After oral administration , the dose-normalized erythromycin exposure ( AUC ) was 1335hngml ( -1 ) after 250mg and 3-fold higher after the 1000mg dose ( 4051hngml ( -1 ) ; P < 0.01 ) , suggesting nonlinear pharmacokinetics of erythromycin .


Both oral doses inhibited CYP3A activity ; midazolam clearance was decreased to 61 % ( 250mg ) and 21 % ( 1000mg ) .


The relationship between erythromycin exposure and CYP3A activity ( Hill equation ) revealed a 50 % reduction of CYP3A activity by an erythromycin AUC of 2106hngml ( -1 ) .


Topical erythromycin did not cause clinically relevant CYP3A alterations , although low systemic availability of erythromycin was observed .


This supports the assumption that treatment with topical erythromycin is not critical in terms of CYP3A inhibition .


Furthermore , substantial nonlinearity of erythromycin pharmacokinetics after two different oral doses was observed , possibly due to autoinhibition .


Socially disadvantaged men are at a substantially higher risk of developing alcohol-related problems .


The frequency of heavy drinking in a single session is high among disadvantaged men .


Brief alcohol interventions were developed for , and are usually delivered in , healthcare settings .


The group who binge drink most frequently , young to middle-aged disadvantaged men , have less contact with health services and there is a need for an alternative method of intervention delivery .


Text messaging has been used successfully to modify other adverse health behaviours .


This study will test whether text messages can reduce the frequency of binge drinking by disadvantaged men .


Disadvantaged men aged 25 to 44years who drank > 8 units of alcohol at least twice in the preceding month will be recruited from the community .


Two recruitment strategies will be used : contacting men listed in primary care registers , and a community outreach method ( time-space sampling ) .


The intended sample of 798 men will be randomised to intervention or control , stratifying by recruitment method .


The intervention group will receive a series of text messages designed to reduce the frequency of binge drinking through the formation of specific action plans .


The control group will receive behaviourally neutral text messages intended to promote retention in the study .


The primary outcome measure is the proportion of men consuming > 8 units on at least three occasions in the previous 30days .


Secondary outcomes include total alcohol consumption and the frequency of consuming more than 16 units of alcohol in one session in the previous month .


Process measures , developed during a previous feasibility study , will monitor engagement with the key behaviour change components of the intervention .


The study will incorporate an economic evaluation comparing the costs of recruitment and intervention delivery with the benefits of reduced alcohol-related harm .


This study will assess the effectiveness of a brief intervention , delivered by text messages , aimed at reducing the frequency of binge drinking in disadvantaged men .


The process measures will identify components of the intervention which contribute to effectiveness .


The study will also determine whether any benefit of the intervention is justified by the costs of intervening .


ISRCTN07695192 .


Date assigned : 14 August 2013 .


Pediatricians underestimate the prevalence of substance misuse among children and adolescents and often fail to screen for and intervene in practice .


The American Academy of Pediatrics recommends training in Screening , Brief Intervention , and Referral to Treatment ( SBIRT ) , but training outcomes and skill acquisition are rarely assessed .


We compared the effects of online versus in-person SBIRT training on pediatrics residents ' knowledge , attitudes , behaviors , and skills .


Forty pediatrics residents were randomized to receive either online or in-person training .


Skills were assessed by pre - and posttraining standardized patient interviews that were coded for SBIRT-adherent and - nonadherent behaviors and global skills by 2 trained coders .


Thirty-two residents also completed pre - and postsurveys of their substance use knowledge , attitudes , and behaviors ( KABs ) .


Two-way repeated measures multivariate analyses of variance ( MANOVAs ) and analyses of variance ( ANOVAs ) estimates were used to assess group differences in skill acquisition and KABs .


Findings indicated that both groups demonstrated skill improvement from pre - to postassessment .


Results indicated that both groups increased their knowledge , self-reported behaviors , confidence , and readiness with no significant between-group differences .


Follow-up univariate analyses indicated that , while both groups increased their SBIRT-adherent skills , the online training group displayed more `` undesirable '' behaviors posttraining .


The current study indicates that brief training , online or in-person , can increase pediatrics residents ' SBIRT skills , knowledge , self-reported behaviors , confidence , and readiness .


The findings further indicate that in-person training may have incremental benefit in teaching residents what not to do .


