Comparable fasting peak plasma levels ( mean standard deviation ) were demonstrated for submicron indomethacin 40 mg ( 2368.79 631.38 ng/ml ) and indomethacin 50 mg ( 2369.40 969.06 ng/ml ) .


The overall systemic exposure ( geometric least squares mean ; 95 % CI ) was > 21 % lower for submicron indomethacin 40 mg ( 6007.71 ngh/mL ; 5585.73-6461 .58 ) compared with indomethacin 50 mg ( 7646.23 ngh/ml ; 7110.44-8222 .40 ) under fasting conditions .


Food delayed the rate but did not affect the extent of indomethacin absorption from submicron indomethacin 40 mg .


Submicron indomethacin 40 mg administration resulted in earlier time to peak plasma levels ( median 1.67 ; min-max 0.5-3 .5 hours ) under fasting conditions compared with indomethacin 50 mg ( 2.02 ; 0.5-5 .0 hours ) .


Submicron indomethacin 20 and 40 mg were dose proportional and generally well tolerated .


Compared with indomethacin 50 mg , submicron indomethacin 40 mg achieved similar peak plasma concentrations , lower systemic exposure , and a faster time to peak plasma concentration , indicating rapid absorption .


The current formulation of low-dose submicron indomethacin has recently demonstrated efficacy in 2 phase 3 studies in patients with acute pain following bunionectomy and represents a new , low-dose treatment option for patients with acute pain .


To describe the profile of patients who participated in the Randomised Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil ( U-MDT/CT-BR ) and determine the level of satisfaction with a uniform therapy regimen , especially among paucibacillary patients .


This is a descriptive cross-sectional epidemiologic study nested in the wider U-MDT/CT-BR .


The study was conducted using a convenience sample composed of patients from the Dona Libnia Dermatology Centre in Fortaleza , Cear and from the Alfredo da Matta Foundation in Manaus , Amazonas in Brazil .


The absolute and relative frequencies of categorical variables and the median age were calculated .


Hypothesis testing was done using the Chi-squared and Mann-Whitney tests with a 0.05 level of significance .


Of the 859 patients included in the clinical trial , 342 were interviewed .


The majority of patients were male ( 58.2 % ) and multibacillary ( 78.3 % ) with a median age of 42 ( 7-65 ) years .


Most of the interviewees had not completed primary education ( 48.0 % ) , earned an income below three times the minimum wage ( 53.8 % ) , were non-smokers ( 85.1 % ) , did not regularly consume alcohol ( 88.3 % ) , had not experienced any leprosy-related discrimination ( 69.2 % ) and showed a basic knowledge of the disease .


With regards to paucibacillary patients , 87.8 % and 90.9 % of the PB U-MDT and PB R-MDT groups , respectively , indicated that they had not thought of defaulting treatment at any time .


On a satisfaction scale of 1-5 ( with five as the highest score ) , 92.7 % of PB U-MDT and 100.0 % of PB R-MDT patients gave a mark between three and five .


The data suggest that the introduction of clofazimine into the therapeutic regimen did not diminish the level of treatment satisfaction among PB patients .


Circulating tumor cells ( CTCs ) have been shown to predict reduced survival outcomes in metastatic breast cancer .


CTCs were analyzed in 2026 patients with early breast cancer before adjuvant chemotherapy and in 1492 patients after chemotherapy using the CellSearch System .


After immuno-magnetic enrichment for cells expressing the epithelial-cell adhesion molecule , CTCs were defined as nucleated cells expressing cytokeratin and lacking CD45 .


The patients were followed for a median of 35 months ( range = 0-54 ) .


Kaplan-Meier analyses and the log-rank test were used for survival analyses .


All statistical tests were two-sided .


Before chemotherapy , CTCs were detected in 21.5 % of patients ( n = 435 of 2026 ) , with 19.6 % ( n = 136 of 692 ) of node-negative and 22.4 % ( n = 299 of 1334 ) of node-positive patients showing CTCs ( P < .001 ) .


No association was found with tumor size , grading , or hormone receptor status .


After chemotherapy , 22.1 % of patients ( n = 330 of 1493 ) were CTC positive .


The presence of CTCs was associated with poor disease-free survival ( DFS ; P < .0001 ) , distant DFS ( P < .001 ) , breast cancer-specific survival ( P = .008 ) , and overall survival ( OS ; P = .0002 ) .


CTCs were confirmed as independent prognostic markers in multivariable analysis for DFS ( hazard ratio [ HR ] = 2.11 ; 95 % confidence interval [ CI ] = 1.49 to 2.99 ; P < .0001 ) and OS ( HR = 2.18 ; 95 % CI = 1.32 to 3.59 ; P = .002 ) .


The prognosis was worst in patients with at least five CTCs per 30 mL blood ( DFS : HR = 4.51 , 95 % CI = 2.59 to 7.86 ; OS : HR = 3.60 , 95 % CI = 1.56 to 8.45 ) .


The presence of persisting CTCs after chemotherapy showed a negative influence on DFS ( HR = 1.12 ; 95 % CI = 1.02 to 1.25 ; P = .02 ) and on OS ( HR = 1.16 ; 95 % CI = 0.99 to 1.37 ; P = .06 ) CONCLUSIONS : These results suggest the independent prognostic relevance of CTCs both before and after adjuvant chemotherapy in a large prospective trial of patients with primary breast cancer .


Reduction of cardiovascular risk with high consumption of fish in diet is still a matter of debate , and concerns about heavy metal contamination have limited consumption of oily fish .


We aimed to evaluate the effect of regular ingestion of white fish on cardiovascular risk factors in patients with metabolic syndrome .


Multicenter randomized crossover clinical trial including 273 individuals with metabolic syndrome .


An 8-week only-one dietary intervention : 100 g/d of white fish ( Namibia hake ) with advice on a healthy diet , compared with no fish or seafood with advice on a healthy diet .


Outcomes were lipid profile , individual components of the metabolic syndrome , serum insulin concentrations , homeostasis model of insulin resistance , serum C-reactive protein and serum fatty acid levels .


We found a significant lowering effect of the intervention with white fish on waist circumference ( P < 0.001 ) and diastolic blood pressure ( P = 0.014 ) .


A significant lowering effect was also shown after the dietary intervention with fish on serum LDL concentrations ( P = 0.048 ) , whereas no significant effects were found on serum HDL or triglyceride concentrations .


A significant rise ( P < 0.001 ) in serum EPA and DHA fatty acids was observed following white fish consumption .


Overall adherence to the intervention was good and no adverse events were found .


In individuals with metabolic syndrome , regular consumption of hake reduces LDL cholesterol concentrations , waist circumference and blood pressure components of the metabolic syndrome .


White Fish for Cardiovascular Risk Factors in Patients with Metabolic Syndrome Study , Registered under ClinicalTrials.gov Identifier : NCT01758601 .


Despite the popularity of hypnotherapy for smoking cessation , the efficacy of this method is unclear .


We aimed to investigate the efficacy of a single-session of group hypnotherapy for smoking cessation compared to relaxation in Swiss adult smokers .


This was a cluster-randomised , parallel-group , controlled trial .


A single session of hypnosis or relaxation for smoking cessation was delivered to groups of smokers ( median size = 11 ) .


Participants were 223 smokers consuming 5 cigarettes per day , willing to quit and not using cessation aids ( 47.1 % females , M = 37.5 years [ SD = 11.8 ] , 86.1 % Swiss ) .


Nicotine withdrawal , smoking abstinence self-efficacy , and adverse reactions were assessed at a 2-week follow-up .


The main outcome , self-reported 30-day point prevalence of smoking abstinence , was assessed at a 6-month follow up .


Abstinence was validated through salivary analysis .


Secondary outcomes included number of cigarettes smoked per day , smoking abstinence self-efficacy , and nicotine withdrawal .


At the 6-month follow up , 14.7 % in the hypnosis group and 17.8 % in the relaxation group were abstinent .


The intervention had no effect on smoking status ( p = .73 ) or on the number of cigarettes smoked per day ( p = .56 ) .


Smoking abstinence self-efficacy did not differ between the interventions ( p = .14 ) at the 2-week follow-up , but non-smokers in the hypnosis group experienced reduced withdrawal ( p = .02 ) .


Both interventions produced few adverse reactions ( p = .81 ) .


A single session of group hypnotherapy does not appear to be more effective for smoking cessation than a group relaxation session .


Current Controlled Trials ISRCTN72839675 .


A review on headache and insomnia revealed that insomnia is a risk factor for increased headache frequency and headache intensity in migraineurs .


The authors designed a randomized , double blind , placebo-controlled , parallel-group , pilot study in which migraineurs who also had insomnia were enrolled , to test this observation .


In the study , the authors treated 79 subjects with IHS-II migraine with and/or without aura and with DSM-IV primary insomnia for 6 weeks with 3 mg eszopiclone ( Lunesta ( ) ) or placebo at bedtime .


The treatment was preceded by a 2-week baseline period and followed by a 2-week run-out period .


Of the 79 subjects treated , 75 were evaluable , 35 in the eszopiclone group , and 40 in the placebo group .


At baseline , the groups were comparable except for sleep latency .


Of the three remaining sleep variables , total sleep time , nighttime awakenings , and sleep quality , the number of nighttime awakenings during the 6-week treatment period was significantly lower in the eszopiclone group than in the placebo group ( P = 0.03 ) .


Of the three daytime variables , alertness , fatigue , and functioning , this was also the case for fatigue ( P = 005 ) .


The headache variables , frequency , duration , and intensity , did not show a difference from placebo during the 6-week treatment period .


The study did not meet primary endpoint , that is , the difference in total sleep time during the 6-week treatment period between eszopiclone and placebo was less than 40 minutes .


Therefore , it failed to answer the question as to whether insomnia is , indeed , a risk factor for increased headache frequency and headache intensity in migraineurs .


The MAINTAIN study is an on-going RCT comparing high-dose micronutrient and anti-oxidant supplementation versus recommended daily allowance ( RDA ) vitamins in slowing HIV immune deficiency progression in ART-nave people with HIV infection .


We planned analysis of the first 127 participants to determine the baseline prevalence of serum micronutrient deficiencies and correlates , as well as tolerance and adherence to study interventions .


Participants receive eight capsules twice daily of 1 ) high-dose or 2 ) RDA supplements for two years and are followed-up quarterly for measures of immune deficiency progression , safety and tolerability .


Regression analysis was used to identify correlates of micronutrient levels at baseline .


Adherence was measured by residual pill count , self-report using the General Treatment Scale ( GTS ) and short-term recall HIV Adherence Treatment Scale ( HATS ) .


Prior micronutrient supplementation ( within 30 days ) was 27 % at screening and 10 % of study population , and was not correlated with baseline micronutrient levels .


Low levels were frequent for carotene ( 24 % < 1 nmol/L ) , vitamin D ( 24 % < 40 nmol/L ) and serum folate ( 20 % < 15 nmol/L ) .


The proportion with B12 deficiency ( < 133 pmol/L ) was 2.4 % .


Lower baseline levels of B12 correlated lower baseline CD4 count ( r = 0.21 , p = 0.02 ) with a 21 pmol/L reduction in B12 per 100 cells/L CD4 .


Vitamin D levels were higher in men ( p < 0.001 ) .


After a median follow-up of 1.63 years , there were 19 ( 15 % ) early withdrawals from the study treatment .


