total of 148 patients met the inclusion criteria and were enrolled: 75 patients were randomly assigned to an intensive handwashing intervention (i.e. handwashing after defecation, after cleaning infants who had defecated, before preparing food, before eating, and before and after sex) and 73 patients were randomly assigned to the control group. Patients in both groups were called weekly by telephone to determine compliance with handwashing and to determine the number of diarrhoeal episodes for the preceding week. Patients were observed for 1 year. Patients assigned to the intensive handwashing intervention group washed their hands more frequently compared with the control group (seven vs four times a day, respectively; P <0.05) and developed fewer episodes of diarrhoeal illness (1.24+/-0.9 vs 2.92+/-0.6 new episodes of diarrhoea, respectively; P <0.001) during the 1 year observation. The most common pathogens identified in both groups in patients who developed diarrhoeal illness were Giardia lamblia, Cryptosporidium, Entamoeba histolytica and Shigella flexneri. These data suggest that intensive handwashing reduces diarrhoeal illness in patients with AIDS.", "The purpose of the study was to evaluate the effect of intensified hygiene with frequent handwashing and several educational procedures in day-care centres. The study was conducted as a controlled trial, with an intervention group and an observation group. There was a 34% reduction in expected sickness in children in the intervention group. In the categories diarrhoea and eye-infection there was a significant drop in sickness. We conclude that broad intervention concerning hand-hygiene has a positive effect on sickness in children attending day-care centres.", "Diarrhea has been recognized as a frequent health problem among children enrolled in day-care centers. Thus, we evaluated the effect of a handwashing program in two day-care centers (HWC) on the incidence of diarrhea among children when compared to children in two control centers (CC). After the program was begun, the incidence of diarrhea at the HWC began to fall and after the second month of the study was consistently lower than that at the CC. The incidence of diarrhea in the HWC was approximately half that of the CC for the entire 35-week study period. Adenoviruses, rotavirus, Giardia lamblia, and enteropathogenic Escherichia coli were found in the stools of a small number of ill children, but not pathogen was identified in the stools of most children with diarrhea. These results suggest that a handwashing program will probably prevent at least some of the diarrhea in day-care centers.", "A 'non-blind' randomized hand washing intervention study was conducted in a low socioeconomic community in Rangoon to determine if hand washing by 494 children under 5 years old and their mothers could reduce the incidence of diarrhoea and dysentery in these children. Children and mothers in the intervention group were asked to wash their hands after defaecation and before preparing or eating their 3 main meals; 2 bars of plain soap were provided. The control group was left to follow customary practice. Diarrhoea and dysentery incidences in the 2 groups were monitored during 4 months by comparing the incidence density ratios (IDR). The diarrhoeal incidence among the children in the hand washing households was significantly lower than that among those in the control households (IDR = 0.70, 95% confidence interval (CI) = 0.54-0.92). For dysentery incidence, although there was a 40% reduction (IDR = 0.58, 95% CI = 0.22-1.55) in the children under 2 years, there seemed to be no impact in older children (IDR = 1.2, 95% CI = 0.52-2.80). The study indicates that hand washing is effective in reducing the morbidity from diarrhoea and dysentery.", "Transmission of enteric pathogens is facilitated in child day care centers, including family day care homes, by frequent and intimate exposure among susceptible hosts, with diaper changing as the highest-risk procedure for such transmission. The objective of this study was to evaluate the effectiveness of an intervention program in decreasing the incidence of infectious disease symptoms in children attending family day care homes during a 12-month period. Each of 24 family day care homes was randomly assigned to an intervention or control group. The intervention included four components: (1) a handwashing educational program and (2) use of vinyl gloves, (3) use of disposable diaper changing pads, and (4) use of an alcohol-based hand rinse by the day care provider. Symptoms of enteric disease (diarrhea and vomiting) were significantly reduced in intervention family day care homes (p less than or equal to 0.05), whereas respiratory symptoms were not significantly different between intervention and control family day care homes (p = 0.35). Diarrhea was reported in 1 of every 100 child care days, representing one diarrhea episode per month in a typical family day care home." ]

[ "6288509", "3116071" ]

[ "Isosorbide dinitrate and nifedipine treatment of achalasia: a clinical, manometric and radionuclide evaluation.", "The effect of terbutaline sulfate, nitroglycerin, and aminophylline on lower esophageal sphincter pressure and radionuclide esophageal emptying in patients with achalasia." ]

[ "The effects of sublingual isosorbide dinitrate (5 mg) and nifedipine (20 mg) were compared in 15 patients with achalasia. The parameters examined included the manometric measurement of the lower esophageal sphincter pressure, the radionuclide assessment of esophageal emptying and the clinical response. The mean basal lower esophageal sphincter pressure fell significantly after both drugs (p less than 0.01), with a maximum fall of 63.5% 10 min after receiving isosorbide dinitrate, but by only 46.7% 30 min after nifedipine. The esophageal radionuclide test meal retention was significantly less (p less than 0.01) only after receiving isosorbide dinitrate. The drug improved initial esophageal emptying by its effect on the lower esophageal sphincter and by relieving the test meal hold-up noted to occur at the junction of the upper and midesophagus. Eight patients cleared their test meal within 10 min after isosorbide dinitrate administration while only two did so after nifedipine. Subjectively, 13 patients had their dysphagia relieved by isosorbide dinitrate and 8 by nifedipine. However, this relief was not confirmed in 4 patients by the radionuclide study and they, as well as the other 3 patients who did not respond to therapy, were referred to pneumatic dilatation. Side effects were more prominent after nitrates. Three of the patients are currently receiving nifedipine and 5 patients received isosorbide dinitrate therapy for 8-14 mo. The radionuclide test meal is currently the best way of objectively evaluating drug therapy in patients with achalasia. Isosorbide dinitrate is more effective than nifedipine in relieving their symptoms.", "We studied the effects of three smooth muscle relaxants on lower esophageal sphincter (LES) pressure and radionuclide esophageal emptying in 15 untreated patients with achalasia. LES pressures were determined before and after the administration of normal saline subcutaneously, terbutaline sulfate subcutaneously, nitroglycerin sublingually, and aminophylline intravenously. All smooth muscle relaxants significantly decreased LES pressures when compared with normal saline controls and pretreatment baseline pressures (p less than 0.01). However, in normal saline controls, LES pressure actually increased over time (p less than 0.01). Control radionuclide esophageal emptying studies were performed in all patients. Subsequent esophageal emptying studies were carried out only in patients responding to smooth muscle relaxants by decreasing LES pressures by greater than or equal to 25% (terbutaline sulfate, n = 8; nitroglycerin, n = 7; and aminophylline, n = 4). Significant improvement in esophageal emptying was observed after nitroglycerin and terbutaline sulfate (p less than 0.05) but not after aminophylline. We conclude that in patients with achalasia (a) terbutaline sulfate, nitroglycerin, and aminophylline can significantly decrease LES pressure; (b) resting LES pressures vary over time; and (c) terbutaline sulfate and nitroglycerin significantly improve esophageal emptying in some subjects." ]

