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Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Association between circulating vitamin K1 and coronary calcium progression in community-dwelling adults: the Multi-Ethnic Study of Atherosclerosis.Background:Animal studies have shown that vitamin K treatment reduced vascular calcification, but human data are limited.Objective:We determined the association between vitamin K status and coronary artery calcium (CAC) progression in the Multi-Ethnic Study of Atherosclerosis by using a case-cohort design.Design:Serum phylloquinone (vitamin K1) was measured in 296 participants with extreme CAC progression and 561 randomly selected participants without extreme CAC progression; all subjects had baseline and follow-up CAC measures (mean follow-up: 2.5 y). A serum vitamin K1 concentration was considered low at <1.0 nmol/L (the distribution median). Outcomes were replicated by using post hoc per-protocol analyses of a vitamin K1 supplementation trial.Results:The OR (95% CI) for extreme CAC progression for subjects with low serum vitamin K1 compared with subjects without extreme CAC progression was 1.34 (0.94, 1.90; NS) when adjusted for demographics and confounders. A significant interaction between low vitamin K1 and antihypertension medication use was detected (P = 0.016). Hypertension medication users with low serum vitamin K1 were more likely to have extreme CAC progression than were medication users without extreme CAC progression [OR (95% CI): 2.37 (1.38, 4.09)]. In replication, baseline antihypertensive medication users in the supplementation group had less CAC progression than did those in the control group [adjusted mean ± SEM of the 3-y CAC change was +5 ± 20 Agatston units (AU) in the vitamin K1 group (n = 40) and +44 ± 13 AU in the placebo group (n = 49); P < 0.01].Conclusions:Although the point estimate of our primary analysis suggests low serum vitamin K1 is associated with greater CAC progression, the difference was NS. Low serum vitamin K1 was significantly associated with CAC progression in antihypertension medication users, which, to our knowledge, is a novel finding conditionally replicated by using an independent sample. Intervention trials are needed to determine whether improving serum vitamin K1 reduces CAC progression, especially in hypertensive individuals. This trial was registered at clinicaltrials.gov as NCT00183001.

Primary Outcome Measures is 3 year change in bone mineral density at the hip|3 year change in coronary calcification score|Hand osteoarthritis score at final visit|Concentration and attention scores at final visit; Extracted Interventionsis is Vitamin K; Conditions is Osteoporosis|Vascular Calcification|Inflammation ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Short-term, high-fat diet increases the expression of key intestinal genes involved in lipoprotein metabolism in healthy men.Background:The modulation of cholesterol and fatty acid homeostasis by dietary fatty acids is thought to be mediated by changes in the expression of key intestinal genes involved in lipoprotein metabolism. However, the short-term effect of dietary fat intake on the expression of these genes has not been fully investigated in humans.Objective:To test whether short-term changes in dietary fatty acid intake affect the expression of key intestinal genes involved in lipoprotein metabolism, we conducted a randomized, double-blind, crossover study in 12 nonobese, healthy men with normal plasma lipid profiles.Design:Participants were subjected to the following 2 intensive 3-d dietary interventions under isocaloric conditions: 1) a high-fat diet (37% of energy from fat and 50% of energy from carbohydrates) and 2) a low-fat diet (25% of energy from fat and 62% of energy from carbohydrates). Expressions of key genes involved in lipoprotein metabolism were compared by using real-time polymerase chain reaction quantification on duodenal biopsy specimens obtained in a fasting state after each diet.Results:After the 3-d high-fat diet, plasma cholesterol, LDL cholesterol, and HDL cholesterol concentrations were significantly higher than concentrations observed after the low-fat diet was consumed. The high-fat diet also resulted in significant increases in the intestinal messenger RNA expression of several key genes involved in lipoprotein metabolism. Plasma triglycerides and apolipoprotein B-48 concentrations were significantly lower after the high-fat diet than after the low-fat diet.Conclusion:These findings suggest that short-term exposure to a high-fat diet upregulates the expression of key genes involved in lipid and lipoprotein metabolism at the enterocyte level. This trial was registered at clinicaltrials.gov as NCT01806441.

Primary Outcome Measures is Change in duodenal mRNA expression of NPC1L1; Extracted Interventionsis is 3-days high fat diet 3-days low fat diet; Conditions is Gene Expression ;Sex is MALE ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of calcium plus vitamin D supplementation during pregnancy in Brazilian adolescent mothers: a randomized, placebo-controlled trial.Background:Pregnancy and lactation in adolescents with habitually low calcium intake may adversely affect maternal bone mass.Objective:We investigated the effect of calcium plus vitamin D supplementation during pregnancy on bone mass during lactation in Brazilian adolescent mothers with low-calcium diets (∼600 mg/d).Design:Pregnant adolescents (14-19 y) randomly received daily calcium (600 mg) plus vitamin D3 (200 IU) (n = 30) or a placebo (n = 26) from 26 wk of pregnancy (baseline) until parturition. The bone mineral content (BMC), bone area (BA), and bone mineral density (BMD) at the total body, lumbar spine, and hip (total and femoral neck) were evaluated by using dual-energy X-ray absorptiometry at 5 and 20 wk postpartum. Serum hormones and 25-hydroxyvitamin D [25(OH)D] were measured. Group comparisons were adjusted for significant covariates.Results:The mean serum 25(OH)D concentration was 59 nmol/L at baseline. In comparison with the placebo, 25(OH)D tended to be 14-15 nmol/L higher postpartum in the supplemented group (P = 0.08). Total body and hip BMC and BMD decreased over time (P ≤ 0.005) in both groups with a group × time interaction at the femoral neck (P < 0.04). Supplemented mothers had higher lumbar spine BA (6.7%; P = 0.002) and lumbar spine BMC (7.9%, P = 0.08) than did mothers who consumed the placebo at 5 wk postpartum. At 20 wk postpartum, differences between groups were more evident, with higher lumbar spine BMC (13.9%), lumbar spine BA (6.2%), and lumbar spine BMD (10.6%) in the supplemented group (P ≤ 0.008).Conclusions:Calcium plus vitamin D supplementation during pregnancy of adolescents with low calcium intake results in higher lumbar spine bone mass and a reduced rate of femoral neck bone loss during lactation. Additional studies are required to determine whether bone effects are temporary or long-lasting. This trial was registered at clinicaltrials.gov as NCT01732328.

Primary Outcome Measures is Differences in maternal bone mass changes postpartum between supplemented and placebo groups; Extracted Interventionsis is Calcium plus vitamin D; Conditions is Lactation Bone Loss|Infant Bone Growth ;Sex is FEMALE ;Age is CHILD, ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise.Background:The major thiol-disulfide couple of reduced glutathione (GSH) and oxidized glutathione is a key regulator of major transcriptional pathways regulating aseptic inflammation and recovery of skeletal muscle after aseptic injury. Antioxidant supplementation may hamper exercise-induced cellular adaptations.Objective:The objective was to examine how thiol-based antioxidant supplementation affects skeletal muscle's performance and redox-sensitive signaling during the inflammatory and repair phases associated with exercise-induced microtrauma.Design:In a double-blind, crossover design, 10 men received placebo or N-acetylcysteine (NAC; 20 mg · kg(-1) · d(-1)) after muscle-damaging exercise (300 eccentric contractions). In each trial, muscle performance was measured at baseline, after exercise, 2 h after exercise, and daily for 8 consecutive days. Muscle biopsy samples from vastus lateralis and blood samples were collected before exercise and 2 h, 2 d, and 8 d after exercise.Results:NAC attenuated the elevation of inflammatory markers of muscle damage (creatine kinase activity, C-reactive protein, proinflammatory cytokines), nuclear factor κB phosphorylation, and the decrease in strength during the first 2 d of recovery. NAC also blunted the increase in phosphorylation of protein kinase B, mammalian target of rapamycin, p70 ribosomal S6 kinase, ribosomal protein S6, and mitogen activated protein kinase p38 at 2 and 8 d after exercise. NAC also abolished the increase in myogenic determination factor and reduced tumor necrosis factor-α 8 d after exercise. Performance was completely recovered only in the placebo group.Conclusion:Although thiol-based antioxidant supplementation enhances GSH availability in skeletal muscle, it disrupts the skeletal muscle inflammatory response and repair capability, potentially because of a blunted activation of redox-sensitive signaling pathways. This trial was registered at clinicaltrials.gov as NCT01778309.

Primary Outcome Measures is Change in reduced glutathione in blood; Extracted Interventionsis is n-acetylcysteine supplementation; Conditions is Skeletal Muscle Damage|Skeletal Muscle Performance|Intgracellular Signaling in Skeletal Muscle|Inflammatory Status ;Sex is MALE ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis.Background:Non-alcoholic steatohepatitis (NASH) is a common cause of serum alanine aminotransferase (ALT) elevations and chronic liver disease, but it is unclear how well ALT elevations reflect the liver injury.Aim:To assess how well changes in ALT elevations reflect improvements in liver histology in response to vitamin E therapy.Methods:The vitamin E and placebo arms of the Pioglitazone vs. Vitamin E vs. Placebo in Non-alcoholic Steatohepatitis (PIVENS) trial were reassessed for associations among changes in ALT levels, body weight and liver histology. An ALT response was defined as a decrease to ≤40 U/L and by ≥30% of baseline. Liver biopsies taken before and after treatment were scored for non-alcoholic fatty liver disease activity (NAS) and fibrosis.Results:ALT responses were more frequent among vitamin E (48%) than placebo (16%) recipients (P < 0.001). Among vitamin E recipients, ALT responses were associated with decreases in NAS (P < 0.001), but not fibrosis scores (P = 0.34), whereas among placebo recipients, ALT responses were associated with significant decreases in both (P < 0.05). Weight loss (≥2 kg) was also associated with ALT response (P < 0.001), improvements in NAS (P < 0.001) and fibrosis (P < 0.02), but vitamin E had an added effect both with and without weight loss. Weight gain (≥2 kg) was associated with lack of ALT response and worsening NAS and fibrosis scores in patients not on vitamin E.Conclusions:Decrease of ALT levels to normal in patients with NASH is usually associated with improved histological activity. Management should stress the value of weight loss and strongly discourage weight gain. Vitamin E can improve both ALT levels and histology with and without weight loss.Clinical trial number:NCT00063622.

Primary Outcome Measures is Number of Participants With Improvement in Non-alcoholic Fatty Liver Disease (NAFLD) Activity Defined by Change in Standardized Scoring of Liver Biopsies at Baseline and After 96 Weeks of Treatment.; Extracted Interventionsis is Pioglitazone Vitamin E Matching placebo; Conditions is Liver Diseases ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Resolution of Clostridium difficile-associated diarrhea in patients with cancer treated with fidaxomicin or vancomycin.Purpose:Patients with cancer are at increased risk for Clostridium difficile-associated diarrhea (CDAD). Little is known about treatment response.Patients and methods:Two double-blind trials randomly allocated 1,105 patients with CDAD to fidaxomicin or vancomycin treatment (modified intent-to-treat [mITT]), and 183 of these had cancer. Univariate and multivariate post hoc analyses compared effects of treatment and patient characteristics on cure, recurrence, and sustained response after 4 weeks. Time to resolution of diarrhea (TTROD) was also evaluated.Results:Patients with cancer had a lower cure rate and longer TTROD than patients without cancer. Recurrence rates were similar. Cure was more likely with fidaxomicin than vancomycin (odds ratio [OR] 2.0; P = .065), recurrence was less likely (OR = 0.37; P = .018), and sustained response more frequent (OR = 2.56; P = .003). Under vancomycin, median TTROD was longer in patients with cancer than in those without (123 v 58 hours; log-rank P < .001). With fidaxomicin, median TTROD was not significantly affected by presence of cancer (74 v 54 hours; log-rank P = .145). In the full mITT population, age, hypoalbuminemia, and cancer were inversely associated with clinical cure by multivariate analysis. Study treatment with vancomycin was a significant predictor of recurrence (P < .001). Within the cancer population, low albumin was negatively and fidaxomicin was positively associated with improved cure.Conclusion:For patients with cancer, fidaxomicin treatment was superior to vancomycin, resulting in higher cure and sustained response rates, shorter TTROD, and fewer recurrences.

Primary Outcome Measures is Cure Rate at End of Therapy; Extracted Interventionsis is PAR-101/OPT-80 Vancomycin; Conditions is Clostridium Infections|Diarrhea ;Sex is ALL ;Age is CHILD, ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Dasatinib in children and adolescents with relapsed or refractory leukemia: results of the CA180-018 phase I dose-escalation study of the Innovative Therapies for Children with Cancer Consortium.Purpose:Dasatinib is a potent BCR-ABL inhibitor with proven efficacy in adults with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP) and in imatinib-resistant/intolerant disease. This phase I study of the Innovative Therapies for Children with Cancer Consortium assessed dasatinib safety and efficacy in pediatric patients.Patients and methods:Escalating once-daily dasatinib doses (60 to 120 mg/m(2)) were administered to children (n = 58) with (i) imatinib-pretreated CML or Philadelphia chromosome (Ph)-positive acute lymhoblastic leukemia (ALL) and (ii) treatment-refractory Ph-negative ALL or acute myeloid leukemia (AML).Results:Dasatinib safety and efficacy profiles compared favorably with those in adults. The most common drug-related nonhematologic adverse events were nausea (31%, all grades; 2%, grade 3 to 4), headache (22%, 3%), diarrhea (21%, 0%), and vomiting (17%, 2%). Of 17 patients with CML-CP, 14 (82%) achieved complete cytogenetic response (CCyR) and eight (47%) achieved major molecular response. After ≥ 24 months of follow-up, median complete hematologic response (CHR) and major cytogenetic response (MCyR) durations were not reached. Of 17 patients with advanced-phase CML or Ph-positive ALL, six (35%) achieved confirmed CHR and 11 (65%) achieved CCyR. Median MCyR duration was 4.6 months (95% CI, 2.1 to 17.4 months). No patient with Ph-negative ALL or AML responded. Dasatinib pediatric pharmacokinetic parameters were comparable with those in adult studies, showing rapid absorption (time to reach maximum concentration, 0.5 to 6.0 hours) and elimination (mean half-life, 3.0 to 4.4 hours).Conclusion:Dasatinib 60 mg/m(2) and 80 mg/m(2) once-daily dosing were selected for phase II studies in children with Ph-positive leukemias.

Primary Outcome Measures is Recommended Phase II Dose of Dasatinib in Children and Adolescents With Relapsed or Refractory Leukemia; Extracted Interventionsis is Dasatinib Dasatinib Dasatinib; Conditions is Leukemia ;Sex is ALL ;Age is CHILD, ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Selection of immunostimulant AS15 for active immunization with MAGE-A3 protein: results of a randomized phase II study of the European Organisation for Research and Treatment of Cancer Melanoma Group in Metastatic Melanoma.Purpose:Active immunization against the tumor-specific MAGE-A3 antigen is followed by a few but impressive and durable clinical responses. This randomized phase II trial evaluated two different immunostimulants combined with the MAGE-A3 protein to investigate whether a more robust and persistent immune response could be associated with increased clinical benefit.Patients and methods:Patients with MAGE-A3-positive stage III or IV M1a melanoma were randomly assigned to receive the MAGE-A3 protein combined either with AS02B or with AS15 immunostimulant. Clinical end points were toxicity and rates of objective clinical responses, progression-free survival (PFS), and overall survival (OS).Results:Seventy-five patients were treated, with 36 eligible patients per arm. Both treatments were well tolerated. In the AS15 arm, four objective responses were observed (three complete responses and one partial response) versus one partial response in the AS02B arm. In the AS15 and AS02B arms, the PFS rates after 6 months were 25% and 14%, respectively; and the median OS times were 33 months and 19.9 months, respectively, with a median observation period of 48 months. Antibodies against MAGE-A3, found in all patients, showed three-fold higher titers in the AS15 arm. The anti-MAGE-A3 cellular response was also more pronounced in the AS15 arm.Conclusion:In the MAGE-A3+AS15 arm, clinical activity was higher and the immune response more robust. Therefore, the AS15 immunostimulant was selected for combination with the MAGE-A3 protein in phase III trials.

Primary Outcome Measures is Response rate (complete response and partial response) as assessed by RECIST criteria|Vaccine-related toxicity as assessed by CTCAE v3; Extracted Interventionsis is D1/3-MAGE-3-His fusion protein SB-AS02B adjuvant SB-AS15 adjuvant; Conditions is Melanoma (Skin) ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: phase II randomized study results.Purpose:The MAGE-A3 protein is expressed in approximately 35% of patients with resectable non-small-cell lung cancer (NSCLC). Several immunization approaches against the MAGE-A3 antigen have shown few, but often long-lasting, clinical responses in patients with metastatic melanoma.Patients and methods:A double-blind, randomized, placebo-controlled phase II study was performed assessing clinical activity, immunologic response, and safety following immunization with recombinant MAGE-A3 protein combined with an immunostimulant (13 doses over 27 months) in completely resected MAGE-A3-positive stage IB to II NSCLC. The primary end point was disease-free interval (DFI).Results:Patients were randomly assigned to either MAGE-A3 immunotherapeutic (n = 122) or placebo (n = 60). After a median postresection period of 44 months, recurrence was observed in 35% of patients in the MAGE-A3 arm and 43% in the placebo arm. No statistically significant improvement in DFI (hazard ratio [HR], 0.75, 95% CI, 0.46 to 1.23; two-sided P = .254), disease-free survival (DFS; HR, 0.76; 95% CI, 0.48 to 1.21; P = .248), or overall survival (HR, 0.81; 95% CI, 0.47 to 1.40; P = .454) was observed. Corresponding analysis after a median of 70 months of follow-up revealed a similar trend for DFI and DFS. All patients receiving the active treatment showed a humoral immune response to the MAGE-A3 antigen, although no correlation was observed with outcome. No significant toxicity was observed.Conclusion:In this early development study with a limited number of patients, postoperative MAGE-A3 immunization proved to be feasible with minimal toxicity. These results are being investigated further in a large phase III study.

Primary Outcome Measures is Number of Patients Reporting Confirmed Non-small-cell Lung Cancer (NSCLC) Recurrence; Extracted Interventionsis is GSK 249553 vaccine Placebo; Conditions is Lung Cancer, Non-Small Cell ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Predictive gene signature in MAGE-A3 antigen-specific cancer immunotherapy.Purpose:To detect a pretreatment gene expression signature (GS) predictive of response to MAGE-A3 immunotherapeutic in patients with metastatic melanoma and to investigate its applicability in a different cancer setting (adjuvant therapy of resected early-stage non-small-cell lung cancer [NSCLC]).Patients and methods:Patients were participants in two phase II studies of the recombinant MAGE-A3 antigen combined with an immunostimulant (AS15 or AS02B). mRNA from melanoma biopsies was analyzed by microarray analysis and quantitative polymerase chain reaction. These results were used to identify and cross-validate the GS, which was then applied to the NSCLC data.Results:In the patients with melanoma, 84 genes were identified whose expression was potentially associated with clinical benefit. This effect was strongest when the immunostimulant AS15 was included in the immunotherapy (hazard ratio [HR] for overall survival, 0.37; 95% CI, 0.13 to 1.05; P = .06) and was less strong with the other immunostimulant AS02B (HR, 0.84; 95% CI, 0.36 to 1.97; P = .70). The same GS was then used to predict the outcome for patients with resected NSCLC treated with MAGE-A3 plus AS02B; actively treated GS-positive patients showed a favorable disease-free interval compared with placebo-treated GS-positive patients (HR, 0.42; 95% CI, 0.17 to 1.03; P = .06), whereas among GS-negative patients, no such difference was found (HR, 1.17; 95% CI, 0.59 to 2.31; P = .65). The genes identified were mainly immune related, involving interferon gamma pathways and specific chemokines, suggesting that their pretreatment expression influences the tumor's immune microenvironment and the patient's clinical response.Conclusion:An 84-gene GS associated with clinical response for MAGE-A3 immunotherapeutic was identified in metastatic melanoma and confirmed in resected NSCLC.

Primary Outcome Measures is Number of Patients Reporting Confirmed Non-small-cell Lung Cancer (NSCLC) Recurrence; Extracted Interventionsis is GSK 249553 vaccine Placebo; Conditions is Lung Cancer, Non-Small Cell ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study.In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) + Reduced tacrolimus (TAC; n = 245), TAC Control (n = 243) or TAC Elimination (n = 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR + Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference -2.2%, 97.5% confidence interval [CI] -8.8%, 4.4%). BPAR was less frequent in the EVR + Reduced TAC group (6.1% vs. 13.3% in TAC Control, p = 0.010). Adjusted change in estimated glomerular filtration rate (eGFR) from randomization to month 24 was superior with EVR + Reduced TAC versus TAC Control: difference 6.7 mL/min/1.73 m(2) (97.5% CI 1.9, 11.4 mL/min/1.73 m(2), p = 0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5) mL/min/1.73 m(2) in the EVR + Reduced TAC group and 66.1 (19.3) mL/min/1.73 m(2) in the TAC Control group (p < 0.001). Study medication was discontinued due to adverse events in 28.6% of EVR + Reduced TAC and 18.2% of TAC Control patients. Early introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation provided a significant and clinically relevant benefit for renal function at 2 years posttransplant.

Primary Outcome Measures is Incidence Rate of Composite Efficacy Failure From Randomization to Month 12; Extracted Interventionsis is Tacrolimus (reduced tacrolimus) Tacrolimus (tacrolimus elimination) Tacrolimus (tacrolimus control) Everolimus (reduced tacrolimus) Everolimus (tacrolimus elimination) Corticosteroids; Conditions is Liver Transplantation ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Prognostic value of the Geneva prediction rule in patients with pulmonary embolism.Background:Assessment of pre-test probability of pulmonary embolism (PE) and prognostic stratification are two widely recommended steps in the management of patients with suspected PE. Some items of the Geneva prediction rule may have a prognostic value. We analyzed whether the initial probability assessed by the Geneva rule was associated with the outcome of patients with PE.Methods:In a post-hoc analysis of a multicenter trial including 1,693 patients with suspected PE, the all-cause death or readmission rates during the 3-month follow-up of patients with confirmed PE were analyzed. PE probability group was prospectively assessed by the revised Geneva score (RGS). Similar analyses were made with the a posteriori-calculated simplified Geneva score (SGS).Results:PE was confirmed in 357 patients and 21 (5.9%) died during the 3-month follow-up. The mortality rate differed significantly with the initial RGS group, as with the SGS group. For the RGS, the mortality increased from 0% (95% Confidence Interval: [0-5.4%]) in the low-probability group to 14.3% (95% CI: [6.3-28.2%]) in the high-probability group, and for the SGS, from 0% (95% CI: [0-5.4%] to 17.9% (95% CI: [7.4-36%]). Readmission occurred in 58 out of the 352 patients with complete information on readmission (16.5%). No significant change of readmission rate was found among the RGS or SGS groups.Conclusions:Returning to the initial PE probability evaluation may help clinicians predict 3-month mortality in patients with confirmed PE. (ClinicalTrials.gov: NCT00117169).