Mean treatment adherence using pill count was 88 % .


Subjective adherence by the GTS was 81 % and was moderately but significantly correlated with pill count ( r = 0.29 , p < 0.001 ) .


Adherence based on short-term recall ( HATS ) was > 80 % in 75 % of participants .


Micronutrient levels in asymptomatic HIV + persons are in keeping with population norms , but micronutrient deficiencies are frequent .


Adherence levels are high , and will permit a valid evaluation of treatment effects .


ClinicalTrials.gov NCT00798772 .


Gestational diabetes mellitus ( GDM ) increases risks for type 2 diabetes and cardiovascular diseases .


Low glycaemic index ( GI ) diets improve cardio-metabolic outcomes in insulin-resistant individuals .


We examined the feasibility of lowering GI through GI-based-education among Asian post-GDM women .


A 3-month investigation was carried out on 60 Malaysian women with a mean age of 31.0 + / - 4.5 years and a history of GDM .


Subjects were randomised into two groups : LGIE and CHDR .


The CHDR group received conventional healthy dietary recommendations only .


The LGIE group received GI based-education in addition to conventional healthy dietary recommendations .


At baseline and after 3-months , dietary intake of energy and macronutrient intakes including GI diet and glycaemic load was assessed using 3-day food records .


Diabetes-Diet and GI-concept scores and physical activity levels were assessed using a questionnaire .


Adherence to dietary instructions was measured at the end of 3 months .


At the end of 3 months , the LGIE group had significant reductions in energy intake ( 241.7 + / - 522.4 Kcal , P = 0.037 , ES = 0.463 ) , total carbohydrate ( 48.7 + / - 83.5 g , P = 0.010 , ES = 0.583 ) , GI ( 3.9 + / - 7.1 , P = 0.017 , ES = 0.549 ) and GL ( 39.0 + / - 55.3 , P = 0.003 , ES = 0.705 ) and significant increases in protein ( 3.7 + / - 5.4 g , 0.003 , ES = 0.685 ) and diet fibre ( 4.6 + / - 7.3 g , P = 0.06 ) .


The CHDR group had a significant reduction in fat only ( 5.7 + / - 9.4 g , P = 0.006 , ES = 0.606 ) .


There was a 30 % increase in GI-concept scores in the LGIE group ( p < 0.001 ) .


Changes in GI-concept scores correlated significantly to the reduction in dietary GI ( r = -0.642 , P = 0.045 ) .


Dietary adherence was comparable in both groups .


GI-education improves GI-concept knowledge and helps lower dietary glycaemic index among women with a history of GDM .


To determine whether single-dose tranexamic acid given intravenously immediately before surgery for presumed advanced ovarian cancer reduces perioperative blood loss and blood transfusions .


A randomized double-blind , placebo-controlled multicenter study .


Two university hospitals and two central hospitals in the southeast health region of Sweden .


One hundred women with presumed advanced ovarian cancer scheduled for radical debulking surgery between March 2008 and May 2012 who complied with inclusion/exclusion criteria were randomized ; 50 were allocated to receive tranexamic acid and 50 to receive placebo .


Analysis was performed according to intention-to-treat principles .


The volume of tranexamic acid ( 15mg/kg body weight , 100mg/mL tranexamic acid ) or the same volume of placebo ( 0.9 % NaCl ) was added to a 100-mL saline solution plastic bag .


The study medication was given immediately before the start of surgery .


Data were analyzed by means of non-parametric statistics and multivariate models adjusted for confounding factors .


Blood loss and red blood cell transfusions .


The total blood loss volume and transfusion rate were significantly lower in the tranexamic acid group compared with the placebo group .


Median total blood loss was 520 and 730mL , respectively ( p = 0.03 ) .


Fifteen ( 30 % ) and 22 ( 44 % ) , respectively received transfusions ( odds ratio 0.44 ; upper 95 % CI 0.97 ; p = 0.02 ) .


A single dose of tranexamic acid given immediately before surgery reduces blood loss and transfusion rates significantly in advanced ovarian cancer surgery .


Tranexamic acid may be recommended as standard prophylactic treatment in advanced ovarian cancer surgery .


To determine the effectiveness of a physical activity intervention for smoking cessation during pregnancy .


Parallel group , randomised controlled , multicentre trial .


13 hospitals in England , April 2009 to January 2014 .


789 pregnant smokers , aged 16-50 years and at 10-24 weeks ' gestation , who smoked at least one cigarette daily and were prepared to quit smoking one week after enrollment were randomised ( 1:1 ) ; 785 were included in the intention to treat analyses , with 392 assigned to the physical activity group .


Interventions began one week before a target quit date .


Participants were randomised to six weekly sessions of behavioural support for smoking cessation ( control ) or to this support plus 14 sessions combining supervised treadmill exercise and physical activity consultations .


The primary outcome was continuous smoking abstinence from the target quit date until end of pregnancy , validated by exhaled carbon monoxide or salivary cotinine levels .


To assess adherence , levels of moderate-vigorous intensity physical activity were self reported and in a 11.5 % ( n = 90 ) random subsample of participants , physical activity was objectively measured by an accelerometer .


No significant difference was found in rates of smoking abstinence at end of pregnancy between the physical activity and control groups ( 8 % v 6 % ; odds ratio 1.21 , 95 % confidence interval 0.70 to 2.10 ) .


For the physical activity group compared with the control group , there was a 40 % ( 95 % confidence interval 13 % to 73 % ) , 34 % ( 6 % to 69 % ) , and 46 % ( 12 % to 91 % ) greater increase in self reported minutes carrying out physical activity per week from baseline to one week , four weeks , and six weeks post-quit day , respectively .


According to the accelerometer data there was no significant difference in physical activity levels between the groups .


Participants attended a median of four treatment sessions in the intervention group and three in the control group .


Adverse events and birth outcomes were similar between the two groups , except for significantly more caesarean births in the control group than in the physical activity group ( 29 % v 21 % , P = 0.023 ) .


Adding a physical activity intervention to behavioural smoking cessation support for pregnant women did not increase cessation rates at end of pregnancy .


During pregnancy , physical activity is not recommended for smoking cessation but remains indicated for general health benefits .


Trial registration Current Controlled Trials ISRCTN48600346 .


Cisplatin and gemcitabine is the standard first-line chemotherapy regimen for patients with advanced biliary tract cancer ; expression of VEGF and its receptors is associated with adverse outcomes .


We aimed to assess the effect of the addition of cediranib ( an oral inhibitor of VEGF receptor 1 , 2 , and 3 ) to cisplatin and gemcitabine on progression-free survival .


In this multicentre , placebo-controlled , randomised phase 2 study , we recruited patients aged 18 years or older with histologically confirmed or cytologically confirmed advanced biliary tract cancer from hepatobiliary oncology referral centres in the UK .


Patients were eligible if they had an ECOG performance status of 0-1 and an estimated life expectancy of longer than 3 months .


Patients were given first-line cisplatin and gemcitabine chemotherapy ( 25 mg/m ( 2 ) cisplatin and 1000 mg/m ( 2 ) gemcitabine [ on days 1 and 8 every 21 days , for up to eight cycles ] ) with either 20 mg oral cediranib or placebo once a day until disease progression .


We randomly assigned patients ( 1:1 ) with a minimisation algorithm , incorporating the stratification factors : extent of disease , primary disease site , previous treatment , ECOG performance status , and centre .


The primary endpoint was progression-free survival in the intention-to-treat population .


This study is registered with ClinicalTrials.gov , number NCT00939848 , and was closed on Sept 30 , 2014 ; results of the final analysis for the primary endpoint are presented .


Between April 5 , 2011 , and Sept 28 , 2012 , we enrolled 124 patients ( 62 in each group ) .


With a median follow-up of 122 months ( IQR 73-185 ) , median progression-free survival was 80 months ( 95 % CI 65-93 ) in the cediranib group and 74 months ( 57-85 ) in the placebo group ( HR 093 , 80 % CI 074-119 , 95 % CI 065-135 ; p = 072 ) .


Patients who received cediranib had more grade 3-4 toxic effects than did patients who received placebo : hypertension ( 23 [ 37 % ] vs 13 [ 21 % ] ; p = 005 ) , diarrhoea ( eight [ 13 % ] vs two [ 3 % ] ; p = 005 ) ; platelet count decreased ( ten [ 16 % ] vs four [ 6 % ] ; p = 009 ) , white blood cell decreased ( 15 [ 24 % ] vs seven [ 11 % ] ; p = 006 ) and fatigue ( 16 [ 24 % ] vs seven [ 11 % ] ; p = 004 ) .


Cediranib did not improve the progression-free survival of patients with advanced biliary tract cancer in combination with cisplatin and gemcitabine , which remains the standard of care .


Although patients in the cediranib group had more adverse events , we recorded no unexpected toxic effects .


The role of VEGF inhibition in addition to chemotherapy for patients with advanced biliary tract cancer remains investigational .


Cancer Research UK and AstraZeneca Pharmaceuticals .


In the United Kingdom , licensed nicotine-containing products can be recommended to reduce the harm associated with smoking .


Many smokers find currently available nicotine replacement products unsatisfactory .


The arterial and venous pharmacokinetics ( PK ) of nicotine delivered via a novel inhaler device were determined .


Results are reported for Parts A ( N = 18 ) and C ( N = 18 ) of a 4-part ( A-D ) Phase I study .


Participants ( 18-55 years , 10 cigarettes/day , smoking within 1 hr of waking , expired carbon monoxide > 10 ppm on screening ) orally inhaled 2 single doses of nicotine ( 2 of 3 dose levels [ 0.22 , 0.45 , and 0.67 mg ] ) ( Part A ) and repeated hourly doses of 0.67 mg nicotine for 12 hr ( Part C ) , via the novel device .


Arterial and venous PK and tolerability were assessed .


In Part A , mean arterial plasma nicotine concentrations at 2 min after the start of inhalation were 1.10 , 2.06 , and 2.59 ng/mL for the 0.22 , 0.45 , and 0.67 mg doses , respectively .


Mean maximum arterial plasma nicotine concentrations ( C ( max ) ) were 2.11 , 3.73 , and 4.38 ng/mL and mean times to C ( max ) were 10.2 , 7.3 , and 6.5 min after the start of inhalation for the 0.22 , 0.45 , and 0.67 mg doses , respectively .


In Part C , the mean pre - and postdose venous plasma nicotine concentration increased steadily and fluctuated in the range 8-10 mg/mL after 9 hr .


The novel device was well tolerated ; most adverse events were mild .


The novel inhaler device delivers nicotine rapidly into the systemic circulation and offers a viable alternative to cigarettes for those finding it difficult to quit the behavioral and sensorial aspects of smoking .


The N-methyl-D-aspartate glutamate receptor antagonist ketamine , delivered via an intravenous route , has shown rapid antidepressant effects in patients with treatment-resistant depression .


The current study was designed to test the safety , tolerability , and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial .


In a randomized , double-blind , crossover study , 20 patients with major depression were randomly assigned , and 18 completed 2 treatment days with intranasal ketamine hydrochloride ( 50 mg ) or saline solution .


The primary efficacy outcome measure was change in depression severity 24 hours after ketamine or placebo , measured using the Montgomery-sberg Depression Rating Scale .