[ "15094269", "12032876" ]

[ "Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study.", "Randomized, open-label, comparative trial to evaluate the efficacy and safety of three antiretroviral drug combinations including two nucleoside analogues and nevirapine for previously untreated HIV-1 Infection: the OzCombo 2 study." ]

[ "The 2NN Study was a randomised comparison of the non-nucleoside reverse-transcriptase inhibitors (NNRTI) nevirapine and efavirenz.\n In this multicentre, open-label, randomised trial, 1216 antiretroviral-therapy-naive patients were assigned nevirapine 400 mg once daily, nevirapine 200 mg twice daily, efavirenz 600 mg once daily, or nevirapine (400 mg) and efavirenz (800 mg) once daily, plus stavudine and lamivudine, for 48 weeks. The primary endpoint was the proportion of patients with treatment failure (less than 1 log(10) decline in plasma HIV-1 RNA in the first 12 weeks or two consecutive measurements of more than 50 copies per mL from week 24 onwards, disease progression [new Centers for Disease Control and Prevention grade C event or death], or change of allocated treatment). Analyses were by intention to treat.\n Treatment failure occurred in 96 (43.6%) of 220 patients assigned nevirapine once daily, 169 (43.7%) of 387 assigned nevirapine twice daily, 151 (37.8%) of 400 assigned efavirenz, and 111 (53.1%) of 209 assigned nevirapine plus efavirenz. The difference between nevirapine twice daily and efavirenz was 5.9% (95% CI -0.9 to 12.8). There were no significant differences among the study groups in the proportions with plasma HIV-1 RNA concentrations below 50 copies per mL at week 48 (p=0.193) or the increases in CD4-positive cells (p=0.800). Nevirapine plus efavirenz was associated with the highest frequency of clinical adverse events, and nevirapine once daily with significantly more hepatobiliary laboratory toxicities than efavirenz. Of 25 observed deaths, two were attributed to nevirapine.\n Antiretroviral therapy with nevirapine or efavirenz showed similar efficacy, so triple-drug regimens with either NNRTI are valid for first-line treatment. There are, however, differences in safety profiles. Combination of nevirapine and efavirenz did not improve efficacy but caused more adverse events.", "To assess and compare the efficacy and safety of three triple combination antiretroviral therapies in HIV-1-infected treatment-naive patients.\n Seventy treatment-naive HIV-infected adults with CD4+ T-cell counts >50/microL were randomized to receive either zidovudine + lamivudine + nevirapine (AZT + 3TC + NVP), stavudine + didanosine + nevirapine (d4T+ddI+NVP), or stavudine + lamivudine + nevirapine (d4T+3TC+NVP) for 52 weeks. Patient assessments were conducted monthly and included measurement of plasma HIV RNA levels and CD4+ T-cell counts and evaluations for drug toxicity.\n The mean time-weighted reductions in plasma HIV RNA in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 1.29, 2.13, and 1.78 log(10) copies/mL, respectively (p =.389). The proportions of patients with HIV RNA <50 copies/mL in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 73%, 68%, and 80%, respectively (p =.71). The mean time-weighted increases in CD4+ T-cell counts in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 139, 113, and 174 cells/microL, respectively (p =.30). Three patients ceased assigned treatment due to rash (one from each treatment arm), and 5 of the 45 patients on d4T (3 from the d4T+3TC+NVP arm and 2 from the d4T+ddI+NVP arm) ceased assigned treatment due to neuropathy.\n All three-drug combinations were equally effective at suppressing viral load and increasing CD4+ T-cell counts. No significant differences were detected between the treatment groups in virological or immunological response or cessation of study drugs due to adverse events, although it is possible that the study was underpowered to detect differences. NVP was safe and efficacious in this setting, and efficacy was not influenced by nucleoside reverse transcriptase inhibitor backbone." ]

[ "2196493", "20107216", "8216115" ]

[ "Augmentation of labor: does internal tocography result in better obstetric outcome than external tocography?", "Outcomes after internal versus external tocodynamometry for monitoring labor.", "Induction of labour: does internal tocography result in better obstetric outcome than external tocography." ]