To investigate effects and functional mechanism of compound Congrongyizhi Capsule ( CCRC ) , a Chinese medicine , on cognitive functions against amnestic mild cognitive impairment ( aMCI ) patients with functional magnetic resonance imaging ( fMRI ) based on n-back task .


Forty-one aMCI participants from hospital and local communities in Beijing and randomly divided into treatment ( 16 patients with CCRC capsule treatment ) , placebo ( 12 patients with placebo capsules ) and control group ( 13 patients with no treatment ) .


The duration of intervention lasted for 3 months .


Neuropsychological tests and fMRI were applied to assess cognitive ability and brain activation changes after three months treatment .


Drug group ( n = 16 ) presented increased significance in the MMSE ( P = 0.008 ) and digit span ( P < 0.001 ) tests , while other scores of neuropsychological tests showed no statistical significance .


fMRI results showed an increased brain negative activation in drug group during performing the n-back working-memory task in posterior cingulate ( PCC ) , inferior frontal gyrus and lingual gyrus regions after 3 months ; placebo and control group did not show the same effect .


Meanwhile , there were negative correlations between left PCC activation levels and changed values of MMSE and digit span separately since increased negative activation was associated with better performance on the scores of MMSE and Digit Span tests .


CCRC can increase negative activation degree of PCC under performing working memory tasks while this modulation are associated with better performance on the MMSE and Digit Span .


187,000 hip and knee joint replacements are performed every year in the National Health Service ( NHS ) .


One of the commonest complications is surgical site infection ( SSI ) , and this represents a significant burden in terms of patient morbidity , mortality and cost to health services around the world .


The aim of this randomised controlled trial ( RCT ) is to determine if the addition of triclosan coated sutures to a standard regimen can reduce the rate of SSI after total knee replacement ( TKR ) and total hip replacement ( THR ) .


2400 patients due to undergo a total hip or knee replacement are being recruited into this two-centre RCT .


Participants are recruited before surgery and randomised to either standard care or intervention group .


Participants , outcome assessors and statistician are blind to treatment allocation throughout the study .


The intervention consists of triclosan coated sutures vs. standard non-coated sutures .


The primary outcome is the Health protection Agency ( HPA ) defined superficial surgical site infection at 30 days .


Secondary outcomes include HPA defined deep surgical site infection at 12 months , length of hospital stay , critical care stay , and payer costs .


To date there are no orthopaedic randomised controlled trials on this scale assessing the effectiveness of a surgical intervention , particularly those that can be translated across the surgical specialities .


The results from this trial will inform evidence-based recommendations for suture selection in the management of patients undergoing total hip or knee replacement .


If triclosan coated sutures are found to be an effective intervention , implementation into clinical practice could improve long-term outcomes for patients undergoing hip and knee replacement .


Current Controlled Trials ISRCTN 17807356 .


Immunogenicity and safety of a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT were evaluated in the second year of life in HibMenCY-TT-primed toddlers .


Healthy infants were randomized ( 5:1 ) and primed at 2 , 4 and 6 months of age with HibMenCY-TT and diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus ( DTaP-HBV-IPV ) vaccine ; or Hib-TT and DTaP-HBV-IPV ( control ) .


Recipients of HibMenCY-TT + DTaP-HBV-IPV were re-randomized ( 2:2:1 ) to receive MenACWY-TT at 12-15 months and DTaP at 15-18 months ; MenACWY-TT co-administered with DTaP at 15-18 months ; or HibMenCY-TT at 12-15 months and DTaP at 15-18 months .


Controls received DTaP only at 15-18 months due to Hib conjugate vaccine shortage .


Serum bactericidal activity using human complement ( hSBA ) and safety were assessed one month after meningococcal vaccination .


After vaccination with MenACWY-TT at 12-15 months or MenACWY-TT + DTaP at 15-18 months , all subjects previously primed for serogroups C/Y had hSBA 1:8 for these serogroups .


At least 96.1 % also had hSBA 1:8 for serogroups A/W .


All subjects in the HibMenCY-TT group had hSBA 1:8 for serogroups C/Y .


All pre-defined statistical criteria for meningococcal immunogenicity were satisfied .


All vaccination regimens had acceptable safety profiles .


Children primed with three doses of HibMenCY-TT who then received a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT had robust increases in hSBA titers for serogroups C/Y .