Secondary outcomes included persistence of benefit , changes in self-reports of depression , changes in anxiety , and proportion of responders .


Potential psychotomimetic , dissociative , hemodynamic , and general adverse effects associated with ketamine were also measured .


Patients showed significant improvement in depressive symptoms at 24 hours after ketamine compared to placebo ( t = 4.39 , p < .001 ; estimated mean Montgomery-sberg Depression Rating Scale score difference of 7.6 3.7 ; 95 % confidence interval , 3.9-11 .3 ) .


Response criteria were met by 8 of 18 patients ( 44 % ) 24 hours after ketamine administration compared with 1 of 18 ( 6 % ) after placebo ( p = .033 ) .


Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters .


This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine .


Treatment was associated with minimal adverse effects .


If replicated , these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression .


High blood pressure is an important public health concern because it is highly prevalent and a risk factor for adverse health outcomes , including coronary heart disease , stroke , decompensated heart failure , chronic kidney disease , and decline in cognitive function .


Observational studies show a progressive increase in risk associated with blood pressure above 115/75 mm Hg .


Prior research has shown that reducing elevated systolic blood pressure lowers the risk of subsequent clinical complications from cardiovascular disease .


However , the optimal systolic blood pressure to reduce blood pressure-related adverse outcomes is unclear , and the benefit of treating to a level of systolic blood pressure well below 140 mm Hg has not been proven in a large , definitive clinical trial .


To describe the design considerations of the Systolic Blood Pressure Intervention Trial ( SPRINT ) and the baseline characteristics of trial participants .


The Systolic Blood Pressure Intervention Trial is a multicenter , randomized , controlled trial that compares two strategies for treating systolic blood pressure : one targets the standard target of < 140 mm Hg , and the other targets a more intensive target of < 120 mm Hg .


Enrollment focused on volunteers of age 50 years ( no upper limit ) with an average baseline systolic blood pressure 130 mm Hg and evidence of cardiovascular disease , chronic kidney disease , 10-year Framingham cardiovascular disease risk score 15 % , or age 75 years .


The Systolic Blood Pressure Intervention Trial recruitment also targeted three pre-specified subgroups : participants with chronic kidney disease ( estimated glomerular filtration rate < 60 mL/min/1 .73 m ( 2 ) ) , participants with a history of cardiovascular disease , and participants 75 years of age or older .


The primary outcome is first the occurrence of a myocardial infarction ( MI ) , acute coronary syndrome , stroke , heart failure , or cardiovascular disease death .


Secondary outcomes include all-cause mortality , decline in kidney function or development of end-stage renal disease , incident dementia , decline in cognitive function , and small-vessel cerebral ischemic disease .


Between 8 November 2010 and 15 March 2013 , Systolic Blood Pressure Intervention Trial recruited and randomized 9361 people at 102 clinics , including 3331 women , 2648 with chronic kidney disease , 1877 with a history of cardiovascular disease , 3962 minorities , and 2636 75 years of age .


Although the overall recruitment target was met , the numbers recruited in the high-risk subgroups were lower than planned .


The Systolic Blood Pressure Intervention Trial will provide important information on the risks and benefits of intensive blood pressure treatment targets in a diverse sample of high-risk participants , including those with prior cardiovascular disease , chronic kidney disease , and those aged 75 years .


To observe the clinical effect of Shen-reinforcing and menstrual cycle-regulating therapy ( SRMCRT ) combined with Western medicine ( WM ) in treating decline in ovarian reserve ( DOR ) .


Totally 78 patients with DOR were assigned to the traditional Chinese medicine combined WM group ( abbreviated as IM group , 40 cases ) , and the WM group ( 38 cases ) according to random digit table method .


Patients in the WM group were treated with hormone replacement therapy , while those in the IM group additionally received SRMCRT .


The therapeutic course for all was 3 consecutive months .


The therapeutic efficacy was compared between the two groups .


The serum levels of follicle stimulating hormone ( FSH ) , FSH/luteinizing hormone ( LH ) , and estradiol ( E2 ) , as well as the development of sinus follicles were compared between before and after treatment in the two groups .


The therapeutic effective rate was 92.5 % in the IM group , higher than that of the WM group ( 73.68 % , P < 0.05 ) .


The serum levels of FSH , FSH/LH , and E2 decreased ( P < 0.05 ) and the number of the sinus follicle increased ( P < 0.05 ) in the two groups after treatment .


Besides , IM was superior in decreasing serum levels of FSH and FSH/LH , and increasing the number of the sinus follicle ( P < 0.05 ) .


SRMCRT was an effective method for treating ROD .


IM was superior in decreasing serum levels of FSH and FSH/LH , and increasing the number of the sinus follicle .


Animal studies suggest that the renin-angiotensin-aldosterone system is involved in neurocognitive function and the response to antihypertensive therapy .


We investigated the impact of circulating aldosterone and renin activity on cognition and cerebral hemodynamics at baseline and after antihypertensive therapy for 1 year .


Participants were older adults ( n = 47 ; mean age = 71 years ) enrolled in a clinical trial .


Routine antihypertensive medications were replaced with the study regimen to achieve a blood pressure < 140/90 mm Hg .


Executive function , memory , cerebral hemodynamics ( blood flow velocity ) , CO2 vasoreactivity ( measured using transcranial Doppler ultrasonography ) , plasma renin activity , and aldosterone were measured at baseline and at 6 and 12 months after the initiation of treatment .


At baseline , higher levels of circulating aldosterone were associated with lower blood flow velocity ( = -0.02 ; P = 0.03 ) , lower CO2 vasoreactivity ( = -0.11 ; P = 0.007 ) , and decreased autoregulation abilities ( = -0.09 ; P = 0.01 ) .


Those with higher levels of aldosterone at baseline demonstrated the greatest improvement in executive function ( P = 0.014 for the aldosterone effect ) and in CO2 vasoreactivity ( P = 0.026 for the aldosterone effect ) after 12 months of lowering blood pressure ( < 140/90 mm Hg ) .


Plasma renin activity was not associated with any of the measures .


Higher levels of aldosterone may be associated with decreased cerebrovascular function in hypertension .


Those with higher aldosterone levels may benefit the most from lowering blood pressure .


The role of aldosterone in brain health warrants further investigation in a larger trial .


To compare the difference in the clinical efficacy on cervical spondylosis between acupuncture at three lines of cervical Jiaji ( EX-B 2 ) and oral administration of jingfukang granules .


Three hundred cases of cervical spondylosis were divided into an acupuncture group and a medication group , 150 cases in each one .


In the acupuncture group , according to the different types of cervical spondylosis , acupuncture was applied at three lines of cervical Jiaji ( EX-B 2 ) , once a day .


In the medication group , jingfukang granules were prescribed for oral administration , one bag each time , three times a day .


The treatment of ten days made one session in the two groups and two sessions were required totally .


Before and after two sessions of treatment , the clinical assessment scale for cervical spondylosis ( CASCS ) was adopted to evaluate the score of subjective symptoms , clinical physical signs and adaptability as well as the total score in the patients of the two groups and the efficacy was compared .


The patients ' symptoms and physical signs were alleviated , the adaptability was improved and the score of each item and the total score were increased in the two groups after treatment ( all P < 0.01 ) .


The improvements in the acupuncture group were better than those in the medication group ( all P < 0.01 ) .


The curative and markedly effective rate was 90.7 % ( 136/150 ) in the acupuncture group , better than 66.0 % ( 99/150 ) in the medication group ( P < 0.01 ) .


Acupuncture at three lines of cervical Jiaji ( EX-B 2 ) achieves the significant clinical efficacy on cervical spondylosis .


This therapy is superior to relieving symptoms and physical signs and recovering adaptability as compared with jingfukang granules .


The standard of care for operable , stage I , non-small-cell lung cancer ( NSCLC ) is lobectomy with mediastinal lymph node dissection or sampling .


Stereotactic ablative radiotherapy ( SABR ) for inoperable stage I NSCLC has shown promising results , but two independent , randomised , phase 3 trials of SABR in patients with operable stage I NSCLC ( STARS and ROSEL ) closed early due to slow accrual .


We aimed to assess overall survival for SABR versus surgery by pooling data from these trials .


Eligible patients in the STARS and ROSEL studies were those with clinical T1-2a ( < 4 cm ) , N0M0 , operable NSCLC .


Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling .


We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint .


Both trials are registered with ClinicalTrials.gov ( STARS : NCT00840749 ; ROSEL : NCT00687986 ) .


58 patients were enrolled and randomly assigned ( 31 to SABR and 27 to surgery ) .


Median follow-up was 402 months ( IQR 230-473 ) for the SABR group and 354 months ( 189-407 ) for the surgery group .


Six patients in the surgery group died compared with one patient in the SABR group .


Estimated overall survival at 3 years was 95 % ( 95 % CI 85-100 ) in the SABR group compared with 79 % ( 64-97 ) in the surgery group ( hazard ratio [ HR ] 014 [ 95 % CI 0017-1190 ] , log-rank p = 0037 ) .


Recurrence-free survival at 3 years was 86 % ( 95 % CI 74-100 ) in the SABR group and 80 % ( 65-97 ) in the surgery group ( HR 069 [ 95 % CI 021-229 ] , log-rank p = 054 ) .


In the surgery group , one patient had regional nodal recurrence and two had distant metastases ; in the SABR group , one patient had local recurrence , four had regional nodal recurrence , and one had distant metastases .


Three ( 10 % ) patients in the SABR group had grade 3 treatment-related adverse events ( three [ 10 % ] chest wall pain , two [ 6 % ] dyspnoea or cough , and one [ 3 % ] fatigue and rib fracture ) .


No patients given SABR had grade 4 events or treatment-related death .


In the surgery group , one ( 4 % ) patient died of surgical complications and 12 ( 44 % ) patients had grade 3-4 treatment-related adverse events .


Grade 3 events occurring in more than one patient in the surgery group were dyspnoea ( four [ 15 % ] patients ) , chest pain ( four [ 15 % ] patients ) , and lung infections ( two [ 7 % ] ) .


SABR could be an option for treating operable stage I NSCLC .


Because of the small patient sample size and short follow-up , additional randomised studies comparing SABR with surgery in operable patients are warranted .


Accuray Inc , Netherlands Organisation for Health Research and Development , NCI Cancer Center Support , NCI Clinical and Translational Science Award .


Major depression is a serious mental disorder that causes substantial distress and impairment in individuals and places an enormous burden on society .


Although antidepressant treatment is the most common therapy provided in routine practice , there is little evidence to guide second-line therapy for patients who have failed to respond to antidepressants .


The aim of this paper is to describe the study protocol for a randomised controlled trial that measures the clinical effectiveness of cognitive behavioural therapy ( CBT ) as an augmentation strategy to treat patients with non-psychotic major depression identified as suboptimal responders to usual depression care .


The current study is a 16-week assessor-blinded randomised , parallel-groups superiority trial with 12-month follow-up at an outpatient clinic as part of usual depression care .


Patients aged 20-65years with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( DSM-IV ) Major Depressive Disorder who have experienced at least one failed trial of antidepressants as part of usual depression care , will be randomly assigned to receive CBT plus treatment as usual , or treatment as usual alone .


The primary outcome is the change in clinician-rated 17-item GRID-Hamilton Depression Rating Scale ( GRID-HAMD ) score at 16weeks , and secondary outcomes include severity and change in scores of subjective depression symptoms , proportion of responders and remitters , safety and quality of life .