[ "Labor was augmented in 250 patients for slow progress. These women were randomized to have uterine contractions recorded by either an external tocotransducer or an intrauterine catheter. Oxytocin was titrated to achieve an optimal frequency of contractions of six to seven every 15 minutes in each group; additional information on active contraction area profiles was available for those patients who had an intrauterine catheter. There was no statistically significant difference between the groups in the length of the post-augmentation period. The mean maximum dose of oxytocin was 11.1 mU/minute in the external tocography group and 11.0 mU/minute in the internal tocography group. Evidence of uterine hyperstimulation requiring temporary reduction of the oxytocin dose occurred in 19 and 20.2% of the patients in the external and internal tocography groups, respectively. Cesarean delivery was necessary in 12.6 and 16.9% of patients in the external and internal tocography groups, respectively, which is a nonsignificant difference. The incidence of low Apgar scores in the neonates and admission to neonatal intensive care was similar in both groups. The incidence of poor Apgar scores was not different between those who had transient hyperstimulation and those who had no hyperstimulation. In the management of augmented labor, monitoring of uterine contractions by intrauterine pressure catheters did not confer any advantage over tocography by external transducers.", "It has been hypothesized that internal tocodynamometry, as compared with external monitoring, may provide a more accurate assessment of contractions and thus improve the ability to adjust the dose of oxytocin effectively, resulting in fewer operative deliveries and less fetal distress. However, few data are available to test this hypothesis.\n We performed a randomized, controlled trial in six hospitals in The Netherlands to compare internal tocodynamometry with external monitoring of uterine activity in women for whom induced or augmented labor was required. The primary outcome was the rate of operative deliveries, including both cesarean sections and instrumented vaginal deliveries. Secondary outcomes included the use of antibiotics during labor, time from randomization to delivery, and adverse neonatal outcomes (defined as any of the following: an Apgar score at 5 minutes of less than 7, umbilical-artery pH of less than 7.05, and neonatal hospital stay of longer than 48 hours).\n We randomly assigned 1456 women to either internal tocodynamometry (734) or external monitoring (722). The operative-delivery rate was 31.3% in the internal-tocodynamometry group and 29.6% in the external-monitoring group (relative risk with internal monitoring, 1.1; 95% confidence interval [CI], 0.91 to 1.2). Secondary outcomes did not differ significantly between the two groups. The rate of adverse neonatal outcomes was 14.3% with internal monitoring and 15.0% with external monitoring (relative risk, 0.95; 95% CI, 0.74 to 1.2). No serious adverse events associated with use of the intrauterine pressure catheter were reported.\n Internal tocodynamometry during induced or augmented labor, as compared with external monitoring, did not significantly reduce the rate of operative deliveries or of adverse neonatal outcomes. (Current Controlled Trials number, ISRCTN13667534; Netherlands Trial number, NTR285.)\n 2010 Massachusetts Medical Society", "A prospective randomized study was undertaken to evaluate the benefit of intrauterine catheters in induced labour. Two hundred and thirty nine women who had induced labour were studied. The patients in one group had intrauterine catheters inserted and oxytocin was titrated to achieve the 75th percentile of uterine activity observed in spontaneous normal labour according to parity. Contractions were assessed by external tocography in the other group and oxytocin was titrated to achieve 6 to 7 contractions per 15 minutes each lasting > 40 seconds. Mean maximum dose of oxytocin, mode of delivery, Apgar score < 7 at 5 minutes, cord arterial blood pH < 7.15 and admission to neonatal intensive care unit did not differ significantly in the 2 groups. In conclusion, women who had intrauterine catheters did not have a shorter duration of labour, lower dose of oxytocin, fewer operative deliveries or fewer babies in poor condition at birth compared with those who had external tocography in induced labour." ]

[ "20232173", "18202889", "19577251" ]

[ "Is the use of T-tube necessary after laparoscopic choledochotomy?", "A randomized comparison of primary closure and T-tube drainage of the common bile duct after laparoscopic choledochotomy.", "Laparoscopic exploration of common bile duct with primary closure versus T-tube drainage: a randomized clinical trial." ]

[ "Traditionally, the common bile duct (CBD) is closed with T-tube drainage after choledochotomy and removal of CBD stones. However, the insertion of a T-tube is not without complication.\n This randomized study was designed to compare the use of T-tube and primary closure of choledochotomy after laparoscopic choledochotomy to determine whether primary closure can be as safe as closure with T-tube drainage.\n Between February 2006 and June 2009, 122 consecutive patients with proven choledocholithiasis had laparoscopic choledochotomy. They were randomized into two equal groups: T-tube (n = 61) and primary closure (n = 61). Demographic data, intraoperative findings, postoperative complications, and postoperative stay were recorded.\n There was no mortality in both groups. There were no differences in the demographic characteristics or clinical presentations between the two groups. Compared with the T-tube group, the operative time and postoperative stay were significantly shorter and the incidences of overall postoperative complications and biliary complications were statistically and significantly lower in the primary closure group.\n Laparoscopic common bile duct exploration with primary closure without external drainage after laparoscopic choledochotomy is feasible, safe, and cost-effective. After verification of ductal clearance, the CBD could be closed primarily without T-tube insertion.", "Traditionally, the common bile duct (CBD) has been closed with T-tube drainage after laparoscopic choledochotomy and removal of CBD stones. However, insertion of the T-tube is related to some potential postoperative complications, and patients must carry the T-tube for several weeks before its removal. Primary closure of the CBD without drainage has been proposed as a safe alternative to T-tube placement after laparoscopic choledochotomy. This randomized study aimed to compare the postoperative course and final outcome between the two methods applied after LCBDE.\n Between January 2000 and January 2004, 80 patients treated with laparoscopic choledochotomy for CBD stones were randomly assigned to primary duct closure (n = 40) or T-tube drainage (n = 40). The primary end points were morbidity, operative time, postoperative stay, hospital expenses, and time until return to work.\n There were no differences in the demographic characteristics or clinical presentations between the two groups. In the primary closure group, the postoperative stay (5.2 +/- 2.2 vs 8.3 +/- 3.6 days) and the time until return to work (12.6 +/- 5.1 vs 20.4 +/- 13.2 days) were significantly shorter, the hospital expenses (8,638 +/- 2,946 vs 12,531 +/- 4,352 yuan) were significantly lower, and the incidences of postoperative complications (15% vs 27.5%) and biliary complications (10% vs 20%) were statistically and insignificantly lower than in the T-tube drainage group. In the primary closure group, six patients experienced postoperative complications, four of whom had biliary complications, compared, respectively, with 11 and 8 patients in the T-tube drainage group.\n This study showed that primary CBC closure after laparoscopic choledochotomy was a viable alternative to mandatory T-tube drainage.", "Traditionally, the common bile duct (CBD) is closed with T-tube drainage after choledochotomy and removal of CBD stones. However, the insertion of a T-tube is not without complication and the patients have to carry it for several weeks before removal. In the laparoscopic era, surgery is performed with minimally invasive techniques in order to reduce the trauma, hasten recovery, and reduce the hospital stay of patients. T-tube insertion seems to negate these benefits. This randomized study was designed to compare the two methods applied after LCBDE and to determine whether primary closure can be as safe as closure with T-tube drainage.\n From May 2000 to January 2008, 93 consecutive patients with common bile duct stones (CBDS) and gallbladder in situ were enrolled in this randomized study to undergo laparoscopic cholecystectomy with laparoscopic common bile duct exploration (LCBDE). Intraoperative findings, postoperative complications, postoperative stay, and hospital expenses were recorded and analyzed.\n There was no mortality in both groups. A T-tube was inserted in 46 patients and the CBD was closed primarily in 47. There were no differences in the demographic characteristics or clinical presentations between the two groups. Compared with the T-tube group, the operative time and postoperative stay were significantly shorter, the hospital expenses were significantly lower, and the incidences of overall postoperative complications and biliary complications were statistically and insignificantly lower in the primary closure group.\n LCBDE with primary closure without external drainage after laparoscopic choledochotomy is feasible and as safe as T-tube insertion." ]

[ "10192666", "392859", "9627610", "9928648", "12131639", "15295247", "8517562", "9832658", "9024445", "14525751", "12204985", "9492126" ]