Primary Outcome Measures is The primary outcome variable will be the number of thromboembolic events in the 3-month follow-up period in each group.; Extracted Interventionsis is multi-detector helical computed tomography; Conditions is Pulmonary Embolism ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Improved function in women with persistent pregnancy-related pelvic pain after a single corticosteroid injection to the ischiadic spine: a randomized double-blind controlled trial.Background:Pregnancy-related low back and pelvic pain is a worldwide problem. A large proportion of women still experience disabling daily back pain 2 years after childbirth, resulting in major changes in activities and general well-being. In spite of this, the source of pain and effective treatment are uncertain.Objective:To evaluate the short-term effects on function of a single corticosteroid injection treatment to the ischiadic spine in women with persistent pregnancy-related pelvic pain (PPPP).Methods:Thirty-six women were allocated to injection treatment with slow-release triamcinolone and lidocain or saline and lidocain, given once at the sacrospinous ligament insertion on the ischiadic spine bilaterally with follow-up at 4 weeks. Outcome measures were Disability Rating Index (DRI), self-rated functional health (SF-36), gait speed and endurance (6MWT), and strength and endurance of trunk muscles (isometric trunk extensor and flexor tests).Results:Women in the triamcinolone group showed significantly improved DRI (p = 0.046), 6MWT (p = 0.016), and isometric trunk extensor tests (p = 0.004), as compared with the saline group. Close co-variation was shown between improved function and reduced pain intensity.Conclusions:Improved function was achieved among women with PPPP after a single injection treatment with slow-release corticosteroid. The effect was positively correlated to the reduced pain intensity.

Primary Outcome Measures is Reported pain intensity on visual analogue scale; Extracted Interventionsis is Triamcinolone Saline solution; Conditions is Back Pain ;Sex is FEMALE ;Age is CHILD, ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Nanoparticle albumin-bound paclitaxel for second-line treatment of metastatic urothelial carcinoma: a single group, multicentre, phase 2 study.Background:No standard treatment exists for patients with platinum-refractory urothelial cancer. Taxanes and vinflunine are commonly used, but response is less than 20% with no survival benefit. In this phase 2 study, we assessed efficacy and tolerability of nanoparticle albumin-bound (nab) paclitaxel in platinum-refractory urothelial cancer.Methods:We did an open-label, single-group, two-stage study at five centres in Canada. We enrolled patients aged at least 18 years with histologically confirmed, locally advanced, or metastatic measurable urothelial cancer, with documented progression on or within 12 months of treatment with one previous platinum-containing regimen. Patients received nab-paclitaxel at 260 mg/m(2) intravenously every 3 weeks. Treatment continued until disease progression or occurrence of unacceptable toxic effects. The primary endpoint was objective tumour response, defined by a complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (version 1.0) criteria. Tumour response and safety were assessed in all patients who received at least one cycle of nab-paclitaxel. This study is registered with ClinicalTrials.gov, number NCT00683059.Findings:We enrolled 48 patients between Oct 16, 2008, and June 23, 2010. Patients received a median of six cycles (range one to 15). 47 patients were evaluable; one (2·1%) had a CR and 12 (25·5%) had PRs, resulting in an overall response of 27·7% (95% CI 17·3-44·4). The most frequently recorded adverse events of any grade were fatigue (38 of 48; 79%), pain (37 of 48; 77%), alopecia (34 of 48; 71%), and neuropathy (30 of 48; 77%). The most frequently recorded adverse events of grade 3 or higher were pain (11 of 48; 23%), fatigue (five of 48; 23%), hypertension (three of 48; 6%), neuropathy (three of 48, 6%), and joint stiffness or pain (two of 48; 4%).Interpretation:Nab-paclitaxel was well tolerated in this population of patients with pretreated advanced urothelial cancer with an encouraging tumour response. These results warrant further study of nab-paclitaxel in second-line treatment of urothelial cancer.Funding:Abraxis Bioscience, Celgene.

Primary Outcome Measures is Response rate; Extracted Interventionsis is Paclitaxel; Conditions is Transitional Cell Carcinoma ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Maternal weight loss during exclusive breastfeeding is associated with reduced weight and length gain in daughters of HIV-infected Malawian women.Maternal weight loss during exclusive breastfeeding may influence the growth of exclusively breast-fed infants through impaired quality or quantity of breast milk. This study evaluated how maternal weight loss from 2 to 24 wk postpartum was related to infant weight and length gain in 1309 lactating HIV-infected mothers and their exclusively breast-fed infants. Malawian mother-infant pairs in the Breastfeeding, Antiretrovirals, and Nutrition Study were randomized with a 2 × 3 factorial design to a 2-arm nutritional intervention with a lipid-based nutrient supplement (LNS), meeting nutritional needs of lactation, or no LNS and a 3-arm antiretroviral (ARV) intervention (maternal, infant, or no ARV regimen). Linear regression models were used to relate maternal weight loss (weight loss vs. no weight loss) to infant weight and length gain from birth to 24 mo, stratifying by gender and controlling for maternal BMI at 2 wk (mean ± SD: 23.2 ± 3.0 kg/m(2)) and interacting maternal BMI with weight loss. In adjusted models, compared with daughters of women who did not lose weight, length and weight gain were lower in daughters whose mothers had a lower BMI at 2 wk postpartum coupled with the weight loss. For example, among mothers with an initial BMI of 18 kg/m(2), daughters of those who lost weight gained less weight [β = -0.29 kg (95% CI: -0.53, -0.06)] and length [β = -0.88 cm (95% CI: -1.52, -0.23)] from birth to 24 wk than daughters of those who gained weight. Though effects were only observed in girls, suggesting possible gender differences in suckling and feeding behavior, these findings indicate that maternal weight loss with low energy reserves represents a risk factor for poor infant growth outcomes.

Primary Outcome Measures is Postpartum weight loss between delivery and 28 weeks; Extracted Interventionsis is Maternal zidovudine/lamivudine/lopinavir-ritonavir Infant nevirapine Maternal protein and calorie supplement; Conditions is HIV Infections ;Sex is ALL ;Age is CHILD, ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Probiotics Lactobacillus reuteri DSM 17938 and Lactobacillus casei CRL 431 modestly increase growth, but not iron and zinc status, among Indonesian children aged 1-6 years.Probiotics and milk calcium may increase resistance to intestinal infection, but their effect on growth and iron and zinc status of Indonesian children is uncertain. We investigated the hypotheses that cow milk with added probiotics would improve growth and iron and zinc status of Indonesian children, whereas milk calcium alone would improve growth but reduce iron and zinc status. A 6-mo randomized trial was conducted in low-socioeconomic urban communities of Jakarta. Healthy children (n = 494) were randomly assigned to receive low-lactose milk with a low calcium content of ∼50 mg/d (LC; n = 124), a regular calcium content of ∼440 mg/d (RC group; n = 126), regular calcium with 5 × 10(8) CFU/d Lactobacillus casei CRL 431 (casei; n = 120), or regular calcium with 5 × 10(8) CFU/d Lactobacillus reuteri DSM 17938 (reuteri; n = 124). Growth, anemia, and iron and zinc status were assessed before and after the intervention. Compared with the RC group, the reuteri group had significantly greater weight gain [0.22 (95% CI: 0.02, 0.42) kg], weight-for-age Z-score (WAZ) changes [0.09 (95% CI: 0.01, 0.17)], and monthly weight [0.03 (95% CI: 0.002, 0.05) kg/mo] and height [0.03 (95% CI: 0.01, 0.05) cm/mo] velocities. Casei significantly increased monthly weight velocity [0.03 (95% CI: 0.001, 0.05) kg/mo], but not height. However, the changes in underweight, stunting, anemia prevalence, and iron and zinc status were similar between groups. In conclusion, L. reuteri DSM 17938 modestly improved growth by increasing weight gain, WAZ changes, and weight and height velocity, whereas L. casei CRL 431 modestly improved weight velocity. Independent from probiotics supplementation, regular milk calcium did not affect growth or iron and zinc status.

Primary Outcome Measures is The mean number of episodes and duration of acute diarrheal disease; Extracted Interventionsis is low calcium milk of 180 ml regular milk of 180 ml regular milk of 180 ml + probiotics regular milk of 180 ml + probiotics; Conditions is Healthy|Diarrhea ;Sex is ALL ;Age is CHILD

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Reading speed improvements in retinal vein occlusion after ranibizumab treatment.Importance:Treatment of macular edema secondary to retinal vein occlusion with ranibizumab has been shown to improve visual acuity compared with macular laser or observation. It is important to determine whether these visual acuity improvements translate into measurable improvements in visual function.Objective:To examine the benefit of ranibizumab (Lucentis) on measured reading speed, a direct performance assessment, through 6 months in eyes of patients with macular edema after retinal vein occlusion (RVO). DESIGN Two multicenter, double-masked, phase 3 trials in which participants with macular edema after branch RVO or central RVO were randomized 1:1:1 to monthly sham, ranibizumab, 0.3 mg, or ranibizumab, 0.5 mg, for 6 months.Setting:Community- and academic-based ophthalmology practices specializing in retinal diseases.Participants:Seven hundred eighty-nine eyes of 789 participants who were at least aged 18 years with macular edema secondary to retinal vein occlusion in the branch vein occlusion (BRAVO) and central vein occlusion (CRUISE) trials.Interventions:Eyes were randomized 1:1:1 to 1 of 3 groups for monthly injections for 6 months: sham (132 in BRAVO and 130 in CRUISE), intravitreal ranibizumab, 0.3 mg (134 in BRAVO and 132 in CRUISE), and intravitreal ranibizumab, 0.5 mg (131 in BRAVO and 130 in CRUISE). Patients were able to receive macular laser after 3 months if they met prespecified criteria.Main outcomes and measures:Reading speed in the study eye was measured with enlarged text (letter size equivalent to approximately 20/1500 at the test distance) at baseline and 1, 3, and 6 months. The number of correctly read words per minute (wpm) was reported. The reading speed test requires a sixth-grade reading level and does not account for literacy or cognitive state. RESULTS In patients with branch RVO, the mean gain for the 0.5-mg group was 31.3 wpm compared with 15.0 wpm in sham-treated eyes (difference, 16.3 wpm; P = .007) at 6 months. In patients with central RVO, the mean gain for the 0.5-mg group was 20.5 wpm compared with 8.1 wpm in sham-treated eyes (difference, 12.4 wpm; P = .01) at 6 months. A gain of 15 or more letters of best-corrected visual acuity letter score corresponded to an increase in reading speed of 12.3 wpm and 15.8 wpm in patients with branch and central RVO, respectively.Conclusions and relevance:These results suggest that patients with macular edema after RVO treated monthly with ranibizumab are more likely to have improvements in reading speed of the affected eyes through 6 months compared with sham treatment. These results demonstrate the relevance of the treatment benefit to functional visual gain.Trial registration:clinicaltrials.gov Identifier: NCT00486018 and NCT00485836.

Primary Outcome Measures is Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at 6 Months; Extracted Interventionsis is Ranibizumab injection 0.3 mg Ranibizumab injection 0.5 mg Sham injection; Conditions is Macular Edema|Retinal Vein Occlusion ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Rapid improvement of acute schizophrenia symptoms after intravenous sodium nitroprusside: a randomized, double-blind, placebo-controlled trial.Importance:The treatment of schizophrenia remains a challenge, and the currently available antipsychotic drugs are slow acting and produce a number of adverse effects.Objective:To examine the effectiveness and safety of a single intravenous administration of sodium nitroprusside (0.5 μg/kg/min for 4 hours) on the positive, negative, anxiety, and depressive symptoms in patients with schizophrenia.Design:Single-center, randomized, double-blind, placebo-controlled trial performed from March 9, 2007, to March 12, 2009.Setting:University teaching hospital in São Paulo, Brazil.Participants:Twenty inpatients aged 19 to 40 years with a diagnosis of schizophrenia who were in the first 5 years of the disease who are taking antipsychotics.Intervention:Sodium nitroprusside administration.Main outcome measures:The 18-item Brief Psychiatric Rating Scale and the negative subscale of the Positive and Negative Syndrome Scale.Results:After the infusion of sodium nitroprusside, a rapid (within 4 hours) improvement of symptoms was observed. The placebo and experimental groups had significant differences in the 18-item Brief Psychiatric Rating Scale total score and subscale scores, which persisted for 4 weeks after infusion.Conclusions:The results clearly show a therapeutic effect of sodium nitroprusside. If this drug is approved for routine clinical use in patients with schizophrenia, this discovery will be an important advance in the pharmacologic treatment of this devastating disorder.Trial registration:clinicaltrials.gov Identifier: NCT01548612.

Primary Outcome Measures is Change in BPRS score; Extracted Interventionsis is Sodium nitroprusside Glucose solution; Conditions is Schizophrenia ;Sex is ALL ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Phase I study of the combination of temsirolimus and pazopanib in advanced solid tumors.Inhibition of either vascular endothelial growth factor receptor or mammalian target of rapamycin (mTOR) signaling improves outcomes in patients with several advanced solid tumors. We conducted a phase I trial of temsirolimus with pazopanib to investigate the feasibility of simultaneous 'vertical inhibition' of vascular endothelial growth factor receptor and mTOR pathways. Patients with advanced solid tumors, no previous pazopanib or mTOR inhibitor, good performance status, and acceptable end-organ function were eligible. In a typical 3+3 escalation design starting at temsirolimus 15 mg by an intravenous infusion weekly and pazopanib 400 mg orally daily, we defined dose-limiting toxicity (DLT) as attributable grade 3 or higher nonhematologic adverse events in the first 28-day cycle and the maximum tolerable dose as the maximum dose level at which less than two patients experienced DLT. At the initial dose level, two patients had four DLTs (anorexia, fatigue, hyponatremia, and hypophosphatemia). After reduction to temsirolimus 10 mg intravenous infusion weekly and pazopanib 200 mg orally daily, one of three patients had DLT (fatigue) and the first patient in the subsequent expansion had dose-limiting hypophosphatemia. Attributable grade 3 or higher adverse events in more than one patient included leukopenia, neutropenia, fatigue, and hypophosphatemia. Tumor reduction not fulfilling the RECIST criteria for partial response was the best response in four of seven evaluable patients. The combination of temsirolimus and pazopanib was not feasible at clinically meaningful doses in this population because of constitutional and electrolyte disturbances.

Primary Outcome Measures is Feasibility and safety of temsirolimus and pazopanib when given in combination to patients with advanced solid tumors.; Extracted Interventionsis is Temsirolimus, Pazopanib; Conditions is Solid Tumors ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Radiological heterogeneity in response to chemotherapy is associated with poor survival in patients with colorectal liver metastases.Background:In patients with colorectal liver metastases (CLM) there is limited knowledge about the occurrence of radiological heterogeneity in response to chemotherapy.Methods:A retrospective analysis was performed in the CAIRO and CAIRO II studies on the incidence of intermetastatic heterogeneity in patients with CLM and its association with survival. Mixed response (MR) was defined as >30% difference in individual lesion response, with all lesions showing a similar behaviour; true mixed response (TMR) as two lesions showing progression versus response; homogeneous response (HR) as similar behaviour of all lesions. Patients were classified according to the Response Evaluation Criteria in Solid Tumours (RECIST) categories (partial response (PR), stable disease (SD), progressive disease (PD), complete response (CR)) and then subdivided into MR and TMR in order to compare survival.Results:In the CAIRO and CAIRO II studies, 140 and 150 patients with liver-only disease were identified. 73/290 (25.2%) patients showed MR, and 25/290 (8.6%) patients TMR, and 192/290 (66.2%) patients HR. Overall survival (OS) at 1-4 years was significantly higher for the homogeneous partial responders category compared to other response categories. Median OS was 22.0 months for the entire population. In the partial response category, patients with MR showed significant poorer survival compared to patients with HR (median OS 23.7 versus 36.0 months, respectively, p=0.019). Multivariate analysis identified four independent predictors for OS: serum lactate dehydrogenase (LDH) level (p=0.002), number of first-line chemotherapy cycles (p=0.001), resection of primary tumour (p=0.001) and response category (p=0.012).Conclusion:Radiological heterogeneity is present in approximately 35% of patients with CLM. Partial responders according to the RECIST criteria, show a significant poorer survival if classified as heterogeneous partial responder compared to homogeneous partial responders.

Primary Outcome Measures is Overall survival; Extracted Interventionsis is capecitabine-irinotecan capecitabine+irinotecan (1st line); Conditions is Advanced Colorectal Cancer ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Immunological priming induced by a two-dose series of H5N1 influenza antigen, administered alone or in combination with two different formulations of AS03 adjuvant in adults: results of a randomised single heterologous booster dose study at 15 months.One influenza pandemic preparedness strategy involves priming a population with a pre-pandemic subtype-specific vaccine and boosting the immunological response at the time of the pandemic with a strain-matched vaccine. In the current study, adults (n=469) randomised 15 months previously to receive an A/Indonesia/5/2005 (H5N1) influenza vaccine (3.75 μg haemagglutinin antigen [HA]) administered alone or in combination with an oil-in-water emulsion based Adjuvant System containing 11.86 mg (AS03(A)) or 5.93 mg (AS03(B)) tocopherol per dose, received one booster dose of A/turkey/Turkey/1/2005 (H5N1) vaccine (3.75 μg HA) with or without AS03(A). An anamnestic antibody response that met US regulatory acceptance criteria was observed 15 months after priming. Although superior immunogenicity of AS03-adjuvanted compared to unadjuvanted priming was not demonstrated, higher antibody titres which persisted longer were seen when both priming and boosting regimens were adjuvanted. This may affect duration of response or heterologous immunity. The booster vaccines had a clinically acceptable safety/reactogenicity profile after adjuvanted or unadjuvanted priming. This study has been registered at www.clinicaltrials.gov NCT00771615.

Primary Outcome Measures is Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.; Extracted Interventionsis is GSK A/turkey H5N1 Influenza vaccine; Conditions is Influenza ;Sex is ALL ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Comparison of high-dose cytarabine and timed-sequential chemotherapy as consolidation for younger adults with AML in first remission: the ALFA-9802 study.To assess the value of administering timed-sequential chemotherapy (TSC; 2 therapeutic sequences separated by a 4-day interval-free chemotherapy) or high-dose cytarabine (HDAraC) cycles in consolidation therapy for acute myeloid leukemia (AML), 459 patients 15 to 50 years of age were enrolled in the prospective randomized Acute Leukemia French Association-9802 trial. Complete remission was achieved in 89%. A total of 237 patients were then randomized to either TSC consolidation (120 patients) or HDAraC consolidation cycles (117 patients). Overall, there was no significant difference between the 2 consolidation arms (5-year event-free survival [EFS]: 41% for HDAraC vs 35% for TSC), or cumulative incidence of relapse, or treatment-related mortality. Cytogenetically normal AML NPM1(+) or CEBPA(+) and FLT3-ITD(-) had the same outcome as those with favorable cytogenetics. When considering favorable and unfavorable risk groups, the trend was in favor of HDAraC. However, the difference became significant when considering intermediate cytogenetics (5-year EFS: 49% vs 29%; P = .02), especially cytogenetically normal AML (5-year EFS: 48% vs 31%; P = .04), which was related to lower relapse rate and less toxicity. This study demonstrates that TSC did not produce any benefit when used as consolidation therapy in younger adults compared with HDAraC. This trial was registered at www.clinicaltrials.gov as #NCT00880243.

Primary Outcome Measures is Assessing the potential value of the daily administration of GM-CSF during induction chemotherapy and post-induction for analyzing and comparing the arms with and without GM-CSF: EFS; Extracted Interventionsis is GM-CSF; Conditions is Acute Myeloid Leukemia ;Sex is ALL ;Age is CHILD, ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura.The safety and efficacy of weekly rituximab 375 mg/m(2) (×4), given within 3 days of acute TTP admission, with standard therapy (PEX and steroids) was evaluated. Clinical outcomes were compared to historical controls (n = 40) who had not received rituximab. Within the trial group, 15 of 40 required ICU admission and 15% of all cases with the highest troponin T levels on admission were ventilated. Before the second rituximab infusion, 68% of cases had a platelet count > 50 × 10(9)/L and 38% > 150 × 10(9)/L. Fewer PEX were required in whites compared to nonwhite in the rituximab group (mean 14 vs 21, P = .0095). Inpatient stay was reduced by 7 days in the non-ICU trial cases compared to historical controls (P = .04), especially in whites, with a mean reduction of 7 days (P = .05). Ten percent of trial cases relapsed, median, 27 months (17-31 months), compared to 57% in historical controls, median 18 months (3-60 months; P = .0011). There were no excess infections or serious adverse events with rituximab. In conclusion, rituximab appears a safe and effective therapy. Inpatient stay and relapse are significantly reduced in the rituximab cohort. Rituximab should be considered in conjunction with standard therapy on acute presentation of TTP. This study was registered at www.clinicaltrials.gov as NCT009-3713.

Primary Outcome Measures is The primary objective of this study is to investigate whether Rituximab and PEX decreases the time to remission of TTP patients.; Extracted Interventionsis is Rituximab; Conditions is Thrombotic Thrombocytopenic Purpura (TTP) ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report.Cerebral adrenoleukodystrophy (cALD) remains a devastating neurodegenerative disease; only allogeneic hematopoietic cell transplantation (HCT) has been shown to provide long-term disease stabilization and survival. Sixty boys undergoing HCT for cALD from 2000 to 2009 were analyzed. The median age at HCT was 8.7 years; conditioning regimens and allograft sources varied. At HCT, 50% demonstrated a Loes radiographic severity score ≥ 10, and 62% showed clinical evidence of neurologic dysfunction. A total of 78% (n = 47) are alive at a median 3.7 years after HCT. The estimate of 5-year survival for boys with Loes score < 10 at HCT was 89%, whereas that for boys with Loes score ≥ 10 was 60% (P = .03). The 5-year survival estimate for boys absent of clinical cerebral disease at HCT was 91%, whereas that for boys with neurologic dysfunction was 66% (P = .08). The cumulative incidence of transplantation-related mortality at day 100 was 8%. Post-transplantation progression of neurologic dysfunction depended significantly on the pre-HCT Loes score and clinical neurologic status. We describe the largest single-institution analysis of survival and neurologic function outcomes after HCT in cALD. These trials were registered at www.clinicaltrials.gov as #NCT00176904, #NCT00668564, and #NCT00383448.

Primary Outcome Measures is Number of Patients Achieving Engraftment; Extracted Interventionsis is Stem Cell Transplantation Cyclophosphamide Campath-1H Busulfan; Conditions is Hurler's Syndrome|Maroteaux-Lamy Syndrome|Sly Syndrome|Alpha Mannosidosis|Fucosidosis|Aspartylglucosaminuria|Sphingolipidoses|Krabbe Disease|Wolman's Disease|Niemann-Pick Disease Type B|Niemann-Pick Disease, Type C ;Sex is ALL ;Age is CHILD, ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Immunogenicity of a combination vaccine containing diphtheria toxoid, tetanus toxoid, three-component acellular pertussis, hepatitis B, inactivated polio virus, and Haemophilus influenzae type b when given concomitantly with 13-valent pneumococcal conjugate vaccine.Two randomized trials of 13-valent pneumococcal conjugate vaccine (PCV13) relative to PCV7 evaluated the immune responses of coadministered antigens comprising Infanrix(®) hexa/Infanrix(®)-IPV+Hib (diphtheria, tetanus, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b). After the 3-dose infant series, immunogenic noninferiority was demonstrated for all concomitantly administered antigens between the PCV13 and PCV7 groups. All antigens elicited good booster responses after the toddler dose except pertussis toxoid; however, 99.6% subjects achieved pertussis toxoid protective antibody level ≥5EU/mL in both groups. These results support the concomitant administration of PCV13 and Infanrix hexa/Infanrix-IPV+Hib as part of routine immunization schedules.