The primary population will be the intention-to-treat patients .


All protocols and the informed consent form comply with the Ethics Guideline for Clinical Research ( Japanese Ministry of Health , Labour and Welfare ) .


Ethics review committees at the Keio University School of Medicine and the Sakuragaoka Memorial Hospital approved the study protocol .


The results of the study will be disseminated at several research conferences and as published articles in peer-reviewed journals .


The study will be implemented and reported in line with the CONSORT statement .


UMIN Clinical Trials Registry : UMIN000001218 .


The enigmatic etiology of neurodegenerative diseases poses a challenge for the development of novel and efficient drugs .


The objective of the present study was to evaluate the efficacy of a polyherbal ( test ) formulation on cognitive functions , inflammatory markers and oxidative stress in healthy elderly as well as senile dementia of Alzheimer 's type ( SDAT ) patients .


A randomized double-blind placebo - and active-controlled clinical trial was performed in healthy elderly subjects and SDAT patients with an age range of 60-75 years .


The polyherbal test formulation along with a placebo was given to healthy elderly subjects while the SDAT patients received either the test formulation containing extracts of Bacopa monnieri ( whole plant ) , Hippophae rhamnoides ( leaves and fruits ) and Dioscorea bulbifera ( bulbils ) at a dose of 500 mg or donepezil drug ( Aricept ) at a dose of 10 mg , twice daily , for a period of 12 months .


After every three months , cognitive functions were assessed by determining the mini mental state examination ( MMSE ) score , digital symbol substitution ( DSS ; subtest of the Wechsler Adult Intelligence Scale-Revised ) , immediate and delayed word recall ( digital memory apparatus-Medicaid systems , Chandigarh , India ) , attention span ( Attention Span Apparatus-Medicaid systems , Chandigarh , India ) , functional activity questionnaire ( FAQ ) and depression ( geriatric depression scale ) scores .


Further inflammatory markers and level of oxidative stress were analyzed using standard biochemical tests .


The trial was performed in 109 healthy subjects and 123 SDAT patients of whom 97 healthy subjects and 104 SDAT patients completed the study .


Administration of the test formulation for a period of 12 months was effective in improving cognitive functions in the SDAT patients , when compared to the donepezil-treated group , as determined by the DSS ( 38.984 3.016 vs 35.852 4.906 , P = 0.0001 ) , word recall immediate ( 3.594 1.003 vs 2.794 0.593 , P < 0.0001 ) and attention span ( 4.918 1.239 vs 4.396 0.913 , P = 0.0208 ) scores .


A significant improvement in the FAQ ( 11.873 2.751 vs 9.801 1.458 , P < 0.0001 ) and depression ( 16.387 2.116 vs 21.006 2.778 , P < 0.0001 ) scores was also observed , whereas no significant differences were observed in the MMSE and word recall delayed scores .


The level of inflammation and oxidative stress was markedly reduced in the SDAT patients treated with the test formulation when compared to the donepezil-treated group indicating a likely mechanism of action of the test formulation ( homocysteine 30.22 3.87 vs 44.73 7.11 nmol/L , P < 0.0001 ; C-reactive protein [ CRP ] 4.751 1.149 vs 5.887 1.049 mg/L , P < 0.0001 ; tumour necrosis factor alpha [ TNF - ] 1139.45 198.87 vs 1598.77 298.52 pg/ml , P < 0.0001 ; superoxide dismutase [ SOD ] 1145.92 228.75 vs 1296 225.72 U/g Hb , P = 0.0013 ; glutathione peroxidase [ GPx ] 20.78 3.14 vs 25.99 4.11 U/g Hb , P < 0.0001 ; glutathione [ GSH ] 9.358 2.139 vs 6.831 1.139 U/g Hb , P < 0.0001 ; thiobarbituric acid reactive substances [ TBARS ] 131.62 29.68 vs 176.40 68.11 nmol/g Hb , P < 0.0001 ) .


Similarly , when healthy elderly subjects treated with the test formulation for 12 months were compared to the placebo group , a significant ( P < 0.001 ) improvement in cognitive measures ( MMSE , DSS , word recall delayed but not immediate , attention span , FAQ and depression scores ) and a reduction in inflammation ( reduction in homocysteine , CRP , IL-6 and TNF - levels ) and oxidative stress levels ( reduction in SOD , GPx and TBARS and increase in GSH ) was observed .


This indicated a protective effect of the test formulation in managing cognitive decline associated with the ageing process .


The results of this study demonstrate the therapeutic potential of this novel polyherbal formulation for the management and treatment of SDAT .


To determine the costs and cost-effectiveness of an early childhood home visiting program delivered to families in socio-economically disadvantaged areas of Sydney , Australia during 2007-2010 .


Economic evaluation of a randomized controlled trial , the healthy beginnings ( HB ) trial , from the perspective of the health funder .


Intervention resources were determined from local health district records in 2012 $ AUD .


Health-care resource utilization was determined through patient-level data linkage .


The cost of HB intervention in the clinical trial over 2 years was $ 1309 per child ( 2012 $ AUD ) .


The incremental cost-effectiveness ratio was $ 4230 per unit BMI avoided and $ 631 per 0.1 reduction in BMI z-score .


It was estimated that the program could be delivered in practice for $ 709 per child ; with incremental cost-effectiveness ratios of $ 2697 per unit BMI avoided and $ 376 per 0.1 reduction in BMI z-score .


We present the first economic evaluation of an effective obesity prevention initiative in early childhood .


HB is a moderately priced intervention with demonstrated effectiveness that offers similar or better value for money than existing obesity prevention or treatment interventions targeted at older children .


To compare the Helicobacter pylori ( H. pylori ) eradication rate of clarithromycin-based triple therapy , metronidazole-based triple therapy , sequential therapy and concomitant therapy .


A total of 680 patients infected with H. pylori were divided into 4 groups and each group was treated with a different eradication therapy .


Clarithromycin-based triple therapy was applied to the first group [ rabeprazole , amoxicillin and clarithromycin ( PAC ) group : proton pump inhibitor ( PPI ) , amoxicillin , clarithromycin ] , whereas the second group was treated with metronidazole-based triple therapy [ rabeprazole , amoxicillin and metronidazole ( PAM ) group : PPI , amoxicillin , metronidazole ] .


The third group was treated with rabeprazole and amoxicillin , followed by rabeprazole , clarithromycin and metronidazole ( sequential group ) .


The final group was simultaneously treated with rabeprazole , amoxicillin clarithromycin and metronidazole ( concomitant therapy group ) .


In the case of a failure to eradicate H. pylori , second-line quadruple and third-line eradication therapies were administered .


The per protocol ( PP ) analysis was performed on 143 , 139 , 141 and 143 patients in the PAC , PAM , sequential and concomitant groups , respectively .


We excluded patients who did not receive a C ( 13 ) - urea breath test ( 22 , 20 , 23 and 22 patients , respectively ) and patients with less than an 80 % compliance level ( 5 , 11 , 6 and 5 patients , respectively ) .


The eradication rates were 76.2 % ( 109/143 ) in the PAC group , 84.2 % ( 117/139 ) in the PAM group , 84.4 % ( 119/141 ) in the sequential group and 94.4 % ( 135/143 ) in the concomitant group ( P = 0.0002 ) .


All 14 patients who failed second-line therapy were treated with third-line eradication therapy .


Among these 14 patients , 6 infections were successfully eradicated with the third-line therapy .


Both PP and intention-to-treat analysis showed an eradication rate of 42.9 % ( 6/14 ) .


In the PAC group , 3 of 4 patients were successfully cured ( 3/4 , 75 % ) ; 2 of 2 patients in the PAM group ( 2/2 , 100 % ) and 1 of 5 patients in the sequential group ( 1/5 , 20 % ) were also cured .


In the concomitant group , all 3 patients failed ( 0/3 , 0 % ) .


The eradication rate for the concomitant therapy was much higher than those of the standard triple therapy or sequential therapy ( ClinicalTrials.gov number NCT01922765 ) .


Ramucirumab is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2 .


We aimed to assess efficacy and safety of treatment with docetaxel plus ramucirumab or placebo as second-line treatment for patients with stage IV non-small-cell-lung cancer ( NSCLC ) after platinum-based therapy .


In this multicentre , double-blind , randomised phase 3 trial ( REVEL ) , we enrolled patients with squamous or non-squamous NSCLC who had progressed during or after a first-line platinum-based chemotherapy regimen .


Patients were randomly allocated ( 1:1 ) with a centralised , interactive voice-response system ( stratified by sex , region , performance status , and previous maintenance therapy [ yes vs no ] ) to receive docetaxel 75 mg/m ( 2 ) and either ramucirumab ( 10 mg/kg ) or placebo on day 1 of a 21 day cycle until disease progression , unacceptable toxicity , withdrawal , or death .


The primary endpoint was overall survival in all patients allocated to treatment .


We assessed adverse events according to treatment received .


This study is registered with ClinicalTrials.gov , number NCT01168973 .


Between Dec 3 , 2010 , and Jan 24 , 2013 , we screened 1825 patients , of whom 1253 patients were randomly allocated to treatment .


Median overall survival was 105 months ( IQR 51-212 ) for 628 patients allocated ramucirumab plus docetaxel and 91 months ( 42-180 ) for 625 patients who received placebo plus docetaxel ( hazard ratio 086 , 95 % CI 075-098 ; p = 0023 ) .


Median progression-free survival was 45 months ( IQR 23-83 ) for the ramucirumab group compared with 30 months ( 14-69 ) for the control group ( 076 , 068-086 ; p < 00001 ) .


We noted treatment-emergent adverse events in 613 ( 98 % ) of 627 patients in the ramucirumab safety population and 594 ( 95 % ) of 618 patients in the control safety population .


The most common grade 3 or worse adverse events were neutropenia ( 306 patients [ 49 % ] in the ramucirumab group vs 246 [ 40 % ] in the control group ) , febrile neutropenia ( 100 [ 16 % ] vs 62 [ 10 % ] ) , fatigue ( 88 [ 14 % ] vs 65 [ 10 % ] ) , leucopenia ( 86 [ 14 % ] vs 77 [ 12 % ] ) , and hypertension ( 35 [ 6 % ] vs 13 [ 2 % ] ) .


The numbers of deaths from adverse events ( 31 [ 5 % ] vs 35 [ 6 % ] ) and grade 3 or worse pulmonary haemorrhage ( eight [ 1 % ] vs eight [ 1 % ] ) did not differ between groups .


Toxicities were manageable with appropriate dose reductions and supportive care .


Ramucirumab plus docetaxel improves survival as second-line treatment of patients with stage IV NSCLC .


Eli Lilly .


We compared the long-term success of desmopressin sublingual lyophilisate formulation and enuretic alarm therapy in children with primary monosymptomatic nocturnal enuresis , and determined predictive factors for treatment success .


A total of 142 children with primary monosymptomatic nocturnal enuresis were randomized to receive treatment consisting of desmopressin or enuretic alarm for 6 months .


Treatment compliance and response were reviewed monthly in each patient using a 30-day bed-wetting diary .


Outcomes were assessed according to International Children 's Continence Society criteria , and success rates at 6 and 12 months were compared for desmopressin and enuretic alarm .