[ "A randomized, clinical trial comparing butylcyanoacrylate with octylcyanoacrylate in the management of selected pediatric facial lacerations.", "[Tissue glue in minor skin lesions. A prospective controlled comparison between tissue glue and the suturing of skin minor lesions].", "A new tissue adhesive for laceration repair in children.", "Randomised trial of histoacryl blue tissue adhesive glue versus suturing in the repair of paediatric lacerations.", "Comparison of tissue adhesive and suturing in the repair of lacerations in the emergency department.", "Randomized controlled comparison of cosmetic outcomes of simple facial lacerations closed with Steri Strip Skin Closures or Dermabond tissue adhesive.", "A randomized, controlled trial comparing a tissue adhesive with suturing in the repair of pediatric facial lacerations.", "Tissue adhesive versus suture wound repair at 1 year: randomized clinical trial correlating early, 3-month, and 1-year cosmetic outcome.", "Long-term appearance of lacerations repaired using a tissue adhesive.", "Evaluation of a new high-viscosity octylcyanoacrylate tissue adhesive for laceration repair: a randomized, clinical trial.", "A randomised, controlled trial comparing a tissue adhesive (2-octylcyanoacrylate) with adhesive strips (Steristrips) for paediatric laceration repair.", "Prospective, randomized, controlled trial of tissue adhesive (2-octylcyanoacrylate) vs standard wound closure techniques for laceration repair. Stony Brook Octylcyanoacrylate Study Group." ]