Primary Outcome Measures is Percentage of Participants Achieving Predefined Meningococcal C Serum Bactericidal Assay (SBA) Titer of ≥ 1:8; Extracted Interventionsis is 13-valent Pneumococcal Conjugate Vaccine 7-valent Pneumococcal Conjugate Vaccine; Conditions is Vaccines, Pneumococcal ;Sex is ALL ;Age is CHILD

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Phase 1 study of epigenetic priming with decitabine prior to standard induction chemotherapy for patients with AML.We conducted an open-label phase 1 study exploring the feasibility, safety, and biologic activity of epigenetic priming with decitabine before standard induction chemotherapy in patients with less-than-favorable risk of acute myelogenous leukemia (AML). We directly compared the clinical and DNA-hypomethylating activity of decitabine delivered at 20 mg/m² by either a 1-hour infusion (Arm A) or a continuous infusion (Arm B) for 3, 5, or 7 days before a single, standard induction with infusional cytarabine (100 mg/m² for 7 days) and daunorubicin (60 mg/m² × 3 doses). Toxicity was similar to that of standard induction chemotherapy alone. Although we did not identify a maximum tolerated dose, there was more gastro-intestinal toxicity with 7 days of decitabine priming. Decitabine induced DNA hypomethylation at all dose levels and there was a trend toward greater hypomethylation in CD34(+) bone marrow cells when decitabine was delivered by a short pulse (Arm A). Twenty-seven subjects (90%) responded to therapy: 17 with complete remission (57%) and 10 with partial remission (33%). Of the patients with partial remission to protocol treatment, 8 achieved remission to their next therapy, bringing the overall complete remission rate to 83%. We conclude that epigenetic priming of intensive chemotherapy can be safely delivered in an attempt to improve response rates. This trial was registered at www.clinicaltrials.gov as NCT00538876.

Primary Outcome Measures is To establish the safety and expected toxicities of decitabine when used as priming for cytarabine and daunorubicin "7+3" induction chemotherapy in AML; Extracted Interventionsis is decitabine; Conditions is Acute Myeloid Leukemia ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Rapid antidepressant changes with sleep deprivation in major depressive disorder are associated with changes in vascular endothelial growth factor (VEGF): a pilot study.While conventional antidepressants benefit many patients with major depressive disorder (MDD), as much as eight to 12 weeks can elapse before significant improvements in depressive symptoms are seen. Treatments that act more rapidly in MDD are urgently needed. Sleep deprivation (SD) has been shown to produce a rapid antidepressant response within one day in 50-60% of patients with MDD; thus, identifying its antidepressant mechanism may contribute to the development of antidepressants that act more rapidly. The present study evaluated the effects of 39 h of SD on mood, as well as on plasma levels of brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in patients with MDD. After a drug-free period of at least two weeks, 11 patients (6 males, 5 females; ages 25-62) who met DSM-IV criteria for MDD underwent total SD. Plasma samples for BDNF and VEGF assays were collected on Days 1 (baseline) and 2. The six-item Hamilton Rating Scale for Depression (HAMD-6) was the primary outcome measure. HAMD-6 scores decreased significantly after SD (Day 2). SD was negatively correlated with change in HAMD-6 score and change in VEGF levels, indicating that as depression scores decreased following SD, VEGF plasma levels increased. In contrast, SD did not alter plasma BDNF concentrations, nor was an association found between BDNF levels and clinical improvement on the HAMD-6. These results suggest that SD is associated with mood-related changes in plasma VEGF levels, but not plasma BDNF levels. Further studies using larger sample sizes are needed to confirm these preliminary findings.

Primary Outcome Measures is Hamilton Depression Rating Scale (6 Items); Extracted Interventionsis is Yohimbine hydrochloride Placebo; Conditions is Depression, Involutional|Major Depresssion ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Ex vivo production of autologous whole inactivated HIV-1 for clinical use in therapeutic vaccines.This study provides a detailed description and characterization of the preparation of individualized lots of autologous heat inactivated HIV-1 virions used as immunogen in a clinical trial designed to test an autologous dendritic-cell-based therapeutic HIV-1 vaccine (Clinical Trial DCV-2, NCT00402142). For each participant, ex vivo isolation and expansion of primary virus were performed by co-culturing CD4-enriched PBMCs from the HIV-1-infected patient with PBMC from HIV-seronegative unrelated healthy volunteer donors. The viral supernatants were heat-inactivated and concentrated to obtain 1 mL of autologous immunogen, which was used to load autologous dendritic cells of each patient. High sequence homology was found between the inactivated virus immunogen and the HIV-1 circulating in plasma at the time of HIV-1 isolation. Immunogens contained up to 10⁹ HIV-1 RNA copies/mL showed considerably reduced infectivity after heat inactivation (median of 5.6 log₁₀), and were free of specified adventitious agents. The production of individualized lots of immunogen based on autologous inactivated HIV-1 virus fulfilling clinical-grade good manufacturing practice proved to be feasible, consistent with predetermined specifications, and safe for use in a clinical trial designed to test autologous dendritic cell-based therapeutic HIV-1 vaccine.

Primary Outcome Measures is Comparison of steady state viremia (so-called viral set point) after 6-12 months after vaccination with viremia before HAART.; Extracted Interventionsis is Dendritic cell vaccine non pulsed dendritic cell untreated patients pulsed dendritic cell vaccine dendritic cell vaccine non pulsed dendritic cell vaccine; Conditions is HIV Infections ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Ticagrelor compared with clopidogrel by geographic region in the Platelet Inhibition and Patient Outcomes (PLATO) trial.Background:In the Platelet Inhibition and Patient Outcomes (PLATO) trial, a prespecified subgroup analysis showed a significant interaction between treatment and region (P=0.045), with less effect of ticagrelor in North America than in the rest of the world.Methods and results:Reasons for the interaction were explored independently by 2 statistical groups. Systematic errors in trial conduct were investigated. Statistical approaches evaluated the likelihood of play of chance. Cox regression analyses were performed to quantify how much of the regional interaction could be explained by patient characteristics and concomitant treatments, including aspirin maintenance therapy. Landmark Cox regressions at 8 time points evaluated the association of selected factors, including aspirin dose, with outcomes by treatment. Systematic errors in trial conduct were ruled out. Given the large number of subgroup analyses performed and that a result numerically favoring clopidogrel in at least 1 of the 4 prespecified regions could occur with 32% probability, chance alone cannot be ruled out. More patients in the United States (53.6%) than in the rest of the world (1.7%) took a median aspirin dose ≥300 mg/d. Of 37 baseline and postrandomization factors explored, only aspirin dose explained a substantial fraction of the regional interaction. In adjusted analyses, both Cox regression with median maintenance dose and landmark techniques showed that, in patients taking low-dose maintenance aspirin, ticagrelor was associated with better outcomes compared with clopidogrel, with statistical superiority in the rest of the world and similar outcomes in the US cohort.Conclusions:The regional interaction could arise from chance alone. Results of 2 independently performed analyses identified an underlying statistical interaction with aspirin maintenance dose as a possible explanation for the regional difference. The lowest risk of cardiovascular death, myocardial infarction, or stroke with ticagrelor compared with clopidogrel is associated with a low maintenance dose of concomitant aspirin.Clinical trial registration:URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Primary Outcome Measures is Participants With Any Event From the Composite of Death From Vascular Causes; Extracted Interventionsis is Ticagrelor Clopidogrel; Conditions is Acute Coronary Syndrome ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Results of the Randomized Aldosterone Antagonism in Heart Failure with Preserved Ejection Fraction trial (RAAM-PEF).Background:Cardiac fibrosis is a major determinant of myocardial stiffness, diastolic dysfunction, and heart failure (HF). By reducing cardiac fibrosis, aldosterone antagonists have the potential to be beneficial in heart failure with preserved ejection fraction (HFpEF).Methods and results:In a randomized, double-blind, placebo-controlled trial of 44 patients with HFpEF, we examined the effects of eplerenone, an aldosterone antagonist, on changes in 6-minute walk distance (primary end point), diastolic function, and biomarkers of collagen turnover (secondary end points). All patients had a history of hypertension, 61% were diabetic, and 52% had prior HF hospitalization. After 6 months of treatment, similar improvements in 6 minute walk distance were noted in the eplerenone and placebo groups (P = .91). However, compared with placebo, eplerenone was associated with a significant reduction in serum markers of collagen turnover (procollagen type I aminoterminal peptide, P = .009 and carboxy-terminal telopeptide of collagen type I, P = .026) and improvement in echocardiographic measures of diastolic function (E/E', P = .01).Conclusions:Although eplerenone was not associated with an improvement in exercise capacity compared to placebo, it was associated with significant reduction in markers of collagen turnover and improvement in diastolic function. Whether these favorable effects will translate into morbidity and mortality benefit in HFpEF remains to be determined.

Primary Outcome Measures is Change in Six Minute Walk Distance from baseline to 24 weeks after randomization; Extracted Interventionsis is Eplerenone Placebo; Conditions is Congestive Heart Failure|Diastole ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Teletransmitted monitoring of blood pressure and bilingual nurse counseling-sustained improvements in blood pressure control during 12 months in hypertensive Korean Americans.This paper reports the results of a clinical investigation to determine the sustainability of intervention effects to lower blood pressure (BP) that were obtained through a short-term education via home telemonitoring of BP and regular counseling by bilingual nurses during 1 year. A total of 359 middle-aged (40-64 years) Korean immigrants completed a 15-month intervention that consisted of 6-week behavioral education followed by home telemonitoring of BP and bilingual nurse telephone counseling for 12 months. The final analysis revealed a sharp increase in BP control rates sustained for more than 12 months. At baseline, only 30% of the sample achieved BP control (<140/90 mm Hg). After the initial education period (approximately 3 months), 73.3% of the participants had controlled BP levels. The levels of control were maintained and continuously improved during a 12-month follow-up period (83.2%, P<.001). These findings suggest that home telemonitoring of BP and tailored counseling are both useful tools to sustain or improve short-term education effects.

Primary Outcome Measures is Blood Pressure; Extracted Interventionsis is Self-Help Intervention Program-High Blood Pressure; Conditions is High Blood Pressure ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Improvement in pregnancy rate by removal of cervical discharge prior to embryo transfer in ICSI cycles: a randomised clinical trial.Aims:The present study aimed to evaluate the effect of removing cervical discharge prior to embryo transfer (ET) on pregnancy rates.Methods:Five hundred and thirty women who were candidates for fresh ET in intracytoplasmic sperm injection (ICSI) cycles were randomly allocated to intervention or control groups. In the intervention group, the cervical canal was cleansed using sterile cotton swabs prior to ET. The control group had routine ET. Multiple logistic regression analysis was used to estimate the adjusted effect of removing the cervical discharge on pregnancy rates.Results:There was a significant difference in pregnancy rates between the two groups. The clinical pregnancy rate was 104/265 (39.2%) in the intervention group compared with 60/265 (22.6%) in the control group (P<0.001). The intervention group also had a higher implantation rate (20.5%) compared with the control group (12.2%; P<0.001). Additionally, the live birth rate in the intervention group (33.6%) was significantly higher than in the control group (17.4%; P<0.001). The logistic regression analysis indicated that the odds ratio of pregnancy in the intervention group was 2.297 (95% CI, 1.552-3.399) compared with the control group.Conclusions:Removal of cervical discharge prior to ET may have a significant effect on the rate of implantation, pregnancy and live birth.

Primary Outcome Measures is Pregnancy rate; Extracted Interventionsis is Cervical discharge removal control; Conditions is Infertility ;Sex is FEMALE ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Suicide attempts and nonsuicidal self-injury in the treatment of resistant depression in adolescents: findings from the TORDIA study.Objective:To evaluate the clinical and prognostic significance of suicide attempts (SAs) and nonsuicidal self-injury (NSSI) in adolescents with treatment-resistant depression.Method:Depressed adolescents who did not improve with an adequate SSRI trial (N = 334) were randomized to a medication switch (SSRI or venlafaxine), with or without cognitive-behavioral therapy. NSSI and SAs were assessed at baseline and throughout the 24-week treatment period.Results:Of the youths, 47.4% reported a history of self-injurious behavior at baseline: 23.9% NSSI alone, 14% NSSI+SAs, and 9.5% SAs alone. The 24-week incidence rates of SAs and NSSI were 7% and 11%, respectively; these rates were highest among youths with NSSI+SAs at baseline. NSSI history predicted both incident SAs (hazard ratio [HR]= 5.28, 95% confidence interval [CI] = 1.80-15.47, z = 3.04, p = .002) and incident NSSI (HR = 7.31, z = 4.19, 95% CI = 2.88-18.54, p < .001) through week 24, and was a stronger predictor of future attempts than a history of SAs (HR = 1.92, 95% CI = 0.81-4.52, z = 2.29, p = .13). In the most parsimonious model predicting time to incident SAs, baseline NSSI history and hopelessness were significant predictors, adjusting for treatment effects. Parallel analyses predicting time to incident NSSI through week 24 identified baseline NSSI history and physical and/or sexual abuse history as significant predictors.Conclusions:NSSI is a common problem among youths with treatment-resistant depression and is a significant predictor of future SAs and NSSI, underscoring the critical need for strategies that target the prevention of both NSSI and suicidal behavior.Clinical trial registration information:Treatment of SSRI-Resistant Depression in Adolescents (TORDIA). URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00018902.

Primary Outcome Measures is nan; Extracted Interventionsis is Fluoxetine Venlafaxine Cognitive Behavioral Therapy (CBT) Citalopram; Conditions is Depression ;Sex is ALL ;Age is CHILD, ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Long-term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: a 5-year open-label extension study.Background:Safety and efficacy of non-ergot dopamine agonists for the treatment of idiopathic restless legs syndrome have been shown in short-term trials. We did a prospective open-label extension of a 6-week, double-blind randomised trial to assess the safety, tolerability, and efficacy of rotigotine transdermal patch for up to 5 years in patients with restless legs syndrome.Methods:Patients (aged 18-75 years) with moderate-to-severe idiopathic restless legs syndrome were treated with once-daily rotigotine transdermal patch in 33 centres in Austria, Germany, and Spain between July 31, 2003, and April 15, 2009. The dose was titrated in weekly increments (up to 4 weeks) from 0·5 mg/24 h to a maximum of 4 mg/24 h, and was followed by up to 5 years of maintenance at the optimum dose. Primary safety outcomes included occurrence of adverse events and dropouts. Efficacy assessments were secondary and included the International Restless Legs Syndrome study group severity rating scale (IRLS). Augmentation of symptoms was assessed by means of standard diagnostic criteria and was confirmed by an international expert panel. All patients who received at least one dose of study drug were included in assessments. This study is registered with ClinicalTrials.gov, number NCT00498186.Findings:295 patients entered the open-label study, of whom 126 (43%) completed 5 years of follow-up. 169 (57%) patients discontinued treatment, 89 (30%) because of adverse events and 31 (11%) because of lack of efficacy. 70 patients (24%) discontinued during year 1 of maintenance. The most common adverse events were application site reactions, which occurred in 37% (106/290) of patients in year 1, 17% (38/220) of patients in year 2, 14% (27/191) of patients in year 3, and in less than 6% of patients during year 4 (8/159) and year 5 (8/147). 56 patients (19%) discontinued because of application site reactions. Mean rotigotine dose was 2·43 mg/24 h (SD 1·21) after initial titration and 3·09 mg/24 h (1·07) at the end of maintenance. Of 89 patients who discontinued because of adverse events, 28 (31%) were on 4 mg/24 h rotigotine. Mean IRLS score of patients entering the open-label study was 27·8 (SD 5·9) at baseline of the double-blind trial. In patients who completed the maintenance period, mean IRLS score was reduced from a baseline score of 27·7 (SD 6·0) by a mean of 18·7 points (SD 9·5) to a score of 9·0 (SD 9·2) at the end of maintenance. 39% (48/123) of patients who completed the trial were classified as symptom free according to the IRLS. Clinically significant augmentation was recorded in 39 patients (13%), of whom 15 (5%) were receiving a dose of rotigotine within the range approved by the European Medicines Agency (EMA; 1-3 mg/24 h) and 24 (8%) were receiving 4 mg/24 h rotigotine.Interpretation:Rotigotine transdermal patch is generally well tolerated after 1 year and provides sustained efficacy for patients with moderate-to-severe restless legs syndrome at a stable dose for up to 5 years. Thus, rotigotine transdermal patch is an appropriate long-term treatment option for moderate-to-severe restless legs syndrome, a disorder that often requires lifelong treatment.Funding:UCB BioSciences, on behalf of Schwarz Pharma, Ireland.

Primary Outcome Measures is Number of Subjects With at Least One Adverse Event; Extracted Interventionsis is Rotigotine; Conditions is Restless Legs Syndrome ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Prevention of menstrual migraine with perimenstrual transdermal 17-β-estradiol: a randomized, placebo-controlled, double-blind crossover study.The effect of treatment with percutaneous E(2) (100 μg/24 h) during 2 weeks perimenstrually on the number and severity of menstrual migraine attacks was studied in 27 women in a randomized, placebo-controlled, double-blind, crossover trial. We were not able to demonstrate any difference between E(2) supplementation and placebo on the number or severity of migraine attacks, but both regimens showed significant effects compared with before treatment. CLINICAL TRIAL IDENTIFICATION NUMBER: NCT00204074.

Primary Outcome Measures is Number of migraine attacks|Severeity of migraine attacks|Analgetics used; Extracted Interventionsis is 17-beta-estradiol (drug); Conditions is Migraine ;Sex is FEMALE ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.A randomized trial of a skin sealant to reduce the risk of incision contamination in cardiac surgery.Background:Immobilizing skin microbes is a rational approach to reducing contamination of surgical sites by endogenous microorganisms.Methods:This randomized, controlled, parallel-group, multicenter, open-label clinical trial (ClinicalTrials.gov NCT00467857) enrolled 300 adults scheduled for elective coronary artery bypass graft surgery. Patients received iodine-based skin preparations followed by a cyanoacrylate-based skin sealant or skin preparations alone. Microbiological samples collected from sternal and graft incision sites immediately before any skin preparation, at the wound border after skin incision, and at the incision after fascial closure were evaluated quantitatively.Results:In evaluable patients, mean microbial counts in collected samples increased at the sternal site after fascial closure compared with after skin incision by 0.37 log10 colony-forming units (CFU)/mL in the skin sealant group (n=120) and by 0.57 log10 CFU/mL in the control group (n=132) (p=0.047, Wilcoxon rank sum test). At the graft site, mean microbial counts increased by 0.09 (n=119) and 0.27 (n=127) log10 CFU/mL, respectively (p=0.037). There was a 35.3% relative risk reduction in surgical site infection (SSI) occurring in the skin sealant group (9 of 146 patients, 6.2%) versus the control group (14 of 147 patients, 9.5%). In obese patients (body mass index [BMI]>30.0 to ≤37.0 kg/m2), the relative risk reduction for SSI associated with skin sealant was 83.3%.Conclusions:Pretreatment with skin sealant protects against contamination of the surgical incision by migration of skin microbes. Further data are needed to confirm the impact of this technology on SSI rates in clinical practice.

Primary Outcome Measures is Change in Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-CABG - Sternal Site; Extracted Interventionsis is InteguSeal* skin sealant and standard surgical preparation Standard preoperative skin preparation; Conditions is Skin Flora Contamination ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.The von Willebrand inhibitor ARC1779 reduces cerebral embolization after carotid endarterectomy: a randomized trial.Background and purpose:Inhibition of von Willebrand factor offers a novel approach to prevention of stroke and myocardial ischemia but has not yet been demonstrated to show efficacy on clinically relevant end points. ARC1779 is an aptamer that inhibits the prothrombotic function of von Willebrand factor by binding to the A1 domain of von Willebrand factor and thereby blocking its interaction with glycoprotein. Phase 1 studies suggest it inhibits platelet aggregation with less increase in bleeding than conventional antiplatelet agents. The effect of ARC 1779 on cerebral emboli immediately after carotid endarterectomy was investigated in a randomized clinical trial.Methods:Patients undergoing carotid endarterectomy were randomized double-blind to ARC1779 or placebo administered intravenously. Transcranial Doppler recording, to detect cerebral embolic signals, was performed in the first 3 hours postoperatively. The primary end point was time to first embolic signals.Results:Thirty-six patients were recruited, 18 in each arm. The Kaplan-Meier median time to first embolic signals was 83.6 minutes for ARC1779 compared with 5.5 minutes for placebo. Using Cox proportional hazards embolic signals occurred statistically significantly later on ARC1779 (P=0.007). Reduced embolic signals counts were correlated with inhibition of von Willebrand factor activity (P=0.03). Increased perioperative bleeding and anemia were seen with ARC1779.Conclusions:von Willebrand factor inhibition reduces thromboembolism in humans. It may play a role in treatment of stroke and myocardial ischemia. The extent to which bleeding complications occur in nonoperated patients needs to be assessed in further studies. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00742612.

Primary Outcome Measures is To determine the effect of ARC1779 Injection on the number of microembolic signals detected by transcranial Doppler (TCD) in the immediate postoperative period; Extracted Interventionsis is ARC1779 Injection Placebo (normal saline); Conditions is Intracranial Embolism|Cerebral Thromboembolism|Carotid Stenosis ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Begin with the real-world patients of non-goal-achieved hypercholesterolemia in taiwan through the ezetimibe/simvastatin tablet - The BRAVO Study.Objective:To assess the efficacy, safety, and tolerability of a combination of 10 mg ezetimibe and 20 mg simvastatin in Taiwanese patients with hypercholesterolemia.Research design and methods:A prospective, open-label, multi-center, hospital-based cohort study was conducted to evaluate the efficacy, safety, and tolerability of a single tablet combination of ezetimibe/simvastatin for the treatment of hypercholesterolemia. Taiwanese adults without low-density lipoprotein cholesterol (LDL-C) goal achievement, based on the National Cholesterol Education Program Adult Treatment Panel III guidelines, were treated with ezetimibe/simvastatin once daily for 6 weeks. The primary endpoint was the percentage of patients achieving LDL-C treatment goals after 6 weeks of treatment. Secondary endpoints included percentage change from baseline of LDL-C, total cholesterol, high-density lipoprotein cholesterol, and triglyceride. Safety and tolerability were assessed via clinical and laboratory examinations. The clinicaltrial.gov identifier of this study was NCT00654628.Results:In total, 173 patients with a mean age of 57.9 ± 10.4 years were included. Of these, 57.8% were female and the average body mass index was 25.5 ± 3.4 kg/m(2). After 6 weeks of treatment, the great majority of the patients had reached their treatment goals (90.4% for LDL-C; 87% for TC; and 59% for TG). LDL-C levels were significantly reduced from 156.8 ± 30.8 mg/dL at baseline to 75.9 ± 25.4 mg/dL (51.4%, P < 0.0001) after only 6 weeks of therapy. Forty-nine adverse events (AEs), including one non-drug related serious AE, were reported. For non-serious AEs, the most common reported AEs during the entire study period were myalgia and upper respiratory infection (both n = 7). Nine patients dropped out of the study, reportedly due to AEs.Conclusions:A single tablet combination of 10 mg ezetimibe and 20 mg simvastatin in Taiwanese patients with hypercholesterolemia provided high LDL-C goal attainment rates and resulted in significant reductions in LDL-C.