These data provide support that MenACWY-TT , given with or without the fourth scheduled dose of DTaP could be administered as an alternative to a fourth dose of HibMenCY-TT in the second year of life .


This study ( 110870/110871 ) is registered at www.clinicaltrials.gov NCT00614614 .


Duration of treatment for patients with vertebral osteomyelitis is mainly based on expert recommendation rather than evidence .


We aimed to establish whether 6 weeks of antibiotic treatment is non-inferior to 12 weeks in patients with pyogenic vertebral osteomyelitis .


In this open-label , non-inferiority , randomised controlled trial , we enrolled patients aged 18 years or older with microbiologically confirmed pyogenic vertebral osteomyelitis and typical radiological features from 71 medical care centres across France .


Patients were randomly assigned to either 6 weeks or 12 weeks of antibiotic treatment ( physician 's choice in accordance with French guidelines ) by a computer-generated randomisation list of permuted blocks , stratified by centre .


The primary endpoint was the proportion of patients who were classified as cured at 1 year by a masked independent validation committee , analysed by intention to treat .


Non-inferiority would be declared if the proportion of cured patients assigned to 6 weeks of treatment was not less than the proportion of cured patients assigned to 12 weeks of treatment , within statistical variability , by an absolute margin of 10 % .


This trial is registered with EudraCT , number 2006-000951-18 , and Clinical Trials.gov , number NCT00764114 .


Between Nov 15 , 2006 , and March 15 , 2011 , 359 patients were randomly assigned , of whom six in the 6-week group and two in the 12-week group were excluded after randomisation .


176 patients assigned to the 6-week treatment regimen and 175 to the 12-week treatment regimen were analysed by intention to treat .


160 ( 909 % ) of 176 patients in the 6-week group and 159 ( 909 % ) of 175 of those in the 12-week group met the criteria for clinical cure .


The difference between the groups ( 005 % , 95 % CI -62 to 63 ) showed the non-inferiority of the 6-week regimen when compared with the 12-week regimen .


50 patients in the 6-week group and 51 in the 12-week group had adverse events , the most common being death ( 14 [ 8 % ] in the 6-week group vs 12 [ 7 % ] in the 12-week group ) , antibiotic intolerance ( 12 [ 7 % ] vs 9 [ 5 % ] ) , cardiorespiratory failure ( 7 [ 4 % ] vs 12 [ 7 % ] ) , and neurological complications ( 7 [ 4 % ] vs 3 [ 2 % ] ) .


6 weeks of antibiotic treatment is not inferior to 12 weeks of antibiotic treatment with respect to the proportion of patients with pyogenic vertebral osteomyelitis cured at 1 year , which suggests that the standard antibiotic treatment duration for patients with this disease could be reduced to 6 weeks .


French Ministry of Health .


TNF - generates inflammatory responses and insulin resistance , lipolysis , and protein breakdown .


It is unclear whether these changes depend on intact hypothalamo-pituitary stress hormone responses to trigger the release of cortisol and growth hormone .


To define differential effects of TNF - on glucose , protein , and lipid metabolism in hypopituitary patients ( without intact hypothalamo-pituitary axis ) and healthy controls .


Randomized , placebo controlled , single-blinded .


Setting , Participants , and Intervention : We studied eight hypopituitary ( HP ) patients and eight matched control subjects [ control volunteers ( CTR ) ] twice during 4-h basal and 2-h hyperinsulinemic clamp conditions with isotope dilution during infusion of saline or TNF - ( 12 ng/kg/h ) for 6 h.


Phenylalanine , urea , palmitate , and glucose fluxes and fat biopsies in basal and clamp periods .


TNF - infusion significantly increased cortisol and GH levels in CTR but not in HP .


TNF - increased phenylalanine fluxes in both groups , with the increase being significantly greater in CTR , and raised urea flux by 40 % in CTR without any alteration in HP .


Endogenous glucose production ( EGP ) was elevated in CTR compared to HP after TNF - administration , whereas insulin sensitivity remained similarly unaffected in both groups .


TNF - increased whole body palmitate fluxes and decreased palmitate specific activity in CTR , but not in HP without statistical difference between groups .


We did not detect significant effects TNF - on lipase expression or regulation in fat .