[ "To compare two tissue adhesives, butylcyanoacrylate and octylcyanoacrylate, in the treatment of small (<4 cm) superficial linear traumatic facial lacerations in children.\n This was a randomized, clinical trial with parallel design. 94 children <18 years of age seen in the ED of a tertiary care pediatric hospital with a facial laceration suitable for tissue adhesive closure underwent laceration closure using either butylcyanoacrylate or octylcyanoacrylate. The primary outcome was the cosmetic result at three months rated from photographs by a plastic surgeon on a visual analog scale (VAS). Secondary outcomes included the time to perform the procedure, the perceived difficulty of the procedure, the pain perceived by the patient, and a wound evaluation score at ten to 14 days and three months.\n Ninety-four patients were randomized with 47 in each group. The two groups were similar for baseline demographic and clinical characteristics. There was no difference in the three-month cosmesis VAS (median, 70.0 mm for n-butyl-2-cyanoacrylate vs 67.5 mm for octylcyanocrylate, p = 0.84). There was no difference between the groups for time to complete the procedure (p = 0.88), parent/patient-perceived pain of the procedure (p = 0.37), or physician-perceived difficulty of the procedure (p = 0.33). Similarly, there was no difference between the groups for the percentage of early (p = 0.58) or late (p = 0.71) optimal wound evaluation scores.\n In the closure of small linear pediatric facial lacerations, octylcyanoacrylate is similar to butylcyanoacrylate in ease of use and early and late cosmetic outcomes. The superior physical properties of octylcyanoacrylate appear to add little benefit to the management of these selected lacerations. Physician preference and differing costs may dictate use for these small selected lacerations.", "nan", "To determine the effectiveness of a new tissue adhesive, 2-Octylcyanoacrylate (2-OCA), for laceration repair, 83 children presenting to T.C. Thompson Children's Hospital Emergency Department with lacerations meeting eligibility requirements between February and June 1996 were randomized to receive 2-OCA or nonabsorbable sutures/staples. The length of time for repair was recorded. The length of time for laceration repair was decreased (2.9 minutes 2-OCA vs 5.8 minutes suture/staple; p < 0.001), the parents' assessment of the pain felt by their children in the 2-OCA group was less, and the wounds closed with tissue adhesive had slightly lower cosmesis scores. 2-OCA is an acceptable alternative to conventional methods of wound repair with comparable cosmetic outcome.", "To compare histoacryl blue tissue adhesive glue with suturing in the repair of simple paediatric lacerations.\n Prospective, randomised controlled trial in tertiary paediatric emergency department. Children 4 years old or older with non-ragged lacerations <5 cm in length, <12-h-old and not involving eyelid or mucous membrane. A total of 163 patients were randomly allocated to either glue (83 cases) or sutures (80 controls) to repair their laceration. Primary outcome measures were cosmetic outcome at 3 and 12 months with secondary outcomes-length of time to perform procedure, and pain assessment of procedure by doctor, nurse, parent and child.\n Cases and controls were similar in age, wound length and width and body part involved, but more females received glue (P = 0.013). Time taken to repair the wound was faster in the glue group (median 0-2 mins vs. 6-10 min suture, P<0.001). Doctors (P = 0.02), nurses (P<0.01) and parents (P = 0.02) but not the children themselves (P = 0.24) rated glue repair as less distressing. Complications at 1 week (wound dehiscence, redness and discharge) were the same for both groups (P>0.2). Cosmetic outcome was the same for both groups at 3 (n = 65) and 12 (n = 65) months (P>0.7).\n Tissue adhesive glue is faster and probably less painful than suturing. Tissue adhesive glue has the same cosmetic result as suturing when used for the repair of simple lacerations in children.", "The objective of this study was to compare the applications of Histoacryl Blue (HAB) and suturing regarding cosmetic outcome, cost and patient and physician satisfaction in the emergency department (ED). A total of 92 consecutive adult patients with lacerations equal to or shorter than 5 cm were enrolled in the study. Patients were randomized to either HAB or suturing. Ten-day and three-month cosmetic outcomes were evaluated via visual analogue scale (VAS) by a blinded surgeon. Cosmetic outcome, cost and patient and physician satisfaction of both groups were compared. Only 52 patients completed the follow-up at three months. Twenty-eight had been repaired with sutures and 24 with HAB. The differences regarding ten-day and three-month cosmetic outcome scales between the patients repaired with HAB and sutures were not statistically significant. Application of HAB resulted in greater satisfaction of the patient and the physician (p=0.007 and p=0.0001, respectively). Costs of HAB were significantly lower than sutures (p=0.0001). It is concluded that HAB is a cheaper method of laceration repair and results in greater satisfaction of both patients and physicians, while cosmetic outcomes were comparable. These results suggest that HAB is a viable alternative to suturing for selected lacerations in the ED.", "To compare the short-term complications and long-term cosmetic outcomes of simple facial lacerations closed with 3M Steri Strip Skin Closures or Dermabond.\n Prospective, randomized controlled trial of children ages 1 to 18 presenting to a pediatric emergency department with simple low-tension lacerations of the face. After standard wound care, patients received wound closure with either Steri Strip Skin Closure or Dermabond. Pain associated with closure was evaluated on a 100-mm visual analogue scale (0 = no pain, 100 = worst pain). A follow-up telephone call was made a week after enrollment to determine short-term complications. Patients returned 2 months after would closure for wound photography. Cosmetic outcomes were evaluated by 2 plastic surgeons blinded to the method of wound closure on a 100-mm visual analogue scale (0 = best scar, 100 = worst scar).\n One hundred children aged 1 to 18 were enrolled. Ninety-seven patients had results analyzed. Forty-eight received Steri Strip Skin Closures and 49 received Dermabond. Patient demographics and wound characteristics were similar between groups. Pain scores on a 100-mm visual analogue scale were 9.0 mm for the Steri Strip group and 6.2 mm for the Dermabond group (P = ns). At short-term follow-up, there was one wound complication in the Steri Strip group and 7 complications in the Dermabond group (P = 0.06). Eighty-nine patients received 2-month evaluation (41 Steri Strip, 45 Dermabond). There was no difference in the mean visual analogue scale cosmesis scores: 37.2 mm (95% CI = 30.8-43.7) versus 43.8 mm (95% CI = 38.4-49.2) (P = 0.12).\n Steri Strip Skin Closures and Dermabond provide similar cosmetic outcomes for closure of simple facial lacerations. Steri Strip Skin Closure may represent a low-cost alternative for closure of simple facial lacerations.", "To compare the tissue adhesive Histoacryl Blue with suturing in the repair of pediatric facial lacerations.\n Prospective, randomized controlled trial.\n Emergency department of a pediatric teaching hospital.\n Eighty-one children presenting with clean facial lacerations less than 4 cm in length and 0.5 cm in width.\n Patients were allocated randomly to have their lacerations repaired with sutures or Histoacryl Blue.\n The two groups were similar for demographic and clinical characteristics. Photographs taken at three months were rated by two plastic surgeons blinded to the method of closure. There was no difference between groups for appearance scores on a visual analog scale (60.5 mm for Histoacryl Blue versus 57.2 mm for suture, P = .45) or on a categorical scale (Histoacryl Blue versus sutures: unacceptable, 11% versus 13%; acceptable, 59% versus 71%; excellent, 30% versus 16%; P = .76). Measures of observer agreement produced Pearson correlations of .72 and .94 on the visual analog scale and kappa coefficients of .46 and .73 on the categorical scale. Histoacryl Blue was assessed as less painful on a visual analog scale (24.7 versus 43.7 mm, P < .01) and faster (7.9 versus 15.6 minutes, P < .001).