Primary Outcome Measures is The Percentage of Participants Achieving Low Density Lipoprotein-C (LDL-C) Treatment Goal After 6-week Treatment.; Extracted Interventionsis is ezetimibe (+) simvastatin; Conditions is Hypercholesterolemia ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Treatment of congenital hyperinsulinism with lanreotide acetate (Somatuline Autogel).Context:Congenital hyperinsulinism (CH) may be treated conservatively in many children with octreotide given by multiple sc injections or via an insulin pump.Objective:We describe two children treated with a once-monthly injection of a long-acting somatostatin analog.Patients and methods:Both patients presented with hypoglycemia 30 min after birth and were subsequently diagnosed with CH. Patients were initially treated with diazoxide, hydrochlorothiazide, frequent feedings, and octreotide via an insulin pump. With this therapy, they were normoglycemic with a good growth rate, normal weight gain, and excellent neurodevelopment. Treatment with the long-acting somatostatin analog lanreotide acetate (Somatuline Autogel), administered by deep sc injection of 30 mg once a month, was started at the ages of 4½ and 4 yr, respectively. Octreotide infusion was gradually weaned over 1 month. Continuous glucose monitoring after discontinuation of pump therapy showed normoglycemia. The first patient has now been treated with the lanreotide acetate for over 5 yr, and the second for 3 yr. Treatment is well-tolerated, and both the patients and their parents are satisfied with the transition from pump therapy to once-a-month injection and prefer it to pump therapy.Conclusion:Lanreotide acetate may be a safe and effective alternative to octreotide pump therapy in patients with CH, offering an improved quality of life. Longer follow-up of a larger patient group is needed.

Primary Outcome Measures is Euglycemia as recorded by Continuous Glucose Monitoring System (CGMS); Extracted Interventionsis is Lanreotide autogel; Conditions is Congenital Hyperinsulinism ;Sex is ALL ;Age is CHILD

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Randomized trial of fortified milk and supplements to raise 25-hydroxyvitamin D concentrations in schoolchildren in Mongolia.Background:The optimal public health strategy for maintaining 25-hydroxyvitamin D [25(OH)D] concentrations in schoolchildren in Mongolia is unknown.Objective:The objective was to compare the effectiveness of different supplement and fortified milk regimens to increase 25(OH)D concentrations in Mongolian schoolchildren.Design:Twenty-one classrooms of 579 children aged 9-11 y were randomized to interventions with an equivalent content of vitamin D(3): 1) a one-time seasonal supplement of 13,700 IU, 2) 300 IU/d from supplements, 3) 300 IU/d from fortified ultra-high-temperature pasteurized milk from the United States, 4) 300 IU/d from fortified pasteurized Mongolian milk, or 5) unfortified pasteurized Mongolian milk (control).Results:In January, the mean (±SD) serum 25(OH)D concentration was 8 ± 4 ng/mL (20 ± 10 nmol/L), and 98% of the children had a concentration <20 ng/mL (50 nmol/L). In March, concentrations were 8 ± 4 ng/mL after unfortified milk, 20 ± 6 ng/mL after fortified Mongolian milk, 29 ± 10 ng/mL after fortified US milk, 21 ± 6 ng/mL after daily supplements, and 12 ± 4 ng/mL after seasonal supplements (each greater than unfortified milk, P < 0.01). Seasonal supplementation was less effective than was daily supplementation (P < 0.0001). Despite consuming daily supplements or fortified milk, 41% of the children still had concentrations <20 ng/mL (50 nmol/L). Children with lower baseline 25(OH)D concentrations experienced slightly larger 25(OH)D responses to intervention than did children with higher concentrations (P = 0.002).Conclusions:In this population with extremely low vitamin D concentrations, delivery of 300 IU vitamin D/d via supplements or in fortified milk improved 25(OH)D concentrations but failed to raise concentrations uniformly to >20 ng/mL (50 nmol/L). The daily low-dose intervention was superior to the seasonal larger-dose intervention. Higher doses may be needed to prevent deficiency in schoolchildren in Mongolia and at other northern latitudes. This trial is registered at clinicaltrials.gov as NCT00886379.

Primary Outcome Measures is Serum 25-hydroxyvitamin D Concentrations in Schoolchildren; Extracted Interventionsis is Mongolian milk without vitamin D Mongolian milk with vitamin D UHT milk Milk Substitute Seasonal D supplement Daily D supplement; Conditions is Vitamin d Deficiency ;Sex is ALL ;Age is CHILD

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Changes in schizophrenia-related hospitalization and ER use among patients receiving paliperidone palmitate: results from a clinical trial with a 52-week open-label extension (OLE).Background:Schizophrenia affects ∼1.1% of the United States population, resulting in substantial direct, indirect and societal costs.Objective:To evaluate hospitalization rates associated with use of paliperidone palmitate (PP).Methods:Data were from a variable-duration double-blind (DB), randomized, relapse-prevention comparison (NCT00111189) of PP vs. placebo (Pbo), followed by a 1-year open-label extension (OLE). Between-phase change in schizophrenia-related hospitalizations was evaluated using data from an investigator-completed questionnaire. Change in hospitalizations using patients before enrollment who participated in the OLE phase was also analyzed. Poisson regression was used to evaluate changes in incidence density within exposure category and by schizophrenia duration.Results:A total of 160 patients in the PP-PP group and 153 in the Pbo-PP group from the DB to the OLE phase were included. Mean age (standard deviation [SD]), gender, and duration of schizophrenia were similar at the start of the DB phase (Pbo: 38.5 years [10.6], 51.0% male, 68.0% ≥5 years' duration; PP: 37.3 years [11.4] (p = 0.342); 51.9% male (p = 0.874); 70.0% ≥5 years' duration (p = 0.698), respectively. From the DB to the end of the OLE phase, the number of hospitalizations per person-year for patients treated during the DB phase with Pbo significantly declined from 0.27 to 0.06 (78% reduction; p = 0.005). A statistically nonsignificant difference was observed for PP patients treated during the DB phase with PP (0.11-0.04; 63.6% reduction; p = 0.076), compared with the OLE phase. Change from before enrollment to the end of the OLE phase (n = 381) produced similar results (0.35-0.04; 88.6% reduction; p < 0.001). Patients who enroll in a clinical trial may be different from the general population and this may affect the generalizability of results.Conclusion:From the double-blind to the open-label phase and from prior to the trial until the end of the open-label phase, hospitalizations significantly decreased for patients with schizophrenia treated with PP.

Primary Outcome Measures is The primary efficacy criteria for this study is the time from randomization to the first recurrence event during the double-blind recurrence prevention period; Extracted Interventionsis is Placebo Paliperidone Palmitate; Conditions is Schizophrenia ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Paraoxonase-1 Q192R polymorphism and antiplatelet effects of clopidogrel in patients undergoing elective coronary stent placement.Background:Recently published data indicate that the paraoxonase-1 (PON1) Q192R genotype-and not as previously shown activity of cytochrome P450 (CYP) 2C19-is the major determinant of metabolic bioactivation of clopidogrel and thereby variability of antiplatelet effect of clopidogrel. We sought to investigate whether the PON1 Q192R gene polymorphism affects platelet reactivity in patients undergoing elective coronary stent placement.Methods and results:The study included 760 consecutive patients undergoing elective coronary stent placement after loading with clopidogrel 600 mg. Platelet function was assessed by adenosine diphosphate-induced (ADP 5 and 20 μmol/L) platelet aggregation and by flow-cytometric analysis of platelet surface protein expression before clopidogrel, at the time of coronary stent placement, and before discharge after coronary stent placement. PON1 Q192R genotype [NM_000446.5:c.575A>G single nucleotide polymorphism (rs662)] was analyzed by TaqMan polymerase chain reaction. Residual platelet aggregation (ADP 5 μmol/L) at predischarge was 8.0% (3.0% to 17.0%) [median (interquartile range)] in PON1 QQ192 patients (n=384), 8.0% (3.0% to 15.0%) in PON1 QR192 (n=304), and 11.0% (3.0% to 18.0%) in PON1 RR192 (n=72; P=0.603). By multivariable linear regression, residual platelet aggregation was not associated with PON1 QQ192/QR192 (partial η(2)<0.001, P=0.728) but with CYP2C19*2 loss-of-function allele (partial η(2)=0.045, P<0.001) as well as any CYP2C19*17 gain-of-function allele (partial η(2)=0.012, P=0.004). All other platelet assays also showed no significant association between PON1 Q192R genotype and antiplatelet effect of clopidogrel. The 1-year incidence of death and myocardial infarction did not differ between PON1 Q192R genotypes.Conclusions:On-treatment platelet reactivity in patients undergoing coronary stent placement after loading with clopidogrel 600 mg was not associated with PON1 Q192R genotype.Clinical trial registration:URL: http://www.clinicaltrials.gov. Unique identifier: NCT00457236.

Primary Outcome Measures is nan; Extracted Interventionsis is nan; Conditions is Coronary Artery Disease|Drug Resistance ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Baseline urodynamic predictors of treatment failure 1 year after mid urethral sling surgery.Purpose:We determined whether baseline urodynamic study variables predict failure after mid urethral sling surgery.Materials and methods:Preoperative urodynamic study variables and postoperative continence status were analyzed in women participating in a randomized trial comparing retropubic to transobturator mid urethral sling. Objective failure was defined by positive standardized stress test, 15 ml or greater on 24-hour pad test, or re-treatment for stress urinary incontinence. Subjective failure criteria were self-reported stress symptoms, leakage on 3-day diary or re-treatment for stress urinary incontinence. Logistic regression was used to assess associations between covariates and failure controlling for treatment group and clinical variables. Receiver operator curves were constructed for relationships between objective failure and measures of urethral function.Results:Objective continence outcomes were available at 12 months for 565 of 597 (95%) women. Treatment failed in 260 women (245 by subjective criteria, 124 by objective criteria). No urodynamic variable was significantly associated with subjective failure on multivariate analysis. Valsalva leak point pressure, maximum urethral closure pressure and urodynamic stress incontinence were the only urodynamic variables consistently associated with objective failure on multivariate analysis. No specific cut point was determined for predicting failure for Valsalva leak point pressure or maximum urethral closure pressure by ROC. The lowest quartile (Valsalva leak point pressure less than 86 cm H2O, maximum urethral closure pressure less than 45 cm H2O) conferred an almost 2-fold increased odds of objective failure regardless of sling route (OR 2.23, 1.20-4.14 for Valsalva leak point pressure and OR 1.88, 1.04-3.41 for maximum urethral closure pressure).Conclusions:Women with a Valsalva leak point pressure or maximum urethral closure pressure in the lowest quartile are nearly 2-fold more likely to experience stress urinary incontinence 1 year after transobturator or retropubic mid urethral sling.

Primary Outcome Measures is Objective Treatment Success at 12 Months; Extracted Interventionsis is retropubic mid-urethral sling (TVT) transobturator mid-urethral sling (TVT-O and the Monarc); Conditions is Urinary Incontinence ;Sex is FEMALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effects of vestibular rehabilitation on multiple sclerosis-related fatigue and upright postural control: a randomized controlled trial.Background:Fatigue and impaired upright postural control (balance) are the 2 most common findings in people with multiple sclerosis (MS), with treatment approaches varying greatly in effectiveness.Objectives:The aim of this study was to investigate the benefits of implementing a vestibular rehabilitation program for the purpose of decreasing fatigue and improving balance in patients with MS.Design:The study was a 14-week, single-blinded, stratified blocked randomized controlled trial.Setting:Measurements were conducted in an outpatient clinical setting, and interventions were performed in a human performance laboratory.Patients:Thirty-eight patients with MS were randomly assigned to an experimental group, an exercise control group, or a wait-listed control group.Intervention:The experimental group underwent vestibular rehabilitation, the exercise control group underwent bicycle endurance and stretching exercises, and the wait-listed control group received usual medical care.Measurements:Primary measures were a measure of fatigue (Modified Fatigue Impact Scale), a measure of balance (posturography), and a measure of walking (Six-Minute Walk Test). Secondary measures were a measure of disability due to dizziness or disequilibrium (Dizziness Handicap Inventory) and a measure of depression (Beck Depression Inventory-II).Results:Following intervention, the experimental group had greater improvements in fatigue, balance, and disability due to dizziness or disequilibrium compared with the exercise control group and the wait-listed control group. These results changed minimally at the 4-week follow-up. Limitations The study was limited by the small sample size. Further investigations are needed to determine the underlying mechanisms associated with the changes in the outcome measures due to the vestibular rehabilitation program.Conclusion:A 6-week vestibular rehabilitation program demonstrated both statistically significant and clinically relevant change in fatigue, impaired balance, and disability due to dizziness or disequilibrium in patients with MS.

Primary Outcome Measures is Self-reported fatigue; Extracted Interventionsis is Exercise Exercise; Conditions is Multiple Sclerosis|Fatigue|Balance|Dizziness ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of computer-generated tailored feedback on glycemic control in people with diabetes in the community: a randomized controlled trial.Objective:It is unknown whether computer-generated, patient-tailored feedback leads to improvements in glycemic control in people with type 2 diabetes.Research design and methods:We recruited people with type 2 diabetes aged ≥ 40 years with a glycated hemoglobin (A1C) ≥ 7%, living in Hamilton, Canada, who were enrolled in a community-based program (Diabetes Hamilton) that provided regular evidence-based information and listings of community resources designed to facilitate diabetes self-management. After completing a questionnaire, participants were randomly allocated to either receive or not receive periodic computer-generated, evidence-based feedback on the basis of their questionnaire responses and designed to facilitate improved glycemic control and diabetes self-management. The primary outcome was a change in A1C after 1 year.Results:A total of 465 participants (50% women, mean age 62 years, and mean A1C 7.83%) were randomly assigned, and 12-month A1C values were available in 96% of all participants, at which time the A1C level had decreased by an absolute amount of 0.24 and 0.15% in the intervention and control groups, respectively. The difference in A1C reduction for the intervention versus control group was 0.09% (95% CI -0.08 to 0.26; P = 0.3). No between-group differences in measures of quality of life, diabetes self-management behaviors, or clinical outcomes were observed.Conclusions:Providing computer-generated tailored feedback to registrants of a generic, community-based program that supports diabetes self-management does not lead to lower A1C levels or a better quality of life than participation in the community-based program (augmented by periodic A1C testing) alone.

Primary Outcome Measures is A1c; Extracted Interventionsis is personal feedback report; Conditions is Diabetes Mellitus, Type 2 ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Durability of radiofrequency ablation in Barrett's esophagus with dysplasia.Background & aims:Radiofrequency ablation (RFA) can eradicate dysplasia and intestinal metaplasia in patients with dysplastic Barrett's esophagus (BE), and reduce rates of esophageal adenocarcinoma. We assessed long-term rates of eradication, durability of neosquamous epithelium, disease progression, and safety of RFA in patients with dysplastic BE.Methods:We performed a randomized trial of 127 subjects with dysplastic BE; after cross-over subjects were included, 119 received RFA. Subjects were followed for a mean time of 3.05 years; the study was extended to 5 years for patients with eradication of intestinal metaplasia at 2 years. Outcomes included eradication of dysplasia or intestinal metaplasia after 2 and 3 years, durability of response, disease progression, and adverse events.Results:After 2 years, 101 of 106 patients had complete eradication of all dysplasia (95%) and 99 of 106 had eradication of intestinal metaplasia (93%). After 2 years, among subjects with initial low-grade dysplasia, all dysplasia was eradicated in 51 of 52 (98%) and intestinal metaplasia was eradicated in 51 of 52 (98%); among subjects with initial high-grade dysplasia, all dysplasia was eradicated in 50 of 54 (93%) and intestinal metaplasia was eradicated in 48 of 54 (89%). After 3 years, dysplasia was eradicated in 55 of 56 of subjects (98%) and intestinal metaplasia was eradicated in 51 of 56 (91%). Kaplan-Meier analysis showed that dysplasia remained eradicated in >85% of patients and intestinal metaplasia in >75%, without maintenance RFA. Serious adverse events occurred in 4 of 119 subjects (3.4%); the rate of stricture was 7.6%. The rate of esophageal adenocarcinoma was 1 per 181 patient-years (0.55%/patient-years); there was no cancer-related morbidity or mortality. The annual rate of any neoplastic progression was 1 per 73 patient-years (1.37%/patient-years).Conclusions:In subjects with dysplastic BE, RFA therapy has an acceptable safety profile, is durable, and is associated with a low rate of disease progression, for up to 3 years.

Primary Outcome Measures is The % of Patients With Complete Eradication of Intestinal Metaplasia (IM) at 12 Month; Extracted Interventionsis is Ablation System plus anti-secretory medication Sham procedure plus anti-secretory medication; Conditions is Barrett Esophagus ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.The effects of L-arabinose on intestinal sucrase activity: dose-response studies in vitro and in humans.Background:On the basis of results in cell cultures, rodents, and pigs, l-arabinose may inhibit intestinal sucrase activity and thereby delay sucrose digestion.Objective:The objective was to investigate the dose-response effects of l-arabinose on intestinal sucrase activity in vitro and glucose tolerance, appetite, and energy intake in humans.Design:In vitro, Caco-2 cells were cultured for 21 d, homogenized, and used as an enzyme preparation with sucrose as substrate in concentrations from 7 to 280 mmol/L with 0.84, 1.4, and 2.8 mmol l-arabinose/L as inhibitor. Released glucose was measured after 30 min. In the human studies, 15 healthy men participated in a randomized, double-blind, crossover study. Sucrose beverages (75 g in 300 mL) supplemented with 0%, 1.3%, 2.7%, and 4% by weight of l-arabinose were tested at breakfast. Blood for the measurement of glucose, insulin, C-peptide, incretin hormones, and triacylglycerol was collected under fasting conditions and for 3 h postprandially. Postprandial appetite sensations and energy intake at lunch were registered.Results:In vitro, the addition of l-arabinose resulted in uncompetitive inhibition of sucrase activity. In the human studies, supplementation with 4% l-arabinose produced an 11% lower glucose peak, a 33% lower and delayed insulin peak, a 23% reduction in the incremental area under the curve (iAUC) for insulin, a 23% lower and delayed C-peptide peak, a 9% reduction in the iAUC for C-peptide, a 53% increase in the iAUC for glucagon-like peptide-1 (GLP-1), and a 28% reduction in the iAUC for glucose-dependent insulinotropic polypeptide. No effects on triacylglycerol, gastrointestinal symptoms, appetite ratings, or energy intake were observed.Conclusions:l-Arabinose inhibits sucrase activity from Caco-2 cells; 4% l-arabinose in sucrose beverages reduces postprandial glucose, insulin, and C-peptide responses and enhances the GLP-1 response in humans without gastrointestinal adverse effects. This trial is registered at clinicaltrials.gov as NCT00302302.

Primary Outcome Measures is Plasma glucose; Extracted Interventionsis is L-arabinose; Conditions is Blood Glucose ;Sex is MALE ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Variations in circulating inflammatory factors are related to changes in calorie and carbohydrate intakes early in the course of surgery-induced weight reduction.Background:Obesity is considered a low-grade inflammatory state that improves with weight loss. In addition to acute-phase proteins, other cytokines might contribute to systemic inflammation.Objective:Our objective was to compare serum concentrations of a large panel of inflammation-related factors in obese and normal-weight subjects and to determine kinetic changes induced by caloric restriction.Design:The cohort comprised 14 normal-weight women and 51 obese women who were followed over 2 y after Roux-en-Y gastric bypass. Multiplexed proteomics were used to simultaneously assay 27 cytokines and growth factors in serum.Results:Concentrations of interleukin (IL)-9, IL-1-receptor antagonist, IL-10, interferon-γ-inducible protein 10, macrophage inflammatory protein 1β, monocyte chemoattractant protein 1, IL-8, RANTES (regulated upon activation, normal T cell expressed and secreted), monokine induced by interferon-γ, and vascular endothelial growth factor were found to be elevated in obesity. IL-10 was further elevated in diabetic obese patients, whereas eotaxin was found to be higher only in diabetic subjects. After surgery, many factors showed a biphasic pattern of variation, decreasing sharply at month 3 before rising back to presurgical values at month 6; these changes closely tracked similar kinetic changes in calorie and carbohydrate intake. After 1 y, an overall reduction in cytokines accompanied the reduction in body mass index and an amelioration in metabolic status.Conclusions:Obesity is associated with elevated circulating concentrations of a large panel of cytokines. Coordinated kinetic changes during weight loss suggest an early influence of calorie and carbohydrate intakes, whereas a longer-term reduction in corpulence might prevail in regulating circulating cytokine concentrations. This trial is registered at clincaltrials.gov as NCT00476658.

Primary Outcome Measures is nan; Extracted Interventionsis is nan; Conditions is Obesity|Diabetes ;Sex is ALL ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Low to moderate sugar-sweetened beverage consumption impairs glucose and lipid metabolism and promotes inflammation in healthy young men: a randomized controlled trial.Background:Sugar-sweetened beverages (SSBs) have unfavorable effects on glucose and lipid metabolism if consumed in high quantities by obese subjects, but the effect of lower doses in normal-weight subjects is less clear.Objective:The aim was to investigate the effects of SSBs consumed in small to moderate quantities for 3 wk on LDL particle distribution and on other parameters of glucose and lipid metabolism as well as on inflammatory markers in healthy young men.Design:Twenty-nine subjects were studied in a prospective, randomized, controlled crossover trial. Six 3-wk interventions were assigned in random order as follows: 600 mL SSBs containing 1)40 g fructose/d [medium fructose (MF)], 2) 80 g fructose/d [high fructose (HF)], 3) 40 g glucose/d [medium glucose (MG)], 4) 80 g glucose/d [high glucose (HG)], 5) 80 g sucrose/d [high sucrose (HS)], or 6) dietary advice to consume low amounts of fructose. Outcome parameters were measured at baseline and after each intervention.Results:LDL particle size was reduced after HF by -0.51 nm (95% CI: -0.19, -0.82 nm) and after HS by -0.43 nm (95% CI: -0.12, -0.74; P < 0.05 for both). Similarly, a more atherogenic LDL subclass distribution was seen when fructose-containing SSBs were consumed (MF, HF, and HS: P < 0.05). Fasting glucose and high-sensitivity C-reactive protein (hs-CRP) increased significantly after all interventions (by 4-9% and 60-109%, respectively; P < 0.05); leptin increased during interventions with SSBs containing glucose only (MG and HG: P < 0.05).Conclusion:The present data show potentially harmful effects of low to moderate consumption of SSBs on markers of cardiovascular risk such as LDL particles, fasting glucose, and hs-CRP within just 3 wk in healthy young men, which is of particular significance for young consumers. This trial was registered at clinicaltrials.gov as NCT01021969.

Primary Outcome Measures is LDL size; Extracted Interventionsis is Fructose; Conditions is Healthy ;Sex is MALE ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Divergent effects of a combined hormonal oral contraceptive on insulin sensitivity in lean versus obese women.Objective:To evaluate the effects of a commonly used combined hormonal oral contraceptive (OC) on carbohydrate metabolism in obese as compared with lean women.Design:6-month prospective study.Setting:Clinical research center at an academic medical center.Patient(s):Premenopausal nondiabetic women with body mass index <25 kg/m(2) (n = 15) or >30 kg/m(2) (n = 14).Intervention(s):Ethinyl estradiol (35 μg) and norgestimate (0.18/0.215/0.25 mg) for 6 cycles.Main outcome measure(s):Insulin sensitivity by frequent sampling intravenous glucose tolerance test; other indices of insulin sensitivity (homeostatic model assessment of insulin sensitivity index [ISI HOMA], the Matsuda index); fasting lipid panel.Result(s):Insulin sensitivity changed from 6.62 ± 3.69 min(-1)/mIU/L (baseline) to 8.23 ± 3.30 min(-1)/mIU/L (6 months) in lean women, and from 4.36 ± 2.32 to 3.82 ± 2.32 min(-1)/mIU/L in obese women. Divergent effects on insulin sensitivity were also observed with ISI HOMA and the Matsuda index. Low-density lipoprotein increased by approximately 20 mg/dL in both the lean and obese groups.Conclusion(s):Lean and obese women exhibit differential changes in insulin sensitivity when given 6 months of a commonly used oral contraceptive. The mechanisms of these differences and whether these divergent effects persist in the long term require further investigation.