Additional intention to treat analyses were performed , considering cases with missing data as failures .


Possible demographic factors predicting success were investigated by logistic regression analysis .


Overall 4 children ( 5.2 % ) in the desmopressin group and 20 ( 30.7 % ) in the enuretic alarm group withdrew after randomization .


Based on patients who completed 6 months of treatment , success ( more than 90 % reduction in wet nights per month ) was achieved in 76.8 % and 61.8 % of children in the desmopressin and enuretic alarm groups , respectively .


At 12 months 77.8 % of those receiving desmopressin and 75 % of those treated with enuretic alarm had success .


However , long-term success rate was significantly higher with desmopressin ( 68.8 % vs 46.2 % ) if intention to treat population was considered .


Multivariate analysis revealed treatment group , severity of enuresis and monthly income as independent predictors of cure at 6 months .


In compliant patients desmopressin lyophilisate and enuretic alarm provided equivalent success at the end of treatment and after extended followup .


Alarm therapy had a high rate of early withdrawal from therapy and consequently lower rates of success on intention to treat analyses .


Severe enuresis ( more than 5 wet nights weekly ) is an important predictive factor for cure after first-line treatment .


Following from previous research in which post-encoding suggestions of threat led to the development of a memory bias ( in the presumed absence of an attentional bias ; Senn & Radomsky , 2012 ) , we sought to examine whether the development of a similar threat-relevant memory bias could be fostered via a purely informational pathway .


A vignette about a classroom interaction was read aloud to ( n = 96 ) undergraduate participants who then completed a post-encoding recall test .


Participants were told that the experimenter forgot to read the last sentence of the vignette , and were then randomly assigned either to the Threat condition , in which the additional statement indicated that a character in the vignette had a highly contagious flu , or to the No-Threat condition , in which the additional statement indicated that a character in the vignette had been accepted to graduate school .


A second recall test was then administered .


Participants in the Threat condition ( but not those in the No-Threat condition ) demonstrated aproportionate memory bias in favor of threatening information .


This bias was not evident at the initial recall test .


Time spent engaging in active recall was not assessed .


Also , although the study was designed to minimize demand characteristics , it is possible that these played a role .


An explicit memory bias for threat can be created through informational means alone , even when no threat was present at encoding .


Results are discussed in terms of pathways to fear and of cognitive approaches to understanding and treating anxiety disorders .


To evaluate the multi-function rapid allergic skin test instrument for application in drug allergy testing .


Three hundred patients were planned to be treated with cephalosporins Injection were divided randomly into 3 groups , the new allergic skin test instrument group , normal allergic skin test instrument group , and traditional skin test group , the true positive rate and false positive rate were calculated .


Using multifunctional rapid allergy skin test was carried out on 210 cases of volunteers preliminary clinical evaluation of traditional Chinese medicine injections skin test .


There were no significance difference between the new allergic skin test instrument group and control group in the true positive rate .


As compared with the control group , a significance difference was found between the new allergic skin test instrument group and control group in false positive rate respectively ( P < 0.05 ) .


The multi-function rapid allergic skin test instrument is safe and easy to use , with a higher rate of accuracy and lower false positive rate .


Current medical knowledge has provided us with a wide range of possibilities of treating chronic wounds .


Over the recent decades , in particular , significant progress has been made in this field .


The authors present an overview of current knowledge of chronic wound healing , pointing out the surgeons role in the process of chronic wound management .


Using surgical therapy , we are able to heal a chronic wound in a shorter period of time , particularly if the treatment is accelerated by the application of platelet-rich plasma ( PRP ) as a source of growth factors .


The pilot randomized prospective study included four patients with chronic wounds of the lower leg after previous failure of conservative therapy who were indicated for skin transplantation .


Following previous vacuum-assisted closure therapy , the patients undergoing skin transplantation were prospectively randomized into two groups .


Autologous PRP was used in one of the groups and standard skin transplantation without PRP was performed in the other one .


In the PRP group , 99 % of the wound areas were healed on the 15th day after the operation .


In the other group , 90 % of the areas were healed on the 15th day following the operation .


In the PRP group , complete healing of the defect occurred in both patients at 15 and 20 days post-surgery .


In the second group , one patient completely healed within 28 days ; the other one was not fully healed even at 3 months post-surgery .


Most patient groups at great risk may benefit from the method using PRP , as well as patients with chronic wounds who have failed conventional methods available for both general and local therapy .


This fact has been confirmed by the authors initial experience presented.Key words : platelet-rich plasma ( PRP ) - platelets wound healing chronic wound .


To compare lag-screw sliding characteristics and fixation stability of two cephalomedullary nails ( CMN ) with different lag-screw designs ( solid and telescopic ) , we conducted a biomechanical study and an analysis of clinical results .


Six pairs of cadaver femurs with simulated intertrochanteric fractures were randomly assigned to one of two CMN fixations .


Femur constructs were statically then cyclically loaded on an MTS machine .


Lag-screw sliding and inferior and lateral femoral head displacements were measured , following which failure strength of the construct was determined .


Forty-five patients with intertrochanteric fractures treated with these CMN were identified .


Medical records and radiographs were reviewed and analyzed using Fisher 's exact test and Student 's t test to determine lag-screw sliding .


No difference was seen with cycling in inferior femoral head displacement between the two screw designs .


The solid screw had an average inferior head displacement of 1.75 mm compared with 1.59 mm for the telescoping screw ( p = 0.772 ) .


The solid lag screws slid an average of 2.79 mm lateral from the nail , whereas the telescoping screws slid an average of 0.27 mm ( p = 0.003 ) .


In our clinical review , the average lateral sliding of the telescoping screw was 0.5 mm and of the solid screw was 3.7 mm ( p < 0.001 ) .


Despite differences in lateral sliding , there were no reoperations for prominent or painful hardware in either group .


Both designs are acceptable devices for stabilization of intertrochanteric fractures .


Clinical and biomechanical data demonstrate greater lateral sliding in the solid lag-screw group , making for greater potential for lateral-sided hip pain in CMNs with solid lag screws as opposed to telescoping lag screws .


Neonatal diagnoses are often used as surrogate endpoints for longer-term outcomes .


We sought to characterize the correlation between neonatal diagnoses and early childhood neurodevelopment .


We conducted secondary analysis of a multicenter randomized controlled trial of antenatal magnesium sulfate vs placebo administered to women at imminent risk for delivery < 32.0 weeks to prevent death and cerebral palsy in their offspring .


Singletons and twins delivering 23.0-33 .9 weeks who survived to hospital discharge and had 2-year-old outcome data were included .


Those surviving to age 2 years were assessed by trained physicians and the Bayley II Scales of Infant Development Mental Development and Psychomotor Development Indices .


Neonatal diagnoses at the time of each baby 's initial hospital discharge were examined singly and in combination to determine those most predictive of childhood neurodevelopmental impairment , defined as a childhood diagnosis of moderate/severe cerebral palsy and/or Bayley scores > 2 SD below the mean .


Data were analyzed by multiple regression models and area under receiver operating characteristic curves .


A total of 1771 children met criteria .


Children were delivered at a mean of 29.4 weeks ' gestation .


In all , 459 ( 25.9 % ) had neurodevelopmental impairment .


In models controlling for gestational age at delivery , maternal education , maternal race , tobacco/alcohol/drug use during pregnancy , randomization to magnesium , fetal sex , and chorioamnionitis , individual neonatal morbidities were moderately predictive of childhood neurodevelopmental impairment ( best model area under receiver operating characteristic curve , 0.68 ; 95 % confidence interval , 0.65-0 .71 ) .


Combinations of 2 , 3 , and 4 morbidities did not improve the prediction of neurodevelopmental impairment .


Approximately 1 in 4 previously preterm children had neurodevelopmental impairment at age 2 years .


Prediction of childhood outcomes from neonatal diagnoses remains imperfect .


This 24-week , multicenter , double-blind , randomized , placebo-controlled study ( NCT00791999 ) compared efficacy and safety of certolizumab pegol ( CZP ) in combination with methotrexate ( MTX ) vs placebo plus MTX in Japanese rheumatoid arthritis ( RA ) patients with inadequate response to MTX .


In total , 316 patients were randomized 1:1:1:1 to subcutaneous CZP 100 , 200 , or 400 mg ( induction dose : 200 mg or 400 mg CZP at Weeks 0 , 2 , and 4 ) plus MTX or placebo plus MTX every 2 weeks .


Primary endpoint was ACR20 response at Week 12 .


ACR20 response rates were 62.5 % , 76.8 % , 77.6 % , and 28.6 % at Week 12 , and 61.1 % , 73.2 % , 71.8 % , and 24.7 % at Week 24 for CZP 100 , 200 , and 400 mg , and placebo groups , respectively , with statistical significance between each CZP group and placebo .


Change in Total Sharp Score over 24 weeks was significantly smaller in CZP 200 and 400 mg groups vs placebo .


Improvements in health-related quality of life ( HRQoL ) were observed in all three CZP groups vs placebo .


Incidence of adverse events was similar between CZP groups .


CZP plus MTX resulted in rapid , sustained reductions in RA signs and symptoms in Japanese patients with inadequate response to MTX , with significant inhibition of radiographic progression and improved HRQoL .


Growth hormone deficiency ( GHD ) is associated with reduced bone mineral content and increased risk of osteoporotic fractures .


Reduced peak bone mass might explain the low bone mineral density ( BMD ) among patients with childhood onset GHD ( CO-GHD ) whilst the cause of osteopenia in adult-onset GHD ( AO-GHD ) is not fully understood .


Prospective multicentric study to asses bone status in GHD adults after two years of recombinant growth hormone replacement treatment .


In 94 GHD adults ( 49 men ; 34.5 yrs ) we have measured BMD and bone markers ( CTX , osteocalcin ) during two years of rhGH treatment ( at baseline , after 3 and 6 months , and after 1 and 2 years ) .


Patients were adequately substituted for GHD and other pituitary deficiencies .


We have observed an increase in BMD-lumbar spine : n = 42 , 0.8155 0.9418 g/cm2 , p < 0.0001 ; femoral neck n = 41 ; 0.8468 0.9031 ; p = 0.0004 ; BMD-whole body 1.0179 1.0774 ; p = 0.0003 .


We have compared gender difference : BMD-L-spine by 15.8 % in men ( n = 21 ) and by 5.6 % in women ( n = 19 ) ( p = 0.008 ) ; BMD-femoral neck increased by 11.03 % in men and by about 3.0 % in women ( p = 0.032 ) .


In women , the initial decrease in BMD was recorded after 3 months .


CO-GHD adults yielded a higher increase in BMD - L-spine ( 16.6 % , p = 0.022 ) .


A correlation exists between IGF-I levels and BMD in lumbar spine ( 1st year : R = 0.348 , p = 0.026 ; 2nd year : R = 0.33 , p = 0.0081 ) and between IGF-I and osteocalcin ( 1st year : R = 0.383 ; p = 0.0038 ) .


Two-year therapy with recombinant human growth hormone improved bone status .


IGF-I appears to be a good indicator of rhGH effect on bone ( Tab .


3 , Fig. 9 , Ref .


36 ) .


Text in PDF www.elis.sk .


Up to 70 % of patients with treatment-resistant schizophrenia do not respond to clozapine .


Pharmacological augmentation to clozapine has been studied with unimpressive results .