\n Histoacryl Blue is a faster and less painful method of facial laceration repair that has cosmetic results similar to the use of sutures.", "To compare the 1-year cosmetic outcome of wounds treated with octylcyanoacrylate tissue adhesive and monofilament sutures and to correlate the early, 3-month, and 1-year cosmetic outcomes.\n We prospectively randomized 136 cases of traumatic laceration to repair with octylcyanoacrylate tissue adhesive or 5-0 or smaller monofilament suture. A wound score was assigned by a research nurse, and validated by a second nurse blinded to the treatment, at 5 to 10 days after injury (early), 3 months, and 1 year. Standardized photographs were taken at 3 months and 1 year and shown to a cosmetic surgeon blinded to the method of closure, who rated the wounds on a validated cosmesis scale.\n We were able to examine 77 lacerations at 1 year for follow-up. No differences were found in the demographic or clinical characteristics between groups. Likewise, at 1 year no difference was found in the optimal wound scores (73% versus 68%, P =.60) or in visual analog scale cosmesis scores (69 versus 69 mm, P =.95) for octylcyanoacrylate and sutures, respectively. Agreement was poor between early and 3-month wound scores (kappa=.34; 95% confidence interval [CI],.10 to.58) but a strong association existed between 3-month and 1-year wound scores (kappa=.71; 95% CI,.52 to.90). We noted a moderate correlation between 3-month and 1-year results on the visual analog cosmesis scale (intraclass correlation,.48; 95% CI, .30 to.63).\n One year after wound repair, no difference is noted in the cosmetic outcomes of traumatic lacerations treated with octylcyanoacrylate tissue adhesive and sutures. The assessment of wounds 3 months after injury and wound repair provides a good measure of long-term cosmetic outcome.", "Histoacryl Blue (HAB), a tissue adhesive, has been shown to decrease laceration repair time, cause less pain to the child, eliminate the need for suture removal, and result in a similar short-term cosmetic outcome compared with conventional suturing. Reports suggest that poor correlation can exist between the short-term and long-term cosmetic outcomes for lacerations repaired by conventional suturing. Therefore, this study compares the long-term cosmetic outcome of HAB to conventional suturing for laceration repair in children.\n Prospective, randomized clinical trial.\n Children presenting an urban pediatric emergency department for laceration repair between October 1994 and February 1995 were eligible. Patients less than 1 or more than 18 years old, those with lacerations more than 5 cm in length, or in areas of high tension or mobility were excluded.\n After routine wound management, including subcutaneous closure when deemed necessary, patients were randomized to receive skin sutures or HAB for cutaneous closure. Photographs taken at the 2-month and 1-year follow-up visits were evaluated for cosmetic appearance by two plastic surgeons blinded to the method of repair.\n Sixty-one children were enrolled: HAB (N = 30), suture (N = 31). Thirty HAB and 25 sutured patients were assessed at 2 months, while 17 HAB and 15 sutured patients were reevaluated at 1 year. Patients that followed-up at 2 months and 1 year were comparable to those with no follow-up in: treatment group (HAB vs suture), demographics, wound characteristics, and initial parental satisfaction. The two plastic surgeons graded the cosmetic appearance of the wounds repaired by HAB to be comparable to those repaired by conventional suturing at both the 2-month and 1-year follow-up.\n The use of HAB is an ideal alternative to conventional suturing for the cutaneous closure of low tension lacerations in children with a long-term cosmetic outcome comparable to conventional suturing.", "Tissue adhesives have recently been approved for skin closure. Their low viscosity may result in inadvertent migration. The authors compared the tendency of the adhesive to migrate after laceration closure with a high- or low-viscosity octylcyanoacrylate (OCA).\n This was a randomized, clinical trial set in university and community-based emergency departments. Participants included patients with simple traumatic lacerations. Patients were randomized to laceration closure with low- or high-viscosity OCA tissue adhesive. The outcome measured was immediate adhesive migration (interobserver agreement, kappa = 0.90). Data analysis was performed with proportions compared with chi-square and Fisher's exact tests.\n Eighty-four patients were randomized to low- (n = 42) or high- (n = 42) viscosity OCA tissue adhesive. Groups were similar in baseline patient and wound characteristics. The high-viscosity OCA was less likely to migrate than the lower-viscosity agent (21% vs. 78%, p < 0.001; odds ratio = 0.3, 95% confidence interval = 0.1 to 0.5). The proportion of patients who noted a sensation of heat during OCA application was higher in the high-viscosity groups (44% vs. 26% respectively, p = 0.11); however, all such patients in both groups would use the device again. At 14 days, there were no wound infections in either group. There was one dehiscence in the high-viscosity group.\n The high-viscosity OCA tissue adhesive was less likely to migrate than the lower-viscosity device. Wound dehiscence and infection rates were acceptably low in both treatment groups.", "To compare the tissue adhesive 2-octylcyanoacrylate (Dermabond) with adhesive strips, Steristrips in paediatric laceration repair.\n Children with suitable lacerations were randomly allocated for wound closure with either a tissue adhesive or adhesive strips. Thirty children were treated in each group. Linear Visual Analogue Scores were used to judge parents' and nurses' opinions of the application of each treatment. A similar scoring system was used to judge the cosmetic outcome as viewed by parents and a plastic surgeon. Complications and trial failures were noted.\n Complete data were available for 44 of the children. Parents viewed the treatments as equally acceptable. In contrast those performing the procedure judged the tissue adhesive more difficult to apply. Scores of cosmetic outcome by both parents and the plastic surgeon showed no significant difference in the treatment method used. There were four children in the tissue adhesive group and one from the adhesive strip group in whom the wounds were unable to be closed.\n Both tissue adhesives and adhesive strips are excellent \"no needle\" alternatives for the closure of suitable paediatric lacerations. This study suggests that the techniques are similar in efficacy, parental acceptability, and cosmetic outcome. The choice as to which is used may come down to economics and operator preference.", "To compare a new tissue adhesive, 2-octylcyanoacrylate, with standard wound closure techniques for the repair of traumatic lacerations.\n A prospective, randomized, controlled clinical trial enrolled consecutive patients > 1 year of age with non-bite, non-crush-induced lacerations who presented < 6 hours after injury. Structured closed-question data sheets were completed at the time of laceration repair and suture removal. Patients were randomly assigned to treatment with either 2-octylcyanoacrylate or standard wound closure. Infection was determined at the time of suture removal. Long-term cosmetic appearance (> 3 months) was assessed by physicians using a previously validated categorical cosmetic scale and by patients using a 100-mm visual analog scale.\n There were 63 patients randomized to the octylcyanoacrylate group and 61 patients treated with standard wound closure techniques. The 2 treatment groups were similar with respect to age, gender, race, medical history, and wound characteristics. At the 5-to-10-day follow-up, only 1 wound was infected and only 2 wounds required reclosure due to dehiscence. These 3 patients received treatment with octylcyanoacrylate. At long-term follow-up, the cosmetic appearances were similar according to the patients (octylcyanoacrylate, 83.8 +/- 19.4 mm vs standard techniques, 82.5 +/- 17.6 mm; p = 0.72) and the physicians (optimal cosmetic appearance, 77% vs 80%; p = 0.67).\n Wounds treated with octylcyanoacrylate and standard wound closure techniques have similar cosmetic appearances 3 months later." ]