Primary Outcome Measures is Changes in Insulin Sensitivity Associated With Oral Contraceptive (OC) Use Compared Among (1) Obese Women and (2) Lean Women; Extracted Interventionsis is Ortho Tri Cyclen; Conditions is Metabolic Syndrome X|Insulin Resistance|Obesity|Cardiovascular Diseases ;Sex is FEMALE ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Acupuncture for the treatment of major depressive disorder: a randomized controlled trial.Background:Over 50% of patients with major depressive disorder (MDD) either do not tolerate or do not respond to antidepressant medications. Several preliminary studies have shown the benefits of acupuncture in the treatment of depression. We sought to determine whether a 2-point electroacupuncture protocol (verum acupuncture) would be beneficial for MDD, in comparison to needling at nonchannel scalp points with sham electrostimulation (control acupuncture).Method:Fifty-three subjects aged 18-80 years, recruited via advertisement or referral, were included in the primary analysis of our randomized controlled trial, which was conducted from March 2004 through May 2007 at UPMC Shadyside, Center for Complementary Medicine, in Pittsburgh, Pennsylvania. Inclusion criteria were mild or moderate MDD (according to the Structured Clinical Interview for DSM-IV Axis I Disorders) and a score of 14 or higher on the Hamilton Depression Rating Scale (HDRS). Exclusion criteria included severe MDD, seizure disorder or risk for seizure disorder, psychosis, bipolar disorder, chronic MDD, treatment-resistent MDD, and history of substance abuse in the prior 6 months. Patients were randomized to receive twelve 30-minute sessions of verum versus control acupuncture over 6 to 8 weeks. The HDRS was the primary outcome measure. The UKU Side Effect Rating Scale was used to assess for adverse effects.Results:Twenty-eight subjects were randomized to verum electroacupuncture and 25 to control acupuncture. The 2 groups did not differ with regard to gender, age, or baseline severity of depression. Both groups improved, with mean (SD) absolute HDRS score decreases of -6.6 (5.9) in the verum group and -7.6 (6.6) in the control group, corresponding to 37.5% and 41.3% relative decreases from baseline. There were no serious adverse events associated with either intervention, and endorsement of adverse effects was similar in the 2 groups.Conclusions:We were unable to demonstrate a specific effect of electroacupuncture. Electroacupuncture and control acupuncture were equally well tolerated, and both resulted in similar absolute and relative improvement in depressive symptoms as measured by the HDRS.Trial registration:clinicaltrials.gov Identifier: NCT00071110.

Primary Outcome Measures is Antidepressant Response; Extracted Interventionsis is Electroacupuncture Sham; Conditions is Depression|Depressive Disorder ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effects of alagebrium, an advanced glycation endproduct breaker, on exercise tolerance and cardiac function in patients with chronic heart failure.Aims:Advanced glycation endproducts (AGEs) have been associated with the development and progression of chronic heart failure (CHF). Advanced glycation endproducts-crosslink breakers might be of benefit in HF, but only small-scale and uncontrolled data are available. Our aim was to conduct a prospective, randomized, double-blind, placebo-controlled study to examine the effects of the AGE-breaker alagebrium on exercise capacity and cardiac function in patients with HF.Methods and results:One hundred and two patients with HF (78% male, aged 62 ± 11 years), and a left ventricular ejection fraction (LVEF) ≤0.45, were randomized to either 200 mg alagebrium twice daily or placebo. After 36 weeks, the primary efficacy end-point peak VO(2) had changed by (mean ± SEM) -2.1 ± 0.5 mL/min/kg in alagebrium vs. -0.5 ± 0.7 mL/min/kg in placebo-treated patients (P= 0.06). No significant changes were observed in a number of secondary end-points, including diastolic function (mean E': P= 0.32; E/E': P= 0.81), systolic function (LVEF: P= 0.43), AGE accumulation (skin-autofluorescence: P= 0.42), N-terminal pro brain natriuretic peptide, P= 0.20); New York Heart Association functional class (P= 0.73), patient global assessment (P= 0.32), physicians global assessment (P= 0.76), and the Minnesota Living with Heart Failure Questionnaire score (P= 0.38). Overall alagebrium was reasonably well tolerated.Conclusion:In the present proof-of-concept study, the AGE-breaker alagebrium did not improve exercise tolerance in patients with HF and systolic dysfunction, and no changes were observed in a number of secondary endpoints. The present data therefore do not support earlier data which suggested a beneficial effect of alagebrium in systolic HF.Clinical trial registration information:NCT00516646 (http://clinicaltrials.gov).

Primary Outcome Measures is The primary end-point of the study will be aerobic capacity (VO2max) measured at exercise testing; Extracted Interventionsis is ALT-711 Placebo; Conditions is Heart Failure ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.The effect of modified quarter laser-assisted zona thinning on the implantation rate per embryo in frozen/vitrified-thawed/warmed embryo transfer cycles: a prospective randomized controlled trial.Background:Freezing/vitrifying and thawing/warming of embryos may impair the successful hatching process of the embryo out of its zona pellucida (ZP) and its following implantation into the uterus. Theoretically, assisted hatching (AH) may facilitate the hatching process and subsequently increase implantation rates (IRs).Methods:In this prospective randomized controlled trial (RCT), the hypothesis was tested that the IR per embryo transferred is higher after transfer (ET) of frozen/vitrified-thawed/warmed embryos with thinned ZP after AH by modified quarter laser-assisted zona thinning (mQLAZT) when compared with ET of frozen/vitrified-thawed/warmed embryos without mQLAZT. Patients with frozen/vitrified embryos were randomized at the time of thawing/warming to a study group (with mQLAZT) or a control group (without mQLAZT). After thawing/warming, embryos were kept in culture for 24h, and mQLAZT was performed prior to ET.Results:A total of 647 thawing cycles were randomized to either the mQLAZT group (n = 324) or the control group (n = 323). Reproductive outcome data were available for 302 cycles in the mQLAZT group and 317 cycles in the control group. Transfer could be performed in 73.5% and in 71.9% of the thawing/warming cycles in the mQLAZT group and the control group (P = 0.78), respectively. No significant differences were observed between the mQLAZT group and the control group for the IR [13.3%; 15.6%; rate ratio 0.85; 95% confidence interval (CI), 0.596-1.224], the ongoing IR (10.5 and 13.5%, P = 0.25) and the live birth rate [10.5%;13.3%; rate ratio 0.79; (95% CI), 0.530-1.189] per embryo transferred.Conclusions:In this RCT, mQLAZT did not improve the IR per embryo transferred in frozen/vitrified-thawed/warmed embryo transfer cycles. ClinicalTrials.govID NCT00593775.

Primary Outcome Measures is clinical implantation rate per embryo transferred; Extracted Interventionsis is assisted hatching; Conditions is Placenta; Implantation ;Sex is ALL ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.First clinical trial of nitinol self-expanding everolimus-eluting stent implantation for peripheral arterial occlusive disease.Background:A novel self-expanding drug-eluting stent was designed to slowly release everolimus to prevent restenosis following peripheral arterial intervention. The purpose of the first-in-human Superficial Femoral Artery Treatment with Drug-Eluting Stents (STRIDES) trial was to evaluate the safety and efficacy of this device for the treatment of symptomatic superficial femoral and proximal popliteal arterial occlusive disease.Methods and results:One hundred four patients were enrolled at 11 European investigative centers in a prospective, nonrandomized, single-arm trial. The patients had severe symptomatic vascular disease, including a significant proportion of patients with critical limb ischemia (17%), diabetes (39%), and single-vessel outflow (26%). The mean lesion length was 9.0 ± 4.3 cm. Ninety-nine percent of patients were available for 12-month follow-up, including duplex imaging in 90% and arteriography in 83%. Clinical improvement, defined as a sustained decrease in Rutherford-Becker clinical category, was achieved in 80% of patients. Primary patency (freedom from ≥50% in-stent restenosis) was 94 ± 2.3% and 68 ± 4.6% at 6 and 12 months, respectively. Plain radiographic examination of 122 implanted devices at 12 months revealed no evidence for stent fracture.Conclusions:The everolimus-eluting self-expanding nitinol stent can be successfully implanted in patients with severe peripheral arterial disease with favorable outcomes and clinical improvements observed in the majority of patients.

Primary Outcome Measures is In-stent binary restenosis (>50% stenosis); Extracted Interventionsis is Dynalink®-E everolimus-eluting peripheral stent Dynalink®-E, everolimus-eluting peripheral stent; Conditions is Atherosclerosis|Peripheral Vascular Disease ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease.Objective:To study efficacy and safety of escalating doses of canakinumab, a fully human anti-IL-1β monoclonal antibody in the severe cryopyrin-associated periodic syndrome, neonatal-onset multisystem inflammatory disease (NOMID).Methods:6 patients were enrolled in this 24-month, open-label phase I/II study. All underwent anakinra withdrawal. The initial subcutaneous canakinumab dose was 150 mg (or 2 mg/kg in patients ≤40 kg) or 300 mg (or 4 mg/kg) with escalation up to 600 mg (or 8 mg/kg) every 4 weeks. Full remission was remission of patient-reported clinical components and measures of systemic inflammation and CNS inflammation. Hearing, vision and safety were assessed. Primary endpoint was full remission at month 6.Results:All patients flared after anakinra withdrawal, and symptoms and serum inflammatory markers improved with canakinumab. All patients required dose escalation to the maximum dose. At month 6, none had full remission, although 4/6 achieved inflammatory remission, based on disease activity diary scores and normal C-reactive proteins. None had CNS remission; 5/6 due to persistent CNS leucocytosis. At the last study visit, 5/6 patients achieved inflammatory remission and 4/6 had continued CNS leucocytosis. Visual acuity and field were stable in all patients, progressive hearing loss occurred in 1/10 ears. Adverse events (AEs) were rare. One serious AE (abscess due to a methicillin-resistant Staphylococcus aureus infection) occurred.Conclusions:Canakinumab at the studied doses improves symptoms and serum inflammatory features of NOMID, although low-grade CNS leukocytosis in four patients and headaches in one additional patient persisted. Whether further dose intensifications are beneficial in these cases remains to be assessed.Clinicaltrialsgov identifier:NCT00770601.

Primary Outcome Measures is Percentage of Participants With Complete Remission and Relapse After 6 Months of Canakinumab Treatment.; Extracted Interventionsis is Canakinumab; Conditions is NOMID|CINCA Syndrome ;Sex is ALL ;Age is CHILD, ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Impact of a nurse-led programme on comorbidity management and impact of a patient self-assessment of disease activity on the management of rheumatoid arthritis: results of a prospective, multicentre, randomised, controlled trial (COMEDRA).Objectives:Rheumatoid arthritis (RA) patients are at an increased risk of developing comorbid conditions. A close monitoring of the disease targeting a status of low disease activity is associated with a better outcome. The aim of this trial was to evaluate the impact of a nurse-led programme on comorbidities and the impact of patient self-assessment of disease activity on the management of RA.Methods:We enrolled 970 patients (mean age 58 years, 79% women) in a prospective, randomised, controlled, open-label, 6-month trial. In the comorbidity group (n=482), the nurse checked comorbidities and sent the programme results to the attending physicians. In the self-assessment group (n=488), the nurse taught the patient how to calculate his/her Disease Activity Score which had to be reported on a booklet to be shared with the treating rheumatologist. The number of measures taken for comorbidities and the percentage of patients recording a change (initiation, switch or increased dose) in disease-modifying antirheumatic drugs (DMARDs) in the 6 months follow-up period of the study defined the outcomes of the trial.Results:The number of measures taken per patient was statistically higher in the comorbidity group: 4.54±2.08 versus 2.65±1.57 (p<0.001); incidence rate ratio: 1.78 (1.61-1.96) and DMARD therapy was changed more frequently in the self-assessment group: 17.2% versus 10.9% (OR=1.70 (1.17; 2.49), p=0.006).Conclusions:This study demonstrates the short-term benefit of a nurse-led programme on RA comorbidity management and the impact of patient self-assessment of disease activity on RA treatment intensification.Trial registration number:NCT #01315652.

Primary Outcome Measures is Comorbidities treatment; Extracted Interventionsis is Comorbidities treatment Auto-DAS; Conditions is Rheumatoid Arthritis ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Implant decontamination with 2% chlorhexidine during surgical peri-implantitis treatment: a randomized, double-blind, controlled trial.Objective:The objective of this randomized, double-blind, controlled trial was to evaluate the clinical, radiographic, and microbiological effects of implant surface decontamination with a 2% chlorhexidine (CHX) solution in comparison with a 0.12% chlorhexidine + 0.05% cetylpyridinium chloride (CPC) solution during resective surgical peri-implantitis treatment.Material and methods:Forty-four patients (108 implants) with peri-implantitis were treated with resective surgical treatment consisting of bone re-contouring, surface debridement and chemical decontamination, and apically repositioned flap. Patients were randomly allocated to decontamination with a 2% CHX solution (test group) or 0.12% CHX + 0.05% CPC (control group). Clinical and radiographic parameters were recorded before treatment (baseline), and at 3, 6, and 12 months after treatment. Microbiological parameters were recorded during surgery.Results:Multilevel analysis showed no significant differences in bleeding, suppuration, probing pocket depth, and radiographic bone loss between control and test group over three follow-up measurements (3, 6, and 12 months) from baseline. Both decontamination procedures resulted in significant reductions in anaerobic bacterial counts on the implant surface, but no significant difference was noted between control and test group (mean log 3.37 ± 2.34 vs. 3.65 ± 2.87, P = 0.99).Conclusions:The use of a 2% CHX solution for implant surface decontamination during resective peri-implantitis therapy does not lead to improved clinical, radiographic, or microbiological results compared with a 0.12% CHX + 0.05% CPC solution. Overall, the additional use of CHX reduces anaerobic bacterial load on the implant surface better than mechanical debridement alone, but does not seem to enhance clinical treatment outcomes (ClinicalTrials.gov number NCT01852253).

Primary Outcome Measures is Change from baseline in modified bleeding index.; Extracted Interventionsis is 2% chlorhexidine 0.12% chlorhexidine; Conditions is Periodontal Diseases|Peri-implantitis ;Sex is ALL ;Age is CHILD, ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Adalimumab in patients with hand osteoarthritis refractory to analgesics and NSAIDs: a randomised, multicentre, double-blind, placebo-controlled trial.Aim:To test the efficiency of tumour necrosis factor blockers (adalimumab) in patients with painful refractory (non-responders to analgesics and non-steroidal anti-inflammatory drugs (NSAIDs)) hand osteoarthritis (OA).Methods:We performed a randomised, double-blind, placebo-controlled, parallel group, multicentre study. Patients were randomised to: 1/1 adalimumab 40 mg for two subcutaneous injections at a 15-day interval or placebo and monitored for 6 months. The primary outcome was the percentage of patients with an improvement of more than 50% in global pain (Visual Analogue Scale) between week 0 (W0) and week 6 (W6). Secondary outcomes included the number of painful joints, swollen joints, morning stiffness duration, patient and practitioner global assessments, functional indexes for hand OA, and consumption of analgesics. Analysis on the mean primary outcome measure was done on patients who received at least one injection.Results:99 patients were recruited and 85 patients were randomised. Among them, 37 patients in the placebo group and 41 in the adalimumab group received at least one injection and were evaluated at W6 (n=78) on the main efficacy outcome. Mean age was 62 years, 85% were women, and mean level of pain was 62 mm at W0. At W6, 35.1% in the adalimumab group versus 27.3% in the placebo group had a pain reduction ≥50% (RR 1.12 (95% CI 0.82 to 1.54; p=0.48). There were no statistical differences for all secondary end points. The rate of adverse events was similar in the two groups.Conclusions:Adalimumab was not superior to placebo to alleviate pain in patients with hand OA not responding to analgesics and NSAIDs.Trials registration number:NCT00597623.

Primary Outcome Measures is Level of Pain on visual analogue scale; Extracted Interventionsis is Adalimumab (Humira®) Placebo; Conditions is Hand Osteoarthritis ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Pilot clinical study of the effects of ginger root extract on eicosanoids in colonic mucosa of subjects at increased risk for colorectal cancer.Colorectal cancer (CRC) remains a significant cause of mortality. Inhibitors of cyclooxygenase (COX) and thus prostaglandin E2, are promising CRC preventives, but have significant toxicities. Ginger has been shown to inhibit COX, to decrease the incidence and multiplicity of adenomas, and decrease PGE2 concentrations in subjects at normal risk for CRC. This study was conducted to determine the effects of 2.0 g/d of ginger given orally on the levels of PGE2, leukotriene B4 (LTB4), 13-hydroxy-octadecadienoic acids, and 5-, 12-, & 15-hydroxyeicosatetraenoic acid, in the colonic mucosa of subjects at increased risk for CRC. We randomized 20 subjects to 2.0 g/d ginger or placebo for 28 d. At baseline and Day 28, a flexible sigmoidoscopy was used to obtain colon biopsies. A liquid chromatography mass spectrometry method was used to determine eicosanoid levels in the biopsies, and levels were expressed per amount of protein or free arachidonic acid (AA). There was a significant decrease in AA between baseline and Day 28 (P = 0.05) and significant increase in LTB4 (P = 0.04) when normalized to protein, in subjects treated with ginger versus placebo. No other changes in eicosanoids were observed. There was no difference between the groups in total adverse events (AE; P = 0.06). Ginger lacks the ability to decrease eicosanoid levels in people at increased risk for CRC. Ginger did appear to be both tolerable and safe; and could have chemopreventive effects through other mechanisms. Further investigation should focus on other markers of CRC risk in those at increased CRC risk.

Primary Outcome Measures is Evaluate Whether 2.0g of Ginger Taken Daily; Extracted Interventionsis is Ginger Root Extract (Pure Encapsulations) Placebo Capsule; Conditions is Colorectal Cancer ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study.Objective:To evaluate the efficacy and safety of subcutaneous blisibimod, an inhibitor of B cell activating factor, in patients with systemic lupus erythematosus (SLE) in a dose-ranging Phase 2b clinical trial.Methods:547 patients with SLE with anti-double stranded DNA or antinuclear antibodies and Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score ≥6 at baseline were randomised to receive placebo or blisibimod at one of 3 dose levels. The primary end point, measured at Week 24, was the SLE Responder Index-5 (SRI-5, meeting established SRI criteria but with ≥5 point improvement in SELENA-SLEDAI).Results:Although SRI-5 response rates were not significantly improved in the pooled blisibimod groups compared with placebo, they were higher in subjects randomised to the highest dose of blisibimod (200 mg once-weekly (QW)) compared with pooled placebo, from Week 16 to Week 24, reaching statistical significance at Week 20 (p=0.02). SRI response rates compared with placebo were higher still in subjects who attained SELENA-SLEDAI improvements of ≥8, and in a subgroup of patients with severe disease (SELENA-SLEDAI ≥10 and receiving corticosteroids at baseline). In subjects with protein:creatine ratios of 1-6 at baseline, significant reductions in proteinuria were observed with blisibimod. Significant (p<0.01) changes in anti-double stranded DNA antibodies, complement C3 and C4, and reductions in B cells were observed with blisibimod.No imbalances in serious adverse events or infections (4/280 and 3/266), deaths (4/280 and 3/266) and malignancies (2/280 and 2/266) were reported for blisibimod compared with placebo.Conclusions:This study successfully identified a safe, effective and convenient dose, study population and end point for evaluation of blisibimod effect in Phase 3.Trial registration number:NCT01162681.

Primary Outcome Measures is SLE response; Extracted Interventionsis is A-623 A-623 A-623 Placebo Comparator; Conditions is Systemic Lupus Erythematosus ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Monitoring Central Venous Catheter Resistance to Predict Imminent Occlusion: A Prospective Pilot Study.Background:Long-term central venous catheters are essential for the management of chronic medical conditions, including childhood cancer. Catheter occlusion is associated with an increased risk of subsequent complications, including bloodstream infection, venous thrombosis, and catheter fracture. Therefore, predicting and pre-emptively treating occlusions should prevent complications, but no method for predicting such occlusions has been developed.Methods:We conducted a prospective trial to determine the feasibility, acceptability, and efficacy of catheter-resistance monitoring, a novel approach to predicting central venous catheter occlusion in pediatric patients. Participants who had tunneled catheters and were receiving treatment for cancer or undergoing hematopoietic stem cell transplantation underwent weekly catheter-resistance monitoring for up to 12 weeks. Resistance was assessed by measuring the inline pressure at multiple flow-rates via a syringe pump system fitted with a pressure-sensing transducer. When turbulent flow through the device was evident, resistance was not estimated, and the result was noted as "non-laminar."Results:Ten patients attended 113 catheter-resistance monitoring visits. Elevated catheter resistance (>8.8% increase) was strongly associated with the subsequent development of acute catheter occlusion within 10 days (odds ratio = 6.2; 95% confidence interval, 1.8-21.5; p <0.01; sensitivity, 75%; specificity, 67%). A combined prediction model comprising either change in resistance greater than 8.8% or a non-laminar result predicted subsequent occlusion (odds ratio = 6.8; 95% confidence interval, 2.0-22.8; p = 0.002; sensitivity, 80%; specificity, 63%). Participants rated catheter-resistance monitoring as highly acceptable.Conclusions:In this pediatric hematology and oncology population, catheter-resistance monitoring is feasible, acceptable, and predicts imminent catheter occlusion. Larger studies are required to validate these findings, assess the predictive value for other clinical outcomes, and determine the impact of pre-emptive therapy.Trial registration:Clinicaltrials.gov NCT01737554.

Primary Outcome Measures is Proportion of attended CRM visits which produce usable resistance data for all lumens of the CVAD; Extracted Interventionsis is Catheter Resistance Monitoring; Conditions is Cancer|Hematologic Disorders ;Sex is ALL ;Age is CHILD, ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism. Rationale for and design of the EINSTEIN CHOICE study.Patients with unprovoked venous thromboembolism (VTE) are at high risk for recurrence. Although rivaroxaban is effective for extended VTE treatment at a dose of 20 mg once daily, use of the 10 mg dose may further improve its benefit-to-risk ratio. Low-dose aspirin also reduces rates of recurrent VTE, but has not been compared with anticoagulant therapy. The EINSTEIN CHOICE study is a multicentre, randomised, double-blind, active-controlled, event-driven study comparing the efficacy and safety of two once daily doses of rivaroxaban (20 and 10 mg) with aspirin (100 mg daily) for the prevention of recurrent VTE in patients who completed 6-12 months of anticoagulant therapy for their index acute VTE event. All treatments will be given for 12 months. The primary efficacy objective is to determine whether both doses of rivaroxaban are superior to aspirin for the prevention of symptomatic recurrent VTE, while the principal safety outcome is the incidence of major bleeding. The trial is anticipated to enrol 2,850 patients from 230 sites in 31 countries over a period of 27 months. In conclusion, the EINSTEIN CHOICE study will provide new insights into the optimal antithrombotic strategy for extended VTE treatment by comparing two doses of rivaroxaban with aspirin (clinicaltrials.gov NCT02064439).