TNF - increased both urea and amino acid fluxes and EGP significantly more in CTR compared to HP , suggesting that increases in endogenous cortisol and GH release are significant components of the metabolic response to TNF - .


The root bark of Aralia is a rich source of bioactive components that may improve glycemic control and lipid status .


In this study , 148 patients with type 2 diabetes mellitus ( T2DM ) were assigned randomly to receive either glipizide alone or glipizide plus Aralia root bark extract ( ARBE ) for 8 weeks to test the effects of ARBE plus glipizide therapy on glycemic control and lipid profiles in these patients .


Levels of HbA1c , fasting plasma glucose ( FPG ) and 2 h postprandial plasma glucose ( 2-h PPG ) in both groups significantly decreased from baseline .


Glycated hemoglobin ( HbA1c ) decreased marginally significantly in participants taking glipizide plus ARBE compared with the glipizide group ( P = 0.06 ) .


Participants in the combination group had significant decreases in total cholesterol ( TC ) and low-density lipoprotein cholesterol ( LDL-C ) , and the between-group difference achieved statistical significance for LDL-C ( P = 0.04 ) .


Reduction in HbA1c in the combination group was significantly associated with changes in TC ( r = 0.32 ; P = 0.006 ) and LDL-C ( r = 0.34 ; P = 0.005 ) , and the change in FPG was inversely correlated with LDL-C reduction ( r = 0.34 ; P = 0.004 ) .


In patients with T2DM , combination therapy with glipizide and ARBE resulted in moderately lowering HbA1c and LDL-C levels compared with glipizide alone .


To evaluate the velocity of canine retraction , anchorage loss and changes on canine and first molar inclinations using self-ligating and conventional brackets .


Twenty-five adults with Class I malocclusion and a treatment plan involving extractions of four first premolars were selected for this randomized split-mouth control trial .


Patients had either conventional or self-ligating brackets bonded to maxillary canines randomly .


Retraction was accomplished using 100-g nickel-titanium closed coil springs , which were reactivated every 4 weeks .


Oblique radiographs were taken before and after canine retraction was completed , and the cephalograms were superimposed on stable structures of the maxilla .


Cephalometric points were digitized twice by a blinded operator for error control , and the following landmarks were collected : canine cusp and apex horizontal changes , molar cusp and apex horizontal changes , and angulation changes in canines and molars .


The blinded data , which were normally distributed , were analyzed through paired t-tests for group differences .


No differences were found between the two groups for all variables tested .


Both brackets showed the same velocity of canine retraction and loss of anteroposterior anchorage of the molars .


No changes were found between brackets regarding the inclination of canines and first molars .


Tacrolimus is an established immunosuppressant used for the prevention and treatment of allograft rejection in solid organ transplantation .


An immediate-release oral formulation of tacrolimus has been commercially available since 1994 that is administered orally BID .


To improve the compliance and quality of life of transplant patients , a once-daily modified release ( MR ) formulation is an attractive option .


However , to be successful , the drug of interest must be sufficiently well absorbed from the distal region of the gastrointestinal tract .


To facilitate the development of an MR formulation , we investigated the absorption of tacrolimus from different regions of the human gastrointestinal tract , proximal and distal small bowels , and ascending colon .


The study was performed as an open-label , randomized , 4-way crossover design in 6 healthy white male subjects .


For each subject , 1 mg ( 2 mg/mL ) of tacrolimus solution in polyethylene glycol 400 was administered to each location in the gastrointestinal tract via a site-specific radiolabeled delivery capsule , which can release tacrolimus solution at specific sites of the gastrointestinal tract .


Real-time visualization of capsule location and tacrolimus release at each target site was performed by using - scintigraphy .


Blood samples were collected to determine tacrolimus levels in the blood .


The pharmacokinetic parameters Cmax , Tmax after the capsule activation , AUC0-24 , and mean residence time were determined from the concentration-time profiles .


Ten healthy male subjects underwent dosing .


Six subjects completed all 4 treatments .


Three adverse events ( mild headache [ n = 1 ] , small amount of blood in stool [ n = 1 ] , and mild syncopal episode [ n = 1 ] ) that were possibly study drug related were reported in 3 different subjects .


Tacrolimus was absorbed from not only the small intestine but also from the colonic region of the gastrointestinal tract .