[ "6924693", "11529977", "11562616", "18841533", "2056358", "10190835" ]

[ "Demand vs. scheduled feedings for premature infants.", "Comparison of caloric intake and weight outcomes of an ad lib feeding regimen for preterm infants in two nurseries.", "A feeding protocol for healthy preterm infants that shortens time to oral feeding.", "Cue-based feeding for preterm infants: a prospective trial.", "Feeding preterm infants. Schedule or demand?", "The effects of prescribed versus ad libitum feedings and formula caloric density on premature infant dietary intake and weight gain." ]

[ "To compare the effects of demand and schedule feeding in premature infants who weighed less than 2500 grams at birth and who were appropriate for gestational age, 36 premature infants were studied. Premature infants were assigned randomly to either demand (N = 18) or scheduled (N = 18) feedings in a regional NICU in a metropolitan hospital. Infants that were allowed to feed on demand took amounts of formula and calories similar to those infants who were fed specified amounts of formula every three or four hours. Demand-fed infants were bottle-feeding well enough to be discharged earlier than schedule-fed infants, required fewer feedings per day, and needed fewer gavage feedings. No complications related to feedings were seen in either group.", "Effects on caloric intake and weight gain of an ad libitum (ad lib) feeding regimen for preterm infants may be specific to a special care nursery.\n To explore across two nurseries the similarity of effect on caloric intake and weight gain of an ad lib feeding regimen compared with a prescribed regimen and the similarity of effect of caloric intake on weight gain.\n All infants participating in the multi-site randomized clinical trial (RCT) of the ad lib feeding regimen were <35 weeks gestational age at birth and had birth weight appropriate for gestational age. Data on caloric intake and weight gain were collected at two nurseries (A, n=22; B, n=78) with the same feeding regimen protocols. Two strategies were used to explore similarity of regimen effect on caloric intake and weight gain. Repeated measures analysis of variance (ANOVA) was used to examine the effect on caloric intake and weight gain of time, feeding regimen, and time-by-regimen interaction for each nursery.\n In both nurseries, regimen effects were reasonably consistent for caloric intake and weight gain. Caloric intake was lower across nurseries for infants fed ad lib. After accounting for caloric intake, the ad lib regimen did not affect weight gain. The time-by-regimen interaction effect on caloric intake was significant in both nurseries. Caloric intake for infants fed ad lib increased significantly over 5 days.\n Despite differences between nurseries in infant characteristics and in protocol implementation, the feeding regimen effect was consistent for caloric intake and weight gain. Further support was found for the development of infant self-regulatory capacity.", "To test the hypothesis that healthy preterm infants randomly assigned to a semi-demand feeding protocol would require fewer days to attain oral feeding and have a satisfactory weight gain compared with control infants receiving standard care.\n In 2 neonatal intensive care nurseries, 81 infants 32 to < or = 34 weeks' postconceptional age were randomly assigned to the control (n = 41) or experimental (n = 40) protocol for transition from gavage to oral feedings. The control protocol followed the standard practice of gradually increasing scheduled oral feedings, whereas the experimental protocol used a semi-demand feeding method contingent on infant behavior. Analysis of variance techniques were used to compare the study groups for number of days to attain oral feeding and weight gain.\n The semi-demand method shortened the time for infants to achieve oral feeding by 5 days (P < .001). There were no differences in weight gain between the study groups, and both groups had satisfactory weight gain.\n The semi-demand method for the transition from gavage to oral feeding in healthy, preterm infants 32 to < or = 34 weeks postconceptional age promotes faster attainment of oral feeding and does not compromise their weight gain.", "We set out to test whether premature infants were able to be fed orally on feeding cues and be discharged home earlier than infants fed by traditional feeding regimens. Attainment of adequate growth, adverse events, and nursing time to provide care were also assessed. After screening, the recruited premature infants (< 36 wks post-conceptual age [PCA]) were divided into two feeding regimens. A control group of 40 infants was fed using an initial combination of scheduled gavage and bottle feeding and then graduating to demand feeds. The intervention group comprised 39 neonates who had gavage feeds discontinued at study entrance and fed orally on cues. Outcomes measured were: weight gain in grams/kg/day, length of stay (in days) after enrollment, PCA on entrance and at discharge, adverse events during feeding, number of cues per feed in the intervention group, and resource utilization using nurse/patient ratios. Differences between groups were evaluated using Mann-Whitney U test, Fisher's exact test, and regression analysis. Two-tailed P values of < 0.05 were considered significant. There was no difference between groups in the mean weight gain; in the control group mean weight gain was 12.5 gm/kg/day and in the intervention group 12.1 gm/kg/day ( P = 0.83). The average length of stay in the control group of 14.5 days was significantly longer than the 10.0 days in the intervention group ( P = 0.009). This difference remained significant after adjusting for gestational age at birth in regression analysis. The average total number of adverse events in the control group (12.5 events) was significantly greater than in the intervention group (3.5 events; P = 0.007). The mean PCA on study entry was 34.4 wks in both groups and on exit 36.5 wks in the control group and 35.8 wks in the intervention group, a significant difference ( P = 0.02), The intervention group elicited 2.8 cues/feed. The nurse to patient ratios was equal in both groups throughout the study period. Cue-based feeding was possible for premature infants with similar weight gain as traditional feeding without affecting workload. Hospitalization and adverse events were decreased.", "Weight gain, length of hospitalization, and feeding behaviors were compared for preterm infants who were fed on demand (n = 15) with preterm infants who were fed on a schedule (n = 14). Weight gain and hospital stays were similar for both groups, and self-regulated feeding was found to be safe for physiologically stable infants. Benefits related to feeding behaviors included longer rest periods between interventions and the opportunity for infants to demonstrate hunger cues. The study findings indicate that feeding on demand may enhance contingency interactions between parents and their preterm infants.", "Although feedings that are organized on an ad lib basis (i.e., in response to infant cues of hunger and of satiation) could enhance an infant's self-regulatory capacities for feeding, ad lib feeding of fully nipple-fed premature infants in a special care nursery has not been examined.\n To study whether the caloric and protein intake and weight change of fully nipple-fed preterm infants differed by the feeding regimen (prescribed or ad lib) and by the caloric density of the formula (20- or 24-kcalories per ounce).\n The 78 infants who participated in the study were randomized to prescribed or ad lib feeding regimens and, within each regimen, were further randomized to receive either 20-calorie or 24-kcalorie per ounce formula. Dietary intake (volume/kg, caloric intake/kg) and weight change (grams/kg gained or lost) were assessed for each of the 5 study days. Multivariate data analysis was used to examine the effects of feeding regimen and caloric density on dietary intake and weight change, controlling biologic variables (infant gender, race, lung disease diagnosis, treatment with supplemental oxygen, gestational age and weight at birth, and weight on the day prior to full nipple-feeding).\n Overall, the ad lib feeding regimen had a negative effect on volume intake and caloric intake. Weight gain was influenced by caloric intake, but not by feeding regimen or the caloric density of the diet. With increased full nipple-feeding experience, caloric intake of ad lib feeders approached that of the infants fed on the prescribed regimen.\n Development of self-regulatory capacities through ad lib feeding experience was indicated by infant regulation of the volume of intake by the caloric density of the formula, an unexpected finding. Furthermore, the approach of the caloric intake of infants on the ad lib regimen to that of infants on the prescribed regimen suggests they had gained skill in regulating intake with experience. Whether or not the trend for similar intakes would continue beyond 5 days is a question for further study." ]

[ "3303813", "791584", "631417", "1101943", "4554553", "1138828" ]

[ "Oxytocin- or low-dose prostaglandin F2 alpha-infusion for stimulation of labor after primary rupture of membranes. A prospective, randomized trial.", "Double-blind trial of prostaglandin F2alpha and oxytocin in the induction of labour.", "A comparison of the efficacy and safety of extra-amniotic prostaglandin E2 and intravenous prostaglandin E2 for the induction of labour in patients with unripe cervices.", "Comparison of intravenous oxytocin and prostaglandin E2 for induction of labour using automatic and non-automatic infusion techniques.", "Prostaglandin F 2 for induction of labor.", "Biochemical and haematological changes during the induction of labour at term with oxytocin, prostaglandin E-2 and prostaglandin F-2alpha." ]