Primary Outcome Measures is Number of Participants With the Composite of Fatal or Non-fatal Symptomatic Recurrent Venous Thromboembolism; Extracted Interventionsis is BAY 59-7939 BAY 59-7939 ASA; Conditions is Pulmonary Embolism|Thromboembolism|Thrombosis|Venous Thrombosis|Venous Thromboembolism ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Vitamin D supplementation to patients with frequent respiratory tract infections: a post hoc analysis of a randomized and placebo-controlled trial.Background:Vitamin D is considered to be important for a healthy immune system. The aim of this study was to test the hypothesis that vitamin D supplementation reduces number of respiratory tract infections (RTIs) and prolong the time to the first RTI in adult patients with frequent RTIs.Methods:We performed a post hoc analysis of a randomized, placebo-controlled and double-blinded study, where adult patients with a high burden of RTIs were randomized to placebo or vitamin D (4000 IE/day for 1 year, n = 124 in the per protocol cohort presented here).Results:Vitamin D supplementation increased the probability to stay free of RTI during the study year (RR 0.64, 95% CI 0.43-0.94). Further, the total number of RTIs was also reduced in the vitamin D-group (86 RTIs) versus placebo (120 RTIs; p = 0.05). Finally, the time to the first RTI was significantly extended in the vitamin D-group (HR 1.68, 95% CI 1.03-2.68, p = 0.0376).Conclusion:Vitamin D supplementation was found to significantly increase the probability of staying infection free during the study period. This finding further supports the notion that vitamin D-status should be monitored in adult patients with frequent RTIs and suggests that selected patients with vitamin D deficiency are supplemented. This could be a safe and cheap way to reduce RTIs and improve health in this vulnerable patient population. The original trial was registered at http://www.clinicaltrials.gov (NCT01131858).

Primary Outcome Measures is Infectious score; Extracted Interventionsis is Vigantol Placebo; Conditions is Primary Immune Deficiency Disorder ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Integrating smoking cessation and alcohol use treatment in homeless populations: study protocol for a randomized controlled trial.Background:Despite progress in reducing cigarette smoking in the general U.S. population, smoking rates, cancer morbidity and related heart disease remain strikingly high among the poor and underserved. Homeless individuals' cigarette smoking rate remains an alarming 70% or greater, and this population is generally untreated with smoking cessation interventions. Furthermore, the majority of homeless smokers also abuse alcohol and other drugs, which makes quitting more difficult and magnifies the health consequences of tobacco use.Methods/design:Participants will be randomized to one of three groups, including (1) an integrated intensive smoking plus alcohol intervention using cognitive behavioral therapy (CBT), (2) intensive smoking intervention using CBT or (3) usual care (i.e., brief smoking cessation and brief alcohol counseling). All participants will receive 12-week treatment with a nicotine patch plus nicotine gum or lozenge. Counseling will include weekly individual sessions for 3 months, followed by monthly booster group sessions for 3 months. The primary smoking outcome is cotinine-verified 7-day smoking abstinence at follow-up week 52, and the primary alcohol outcome will be breathalyzer-verified 90-day alcohol abstinence at week 52.Discussion:This study protocol describes the design of the first community-based controlled trial (n = 645) designed to examine the efficacy of integrating alcohol abuse treatment with smoking cessation among homeless smokers. To further address the gap in effectiveness of evidence-based smoking cessation interventions in the homeless population, we are conducting a renewed smoking cessation clinical trial called Power to Quit among smokers experiencing homelessness.Trial registration:ClinicalTrials.gov Identifier: NCT01932996. Date of registration: 20 November 2014.

Primary Outcome Measures is CO-verified Smoking Status at 26 Weeks; Extracted Interventionsis is nicotine patch plus nicotine gum/lozenge Intensive Alcohol Intervention; Conditions is Cigarette Smoking|Tobacco Smoking|Smoking, Tobacco ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Impact of referral templates on the quality of referrals from primary to secondary care: a cluster randomised trial.Background:The referral letter is an important document facilitating the transfer of care from a general practitioner (GP) to secondary care. Hospital doctors have often criticised the quality and content of referral letters, and the effectiveness of improvement efforts remains uncertain.Methods:A cluster randomised trial was conducted using referral templates for patients in four diagnostic groups: dyspepsia, suspected colorectal cancer, chest pain and chronic obstructive pulmonary disease. The GP surgery was the unit of randomisation. Of the 14 surgeries served by the University Hospital of North Norway Harstad, seven were randomised to the intervention group. Intervention GPs used referral templates soliciting core clinical information when initiating a new referral in one of the four clinical areas. Intermittent surgery visits by study personnel were also carried out. A total of 500 patients were included, with 281 in the intervention and 219 in the control arm. Referral quality scoring was performed by three blinded raters. Data were analysed using multi-level regression modelling. All analyses were conducted on intention-to-treat basis.Results:In the final multilevel model, referrals in the intervention group scored 18% higher (95% CI (11%, 25%), p < 0.001) on the referral quality score than the control group. The model also showed that board certified GPs and GPs in larger surgeries produced referrals of significantly higher quality.Conclusion:In this study, the dissemination of referral templates coupled with intermittent surgery visits produced higher quality referrals.Trial registration:This trial has been registered at ClinicalTrials.gov. The trial registration number is NCT01470963.

Primary Outcome Measures is Collated quality indicator score; Extracted Interventionsis is Implementation of referral template; Conditions is Referral|Quality of Health Care ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effects of High-Intensity Interval Exercise versus Moderate Continuous Exercise on Glucose Homeostasis and Hormone Response in Patients with Type 1 Diabetes Mellitus Using Novel Ultra-Long-Acting Insulin.Introduction:We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM).Material and methods:Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/ Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system.Results:BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C.Conclusion:Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM.Trial registration:ClinicalTrials.gov NCT02075567 http://www.clinicaltrials.gov/ct2/show/NCT02075567.

Primary Outcome Measures is Number of Participants with no Adverse Events as a Measure of Safety and Tolerability; Extracted Interventionsis is Experimental; Conditions is Blood Glucose Decrease During and After Defined Individual Exercise in T1DM ;Sex is MALE ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.High Platelet Reactivity in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Randomised Controlled Trial Comparing Prasugrel and Clopidogrel.Background:Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited.Objectives:To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS).Patients:Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. "poor responders" were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors.Results:At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively.Conclusions:Routine platelet function testing identifies patients with high residual platelet reactivity ("poor responders") on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit.Trial registration:ClinicalTrials.gov NCT01339026.

Primary Outcome Measures is Platelet Reactivity; Extracted Interventionsis is Prasugrel Plavix; Conditions is Cardiovascular Disease|Acute Coronary Syndrome ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.The Intraocular Pressure under Deep versus Moderate Neuromuscular Blockade during Low-Pressure Robot Assisted Laparoscopic Radical Prostatectomy in a Randomized Trial.Background:This study aimed to determine whether continuous deep neuromuscular blockade (NMB) improves the surgical conditions and facilitates robotic-assisted laparoscopic radical prostatectomy (RALRP) under low intra-abdominal pressure (IAP) to attenuate the increase in intraocular pressure (IOP) during CO2 pneumoperitoneum in the steep Trendelenburg (ST) position.Methods:Sixty-seven patients undergoing RALRP were randomly assigned to a moderate NMB group (Group M), including patients who received atracurium infusion until the end of the ST position, maintaining a train of four count of 1-2; and the deep NMB group (Group D), including patients who received rocuronium infusion, maintaining a post-tetanic count of 1-2. IOP was measured in all patients at nine separate time points. All RALRPs were performed by one surgeon, who rated the overall and worst surgical conditions at the end of the ST position.Results:The highest IOP value was observed at T4 (60 min after the ST position) in both Group M (23.3 ± 2.7 mmHg) and Group D (19.8 ± 2.1 mmHg). RALRP was accomplished at an IAP of 8 mmHg in 88% Group D patients and 25% Group M patients. The overall surgical condition grade was 4.0 (3.0-5.0) in Group D and 3.0 (2.0-5.0) in Group M (P < 0.001).Conclusion:The current study demonstrated that continuous deep NMB may improve surgical conditions and facilitate RALRP at a low IAP, resulting in significant attenuation of the increase on IOP. Moreover, low-pressure pneumoperitoneum, facilitated by deep NMB still provided acceptable surgical conditions.Trial registration:ClinicalTrials.gov NCT02109133.

Primary Outcome Measures is Maximum Intraocular Pressure During RALRP Under Deep Neuromuscular Blockade; Extracted Interventionsis is deep neuromuscular blockade moderate neuromuscular blockade Rocuronium Sugammadex Atracurium Neostigmine; Conditions is Robot-Assisted Laparoscopic Radical Prostatectomy ;Sex is MALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Explore Transplant at Home: a randomized control trial of an educational intervention to increase transplant knowledge for Black and White socioeconomically disadvantaged dialysis patients.Background:Compared to others, dialysis patients who are socioeconomically disadvantaged or Black are less likely to receive education about deceased donor kidney transplant (DDKT) and living donor kidney transplant (LDKT) before they reach transplant centers, often due to limited availability of transplant education within dialysis centers. Since these patients are often less knowledgeable or ready to pursue transplant, educational content must be simplified, made culturally sensitive, and presented gradually across multiple sessions to increase learning and honor where they are in their decision-making about transplant. The Explore Transplant at Home (ETH) program was developed to help patients learn more about DDKT and LDKT at home, with and without telephone conversations with an educator.Methods and study design:In this randomized controlled trial (RCT), 540 low-income Black and White dialysis patients with household incomes at or below 250 % of the federal poverty line, some of whom receive financial assistance from the Missouri Kidney Program, will be randomly assigned to one of three education conditions: (1) standard-of-care transplant education provided by the dialysis center, (2) patient-guided ETH (ETH-PG), and (3) health educator-guided ETH (ETH-EG). Patients in the standard-of-care condition will only receive education provided in their dialysis centers. Those in the two ETH conditions will receive four video and print modules delivered over an 8 month period by mail, with the option of receiving supplementary text messages weekly. In addition, patients in the ETH-EG condition will participate in multiple telephonic educational sessions with a health educator. Changes in transplant knowledge, decisional balance, self-efficacy, and informed decision making will be captured with surveys administered before and after the ETH education.Discussion:At the conclusion of this RCT, we will have determined whether an education program administered to socioeconomically disadvantaged dialysis patients, over several months directly in their homes, can help more individuals learn about the options of DDKT and LDKT. We also will be able to examine the efficacy of different educational delivery approaches to further understand whether the addition of a telephone educator is necessary for increasing transplant knowledge.Trial registration:ClinicalTrials.gov, NCT02268682.

Primary Outcome Measures is Deceased Donor Kidney Transplant (DDKT) and Living Donor Kidney Transplant (DDKT) Knowledge; Extracted Interventionsis is Patient-Guided Educator-Guided; Conditions is End Stage Renal Disease ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Early rehabilitation using a passive cycle ergometer on muscle morphology in mechanically ventilated critically ill patients in the Intensive Care Unit (MoVe-ICU study): study protocol for a randomized controlled trial.Background:Patients in Intensive Care Units (ICU) are often exposed to prolonged immobilization which, in turn, plays an important role in neuromuscular complications. Exercise with a cycle ergometer is a treatment option that can be used to improve the rehabilitation of patients on mechanical ventilation (MV) in order to minimize the harmful effects of immobility.Methods/design:A single-blind randomized controlled trial (the MoVe ICU study) will be conducted to evaluate and compare the effects of early rehabilitation using a bedside cycle ergometer with conventional physical therapy on the muscle morphology of the knee extensors and diaphragm in critical ill patients receiving MV. A total of 28 adult patients will be recruited for this study from among those admitted to the intensive care department at the Hospital de Clínicas de Porto Alegre. Eligible patients will be treated with MV from a period of 24 to 48 h, will have spent maximum of 1 week in hospital and will not exhibit any characteristics restricting lower extremity mobility. These subjects will be randomized to receive either conventional physiotherapy or conventional physiotherapy with an additional cycle ergometer intervention. The intervention will be administered passively for 20 min, at 20 revolutions per minute (rpm), once per day, 7 days a week, throughout the time the patients remain on MV. Outcomes will be cross-sectional quadriceps thickness, length of fascicle, pennation angle of fascicles, thickness of vastus lateralis muscle, diaphragm thickness and excursion of critical ICU patients on MV measured with ultrasound.Discussion:The MoVe-ICU study will be the first randomized controlled trial to test the hypothesis that early rehabilitation with a passive cycle ergometer can preserve the morphology of knee extensors and diaphragm in critical patients on MV in ICUs.Trial registration:NCT02300662 (25 November 2014).

Primary Outcome Measures is change in cross-sectional quadriceps thickness; Extracted Interventionsis is Cycle Ergometer Conventional physiotherapy; Conditions is Critical Illness ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.The PRECious trial PREdiction of Complications, a step-up approach, CRP first followed by CT-scan imaging to ensure quality control after major abdominal surgery: study protocol for a stepped-wedge trial.Background:After major abdominal surgery (MAS), 20% of patients endure major complications, which require invasive treatment and are associated with increased morbidity and mortality. A quality control algorithm after major abdominal surgery aimed at early identification of patients at risk of developing major complications can decrease associated morbidity and mortality. Literature studies show promising results for C-reactive protein (CRP) as an early marker for postoperative complications, however clinical significance has yet to be determined.Methods:A multicenter, stepped wedge, prospective clinical trial including all adult patients planned to undergo elective MAS. The first period consists of standard postoperative monitoring, which entails on demand additional examinations. This is followed by a period with implementation of postoperative control according to the PRECious protocol, which implicates standardized measurement of CRP levels. If CRP levels exceed 140 mg/L on postoperative day 3,4 or 5, an enhanced CT-scan is performed. Primary outcome in this study is a combined primary outcome, entailing all morbidity and mortality due to postoperative complications. Complications are graded according to the Clavien-Dindo classification. Secondary outcomes are hospital length of stay, patients reported outcome measures (PROMs) and cost-effectiveness. Data will be collected during admission, three months and one year postoperatively. Approval by the medical ethics committee of the VU University Medical Center was obtained (ID 2015.114).Discussion:the PRECious trial is a stepped-wedge, multicenter, open label, prospective clinical trial to determine the effect of a standardized postoperative quality control algorithm on postoperative morbidity and mortality, and cost-effectiveness.Trial registration:www.ClinicalTrials.gov, NCT02102217. Registered 5 February 2015.

Primary Outcome Measures is Morbidity and mortality after major complications; Extracted Interventionsis is PRECious; Conditions is Postoperative Complications ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Improving medication adherence in stroke patients through Short Text Messages (SMS4Stroke)-study protocol for a randomized, controlled trial.Background:Stroke is a major cause of morbidity and mortality, especially in low and middle income countries. Medical management is the mainstay of therapy to prevent recurrence of stroke. Current estimates are that only 1 in 6 patients have perfect adherence to medication schedules. Using SMS (Short Messaging Service) as reminders to take medicines have been used previously for diseases such as diabetes and HIV with moderate success. We aim to explore the effectiveness and acceptability of SMS in increasing adherence to medications in patients with stroke.Methods:This will be a randomized, controlled, assessor blinded single center superiority trial. Adult participants with access to a cell phone and a history of stroke longer than 1 month on multiple risk modifying medications will be selected from Neurology and Stroke Clinic. They will be randomized into two parallel groups in a 1:1 ratio via block technique with one group receiving the standard of care as per institutional guidelines while the parallel group receiving SMS reminders for each dose of medicine in addition to the standard of care. In addition intervention group will receive messages for lifestyle changes, medication information, risk factors and motivation for medication adherence. These will bemodeled on Social Cognitive Theory and Health Belief Model and will be categorized by Michies Taxonomy of Behavioral Change Communication. Patient compliance to medicines will be measured at baseline and then after 2 months in each group by using the Morisky Medication Adherence Scale. The change in compliance to medication regimen after the intervention and the difference between the two groups will be used to determine the effectiveness of SMS reminders as a tool to increase medication compliance. The acceptability of the SMS will be determined by a tool designed for this study whose attributes are based Rogers Diffusion of innovation theory. A sample size of 86 participants in each arm will be sufficient to detect a difference of 1 point on the MMAS with a power of 90 % and significance level of 5 % between the two groups; using an attrition rate of 15 %, 200 participants in all will be randomized.Discussion:The SMS for Stroke Study will provide evidence for feasibility and effectiveness of SMS in improving post stroke medication adherence in an LMIC setting.Trial registration:https://clinicaltrials.gov/ct2/show/NCT01986023 11 /11/2013.

Primary Outcome Measures is Medication Adherence Score; Extracted Interventionsis is SMS- Short Messaging Service; Conditions is Medication Adherence|Stroke ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Efficacy of a respiratory rehabilitation exercise training package in hospitalized elderly patients with acute exacerbation of COPD: a randomized control trial.Clinical trials identifier:NCT02329873.Background:Acute exacerbation (AE) of COPD is characterized by a sudden worsening of COPD symptoms. Previous studies have explored the effectiveness of respiratory rehabilitation for patients with COPD; however, no training program specific to acute exacerbation in elderly patients or unstable periods during hospitalization has been developed.Objective:To evaluate the effects of a respiratory rehabilitation exercise training package on dyspnea, cough, exercise tolerance, and sputum expectoration among hospitalized elderly patients with AECOPD.Methods:A randomized control trial was conducted. Pretest and posttest evaluations of 61 elderly inpatients with AECOPD (experimental group n=30; control group n=31) were performed. The experimental group received respiratory rehabilitation exercise training twice a day, 10-30 minutes per session for 4 days. The clinical parameters (dyspnea, cough, exercise tolerance, and sputum expectoration) were assessed at the baseline and at the end of the fourth day.Results:All participants (median age =70 years, male =60.70%, and peak expiratory flow 140 L) completed the study. In the patients of the experimental group, dyspnea and cough decreased and exercise tolerance and sputum expectoration increased significantly compared with those of the patients in the control group (all P<0.05). Within-group comparisons revealed that the dyspnea, cough, and exercise tolerance significantly improved in the experimental group by the end of the fourth day (all P<0.05).Conclusion:Results of this study suggest that the respiratory rehabilitation exercise training package reduced symptoms and enhanced the effectiveness of the care of elderly inpatients with AECOPD.

Primary Outcome Measures is Change from baseline in dyspnea at 4th day; Extracted Interventionsis is Respiratory rehabilitation exercise training; Conditions is Chronic Obstructive Pulmonary Disease (COPD) ;Sex is ALL ;Age is OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Albumin Kinetics in Patients Undergoing Major Abdominal Surgery.Background:The drop in plasma albumin concentration following surgical trauma is well known, but the temporal pattern of the detailed mechanisms behind are less well described. The aim of this explorative study was to assess changes in albumin synthesis and transcapillary escape rate (TER) following major surgical trauma, at the time of peak elevations in two well-recognized markers of inflammation.Methods:This was a clinical trial of radiolabeled human serum albumin for the study of TER and plasma volume. Ten patients were studied immediately preoperatively and on the 2nd postoperative day after major pancreatic surgery. Albumin synthesis rate was measured by the flooding dose technique employing incorporation of isotopically labelled phenylalanine.Results:Fractional synthesis rate of albumin increased from 11.7 (95% CI: 8.9, 14.5) to 15.0 (11.7, 18.4) %/day (p = 0.027), whereas the corresponding absolute synthesis rate was unchanged, 175 (138, 212) versus 150 (107, 192) mg/kg/day (p = 0.21). TER was unchanged, 4.9 (3.1, 6.8) %/hour versus 5.5 (3.9, 7.2) (p = 0.63). Plasma volume was unchanged but plasma albumin decreased from 33.5 (30.9, 36.2) to 22.1 (19.8, 24.3) g/L. (p<0.001).Conclusion:Two days after major abdominal surgery, at the time-point when two biomarkers of generalised inflammation were at their peak and the plasma albumin concentration had decreased by 33%, we were unable to show any difference in the absolute synthesis rate of albumin, TER and plasma volume as compared with values obtained immediately pre-operatively. This suggests that capillary leakage, if elevated postoperatively, had ceased at that time-point. The temporal relations between albumin kinetics, capillary leakage and generalised inflammation need to be further explored.Trial registration:clinicaltrialsregister.eu: EudraCT 2010-08529-21 ClinicalTrials.gov NCT01194492.

Primary Outcome Measures is Change from baseline in albumin transcapillary escape rate; Extracted Interventionsis is Albumin transcapillary escape rate (125I-albumin); Conditions is Major Abdominal Surgery ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.PATHOS: a phase II/III trial of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery for Human papillomavirus (HPV) positive oropharyngeal cancer.Background:Human papillomavirus-positive oropharyngeal squamous cell carcinoma is increasing in incidence worldwide. Current treatments are associated with high survival rates but often result in significant long-term toxicities. In particular, long-term dysphagia has a negative impact on patient quality of life and health. The aim of PATHOS is to determine whether reducing the intensity of adjuvant treatment after minimally invasive transoral surgery in this favourable prognosis disease will result in better long-term swallowing function whilst maintaining excellent disease-specific survival outcomes.Methods/design:The study is a multicentre phase II/III randomised controlled trial for patients with biopsy-proven Human papillomavirus-positive oropharyngeal squamous cell cancer staged T1-T3 N0-N2b with a primary tumour that is resectable via a transoral approach. Following transoral surgery and neck dissection, patients are allocated into three groups based on pathological risk factors for recurrence. Patients in the low-risk pathology group will receive no adjuvant treatment, as in standard practice. Patients in the intermediate-risk pathology group will be randomised to receive either standard dose post-operative radiotherapy (control) or reduced dose radiotherapy. Patients in the high-risk pathology group will be randomised to receive either post-operative chemoradiotherapy (control) or radiotherapy alone. The primary outcome of the phase II study is patient reported swallowing function measured using the MD Anderson Dysphagia Inventory score at 12 months post-treatment. If the phase II study is successful, PATHOS will proceed to a phase III non-inferiority trial with overall survival as the primary endpoint.Discussion:PATHOS is a prospective, randomised trial for Human papillomavirus-positive oropharyngeal cancer, which represents a different disease entity compared with other head and neck cancers. The trial aims to demonstrate that long-term dysphagia can be lessened by reducing the intensity of adjuvant treatment without having a negative impact on clinical outcome. The study will standardise transoral surgery and post-operative intensity-modulated radiotherapy protocols in the UK and develop a gold-standard swallowing assessment panel. An associated planned translational research programme, underpinned by tumour specimens and sequential blood collected as part of PATHOS, will facilitate further empirical understanding of this new disease and its response to treatment.Trial registration:This study is registered with ClinicalTrials.gov identifier NCT02215265 .