Although AUC0-24 values revealed some site-specific absorption tendencies , the mean AUC0-24 values obtained were similar regardless of the location of tacrolimus release from the capsule .


Tacrolimus was absorbed from the duodenum to the colon in these male subjects , although differences were observed in the value of AUC0-24 , possibly due to variation in cytochrome P450 3A4 activity in the intestine .


Although this study was conducted in small group of healthy fasting men , the present results indicate that tacrolimus is suitable for MR formulation development due to a wide absorption window throughout the intestine in humans .


Roughly one third of disability pensions in Norway are issued for mental and behavioral disorders , and vocational rehabilitation offered to this group has traditionally been dominated by train-and-place approaches with assisted or sheltered employment .


Based on a more innovative place-and-train approach , Individual Placement and Support ( IPS ) involves supported employment in real-life competitive work settings , and has shown great promise for patients with severe mental illness .


The study is a multicenter Randomized Controlled Trial ( RCT ) of IPS in a Norwegian context , involving an effect evaluation , a process evaluation , and a cost/benefit analysis .


IPS will be compared to high quality treatment as usual ( TAU ) , with labor market participation and educational activity at 12 months post inclusion as the primary outcome .


The primary outcome will be measured using register data , and the project will also include complete follow-up up to 4 years after inclusion for long-term outcome data .


Secondary outcomes include mental health status , disability and quality of life , collected through survey questionnaires at baseline , and after 6 and 12 months .


Participants will include patients undergoing treatment for moderate to severe mental illness who are either unemployed or on sickness or social benefits .


The estimated total sample size of 400-500 will be randomly assigned to the interventions .


To be eligible , participants must have an expressed desire to work , and sufficient Norwegian reading and writing skills to fill out the questionnaires .


The Effect Evaluation of Individual Placement and Support ( IPS ) will be one of the largest randomized controlled trials to date investigating the effectiveness of IPS on competitive employment , and the first study to evaluate the effectiveness of IPS for patients with moderate to severe mental illness within a Norwegian context .


Clinicaltrials.gov : NCT01964092 .


Registered October 16th , 2013 .


Induction immunosuppression with anti-thymocyte globulin ( ATG ) provides potential benefits after liver transplantation ( LT ) .


However , its use in patients with LT and hepatitis C ( HCV ) is controversial .


To evaluate the 1 - and 2-year patient survival and HCV recurrence rate in patients receiving ATG during the induction phase of immunosuppression ( IPI ) after LT.


A total of 49 patients undergoing their first LT for HCV were randomized to receive ATG during IPI .


Patient survival and HCV recurrence were determined at 1 and 2years .


The frequency of acute cellular rejection ( ACR ) , infections , and neoplasms was also evaluated .


Twenty-six patients were randomized to receive ATG ( Arm-1 ) and 23 to standard induction therapy ( Arm-2 ) .


Those given ATG had lower HCV recurrence ( 26.9 vs 73.9 % , p = 0.001 ) .


The 1 - and 2-year patient survival rates were similar for both arms ( p = 0.33 ) .


Infections occurred in 46.1 % subjects in Arm-1 and 34.7 % in Arm-2 ( p = 0.562 ) .


There was a greater proportion of fungal infections in Arm-1 ( 19.2 vs 0 % , p = 0.032 ) .


ATG during the IPI was associated with lower frequency of recurrence of HCV in patients undergoing LT. This , however , did not affect the 1 - and 2-year survival and the frequency of ACR , infections , or neoplasms .


To compare the safety and effectiveness of small particle hyaluronic acid plus lidocaine ( SPHAL ) versus no treatment for lip augmentation and perioral rhytides .


Adults scoring 1 ( very thin ) to 2 ( thin ) on the Medicis Lip Fullness Scale ( MLFS ) for upper and lower lips were randomized ( 3:1 ) to SPHAL or no treatment .


Treatment success was an MLFS increase 1 point at Week 8 .


Secondary end points ( MLFS score , independent photographic review , Global Aesthetic Improvement Scale , Wrinkle Assessment Scale for Upper Lip Lines ) and safety were assessed throughout .


Statistically significantly more patients were treatment successes with SPHAL ( upper lip [ 80.2 % vs 11.9 % ] , lower lip [ 84.2 % vs 18.4 % ] , and upper and lower lips combined [ 76.1 % vs 11.6 % ] ) , compared with no treatment ( p < .001 , all outcomes ) .