The authors examined the use of ECT as an augmentation to clozapine for treatment-refractory schizophrenia .


In a randomized single-blind 8-week study , patients with clozapine-resistant schizophrenia were assigned to treatment as usual ( clozapine group ) or a course of bilateral ECT plus clozapine ( ECT plus clozapine group ) .


Nonresponders from the clozapine group received an 8-week open trial of ECT ( crossover phase ) .


ECT was performed three times per week for the first 4 weeks and twice weekly for the last 4 weeks .


Clozapine dosages remained constant .


Response was defined as 40 % reduction in symptoms based on the psychotic symptom subscale of the Brief Psychiatric Rating Scale , a Clinical Global Impressions ( CGI ) - severity rating < 3 , and a CGI-improvement rating 2 .


The intent-to-treat sample included 39 participants ( ECT plus clozapine group , N = 20 ; clozapine group , N = 19 ) .


All 19 patients from the clozapine group received ECT in the crossover phase .


Fifty percent of the ECT plus clozapine patients met the response criterion .


None of the patients in the clozapine group met the criterion .


In the crossover phase , response was 47 % .


There were no discernible differences between groups on global cognition .


Two patients required the postponement of an ECT session because of mild confusion .


The augmentation of clozapine with ECT is a safe and effective treatment option .


Further research is required to determine the persistence of the improvement and the potential need for maintenance treatments .


To evaluate the performance effect of short-term catheter-directed thrombolysis with different dosage of rt-PA allied with endovascular interventional therapy for patients with acute lower limb ischemia .


To separate 84 consecutive patients suffered from acute lower limb ischemia into two groups at random , then adopt catheter-directed thrombolysis for each group of patients injected 20 mg ( Group A ) or 10 mg ( Group B ) rt-PA into the occlusive lesion correspondingly , and subsequently perform endovascular intervention on significant underlying lesions on the base of angiography results .


Adopt statistical methods to assess treatment effectiveness , rates of complication and amputation rates within 30 days , 6 months or 12 months .


The statistic analysis was performed under SPSS 16.0 format , and adopts t test and ( 2 ) test .


There was no statistical difference on patient characteristics and lesions between both groups ( P > 0.05 ) .


Procedural success rates as well clinical success rates were all 100 % .


Not incur any diversity on thrombolysis effectiveness between both groups injected different dosage of rt-PA ( P > 0.05 ) .


Not found major differences on ratios of PTA or implant stent between both groups ( P > 0.05 ) .


During the follow-up period of 30-day , 6 - , 12 - months , there were no statistical differences on the amputation-free survival rates and complication rates between both groups .


Whereas short-term catheter-directed thrombolysis combined with endovascular interventional therapy won good operation effectiveness on patients with acute lower limb ischemia , moreover the dosage of rt-PA did not impact on thrombolysis , it is worthy to be applied in the clinical practice .


The Prevencin con Dieta Mediterrnea ( PREDIMED ) trial showed that a Mediterranean diet ( MedDiet ) supplemented with either extra virgin olive oil or 30 g/d of mixed nuts reduced incident cardiovascular events compared with a control ( low fat ) diet .


The mechanisms of cardiovascular protection afforded by MedDiets remain to be uncovered .


We assessed the effect of both supplemented MedDiets on internal carotid intima-media thickness ( ICA-IMT ) and plaque height , the ultrasound features that best predict future cardiovascular events , in subjects at high cardiovascular risk .


In a PREDIMED subcohort ( n = 175 ) , plaque height and carotid IMT of 3 prespecified segments ( ICA , bifurcation , and common ) were sonographically assessed at baseline and after intervention for a mean of 2.4 years .


We evaluated 164 subjects with complete data .


In a multivariate model , mean ICA-IMT progressed in the control diet group ( mean [ 95 % confidence interval ] , 0.052 mm [ -0.014 to 0.118 mm ] ) , whereas it regressed in the MedDiet + nuts group ( -0.084 mm [ -0.158 to -0.010 mm ] ; P = 0.024 versus control ) .


Similar results were observed for maximum ICA-IMT ( control , 0.188 mm [ 0.077 to 0.299 mm ] ; MedDiet + nuts , -0.030 mm [ -0.153 to 0.093 mm ] ; P = 0.034 ) and maximum plaque height ( control , 0.106 mm [ 0.001 to 0.210 mm ] ; MedDiet + nuts , -0.091 mm [ -0.206 to 0.023 mm ] ; P = 0.047 ) .


There were no changes in ICA-IMT or plaque after the MedDiet + extra virgin olive oil .


Compared with a control diet , consumption of a MedDiet supplemented with nuts is associated with delayed progression of ICA-IMT and plaque .


The results contribute mechanistic evidence for the reduction of cardiovascular events observed in the PREDIMED trial .


http://www.controlled-trials.com .


Unique identifier : ISRCTN35739639 .


This study assessed the efficacy and safety of the once-daily glucagon-like peptide-1 receptor agonist , lixisenatide , in Asian patients with type 2 diabetes mellitus inadequately controlled on metforminsulfonylurea .


In this 24-week , double-blind , placebo-controlled , multinational study , patients were randomized to lixisenatide 20 g once daily or placebo .


The primary endpoint was absolute change in glycated haemoglobin ( HbA1c ) from baseline to week 24 .


A total of 391 patients were randomized .


Lixisenatide significantly reduced HbA1c levels compared with placebo ( LS mean difference : -0.36 % , p = 0.0004 ) .


A significantly higher proportion of lixisenatide-treated patients achieved HbA1c targets of < 7 % ( p = 0.003 ) and 6.5 % ( p = 0.001 ) versus placebo .


Lixisenatide was associated with a statistically significant reduction in 2-h postprandial plasma glucose after a standardized breakfast versus placebo ( LS mean difference : -4.28 mmol/L , p < 0.0001 ) and a significant reduction in fasting plasma glucose ( p = 0.0109 ) .


There was no difference in weight loss versus placebo , with a modest reduction in body weight reported for both groups ( lixisenatide : -1.50 kg , placebo : -1.24 kg ; p = 0.296 ) .


The incidence of treatment-emergent adverse events ( TEAEs ) was 64.3 % with lixisenatide versus 47.4 % with placebo , with serious TEAEs reported in 1.5 % versus 2.1 % of patients , respectively .


The most common TEAE in the lixisenatide group was nausea ( 16.3 % vs 2.6 % with placebo ) .


The incidence of symptomatic hypoglycaemia was 5.6 % with lixisenatide treatment and 2.6 % with placebo ( p = 0.1321 ) , with no severe symptomatic hypoglycaemia events reported .


In Asian patients with type 2 diabetes mellitus insufficiently controlled on metforminsulfonylurea , lixisenatide significantly improved glycaemic control and was well tolerated during the 24-week study .


School absenteeism because of infections is one of the most important problems facing both public and private primary schools .


The aim of the study was to assess the impact of infections on school absenteeism and their reduction with a handwashing program using hand sanitizer .


The study was an 8-month-long , randomized , controlled open study ( N = 1,609 children , aged 4-12 years old ) at 5 state schools in Almeria ( Spain ) .


The experimental group ( EG ) washed their hands with soap and water , complemented with the use of hand sanitizer , and the control group ( CG ) followed the usual handwashing procedure .


The total number of episodes and days missed as well as those because of upper respiratory infections and gastrointestinal infections were compared in both groups with a Z-test .


The students were absent 12,386 days in 7,945 episodes .


The incidence of total absent episodes and percent of missed days , including those because of upper respiratory infections and gastrointestinal infections , were significantly lower in the EG than the CG ( P < .001 ) , and this was maintained through the flu pandemic period .


School absenteeism because of infections in schools is reduced when a hand hygiene program utilizing sanitizing gels is properly carried out , especially during the flu season .


The purpose of the study was to measure contact lens lipid spoliation of silicone hydrogel PureVision ( balafilcon A ) and hydrogel Acuvue 2 ( etafilcon A ) contact lenses worn for 10 hours single use ( DD ) and 7 days of extended wear ( EW ) .


Two similar study populations ( DD , n = 55 ; EW , n = 53 ) , were enrolled at four study sites .


In each population , a bilateral , randomized , crossover ( lens material ) , subject-masked experimental design was followed .


Worn contact lenses were analyzed for lipid uptake using high-performance liquid chromatography by two laboratories : Alcon Laboratories ( right lens total uptake ) and OTG Research & Consultancy ( left lens total uptake and individual lipid classes ) .


Lipid uptake was different for the two materials : total lipid ( p < 0.007 ) , cholesterol esters ( p < 0.001 ) , cholesterol ( p < 0.001 EW only ) , and triglycerides/phospholipids ( p < 0.001 ) were higher for balafilcon A , whereas fatty acid ( p < 0.0025 EW only ) was higher for etafilcon A.


The ratio of the extracted lipids was also different : higher percentages of triglycerides/phospholipids ( p < 0.001 ) and cholesterol ( p < 0.001 EW only ) for balafilcon A and higher percentages of fatty acids/di - and monoglycerides ( p < 0.014 ) for etafilcon A.


Total lipid uptake was highly material dependent .


Both laboratories measured a greater uptake of lipids by the silicone hydrogel than the hydrogel material , a difference that was evident after only 10 hours of DD .


Total lipid uptake was greater after 7 days of EW compared with 10 hours of DD .


Of interest for contact lens spoliation and its avoidance was the differential lipid uptake profile , indicating material selectivity .


Whereas greater differentiation between materials was possible after 7 days of EW for each material , the lipid uptake profile was similar for DD and EW , indicating a greater material effect than a wear modality effect .


This study was done to investigate how nicardipine , remifentanil and dexmedetomidine affect the balance of the autonomic nervous system in patients receiving controlled hypotension under general anaesthesia by evaluating heart rate variability indices .


Sixty-two patients were randomly allocated to either the nicardipine-sevoflurane ( Group N , n = 21 ) , remifentanil-sevoflurane ( Group R , n = 21 ) or dexmedetomidine-sevoflurane ( Group D , n = 20 ) group for controlled hypotension during orthognathic surgery .


Electrocardiogram data acquisition was done after vital sign stabilization following anaesthesia induction ( T1 ) and 30min after controlled hypotension was induced ( T2 ) .


Total power and low frequency ( LF ) power was significantly decreased at T2 compared with T1 in all groups , while a decrease in high frequency ( HF ) power was only observed in Group N ( P < 0.001 ) .


LF/HF ratios of Group R and D were significantly suppressed at T2 compared with T1 ( P = 0.001 and P < 0.001 , respectively ) , but was increased Group N ( P = 0.009 ) .


The LF/HF ratio of Group N was significantly higher than Group R and D at T2 ( P < 0.001 in both ) , with Group D showing a significantly lower LF/HF ratio compared with Group R ( P < 0.001 ) .


Remifentanil and dexmedetomidine did not have sympathetic nervous system-stimulating effects during controlled hypotension , while remifentanil seemed to be superior in preserving the overall balance in autonomic nervous system activity .


Nicardipine was found to stimulate the sympathetic nervous system , which may be problematic in patients vulnerable to disturbances in the autonomic nervous system .


Vortioxetine ( Lu AA21004 ) is an antidepressant with a mechanism of action thought to be related to a combination of 2 pharmacologic actions : direct modulation of several receptors and inhibition of the serotonin transporter .