Primary Outcome Measures is MDADI/Overall survival co-primary endpoint; Extracted Interventionsis is Cisplatin Postoperative radiotherapy; Conditions is Human Papillomavirus (HPV)-Positive Oropharyngeal Cancer ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension.Background:Data on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce.Methods:In this event-driven, double-blind study, we randomly assigned, in a 2:1:1 ratio, participants with World Health Organization functional class II or III symptoms of pulmonary arterial hypertension who had not previously received treatment to receive initial combination therapy with 10 mg of ambrisentan plus 40 mg of tadalafil (combination-therapy group), 10 mg of ambrisentan plus placebo (ambrisentan-monotherapy group), or 40 mg of tadalafil plus placebo (tadalafil-monotherapy group), all administered once daily. The primary end point in a time-to-event analysis was the first event of clinical failure, which was defined as the first occurrence of a composite of death, hospitalization for worsening pulmonary arterial hypertension, disease progression, or unsatisfactory long-term clinical response.Results:The primary analysis included 500 participants; 253 were assigned to the combination-therapy group, 126 to the ambrisentan-monotherapy group, and 121 to the tadalafil-monotherapy group. A primary end-point event occurred in 18%, 34%, and 28% of the participants in these groups, respectively, and in 31% of the pooled-monotherapy group (the two monotherapy groups combined). The hazard ratio for the primary end point in the combination-therapy group versus the pooled-monotherapy group was 0.50 (95% confidence interval [CI], 0.35 to 0.72; P<0.001). At week 24, the combination-therapy group had greater reductions from baseline in N-terminal pro-brain natriuretic peptide levels than did the pooled-monotherapy group (mean change, -67.2% vs. -50.4%; P<0.001), as well as a higher percentage of patients with a satisfactory clinical response (39% vs. 29%; odds ratio, 1.56 [95% CI, 1.05 to 2.32]; P=0.03) and a greater improvement in the 6-minute walk distance (median change from baseline, 48.98 m vs. 23.80 m; P<0.001). The adverse events that occurred more frequently in the combination-therapy group than in either monotherapy group included peripheral edema, headache, nasal congestion, and anemia.Conclusions:Among participants with pulmonary arterial hypertension who had not received previous treatment, initial combination therapy with ambrisentan and tadalafil resulted in a significantly lower risk of clinical-failure events than the risk with ambrisentan or tadalafil monotherapy. (Funded by Gilead Sciences and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.).

Primary Outcome Measures is Number of Participants With First Adjudicated Clinical Failure (CF) Event; Extracted Interventionsis is ambrisentan tadalafil; Conditions is Hypertension, Pulmonary ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa.Background:In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast.Methods:We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies.Results:A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies.Conclusions:In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.).

Primary Outcome Measures is Death (all-cause); Extracted Interventionsis is Antiretroviral medications Antiretroviral medications+Isoniazid prophylaxis Antiretroviral medications Antiretroviral medications+Isoniazid prophylaxis; Conditions is HIV Infections|Tuberculosis ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection.Background:Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.Methods:We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause.Results:A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions.Conclusions:The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.).

Primary Outcome Measures is Composite Endpoint of AIDS; Extracted Interventionsis is All licensed antiretroviral medications; Conditions is HIV Infection ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A.Current management of hemophilia A includes prophylaxis with factor VIII (FVIII) replacement every 2 to 3 days. BAX 855, Baxalta's pegylated full-length recombinant FVIII (rFVIII), was designed to increase half-life and, thus, reduce the frequency of prophylactic infusions while maintaining hemostatic efficacy. BAX 855 was evaluated in previously treated patients with severe hemophilia A who were aged 12 to 65 years. A phase 1 study compared the pharmacokinetic (PK) profile of BAX 855 with that of licensed rFVIII (Advate). In a pivotal study, the annualized bleeding rate (ABR), PK parameters, and efficacy of bleeding treatment were assessed. In the phase 1 study, the mean half-life (T1/2) and the mean residence time of BAX 855 compared with Advate were 1.4- to 1.5-fold higher. These results were confirmed in the pivotal study. The pivotal study met its primary endpoint: Prophylaxis with BAX 855 resulted in an ABR that was significantly lower than half the ABR of on-demand treatment (P < .0001). The median ABR was 1.9, and 39.6% of compliant subjects had no bleeding episodes during prophylaxis, whereas subjects treated on-demand had a median ABR of 41.5. BAX 855 was also efficacious for the treatment of bleeding episodes, with 95.9% of bleeding episodes treated with 1 to 2 infusions and 96.1% having efficacy ratings of excellent/good. No FVIII inhibitory antibodies or safety signals were identified. These studies provide evidence that BAX 855 was safe and efficacious for on-demand treatment and prophylaxis administered twice weekly in patients with hemophilia A. The trials were registered at www.clinicaltrials.gov as #NCT01736475 and #NCT01599819.

Primary Outcome Measures is Annualized Bleeding Rate (ABR); Extracted Interventionsis is Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method PEGylated Recombinant Factor VIII PEGylated Recombinant Factor VIII PEGylated Recombinant Factor VIII; Conditions is Hemophilia A ;Sex is MALE ;Age is CHILD, ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation.Background:It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding.Methods:We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding.Results:In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], -0.6 to 0.8; P=0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority).Conclusions:In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health; BRIDGE ClinicalTrials.gov number, NCT00786474.).

Primary Outcome Measures is Number of Arterial Thromboembolic Events; Extracted Interventionsis is Placebo Dalteparin; Conditions is Arterial Thromboembolic Events|Atrial Fibrillation ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.A Retinotopic Basis for the Division of High-Level Scene Processing between Lateral and Ventral Human Occipitotemporal Cortex.In humans, there is a repeated category-selective organization across the lateral and ventral surfaces of the occipitotemporal cortex. This apparent redundancy is often explained as a feedforward hierarchy, with processing within lateral areas preceding the processing within ventral areas. Here, we tested the alternative hypothesis that this structure better reflects distinct high-level representations of the upper (ventral surface) and lower (lateral surface) contralateral quadrants of the visual field, consistent with anatomical projections from early visual areas to these surfaces in monkey. Using complex natural scenes, we provide converging evidence from three independent functional imaging and behavioral studies. First, population receptive field mapping revealed strong biases for the contralateral upper and lower quadrant within the ventral and lateral scene-selective regions, respectively. Second, these same biases were observed in the position information available both in the magnitude and multivoxel response across these areas. Third, behavioral judgments of a scene property strongly represented within the ventral scene-selective area (open/closed), but not another equally salient property (manmade/natural), were more accurate in the upper than the lower field. Such differential representation of visual space poses a substantial challenge to the idea of a strictly hierarchical organization between lateral and ventral scene-selective regions. Moreover, such retinotopic biases seem to extend beyond these regions throughout both surfaces. Thus, the large-scale organization of high-level extrastriate cortex likely reflects the need for both specialized representations of particular categories and constraints from the structure of early vision.Significance statement:One of the most striking findings in fMRI has been the presence of matched category-selective regions on the lateral and ventral surfaces of human occipitotemporal cortex. Here, we focus on scene-selective regions and provide converging evidence for a retinotopic explanation of this organization. Specifically, we demonstrate that scene-selective regions exhibit strong biases for different portions of the visual field, with the lateral region representing the contralateral lower visual field and the ventral region the contralateral upper visual field. These biases are consistent with the retinotopy found in the early visual areas that lie directly antecedent to category-selective areas on both surfaces. Furthermore, these biases extend beyond scene-selective cortex and provide a retinotopic basis for the large-scale organization of occipitotemporal cortex.

Primary Outcome Measures is Cognitive tasks and neuroimaging.; Extracted Interventionsis is 0-15 Water; Conditions is Healthy Volunteer ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effectiveness of Provider and Community Interventions to Improve Treatment of Uncomplicated Malaria in Nigeria: A Cluster Randomized Controlled Trial.The World Health Organization recommends that malaria be confirmed by parasitological diagnosis before treatment using Artemisinin-based Combination Therapy (ACT). Despite this, many health workers in malaria endemic countries continue to diagnose malaria based on symptoms alone. This study evaluates interventions to help bridge this gap between guidelines and provider practice. A stratified cluster-randomized trial in 42 communities in Enugu state compared 3 scenarios: Rapid Diagnostic Tests (RDTs) with basic instruction (control); RDTs with provider training (provider arm); and RDTs with provider training plus a school-based community intervention (provider-school arm). The primary outcome was the proportion of patients treated according to guidelines, a composite indicator requiring patients to be tested for malaria and given treatment consistent with the test result. The primary outcome was evaluated among 4946 (93%) of the 5311 patients invited to participate. A total of 40 communities (12 in control, 14 per intervention arm) were included in the analysis. There was no evidence of differences between the three arms in terms of our composite indicator (p = 0.36): stratified risk difference was 14% (95% CI -8.3%, 35.8%; p = 0.26) in the provider arm and 1% (95% CI -21.1%, 22.9%; p = 0.19) in the provider-school arm, compared with control. The level of testing was low across all arms (34% in control; 48% provider arm; 37% provider-school arm; p = 0.47). Presumptive treatment of uncomplicated malaria remains an ingrained behaviour that is difficult to change. With or without extensive supporting interventions, levels of testing in this study remained critically low. Governments and researchers must continue to explore alternative ways of encouraging providers to deliver appropriate treatment and avoid the misuse of valuable medicines.Trial registration:ClinicalTrials.gov NCT01350752.

Primary Outcome Measures is Proportion of febrile patients receiving treatment as recommended in clinical guidelines for uncomplicated malaria; Extracted Interventionsis is RDTs & Provider Training on Malaria Diagnosis and Treatment Extended provider training (Cameroon only) School based malaria education (Nigeria only); Conditions is Malaria ;Sex is ALL ;Age is CHILD, ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.FFCD-1004 Clinical Trial: Impact of Cytidine Deaminase Activity on Clinical Outcome in Gemcitabine-Monotherapy Treated Patients.Purpose:Because cytidine deaminase (CDA) is the key enzyme in gemcitabine metabolism, numerous studies have attempted to investigate impact of CDA status (i.e. genotype or phenotype) on clinical outcome. To date, data are still controversial because none of these studies has fully investigated genotype-phenotype CDA status, pharmacokinetics and clinical outcome relationships in gemcitabine-treated patients. Besides, most patients were treated with gemcitabine associated with other drugs, thus adding a confounding factor. We performed a multicenter prospective clinical trial in gemcitabine-treated patients which aimed at investigating the link between CDA deficiency on the occurrence of severe toxicities and on pharmacokinetics, and studying CDA genotype-phenotype relationships.Experimental design:One hundred twenty patients with resected pancreatic adenocarcinoma eligible for adjuvant gemcitabine monotherapy were enrolled in this study promoted and managed by the Fédération Francophone de Cancérologie Digestive. Toxicities were graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4. They were considered severe for grade ≥ 3, and early when occurring during the first eight weeks of treatment. CDA status was evaluated using a double approach: genotyping for 79A>C and functional testing. Therapeutic drug monitoring of gemcitabine and its metabolite were performed on the first course of gemcitabine.Results:Five patients out of 120 (i.e., 4.6%) were found to be CDA deficient (i.e., CDA activity <1.3 U/mg), and only one among them experienced early severe hematological toxicity. There was no statistically significant difference in CDA activity between patients experiencing hematological severe toxicities (28.44%) and patients who tolerated the treatment (71.56%). CDA genetic analysis failed in evidencing an impact in terms of toxicities or in CDA activity. Regarding pharmacokinetics, a wide inter-individual variability has been observed in patients.Conclusion:This study, which included only 4.6% of CDA-deficient patients, failed in identifying CDA status as a predictive marker of toxicities with gemcitabine. A lack of statistical power because of smoothing effect of CDA variability as compared with real life conditions could explain this absence of impact.Trial registration:ClinicalTrials.gov NCT01416662.

Primary Outcome Measures is capability of CDA to predict the occurrence of early severe hematological toxicity upon gemcitabine; Extracted Interventionsis is gemcitabine hydrochloride; Conditions is Pancreatic Cancer ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Safety and immunogenicity of a candidate bioconjugate vaccine against Shigella dysenteriae type 1 administered to healthy adults: A single blind, partially randomized Phase I study.Background:Shigellae cause severe disease in endemic countries, especially in children. Several efficacy trials have been conducted with candidate vaccines against Shigellae, but the lack of protection, the safety concerns, or manufacturing challenges hindered successful market approval. Conjugated vaccines have been shown to be safe and effective for different pathogens (i.e., Neisseria meningitidis, Shigella pneumonia, Haemophilus influenzae). The bio-conjugation technology, exploited here for the Shigella dysenteriae candidate vaccine, offers a novel and potentially simpler way to develop and produce vaccines against one of the major causes of morbidity and mortality in developing countries.Methods:A novel S. dysenteriae bioconjugate vaccine (GVXN SD133) made of the polysaccharide component of the Shigella O1 lipopolysaccharide, conjugated to the exotoxin protein A of Pseudomonas aeruginosa (EPA), was evaluated for immunogenicity and safety in healthy adults in a single blind, partially randomized Phase I study. Forty subjects (10 in each dose group; 2 μg or 10 μg with or without aluminium adjuvant) received two injections 60 days apart and were followed-up for 150 days.Results:Both doses and formulations were well tolerated; the safety and reactogenicity profiles were consistent with that of other conjugated vaccines, adjuvanted or not, independent of the dose and the number of injections. The GVXN SD133 vaccine elicited statistically significant O1 specific humoral responses at all time points in all vaccination groups. Between-group comparisons did not show statistically significant differences in geometric mean titers of immunoglobulin G and A at any post-vaccination time point.Conclusions:This study demonstrated that the GVXN SD133 vaccine has a satisfactory safety profile. It elicited a significant humoral response to Shigella O1 polysaccharides at all doses tested. The protein carrier also elicited functional antibodies, showing the technology's advantages in preserving both sugar and conjugated protein epitopes. This trial is registered at ClinicalTrials.gov (NCT01069471).

Primary Outcome Measures is Safety and reactogenicity of the bioconjugate vaccine; Extracted Interventionsis is Shigella vaccine; Conditions is Shigellosis ;Sex is ALL ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Immunogenicity and safety of concomitant MF59-adjuvanted influenza vaccine and 23-valent pneumococcal polysaccharide vaccine administration in older adults.Background:Concomitant administration of influenza and pneumococcal vaccines facilitates their uptake by older adults; however, data on immunogenicity and safety of concomitant administration of adjuvanted trivalent inactivated influenza vaccine (aIIV3) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) have not been reported.Methods:Subjects aged ≥65 years (N=224) were randomized 1:1:1:1 to receive MF59-aIIV3 alone, MF59-aIIV3+PPSV23 in contralateral arms, MF59-aIIV3+PPSV23 in the same arm or PPSV23 alone (Clinical Trial Number - NCT02225327). Hemagglutination inhibition assay and multiplex opsonophagocytic killing assay were used to compare immunogenicity after single or concomitant vaccination.Results:All groups met immunogenicity criteria for the influenza vaccine in older adults with similar seroconversion rates and geometric mean fold-increases, irrespective of concomitant vaccinations and injection site. For each pneumococcal serotype, opsonic index (OI) increased markedly after the PPSV23 vaccination, irrespective of the concomitant influenza vaccine. All subjects showed an OI≥8 for serotypes 6B, 18C and 19A post-vaccination, with a suggestion that the ipsilateral concomitant vaccination might be associated with higher OIs for some antigens. Local and systemic adverse events were more common in subjects receiving PPSV23 compared to those receiving aIIV3 alone.Conclusions:No interference was observed with antibody responses to influenza or pneumococcal antigens when aIIV3 and PPSV23 were administered concomitantly.

Primary Outcome Measures is Seroconversion rates (A/H1N1; Extracted Interventionsis is Fluad alone Fluad and PPV23 on the different arms Fluad and PPV23 on the same arm PPV23 alone; Conditions is Influenza, Human|Pneumococcal Infections ;Sex is ALL ;Age is OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Testing health information technology tools to facilitate health insurance support: a protocol for an effectiveness-implementation hybrid randomized trial.Background:Patients with gaps in health insurance coverage often defer or forgo cancer prevention services. These delays in cancer detection and diagnoses lead to higher rates of morbidity and mortality and increased costs. Recent advances in health information technology (HIT) create new opportunities to enhance insurance support services that reduce coverage gaps through automated processes applied in healthcare settings. This study will assess the implementation of insurance support HIT tools and their effectiveness at improving patients' insurance coverage continuity and cancer screening rates.Methods/design:This study uses a hybrid cluster-randomized design-a combined effectiveness and implementation trial-in community health centers (CHCs) in the USA. Eligible CHC clinic sites will be randomly assigned to one of two groups in the trial's implementation component: tools + basic training (Arm I) and tools + enhanced training + facilitation (Arm II). A propensity score-matched control group of clinics will be selected to assess the tools' effectiveness. Quantitative analyses of the tools' impact will use electronic health record and Medicaid data to assess effectiveness. Qualitative data will be collected to evaluate the implementation process, understand how the HIT tools are being used, and identify facilitators and barriers to their implementation and use.Discussion:This study will test the effectiveness of HIT tools to enhance insurance support in CHCs and will compare strategies for facilitating their implementation in "real-world" practice settings. Findings will inform further development and, if indicated, more widespread implementation of insurance support HIT tools.Trial registration:Clinical trial NTC02355262.

Primary Outcome Measures is Changes in the proportion of clinic patients who receive age- and gender-appropriate recommended cancer screening and preventive care (clinic-level); Extracted Interventionsis is Informational Intervention; Conditions is Breast Carcinoma|Cervical Carcinoma|Colorectal Carcinoma|Health Status Unknown|Human Papillomavirus Infection|Malignant Neoplasm ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Infusion of Reconstituted High-Density Lipoprotein, CSL112, in Patients With Atherosclerosis: Safety and Pharmacokinetic Results From a Phase 2a Randomized Clinical Trial.Background:CSL112 is a new formulation of human apolipoprotein A-I (apoA-I) being developed to reduce cardiovascular events following acute coronary syndrome. This phase 2a, randomized, double-blind, multicenter, dose-ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics/pharmacodynamics of a CSL112 infusion among patients with stable atherosclerotic disease.Methods and results:Patients were randomized to single ascending doses of CSL112 (1.7, 3.4, or 6.8 g) or placebo, administered over a 2-hour period. Primary safety assessments consisted of alanine aminotransferase or aspartate aminotransferase elevations >3× upper limits of normal and study drug-related adverse events. Pharmacokinetic/pharmacodynamic assessments included apoA-I plasma concentration and measures of the ability of serum to promote cholesterol efflux from cells ex vivo. Of 45 patients randomized, 7, 12, and 14 received 1.7-, 3.4-, and 6.8-g CSL112, respectively, and 11 received placebo. There were no clinically significant elevations (>3× upper limit of normal) in alanine aminotransferase or aspartate aminotransferase. Adverse events were nonserious and mild and occurred in 5 (71%), 5 (41%), and 6 (43%) patients in the CSL112 1.7-, 3.4-, and 6.8-g groups, respectively, compared with 3 (27%) placebo patients. The imbalance in adverse events was attributable to vessel puncture/infusion-site bruising. CSL112 resulted in rapid (T(max)≈2 hours) and dose-dependent increases in apoA-I (145% increase in the 6.8-g group) and total cholesterol efflux (up to 3.1-fold higher than placebo) (P<0.001).Conclusions:CSL112 infusion was well tolerated in patients with stable atherosclerotic disease. CSL112 immediately raised apoA-I levels and caused a rapid and marked increase in the capacity of serum to efflux cholesterol. This potential novel approach for the treatment of atherosclerosis warrants further investigation.Clinical trial registration:URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01499420.

Primary Outcome Measures is Safety; Extracted Interventionsis is CSL112 (reconstituted high density lipoprotein) Placebo; Conditions is Stable Atherothrombotic Disease ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Pelvic Belt Effects on Health Outcomes and Functional Parameters of Patients with Sacroiliac Joint Pain.Introduction:The sacroiliac joint (SIJ) is a common source of low back pain. However, clinical and functional signs and symptoms correlating with SIJ pain are widely unknown. Pelvic belts are routinely applied to treat SIJ pain but without sound evidence of their pain-relieving effects. This case-control study compares clinical and functional data of SIJ patients and healthy control subjects and evaluates belt effects on SIJ pain.Methods:17 SIJ patients and 17 healthy controls were included in this prospective study. The short-form 36 survey and the numerical rating scale were used to characterize health-related quality of life in patients in a six-week follow-up and the pain-reducing effects of pelvic belts. Electromyography data were obtained from the gluteus maximus, biceps femoris, rectus femoris and medial vastus. Alterations of muscle activity, variability and gait patterns were compared in patients and controls along with the belts' effects in a dynamic setting when walking.Results:Significant improvements were observed in the short-form 36 survey of the SIJ patients, especially in the physical health subscores. Minor declines were also observed in the numerical rating scale on pain. Belt-related changes of muscle activity and variability were similar in patients and controls with one exception: the rectus femoris activity decreased significantly in patients with belt application when walking. Further belt effects include improved cadence and gait velocity in patients and controls.Conclusions:Pelvic belts improve health-related quality of life and are potentially attributed to decreased SIJ-related pain. Belt effects include decreased rectus femoris activity in patients and improved postural steadiness during locomotion. Pelvic belts may therefore be considered as a cost-effective and low-risk treatment of SIJ pain.Trial registration:ClinicalTrials.gov NCT02027038.

Primary Outcome Measures is Change in pelvic bone alignment by pelvic belt; Extracted Interventionsis is Pelvic belt application; Conditions is Sacroiliac Joint Pain|Helath Related Quality of Life|Electromuscular Activation of the Pelis and Limbs|Ground Reaction Force Data ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial.Importance:Observational data have suggested that high dietary intake of saturated fat and low intake of vegetables may be associated with increased risk of Alzheimer disease.Objective:To test the effects of oral supplementation with nutrients on cognitive function.Design, setting, and participants:In a double-masked randomized clinical trial (the Age-Related Eye Disease Study 2 [AREDS2]), retinal specialists in 82 US academic and community medical centers enrolled and observed participants who were at risk for developing late age-related macular degeneration (AMD) from October 2006 to December 2012. In addition to annual eye examinations, several validated cognitive function tests were administered via telephone by trained personnel at baseline and every 2 years during the 5-year study.Interventions:Long-chain polyunsaturated fatty acids (LCPUFAs) (1 g) and/or lutein (10 mg)/zeaxanthin (2 mg) vs placebo were tested in a factorial design. All participants were also given varying combinations of vitamins C, E, beta carotene, and zinc.Main outcomes and measures:The main outcome was the yearly change in composite scores determined from a battery of cognitive function tests from baseline. The analyses, which were adjusted for baseline age, sex, race, history of hypertension, education, cognitive score, and depression score, evaluated the differences in the composite score between the treated vs untreated groups. The composite score provided an overall score for the battery, ranging from -22 to 17, with higher scores representing better function.Results:A total of 89% (3741/4203) of AREDS2 participants consented to the ancillary cognitive function study and 93.6% (3501/3741) underwent cognitive function testing. The mean (SD) age of the participants was 72.7 (7.7) years and 57.5% were women. There were no statistically significant differences in change of scores for participants randomized to receive supplements vs those who were not. The yearly change in the composite cognitive function score was -0.19 (99% CI, -0.25 to -0.13) for participants randomized to receive LCPUFAs vs -0.18 (99% CI, -0.24 to -0.12) for those randomized to no LCPUFAs (difference in yearly change, -0.03 [99% CI, -0.20 to 0.13]; P = .63). Similarly, the yearly change in the composite cognitive function score was -0.18 (99% CI, -0.24 to -0.11) for participants randomized to receive lutein/zeaxanthin vs -0.19 (99% CI, -0.25 to -0.13) for those randomized to not receive lutein/zeaxanthin (difference in yearly change, 0.03 [99% CI, -0.14 to 0.19]; P = .66). Analyses were also conducted to assess for potential interactions between LCPUFAs and lutein/zeaxanthin and none were found to be significant.Conclusions and relevance:Among older persons with AMD, oral supplementation with LCPUFAs or lutein/zeaxanthin had no statistically significant effect on cognitive function.Trial registration:clinicaltrials.gov Identifier: NCT00345176.