Patients treated for both lip augmentation and perioral rhytides were rated as having an aesthetically meaningful improvement in perioral rhytides ( p < .001 ) .


Most common treatment-emergent adverse events ( AEs ) included lip bruising , swelling , and pain and were mostly mild and transient in nature , without anticipated device AEs .


Small particle hyaluronic acid plus lidocaine was effective and well tolerated and significantly more effective when both lips and perioral rhytides were treated , with improvement evident up to 6 months after treatment .


ABT-288 is a highly potent histamine-3 receptor antagonist that has demonstrated pro-cognitive effects in preclinical models relevant to schizophrenia .


This study evaluated the efficacy and safety of two doses of ABT-288 in the treatment of cognitive impairment associated with schizophrenia .


A randomized , double-blind , placebo-controlled , parallel-group 12-week study was conducted at 23 centers in the United States .


Clinically stable subjects with schizophrenia were randomized in an equal ratio to ABT-288 10 mg , ABT-288 25 mg , or placebo once daily while continuing their antipsychotic regimen .


The primary efficacy measure was the change from baseline to day 84 evaluation on the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery ( MCCB ) composite score vs placebo .


Secondary measures included cognitive functioning and psychiatric scales .


Safety assessments and sparse pharmacokinetic sampling were also conducted .


A total of 214 subjects were randomized .


The mean baseline MCCB composite score was 28.4 .


Approximately 80 % of subjects completed the study .


The MCCB composite score mean change from baseline to day 84 was numerically worse for both the 10 mg ( 1.90 , P = .618 ) and 25 mg ( 0.64 , P = .946 ) doses of ABT-288 vs placebo ( 2.19 ) .


Results from the secondary measures were consistent with the primary analysis .


Subjects ' schizophrenia symptoms remained stable throughout the study as evidenced by stable Positive and Negative Syndrome Scale scores .


Overall , study medication was tolerated ; however , an increased incidence of psychosis-related and sleep-related adverse events was associated with ABT-288 .


Neither dose of ABT-288 resulted in cognitive improvement in clinically stable adults with schizophrenia .


Aromatase inhibitors prevent breast cancer in postmenopausal women at high risk of the disease but are associated with accelerated bone loss .


We assessed effectiveness of oral risedronate for prevention of reduction in bone mineral density ( BMD ) after 3 years of follow-up in a subset of patients in the IBIS-II trial .


The double-blind IBIS-II trial recruited 3864 healthy , postmenopausal women at increased risk of breast cancer and randomly allocated them oral anastrozole ( 1 mg/day ) or matched placebo .


1410 ( 36 % ) postmenopausal women were then enrolled in a bone substudy and stratified at baseline according to their lowest baseline T score at spine or femoral neck ( stratum I : T score at least -10 ; stratum II : T score at least -25 but less than -10 ; stratum III : T score less than -25 but greater than -40 ) .


Women in stratum I were monitored only ; women in stratum III were all given risedronate ( 35 mg/week ) .


Women in stratum II were randomly assigned ( 1:1 ) to risedronate ( 35 mg/week ) or matched placebo by use of a block randomisation schedule via a web-based programme .


The primary outcome of this per-protocol analysis ( done with all women with a baseline and 3 year DXA assessment ) was the effect of risedronate versus placebo for osteopenic women in stratum II randomly allocated to anastrozole ( 1 mg/day ) .


Secondary outcomes included effect of anastrozole ( 1 mg/day ) on BMD in women not receiving risedronate ( strata I and II ) and in osteoporotic women who were all treated with risedronate ( stratum III ) .


The trial is ongoing , but no longer recruiting .


This trial is registered , number ISRCTN31488319 .


Between Feb 2 , 2003 , and Sept 30 , 2010 , 150 ( 58 % ) of 260 women in stratum II who had been randomly allocated to anastrozole and either risedronate or placebo had baseline and 3 year assessments .


At the lumbar spine , 3 year mean BMD change for the 77 women receiving anastrozole/risedronate was 11 % ( 95 % CI 02 to 21 ) versus -26 % ( -40 to -13 ) for the 73 women receiving anastrozole/placebo ( p < 00001 ) .