[ "One hundred consecutive women with singleton pregnancies and primary rupture of membranes (PROM) after 36 weeks of gestation were included in a prospective, randomized trial of intravenous infusion of oxytocin (up to 30 mIU/min) versus low-dose prostaglandin F2 alpha(PGF2 alpha, up to 6.0 micrograms/min). Cesarean section was performed in 12 patients because of suspected disproportion or intra-uterine asphyxia. Effective contractions or labor progress failed to become established within 8 hours in another 4 women stimulated with PGF2 alpha and 2 stimulated by oxytocin. The stimulation delivery time (hours) for the remaining 82 women treated with PGF2 alpha or oxytocin, respectively was 8.7 against 12.1 for initial Bishop score less than 5 (p less than 0.01), (Mann-Whitney test), 7.2 vs. 7.1 for Bishop score 5-8 and 5.7 vs. 4.2 for Bishop score greater than 8. Patients with initial Bishop score less than 5 seemed to need analgetics less often when treated with PGF2 alpha than with oxytocin. Frequencies of side effects and instrumental deliveries as well as the fetal outcome were similar for the two treatment schedules. The results of the study suggest that low-dose PGF2 alpha infusion may be the more appropriate treatment for women with an unfavorable initial Bishop score.", "In a random double-blind trial in 28 pregnant women at term, labour was induced with either prostaglandin F2alpha or oxytocin given by intravenous infusion. The results showed that prostaglandin F2alpha was as active as oxytocin and induction was successfully carried out in 24 patients; 3 patients had a caesarean section because of an obstructed labour and 1 patient on oxytocin did not have regular contractions after 10-hours' infusion although she delivered spontaneously 2 days later. No difference was found in the induction--delivery interval in the 8 patients in each group who had early amniotomy (first 90 minutes). No adverse effects were noted in either mother or the child. The authors recommend that to avoid side-effects the dosage of 20 mug prostaglandin F2alpha per minute should not be exceeded and that, although no cardiotocographic abnormalities were noted, this method of control should be used.", "In a study comparing intravenous prostaglandin E2 (PGE2) with extra-amniotic PGE2 for the induction of labour, in patients with unfavourable induction features, we found no difference between the two methods in either safety or efficacy. However, we would not recommend the use of the extra-amninotic route as a routine method because of some technical difficulties.", "A double blind trial of prostaglandin E2 and oxytocin given by intravenous infusion after amniotomy for induction of labour in 100 primigravidae with unfavourable induction features is reported. No clear-cut advantage of either drug emerged although PGE2 was perhaps superior when the cervix was highly unfavourable. Prostaglandin E2 appeared to produce less deleterious effects on the fetus but was associated with a higher incidence of maternal side effects. The automatic Cardiff Infusion apparatus was found to be a safe means of PGE2 infusion and to have advantages over the use of non-automatic techniques both for PGE2 and for oxytocin infusion.", "nan", "A total of 75 patients had labour induced near term using intravenous oxytocin, prostaglandin E-2 or prostaglandin F-2alpha. Biochemical and haematological investigations were performed to assess hepatic, renal and adrenocortical function and changes in platelet adhesiveness. In doses which were similarly effective in inducing labour, both prostaglandins were without the water-retaining effect of oxytocin. Adrenocortical stimulation was greatest with oxytocin. No difference between these agents was observed for the other measurements made." ]

[ "6150275", "16464325", "12452403", "10457813" ]

[ "Controlled trial of hypnotherapy in the treatment of severe refractory irritable-bowel syndrome.", "Gut-directed hypnotherapy for irritable bowel syndrome: piloting a primary care-based randomised controlled trial.", "Hypnosis treatment for severe irritable bowel syndrome: investigation of mechanism and effects on symptoms.", "The treatment of irritable bowel syndrome with hypnotherapy." ]

[ "30 patients with severe refractory irritable-bowel syndrome were randomly allocated to treatment with either hypnotherapy or psychotherapy and placebo. The psychotherapy patients showed a small but significant improvement in abdominal pain, abdominal distension, and general well-being but not in bowel habit. The hypnotherapy patients showed a dramatic improvement in all features, the difference between the two groups being highly significant. In the hypnotherapy group no relapses were recorded during the 3-month follow-up period, and no substitution symptoms were observed.", "In western populations irritable bowel syndrome (IBS) affects between 10% and 30% of the population and has a significant effect on quality of life. It generates a substantial workload in both primary and secondary care and has significant cost implications. Gut-directed hypnotherapy has been demonstrated to alleviate symptoms and improve quality of life but has not been assessed outside of secondary and tertiary referral centres.\n To assess the effectiveness of gut-directed hypnotherapy as a complementary therapy in the management of IBS.\n Randomised controlled trial.\n Primary care patients aged 18-65 years inclusive, with a diagnosis of IBS of greater than 6 weeks' duration and having failed conventional management, located in South Staffordshire and North Birmingham, UK.\n Intervention patients received five sessions of hypnotherapy in addition to their usual management. Control patients received usual management alone. Data regarding symptoms and quality of life were collected at baseline and again 3, 6, and 12 months post-randomisation.\n Both groups demonstrated a significant improvement in all symptom dimensions and quality of life over 12 months. At 3 months the intervention group had significantly greater improvements in pain, diarrhoea and overall symptom scores (P<0.05). No significant differences between groups in quality of life were identified. No differences were maintained over time. Intervention patients, however, were significantly less likely to require medication, and the majority described an improvement in their condition.\n Gut-directed hypnotherapy benefits patients via symptom reduction and reduced medication usage, although the lack of significant difference between groups beyond 3 months prohibits its general introduction without additional evidence. A large trial incorporating robust economic analysis is, therefore, urgently recommended.", "Hypnosis improves irritable bowel syndrome (IBS), but the mechanism is unknown. Possible physiological and psychological mechanisms were investigated in two studies. Patients with severe irritable bowel syndrome received seven biweekly hypnosis sessions and used hypnosis audiotapes at home. Rectal pain thresholds and smooth muscle tone were measured with a barostat before and after treatment in 18 patients (study I), and treatment changes in heart rate, blood pressure, skin conductance, finger temperature, and forehead electromyographic activity were assessed in 24 patients (study II). Somatization, anxiety, and depression were also measured. All central IBS symptoms improved substantially from treatment in both studies. Rectal pain thresholds, rectal smooth muscle tone, and autonomic functioning (except sweat gland reactivity) were unaffected by hypnosis treatment. However, somatization and psychological distress showed large decreases. In conclusion, hypnosis improves IBS symptoms through reductions in psychological distress and somatization. Improvements were unrelated to changes in the physiological parameters measured.", "Previous research from the United Kingdom has shown hypnotherapy to be effective in the treatment of irritable bowel syndrome (IBS). The current study provides a systematic replication of this work in the United States. Six matched pairs of IBS patients were randomly assigned to either a gut-directed hypnotherapy (n = 6) or to a symptom monitoring wait-list control condition (n = 6) in a multiple baseline across subjects design. Those assigned to the control condition were later crossed over to the treatment condition. Subjects were matched on concurrent psychiatric diagnoses, susceptibility to hypnosis, and various demographic features. On a composite measure of primary IBS symptoms, treatment was superior (p = .016) to symptom monitoring. Results from the entire treated sample (n = 11; one subject was removed from analysis) indicate that the individual symptoms of abdominal pain, constipation, and flatulence improved significantly. State and trait anxiety scores were also seen to decrease significantly. Results at the 2-month follow-up point indicated good maintenance of treatment gains. No significant correlation was found between initial susceptibility to hypnosis and treatment gain. A positive relationship was found between the incidence of psychiatric diagnosis and overall level of improvement." ]