To evaluate the efficacy of vortioxetine 10 and 20 mg once daily in outpatients with major depressive disorder .


This 8-week , multicenter , randomized , double-blind , placebo-controlled , parallel-group study was conducted from July 2010 to January 2012 among adults with a primary diagnosis of recurrent major depressive disorder ( DSM-IV-TR ) .


Eligible subjects were randomized in 1:1:1 ratio to 1 of 3 treatment arms : vortioxetine 10 mg , vortioxetine 20 mg , or placebo once daily for 8 weeks .


Subjects who completed the 8-week trial entered a 2-week blinded discontinuation period to assess potential discontinuation symptoms .


The primary endpoint was the least squares mean change in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score from baseline .


Key secondary outcomes were analyzed in the following prespecified sequential order : MADRS response ( 50 % decrease from baseline in total score ) , Clinical Global Impressions-Improvement score , change from baseline in MADRS total score in subjects with baseline Hamilton Anxiety Rating Scale score 20 , MADRS remission ( total score 10 ) , and change from baseline in Sheehan Disability Scale total score ( all at week 8 ) .


A total of 462 subjects were randomized to placebo ( n = 157 ) , vortioxetine 10 mg ( n = 155 ) , and vortioxetine 20 mg ( n = 150 ) .


Mean ( SE ) reductions from baseline in MADRS total score ( week 8 ) were -10.77 ( 0.807 ) , -12.96 ( 0.832 ) , and -14.41 ( 0.845 ) for the placebo , vortioxetine 10 mg ( P = .058 vs placebo ) , and vortioxetine 20 mg ( P = .002 vs placebo ) groups .


MADRS response/remission was achieved in 28.4 % / 14.2 % , 33.8 % / 21.4 % , and 39.2 % / 22.3 % of subjects , respectively , in the 3 groups .


Only MADRS response for vortioxetine 20 mg significantly separated from placebo ( P = .044 ) .


Treatment was well tolerated , with the most frequently reported adverse events consisting of nausea , headache , diarrhea , and dizziness .


Vortioxetine 20 mg significantly reduced MADRS total score at 8 weeks in this study population .


Overall , vortioxetine was well tolerated in this study .


ClinicalTrials.gov identifier : NCT01163266 .


Experimental evidence has indicated the benefits of simvastatin for the treatment of subarachnoid hemorrhage .


Two randomized placebo-controlled pilot trials that used the highest clinically approved dose of simvastatin ( 80 mg daily ) gave positive results despite the fact that a lower dose of simvastatin ( 40 mg daily ) did not improve clinical outcomes .


We hypothesized that a high dose of 80 mg of simvastatin daily for 3 weeks would reduce the incidence of delayed ischemic deficits after subarachnoid hemorrhage compared with a lower dose ( 40 mg of simvastatin daily ) and lead to improved clinical outcomes .


The study design was a randomized controlled double-blinded clinical trial .


Patients with aneurysmal subarachnoid hemorrhage ( presenting within 96 hours of the ictus ) from 6 neurosurgical centers were recruited for 3 years .


The primary outcome measure was the presence of delayed ischemic deficits , and secondary outcome measures included a modified Rankin disability score at 3 months and an analysis of cost-effectiveness .


No difference was observed between the groups treated with the higher dose or the lower dose of simvastatin in the incidence of delayed ischemic deficits ( 27 % versus 24 % ; odds ratio , 1.2 ; 95 % confidence interval , 0.7-2 .0 ; P = 0.586 ) or in the rate of favorable outcomes ( modified Rankin Scale score , 0-2 ) at 3 months ( 73 % versus 72 % ; odds ratio , 1.1 ; 95 % confidence interval , 0.6-1 .9 ; P = 0.770 ) .


High-dose simvastatin treatment should not be prescribed routinely for aneurysmal subarachnoid hemorrhage .


http://www.clinicaltrials.gov .


Unique identifier : NCT01077206 .


We examined the cost-effectiveness of an intervention to reduce coronary heart disease ( CHD ) risk and blood pressure in African Americans .


Stochastic cost-effectiveness analysis alongside a clinical trial , augmented by a Markov model of lifetime cost-effectiveness .


In 2 urban academic primary care practices , we randomized African American patients with uncontrolled hypertension to a 6-month intervention of office practice and peer coach behavioral support ( N = 136 ) or informational brochures about CHD risk factors ( N = 144 ) .


Costs were estimated from the perspective of the provider .


Outcomes included estimated CHD events avoided over 6 months and reduction in systolic blood pressure ( SBP ) ( mm Hg ) .


Subgroup analysis was performed for compliers who received an `` effective '' dose of the peer coach and office staff visits .


Long-term cost-effectiveness was estimated by applying the clinical trial cost and effectiveness into a Markov model of CHD risk .


The average cost for the behavioral support intervention group was $ 435.36 compared with $ 74.39 for the brochure control group .


The incremental cost-effectiveness ratio ( ICER ) was $ 47 per mm Hg reduction in SBP and $ 453,419 per CHD event avoided in 6 months .


Modeled over a 10-year horizon , the intervention had an ICER only as high as $ 3998 per incremental quality-adjusted life-year .


A community-primary care practice behavioral intervention to reduce hypertension in African Americans with sustained uncontrolled hypertension does not appear to be cost-effective in the first 6 months .


If intervention results are sustained over the long term , the program may be cost-effective over the patient 's lifetime .


Our primary objective was to determine the proportion of patients with atrial fibrillation ( AF ) eligible for enrollment in a randomized controlled trial for a novel oral anticoagulant , the ARISTOTLE trial .


A secondary objective was to describe the reasons for trial ineligibility .


We performed a cross-sectional study of an unselected population including 2274 patients in Skellefte , Sweden with at least one verified episode of AF on or before December 31 , 2010 .


Patients were classified as suitable or unsuitable for anticoagulant treatment according to current guidelines .


The enrollment criteria from the ARISTOTLE trial were extracted from the original publication and applied to the population .


Among all patients with AF , 1579 were classified as suitable for anticoagulant treatment .


Of these , only 658 patients ( 42 % ) were eligible for participation in the ARISTOTLE trial .


Among the 921 patients ineligible for participation , 498 did not meet the ECG criteria , 272 had psychosocial problems , and in addition , 78 patients were excluded due to both of these criteria .


Our study shows that a majority of the patients in an unselected population with AF suitable for anticoagulant treatment were ineligible for participation in the ARISTOTLE trial .


The applicability of the ARISTOTLE trial is therefore unknown for a considerable proportion of patients with AF in real life .


The purpose of this study was to evaluate the safety and effectiveness of 2-level total disc replacement ( TDR ) using a Mobi-C cervical artificial disc at 48 months ' follow-up .


A prospective randomized , US FDA investigational device exemption pivotal trial of the Mobi-C cervical artificial disc was conducted at 24 centers in the U.S. Three hundred thirty patients with degenerative disc disease were randomized and treated with cervical total disc replacement ( 225 patients ) or the control treatment , anterior cervical discectomy and fusion ( ACDF ) ( 105 patients ) .


Patients were followed up at regular intervals for 4 years after surgery .


At 48 months , both groups demonstrated improvement in clinical outcome measures and a comparable safety profile .


Data were available for 202 TDR patients and 89 ACDF patients in calculation of the primary endpoint .


TDR patients had statistically significantly greater improvement than ACDF patients for the following outcome measures compared with baseline : Neck Disability Index scores , 12-Item Short Form Health Survey Physical Component Summary scores , patient satisfaction , and overall success .


ACDF patients experienced higher subsequent surgery rates and displayed a higher rate of adjacent-segment degeneration as seen on radiographs .


Overall , TDR patients maintained segmental range of motion through 48 months with no device failure .


Four-year results from this study continue to support TDR as a safe , effective , and statistically superior alternative to ACDF for the treatment of degenerative disc disease at 2 contiguous cervical levels .


Clinical trial registration no. : NCT00389597 ( clinicaltrials.gov ) .


The objective of this study was to test the effect of a brief educational and counseling intervention on increasing the uptake of free testing for Chlamydia trachomatis ( chlamydia ) and Neisseria gonorrhea ( gonorrhea ) among young female emergency department ( ED ) patients .


Women are particularly vulnerable to more serious consequences of these infections due to asymptomatic presentation .


Increased testing is important to detect , treat , and halt the spread of these infections among asymptomatic women .


This was a randomized controlled trial .


Research assistants ( RAs ) approached female patients in two EDs .


Eligible patients were between 18 and 35 years of age , who reported having sex with males , but were not attending the ED for either treatment of sexually transmitted infection ( STI ) or testing for possible STI exposure .


Participants responded to survey questions about their lifetime and past 3-month substance use , number of recent sexual partners , condom use , and perception of risks for chlamydia and gonorrhea infections .


Following the survey , the RAs randomized participants into study control or treatment arms .


Each treatment arm participant received a brief educational/counseling intervention from the RA .


The brief intervention focused on the woman 's personal risks for chlamydia and gonorrhea and condoms attitudes and usage .


As the primary outcome of this study , participants were offered free urine tests for chlamydia and gonorrhea infection postintervention or post-survey completion , depending on group assignment .


A total of 171 women completed the baseline assessment and were offered chlamydia and gonorrhea testing .


The mean ( SD ) age was 26 ( 4.76 ) years , 18 % were Hispanic , and 12 % were Spanish-speaking only .


The brief intervention that was offered to increase these women 's awareness of their STI risk did not result in increased acceptance of testing ; 48 % in the brief intervention group accepted testing ( 95 % confidence interval [ CI ] = 32 % to 64 % ) versus 36 % in the control group ( 95 % CI = 19 % to 53 % ) .


In a multivariable logistic regression , only self-identifying as being Hispanic was associated with greater willingness to be tested .


Of the asymptomatic women tested ( n = 71 ) , five tested positive for chlamydia .


This represents a positivity rate of 7 % .


There were no positive test results for gonorrhea .


Women who reported high-risk factors for STI , such as younger age ( 25 years ) , having sex in the past 90 days without using condoms , identified substance use , or previous STI , were not more likely to accept the offer of chlamydia and gonorrhea testing .


The brief intervention used in this study did not increase the uptake of testing for chlamydia and gonorrhea infections in this sample , in comparison to receiving no intervention .


Although Hispanic women were more likely to accept chlamydia and gonorrhea testing , it is concerning that those women who report STI risk factors were not more likely to accept the offer of chlamydia and gonorrhea testing .


Future research should focus on the refinement of an intervention protocol to focus on prior STI and lack of condom use to increase the uptake of testing among this high-risk group .


Preclinical studies support the hypothesis that endogenous neuroactive steroids mediate some effects of alcohol .


The aim of this study was to examine the effect of dutasteride inhibition of 5-reduced neuroactive steroid production on subjective responses to alcohol in adult men .


Using a within-subject factorial design , 70 men completed four randomly ordered monthly sessions in which pretreatment with 4 mg dutasteride or placebo was paired with a moderate dose of alcohol ( 0.8 g/kg ) or placebo beverage .


The pharmacologic effect of dutasteride was measured by an assay of serum androstanediol glucuronide .


Self-reports of alcohol effects were obtained at 40-min intervals following alcohol administration using the Biphasic Alcohol Effects Scale ( BAES ) and the Alcohol Sensation Scale ( SS ) .