Primary Outcome Measures is Development of Advanced AMD in People at Moderate to High Risk for Progression.; Extracted Interventionsis is Lutein/zeaxanthin DHA/EPA Lutein/zeaxanthin and DHA/EPA; Conditions is Age-related Macular Degeneration|Cataract ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Effect of a 24-Month Physical Activity Intervention vs Health Education on Cognitive Outcomes in Sedentary Older Adults: The LIFE Randomized Trial.Importance:Epidemiological evidence suggests that physical activity benefits cognition, but results from randomized trials are limited and mixed.Objective:To determine whether a 24-month physical activity program results in better cognitive function, lower risk of mild cognitive impairment (MCI) or dementia, or both, compared with a health education program.Design, setting, and participants:A randomized clinical trial, the Lifestyle Interventions and Independence for Elders (LIFE) study, enrolled 1635 community-living participants at 8 US centers from February 2010 until December 2011. Participants were sedentary adults aged 70 to 89 years who were at risk for mobility disability but able to walk 400 m.Interventions:A structured, moderate-intensity physical activity program (n = 818) that included walking, resistance training, and flexibility exercises or a health education program (n = 817) of educational workshops and upper-extremity stretching.Main outcomes and measures:Prespecified secondary outcomes of the LIFE study included cognitive function measured by the Digit Symbol Coding (DSC) task subtest of the Wechsler Adult Intelligence Scale (score range: 0-133; higher scores indicate better function) and the revised Hopkins Verbal Learning Test (HVLT-R; 12-item word list recall task) assessed in 1476 participants (90.3%). Tertiary outcomes included global and executive cognitive function and incident MCI or dementia at 24 months.Results:At 24 months, DSC task and HVLT-R scores (adjusted for clinic site, sex, and baseline values) were not different between groups. The mean DSC task scores were 46.26 points for the physical activity group vs 46.28 for the health education group (mean difference, -0.01 points [95% CI, -0.80 to 0.77 points], P = .97). The mean HVLT-R delayed recall scores were 7.22 for the physical activity group vs 7.25 for the health education group (mean difference, -0.03 words [95% CI, -0.29 to 0.24 words], P = .84). No differences for any other cognitive or composite measures were observed. Participants in the physical activity group who were 80 years or older (n = 307) and those with poorer baseline physical performance (n = 328) had better changes in executive function composite scores compared with the health education group (P = .01 for interaction for both comparisons). Incident MCI or dementia occurred in 98 participants (13.2%) in the physical activity group and 91 participants (12.1%) in the health education group (odds ratio, 1.08 [95% CI, 0.80 to 1.46]).Conclusions and relevance:Among sedentary older adults, a 24-month moderate-intensity physical activity program compared with a health education program did not result in improvements in global or domain-specific cognitive function.Trial registration:clinicaltrials.gov Identifier: NCT01072500.

Primary Outcome Measures is Major Mobility Disability; Extracted Interventionsis is Physical Activity Successful Aging; Conditions is Sedentary Lifestyle|Risk of Disability|Aging ;Sex is ALL ;Age is OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Influence of Baseline Characteristics, Operative Conduct, and Postoperative Course on 30-Day Outcomes of Coronary Artery Bypass Grafting Among Patients With Left Ventricular Dysfunction: Results From the Surgical Treatment for Ischemic Heart Failure (STICH) Trial.Background:Patients with severe left ventricular dysfunction, ischemic heart failure, and coronary artery disease suitable for coronary artery bypass grafting (CABG) are at higher risk for surgical morbidity and mortality. Paradoxically, those patients with the most severe coronary artery disease and ventricular dysfunction who derive the greatest clinical benefit from CABG are also at the greatest operative risk, which makes decision making regarding whether to proceed to surgery difficult in such patients. To better inform such decision making, we analyzed the Surgical Treatment for Ischemic Heart Failure (STICH) CABG population for detailed information on perioperative risk and outcomes.Methods and results:In both STICH trials (hypotheses), 2136 patients with a left ventricular ejection fraction of ≤35% and coronary artery disease were allocated to medical therapy, CABG plus medical therapy, or CABG with surgical ventricular reconstruction. Relationships of baseline characteristics and operative conduct with morbidity and mortality at 30 days were evaluated. There were a total of 1460 patients randomized to and receiving surgery, and 346 (≈25%) of these high-risk patients developed a severe complication within 30 days. Worsening renal insufficiency, cardiac arrest with cardiopulmonary resuscitation, and ventricular arrhythmias were the most frequent complications and those most commonly associated with death. Mortality at 30 days was 5.1% and was generally preceded by a serious complication (65 of 74 deaths). Left ventricular size, renal dysfunction, advanced age, and atrial fibrillation/flutter were significant preoperative predictors of mortality within 30 days. Cardiopulmonary bypass time was the only independent surgical variable predictive of 30-day mortality.Conclusions:CABG can be performed with relatively low 30-day mortality in patients with left ventricular dysfunction. Serious postoperative complications occurred in nearly 1 in 4 patients and were associated with mortality.Clinical trial registration:URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595.

Primary Outcome Measures is H01: All Cause Mortality; Extracted Interventionsis is CABG surgery plus MED Active Medication Alone CABG plus MED and SVR; Conditions is Cardiovascular Diseases|Coronary Disease|Heart Failure, Congestive|Heart Diseases ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Alternation as a form of allocation for quality improvement studies in primary healthcare settings: the on-off study design.Background:Randomized controlled trials are considered the "gold standard" for scientific rigor in the assessment of benefits and harms of interventions in healthcare. They may not always be feasible, however, when evaluating quality improvement interventions in real-world healthcare settings. Non-randomized controlled trials (NCTs) are designed to answer questions of effectiveness of interventions in routine clinical practice to inform a decision or process. The on-off NCT design is a relatively new design where participant allocation is by alternation. In alternation, eligible patients are allocated to the intervention "on" or control "off " groups in time series dependent sequential clusters.Methods:We used two quality improvement studies undertaken in a Canadian primary care setting to illustrate the features of the on-off design. We also explored the perceptions and experiences of healthcare providers tasked with implementing the on-off study design.Results and discussion:The on-off design successfully allocated patients to intervention and control groups. Imbalances between baseline variables were attributed to chance, with no detectable biases. However, healthcare providers' perspectives and experiences with the design in practice reveal some conflict. Specifically, providers described the process of allocating patients to the off group as unethical and immoral, feeling it was in direct conflict with their professional principle of providing care for all. The degree of dissatisfaction seemed exacerbated by: 1) the patient population involved (e.g., patient population viewed as high-risk (e.g., depressed or suicidal)), 2) conducting assessments without taking action (e.g., administering the PHQ-9 and not acting on the results), and 3) the (non-blinded) allocation process.Conclusions:Alternation, as in the on-off design, is a credible form of allocation. The conflict reported by healthcare providers in implementing the design, while not unique to the on-off design, may be alleviated by greater emphasis on the purpose of the research and having research assistants allocate patients and collect data instead of the healthcare providers implementing the trial. In addition, consultation with front-line staff implementing the trials with an on-off design on appropriateness to the setting (e.g., alignment with professional values and the patient population served) may be beneficial.Trial registration:Health Eating and Active Living with Diabetes: ClinicalTrials.gov identifier: NCT00991380. Date registered: 7 October 2009. Controlled trial of a collaborative primary care team model for patients with diabetes and depression: Clintrials.gov Identifier: NCT01328639 Date registered: 30 March 2011.

Primary Outcome Measures is Change in Patient Health Questionnaire-9 items (PHQ-9) score; Extracted Interventionsis is TeamCare Depression Intervention Usual diabetes and depression care; Conditions is Depression|Depressive Symptoms|Type 2 Diabetes ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.The effect of citrate dialysate on intradialytic heparin dose in haemodialysis patients: study design of a randomised controlled trial.Background:Unfractionated heparin is the most common anticoagulant used in haemodialysis (HD), although it has many potential adverse effects. Citrate dialysate (CD) has an anticoagulant effect which may allow reduction in cumulative heparin dose (CHD) compared to standard acetate dialysate (AD).Methods:This double-blinded, randomised, cross-over trial of chronic haemodialysis patients determines if CD allows reduction in CHD during HD compared with AD. After enrolment, intradialytic heparin is minimised during a two-week run-in period using a standardised protocol based on a visual clotting score. Patients still requiring intradialytic heparin after the run-in period are randomised to two weeks of HD with AD followed by two weeks of CD (Sequence 1) or two weeks of HD with CD followed by two weeks of AD (Sequence 2). The primary outcome is the change in CHD with CD compared with AD. Secondary outcomes include metabolic and haemodynamic parameters, and dialysis adequacy.Discussion:This randomised controlled trial will determine the impact of CD compared with AD on CHD during HD.Trial registration:ClinicalTrials.gov NCT01466959.

Primary Outcome Measures is The change from baseline in the cumulative dose of heparin anticoagulation used during conventional HD; Extracted Interventionsis is citrate dialysate (CD) acetic-acid based dialysate (AD); Conditions is Chronic Kidney Disease ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Assessing Odor Level when Using PrePex for HIV Prevention: A Prospective, Randomized, Open Label, Blinded Assessor Trial to Improve Uptake of Male Circumcision.The PrePex is a WHO--prequalified medical device for adult male circumcision for HIV prevention. The Government of Rwanda was the first country to implement the PrePex device and acts as the leading center of excellence providing training and formal guidelines. As part of the Government's efforts to improve PrePex implementation, it made efforts to improve the psychological acceptability of device by men, thus increasing uptake with VMMC in sub-Saharan Africa. Some men who underwent the PrePex procedure complained of foreskin odor while wearing the PrePex 3-7 days after it was placed. This complaint was identified as potential risk for uptake of the device. Researchers from Rwanda assumed there is a possible relation between the level of foreskin odor and patient foreskin hygiene technique. The Government of Rwanda decided to investigate those assumptions in a scientific way and conduct a trial to test different hygiene-cleaning methods in order to increase the acceptability of PrePex and mitigate the odor concern. The main objective of the trial was to compare odor levels between three arms, having identical personal hygiene but different foreskin hygiene techniques using either clear water with soap during a daily shower, soapy water using a syringe, or chlorhexidine using a syringe. One hundred and one subjects were enrolled to the trial and randomly allocated into three trial arms. Using chlorhexidine solution daily almost completely eliminated odor, and was statistically significant more effective that the other two arms. The trial results suggest that odor from the foreskin, while wearing the PrePex device, could be related to the growth of anaerobic bacteria, which can be prevented by a chlorhexidine cleaning method. This finding can be used to increase acceptability by men when considering PrePex as one of the leading methods for HIV prevention in VMMC programs.

Primary Outcome Measures is Change in Dilution-to-Threshold" (D/T) values; Extracted Interventionsis is Subjects cleaned the foreskin with soapy water using a syringe once a day. Subjects cleaned the foreskin with diluted chlorhexidine (1%) using a syringe once a day.; Conditions is Odor Levels of Study Arms ;Sex is MALE ;Age is ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.A Phase I Trial of DFMO Targeting Polyamine Addiction in Patients with Relapsed/Refractory Neuroblastoma.Background:Neuroblastoma (NB) is the most common cancer in infancy and most frequent cause of death from extracranial solid tumors in children. Ornithine decarboxylase (ODC) expression is an independent indicator of poor prognosis in NB patients. This study investigated safety, response, pharmacokinetics, genetic and metabolic factors associated with ODC in a clinical trial of the ODC inhibitor difluoromethylornithine (DFMO) ± etoposide for patients with relapsed or refractory NB.Methods and findings:Twenty-one patients participated in a phase I study of daily oral DFMO alone for three weeks, followed by additional three-week cycles of DFMO plus daily oral etoposide. No dose limiting toxicities (DLTs) were identified in patients taking doses of DFMO between 500-1500 mg/m2 orally twice a day. DFMO pharmacokinetics, single nucleotide polymorphisms (SNPs) in the ODC gene and urinary levels of substrates for the tissue polyamine exporter were measured. Urinary polyamine levels varied among patients at baseline. Patients with the minor T-allele at rs2302616 of the ODC gene had higher baseline levels (p=0.02) of, and larger decreases in, total urinary polyamines during the first cycle of DFMO therapy (p=0.003) and had median progression free survival (PFS) that was over three times longer, compared to patients with the major G allele at this locus although this last result was not statistically significant (p=0.07). Six of 18 evaluable patients were progression free during the trial period with three patients continuing progression free at 663, 1559 and 1573 days after initiating treatment. Median progression-free survival was less among patients having increased urinary polyamines, especially diacetylspermine, although this result was not statistically significant (p=0.056).Conclusions:DFMO doses of 500-1500 mg/m2/day are safe and well tolerated in children with relapsed NB. Children with the minor T allele at rs2302616 of the ODC gene with relapsed or refractory NB had higher levels of urinary polyamine markers and responded better to therapy containing DFMO, compared to those with the major G allele at this locus. These findings suggest that this patient subset may display dependence on polyamines and be uniquely susceptible to therapies targeting this pathway.Trial registration:Clinicaltrials.gov NCT#01059071.

Primary Outcome Measures is Number of Participants With Adverse Events as a Measure of Safety and Tolerability; Extracted Interventionsis is DFMO Etoposide; Conditions is Neuroblastoma ;Sex is ALL ;Age is CHILD, ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Randomized, Double-Blind, Placebo-Controlled Study on Decolonization Procedures for Methicillin-Resistant Staphylococcus aureus (MRSA) among HIV-Infected Adults.Background:HIV-infected persons have increased risk of MRSA colonization and skin and soft-tissue infections (SSTI). However, no large clinical trial has examined the utility of decolonization procedures in reducing MRSA colonization or infection among community-dwelling HIV-infected persons.Methods:550 HIV-infected adults at four geographically diverse US military HIV clinics were prospectively screened for MRSA colonization at five body locations every 6 months during a 2-year period. Those colonized were randomized in a double-blind fashion to nasal mupirocin (Bactroban) twice daily and hexachlorophene (pHisoHex) soaps daily for 7 days compared to placeboes similar in appearance but without specific antibacterial activity. The primary endpoint was MRSA colonization at 6-months post-randomization; secondary endpoints were time to MRSA clearance, subsequent MRSA infections/SSTI, and predictors for MRSA clearance at the 6-month time point.Results:Forty-nine (9%) HIV-infected persons were MRSA colonized and randomized. Among those with 6-month colonization data (80% of those randomized), 67% were negative for MRSA colonization in both groups (p = 1.0). Analyses accounting for missing 6-month data showed no significant differences could have been achieved. In the multivariate adjusted models, randomization group was not associated with 6-month MRSA clearance. The median time to MRSA clearance was similar in the treatment vs. placebo groups (1.4 vs. 1.8 months, p = 0.35). There was no difference on subsequent development of MRSA infections/SSTI (p = 0.89). In a multivariable model, treatment group, demographics, and HIV-specific factors were not predictive of MRSA clearance at the 6-month time point.Conclusion:A one-week decolonization procedure had no effect on MRSA colonization at the 6-month time point or subsequent infection rates among community-dwelling HIV-infected persons. More aggressive or novel interventions may be needed to reduce the burden of MRSA in this population.Trial registration:ClinicalTrials.gov NCT00631566.

Primary Outcome Measures is The Presence of MRSA on Repeated Swabs to Assess the Efficacy of These Medications on Clearing MRSA Colonization; Extracted Interventionsis is Mupirocin (Bactroban) 2%; hexachlorophene (pHisoHex) 3% Placebo; Conditions is HIV Infections|Staphylococcal Infections ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Efficacy of a Multi-level Intervention to Reduce Injecting and Sexual Risk Behaviors among HIV-Infected People Who Inject Drugs in Vietnam: A Four-Arm Randomized Controlled Trial.Introduction:Injecting drug use is a primary driver of HIV epidemics in many countries. People who inject drugs (PWID) and are HIV infected are often doubly stigmatized and many encounter difficulties reducing risk behaviors. Prevention interventions for HIV-infected PWID that provide enhanced support at the individual, family, and community level to facilitate risk-reduction are needed.Methods:455 HIV-infected PWID and 355 of their HIV negative injecting network members living in 32 sub-districts in Thai Nguyen Province were enrolled. We conducted a two-stage randomization: First, sub-districts were randomized to either a community video screening and house-to-house visits or standard of care educational pamphlets. Second, within each sub-district, participants were randomized to receive either enhanced individual level post-test counseling and group support sessions or standard of care HIV testing and counseling. This resulted in four arms: 1) standard of care; 2) community level intervention; 3) individual level intervention; and 4) community plus individual intervention. Follow-up was conducted at 6, 12, 18, and 24 months. Primary outcomes were self-reported HIV injecting and sexual risk behaviors. Secondary outcomes included HIV incidence among HIV negative network members.Results:Fewer participants reported sharing injecting equipment and unprotected sex from baseline to 24 months in all arms (77% to 4% and 24% to 5% respectively). There were no significant differences at the 24-month visit among the 4 arms (Wald = 3.40 (3 df); p = 0.33; Wald = 6.73 (3 df); p = 0.08). There were a total of 4 HIV seroconversions over 24 months with no significant difference between intervention and control arms.Discussion:Understanding the mechanisms through which all arms, particularly the control arm, demonstrated both low risk behaviors and low HIV incidence has important implications for policy and prevention programming.Trial registration:ClinicalTrials.gov NCT01689545.

Primary Outcome Measures is HIV injecting risk behavior; Extracted Interventionsis is Individual level Structural level Individual level standard of care Structural level standard of care; Conditions is HIV ;Sex is MALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders: a randomised controlled study.The study aims to investigate the effect of repeated infusions of recombinant erythropoietin (EPO) on plasma brain derived neurotrophic factor (BDNF) levels in patients with affective disorders. In total, 83 patients were recruited: 40 currently depressed patients with treatment-resistant depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS) ≤ 14) (study 2). In both studies, patients were randomised to receive eight weekly EPO (Eprex; 40,000 IU) or saline (0.9% NaCl) infusions in a double-blind, placebo-controlled, parallel--group design. Plasma BDNF levels were measured at baseline and at weeks 5, 9 and at follow up, week 14. In contrast with our hypothesis, EPO down regulated plasma BDNF levels in patients with TRD (mean reduction at week 9 (95% CI): EPO 10.94 ng/l (4.51-21.41 ng/l); mean increase at week 9: Saline 0.52 ng/l, p=0.04 (-5.88-4.48 ng/l) p=0.04, partial ŋ2=0.12). No significant effects were found on BDNF levels in partially remitted patients with BD (p=0.35). The present effects of EPO on BDNF levels in patients with TRD point to a role of neurotrophic factors in the potential effects of EPO seen in TRD and BD. The neurobiological mechanisms underlying these effects and the interaction between EPO and peripheral levels on BDNF need to be further elucidated in human studies including a broad range of biomarkers.Trial registration:ClinicalTrials.gov: NCT00916552.

Primary Outcome Measures is a) For treatment-resistant depressed patients: Antidepressant effect measured with the Hamilton Depression Rating Scale (HDRS); b) For bipolar patients in remission: Memory measured with the Rey Auditory Verbal Memory Test.; Extracted Interventionsis is Erythropoietin; Conditions is Mood Disorders ;Sex is ALL ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Hyperbaric oxygen therapy can diminish fibromyalgia syndrome--prospective clinical trial.Background:Fibromyalgia Syndrome (FMS) is a persistent and debilitating disorder estimated to impair the quality of life of 2-4% of the population, with 9:1 female-to-male incidence ratio. FMS is an important representative example of central nervous system sensitization and is associated with abnormal brain activity. Key symptoms include chronic widespread pain, allodynia and diffuse tenderness, along with fatigue and sleep disturbance. The syndrome is still elusive and refractory. The goal of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on symptoms and brain activity in FMS.Methods and findings:A prospective, active control, crossover clinical trial. Patients were randomly assigned to treated and crossover groups: The treated group patients were evaluated at baseline and after HBOT. Patients in the crossover-control group were evaluated three times: baseline, after a control period of no treatment, and after HBOT. Evaluations consisted of physical examination, including tender point count and pain threshold, extensive evaluation of quality of life, and single photon emission computed tomography (SPECT) imaging for evaluation of brain activity. The HBOT protocol comprised 40 sessions, 5 days/week, 90 minutes, 100% oxygen at 2ATA. Sixty female patients were included, aged 21-67 years and diagnosed with FMS at least 2 years earlier. HBOT in both groups led to significant amelioration of all FMS symptoms, with significant improvement in life quality. Analysis of SPECT imaging revealed rectification of the abnormal brain activity: decrease of the hyperactivity mainly in the posterior region and elevation of the reduced activity mainly in frontal areas. No improvement in any of the parameters was observed following the control period.Conclusions:The study provides evidence that HBOT can improve the symptoms and life quality of FMS patients. Moreover, it shows that HBOT can induce neuroplasticity and significantly rectify abnormal brain activity in pain related areas of FMS patients.Trial registration:ClinicalTrials.gov NCT01827683.

Primary Outcome Measures is Pain evaluation; Extracted Interventionsis is Hyperbaric oxygen; Conditions is Fibromyalgia ;Sex is FEMALE ;Age is ADULT, OLDER_ADULT

Extract PICO elements from the following titles and abstracts, including gender, age, condition, intervention, and outcome.Smartphone-Supported versus Full Behavioural Activation for Depression: A Randomised Controlled Trial.Background:There is need for more cost and time effective treatments for depression. This is the first randomised controlled trial in which a blended treatment--including four face-to-face sessions and a smartphone application--was compared against a full behavioural treatment. Hence, the aim of the current paper was to examine whether a blended smartphone treatment was non-inferior to a full behavioural activation treatment for depression.Methods:This was a randomised controlled non-inferiority trial (NCT01819025) comparing a blended treatment (n=46) against a full ten-session treatment (n=47) for people suffering from major depression. Primary outcome measure was the BDI-II, that was administered at pre- and post-treatment, as well as six months after the treatment.Results:Results showed significant improvements in both groups across time on the primary outcome measure (within-group Cohen's d=1.35; CI [-0.82, 3.52] to d=1.47; CI [-0.41, 3.35]; between group d=-0.13 CI [-2.37, 2.09] and d=-0.10 CI [-2.53, 2.33]). At the same time, the blended treatment reduced the therapist time with an average of 47%.Conclusions:We could not establish whether the blended treatment was non-inferior to a full BA treatment. Nevertheless, this study points to that the blended treatment approach could possibly treat nearly twice as many patients suffering from depression by using a smartphone application as add-on. More studies are needed before we can suggest that the blended treatment method is a promising cost-effective alternative to regular face-to-face treatment for depression.Trial registration:Cognitive Behavioral Therapy Treatment of Depression With Smartphone Support NCT01819025.

Primary Outcome Measures is Patient Health Questionnaire (PHQ-9)- Change from baseline; Extracted Interventionsis is 4 face-to-face therapy session and a smartphone-app CBT, treatment as usual; Conditions is Depression ;Sex is ALL ;Age is ADULT, OLDER_ADULT