We used linear mixed models to examine the effects of dutasteride and alcohol on BAES and SS responses and the interaction of dutasteride with the GABRA2 alcohol dependence-associated polymorphism rs279858 .


We also examined whether exposure to dutasteride influenced drinking in the weeks following each laboratory session .


A single 4-mg dose of dutasteride produced a 70 % reduction in androstanediol glucuronide .


Dutasteride pretreatment reduced alcohol effects on the BAES sedation and SS anesthesia scales .


There was no interaction of dutasteride with rs279858 .


Heavy drinkers had fewer heavy drinking days during the 2 weeks following the dutasteride sessions and fewer total drinks in the first week after dutasteride .


These results provide evidence that neuroactive steroids mediate some of the sedative effects of alcohol in adult men and that dutasteride may reduce drinking , presumably through its effects on neuroactive steroid concentrations .


Tapentadol prolonged release ( PR ) is effective and well tolerated for chronic osteoarthritis , low back , and diabetic peripheral neuropathic pain .


To evaluate the efficacy and tolerability of tapentadol PR compared with placebo and morphine controlled release ( CR ) for managing moderate to severe chronic malignant tumor-related pain .


Randomized-withdrawal , parallel group , active - and placebo-controlled , double-blind phase 3 study ( NCT00472303 ) .


Primary , secondary , and tertiary care settings in 16 countries .


Eligible patients ( pain intensity 5 [ 11-point numerical rating scale ] on prior analgesics ) were randomized ( 2:1 ) and titrated to their optimal dose of tapentadol PR ( 100-250 mg bid ) or morphine sulfate CR ( 40-100 mg bid ) over 2 weeks .


Morphine sulfate immediate release 10 mg was permitted as needed for rescue medication ( no maximum dose ) .


Patients who completed titration and , during the last 3 days of titration , had mean pain intensity < 5 ( based on twice-daily ratings ) and mean rescue medication use = 20 mg/day continued into a 4-week maintenance period ; patients who received morphine CR during titration continued taking morphine CR , and those who received tapentadol PR were re-randomized ( 1:1 ) to tapentadol PR or placebo bid .


Response during maintenance ( primary efficacy endpoint ) was defined as having : ( 1 ) completed the maintenance period , ( 2 ) a mean pain intensity < 5 during maintenance , and ( 3 ) used an average of = 20 mg/day of rescue medication during maintenance .


Response at the end of titration was defined similarly , with pain intensity and rescue medication averages based on the last 3 days of titration .


Of 622 patients screened , 496 were randomized , treated during titration , and evaluable for safety ; 327 were re-randomized , treated during maintenance , and evaluable for safety ; and 325 were evaluable for efficacy .


The adjusted responder rate estimate during maintenance ( logistic regression adjusting for treatment group , pooled center , and pain intensity at start of maintenance ) was significantly higher with tapentadol PR ( 64.3 % ) than with placebo ( 47.1 % ; odds ratio ( OR ) , 2.02 [ 95 % confidence interval ( CI ) , 1.12 - 3.65 ] ; P = 0.02 ) .


Based on responder rates at the end of titration , tapentadol PR ( 76.0 % [ 174/229 ] ) was non-inferior to morphine CR ( 83.0 % [ 83/100 ] ) .


The lower limit of the 95 % CI for the between-groups difference ( -15.5 % ) was within the pre-specified 20 % non-inferiority margin .


During titration , incidences of treatment-emergent adverse events ( TEAEs ) were 50.0 % ( 169/338 ) with tapentadol PR and 63.9 % ( 101/158 ) with morphine CR ; incidences of nausea , vomiting , and dry mouth were lower with tapentadol PR than with morphine CR .


During maintenance , incidences of TEAEs were 56.3 % ( 63/112 ) , 62.3 % ( 66/106 ) , and 62.4 % ( 68/109 ) with placebo , tapentadol PR , and morphine CR , respectively .


Statistical comparisons between tapentadol PR and morphine CR were limited to descriptive statistics during the maintenance period because of the pre-selection of responders to tapentadol PR or morphine CR during titration .


Results obtained during maintenance indicate that tapentadol PR ( 100-250 mg bid ) is effective compared with placebo for managing moderate to severe chronic malignant tumor-related pain .


Based on results obtained during titration , tapentadol PR provides comparable efficacy to that of morphine sulfate CR ( 40-100 mg bid ) , but is associated with better gastrointestinal tolerability .


The aim of this study was to determine the effect of a single dose of 150g of clonidine as an adjuvant to levobupivacaine ( Chirocaine ( ) ) in retrobulbar block on postoperative safety and analgesia .


This was a prospective , randomized , controlled , double-blind trial .


One hundred twenty patients with a rhegmatogenous retinal detachment scheduled to undergo external buckling surgery and cryocoagulation were asked to participate .


Participants were randomly assigned either to receive 3-5mL Chirocaine ( 22.5-37 .5 mg ) or 3-5mL Chirocaine and 1mL clonidine ( 150g ) before surgery .


Main outcome measures were postoperative pain , use of analgesics , blood pressure , and plasma clonidine concentration .


Nine nonrandomized patients consented to give blood samples for pharmacokinetic analysis .


There was no significant difference in pain score between both groups .


On average , the use of analgesic medication occurred later in the clonidine group ( P = 0.0004 ) , but there was no statistical difference in the first time that postoperative medication was taken ( P = 0.13 ) .


Blood pressure was reduced by clonidine ( systolic : P = 0.02 , diastolic : P = 0.006 ) .


Clonidine levels could be demonstrated during the 24-h postoperative period , with an average half-life of 22h .


Administration of clonidine as an adjuvant to conventional retrobulbar block is safe , and delays the postoperative use of analgesics .


The reduction of postoperative pain and the time of first use of analgesic medication , however , were not significantly different between groups .


Further , pain scores in both study groups remained low .


Therefore , the beneficial effect of clonidine in conventional scleral buckle surgery appears to be limited .


Osteoporosis is a skeletal disorder characterized by impaired bone turnover and compromised bone strength , thereby predisposing to increased risk of fracture .


Preclinical research has shown that compounds produced by the olive tree ( Olea europaea ) , may protect from bone loss , by increasing osteoblast activity at the expense of adipocyte formation .


The aim of this exploratory study was to obtain a first insight on the effect of intake of an olive extract on bone turnover in postmenopausal women with decreased bone mass ( osteopenia ) .


For that , a double blind , placebo-controlled study was performed in which participants were randomly allocated to either treatment or placebo groups .


64 osteopenic patients , with a mean bone mineral density ( BMD ) T-score between -1.5 and -2.5 in the lumbar spine ( L2-L4 ) were included in the study .


PARTICIPANTS received for 12 months daily either 250 mg/day of olive extract and 1000 mg Ca ( treatment ) or 1000 mg Ca alone ( placebo ) .


Primary endpoints consisted of evaluation of bone turnover markers .


Secondary endpoints included BMD measurements and blood lipid profiles .


After 12 months , the levels of the pro-osteoblastic marker osteocalcin were found to significantly increase in the treatment group as compared to placebo .


Simultaneously , BMD decreased in the placebo group , while remaining stable in the treatment group .


In addition , improved lipid profiles were observed , with significant decrease in total - and LDL-cholesterol in the treatment group .


This exploratory study supports preclinical observations and warrants further research by showing that a specific olive polyphenol extract ( Bonolive ) affects serum osteocalcin levels and may stabilize lumbar spine BMD .


Moreover , the improved blood lipid profiles suggest additional health benefits associated to the intake of the olive polyphenol extract .


Recruitment is a challenge in developing population-representative pregnancy and birth cohorts .


We developed a collaborative recruitment infrastructure ( CRI ) to recruit pregnant women for 4 pregnancy cohorts using : faxes from obstetrical offices , in-clinic recruiters , university and funder-driven free-media events , paid-media , and attendance at relevant tradeshows .


Recruitment rates and demographic differences were compared between recruitment methods .


We received 5008 referrals over 40 months .


Compared to fax , free-media referrals were 13 times more likely to be recruited ( OR 13.0 , 95 % CI 4.2 , 40.4 : p < 0.001 ) and paid-media referrals were 4 times more likely to be recruited ( OR 4.6 , 95 % CI 2.1 , 10.3 : p < 0.001 ) .


Among paid-media advertisements , free-to-read print ( e.g. Metro ) was the most effective ( OR 3.3 , 95 % CI 2.3 , 4.5 : p < 0.05 ) .


Several demographic differences were identified between recruitment methods and against a reference population .


Between recruitment methods , media recruits had a similar proportion families with incomes $ 40,000 ( paid-media : 94.4 % ; free-media : 93.3 % ) compared to fax recruits ( 95.7 % ) , while in-clinic recruits were less likely to have family incomes $ 40,000 ( 88.8 % , p < 0.05 ) .


Maternal recruits from fax and in-clinic were more likely to attend university ( Fax : 92.6 % , in-clinic 89.8 % ) versus the reference population ( 52.0 % ; p < 0.05 for both ) and both were less likely to smoke ( Fax : 6.8 % , in-clinic 4.2 % ) versus reference ( 18.6 % ; p < 0.05 for both ) .


However , while fax referrals were more likely to be Caucasian ( 85.9 % versus reference 77.5 % ; p < 0.05 ) , in-clinic referrals were not significantly different ( 78.2 % ; P > 0.05 ) .


Recruitment methods result in different recruitment rates and participant demographics .


A variety of methods are required to recruit a generalizable sample .


Research on contingency management to treat excessive alcohol use is limited due to feasibility issues with monitoring adherence .


This study examined the effectiveness of using transdermal alcohol monitoring as a continuous measure of alcohol use to implement financial contingencies to reduce heavy drinking .


Twenty-six male and female drinkers ( from 21 to 39 years old ) were recruited from the community .


Participants were randomly assigned to one of the two treatment sequences .


Sequence 1 received 4 weeks of no financial contingency ( i.e. , $ 0 ) drinking followed by 4 weeks each of $ 25 and then $ 50 contingency management ; Sequence 2 received 4 weeks of $ 25 contingency management followed by 4 weeks each of no contingency ( i.e. , $ 0 ) and then $ 50 contingency management .


During the $ 25 and $ 50 contingency management conditions , participants were paid each week when the Secure Continuous Remote Alcohol Monitor ( SCRAM-II ) identified no heavy drinking days .


Participants in both contingency management conditions had fewer drinking episodes and reduced frequencies of heavy drinking compared to the $ 0 condition .


Participants randomized to Sequence 2 ( receiving $ 25 contingency before the $ 0 condition ) exhibited less frequent drinking and less heavy drinking in the $ 0 condition compared to participants from Sequence 1 .


Transdermal alcohol monitoring can be used to implement contingency management programs to reduce excessive alcohol consumption .


In the European HIT-SIOP PNET4 randomized controlled trial , children with standard risk medulloblastoma were allocated to hyperfractionated radiation therapy ( HFRT arm , including a partially focused boost ) or standard radiation therapy ( STRT arm ) , followed , in both arms , by maintenance chemotherapy .


Event-free survival was similar in both arms .


Previous work showed that the HFRT arm was associated with worse growth and better questionnaire-based executive function , especially in children < 8years of age at diagnosis .


Therefore , the aim of this study was to compare performance-based cognitive outcomes between treatment arms .


Neuropsychological data were collected prospectively in 137 patients .