For the total hip , 3 year mean BMD change for women receiving anastrozole/risedronate was -07 % ( -16 to 02 ) versus -35 % ( -46 to -23 ) for women receiving anastrozole/placebo ( p = 00001 ) .


652 ( 65 % ) of 1008 women in strata I and II who were not randomly allocated to risedronate had both baseline and 3 year assessments .


Women not receiving risedronate in stratum I and II who received anastrozole ( 310 women ) had a significant BMD decrease after 3 years of follow-up compared with women who received placebo ( 342 women ) at the lumbar spine ( -40 % [ -45 to -34 ] vs -12 % [ -17 to -07 ] , p < 00001 ) and total hip ( -40 % [ -44 to -36 ] vs -18 % [ -21 to -14 ] , p < 00001 ) .


106 ( 79 % ) of 149 women in stratum III had a baseline and a 3 year assessment .


The 46 women allocated to anastrozole had a modest BMD increase of 12 % ( -01 to 26 ) at the spine compared with a 39 % ( 26 to 52 ) increase for the 60 women allocated to placebo ( p = 0006 ) .


For the total hip , a small 03 % ( -09 to 15 ) increase was noted for women allocated anastrozole compared with a 15 % ( 05 to 25 ) increase for women allocated placebo , but the difference was not significant ( p = 012 ) .


The most common adverse event reported was arthralgia ( stratum I : 94 placebo and 114 anastrozole ; stratum II : 39 placebo/placebo , 25 placebo/risedronate , 34 anastrozole/placebo , and 34 anastrozole/risedronate ; stratum III : 21 placebo/risedronate , 17 anastrozole/risedronate ) .


Other adverse events included hot flushes , alopecia , abdominal pain , and back pain .


Risedronate counterbalances the effect of anastrozole-induced bone loss in osteopenic and osteoporotic women and might be offered in combination with anastrozole treatment to provide an improved risk-benefit profile .


Cancer Research UK ( C569/A5032 ) , National Health and Medical Research Council Australia ( GNT300755 , GNT569213 ) , Sanofi-Aventis , and AstraZeneca .


Exercise and diet are the cornerstones for the treatment of obesity in obese children and adolescents .


However , compensatory changes in appetite and energy expenditure elicited by exercise and dieting make it hard to maintain a reduced weight over the longterm .


The anorexic effect of hypoxia can be potentially utilized to counteract this compensatory increase , thereby enhancing the success of weight loss .


The purpose of the study is to assess the effectiveness of four week intermittent hypoxia exposure added to a traditional exercise and diet intervention on inducing short - and longterm weight loss in obese adolescents .


In this randomized parallel group controlled clinical trial , 40 obese adolescents ( 20 boys and 20 girls , 11 to 15-years-old ) , will be recruited from a summer weight loss camp at the Shanghai University of Sport , China .


Participants will be stratified by gender and randomly assigned to either the control group or the hypoxia group .


During the four-week intervention period , both groups will exercise and eat a balanced diet .


Additionally , the control group will sleep in normal conditions , while the hypoxia group will sleep in a normobaric hypoxia chamber ( sleep high and train low ) .


The primary outcome will be body composition and the main secondary outcomes will be the circulating levels of appetite regulatory gastrointestinal hormones .


All the outcome measures will be assessed at baseline , after the four-week intervention , and at two months follow-up .


Our study will be the first to evaluate the effectiveness of ` sleep high and train low ' on short - and longterm weight loss among obese adolescents .


A potential mechanism for the appetite regulatory effect of hypoxia will also be explored .


The results of the study will provide an evidence-based recommendation for the use of hypoxia in a weight loss intervention among obese children and adolescents .


Furthermore , the clarification of mechanisms leading to weight loss in ` sleep high and train low ' might provide information for the development of new strategies in combating obesity .


This trial was registered on 10 January 2014 at the Chinese Clinical Trial Registry with the registration number : ChiCTR-TRC-14004106 .


Periprocedural myocardial injury ( PMI ) following percutaneous coronary intervention ( PCI ) has received great attention due to its significant association with mortality and morbidity .


Accordingly , cardioprotection during PCI is one of the important therapeutic concerns .


Regarding the potential cardiovascular benefits of pentoxifylline this study was performed to evaluate whether the pretreatment pentoxifylline could reduce PMI in patients who are undergoing elective PCI .


A randomized clinical trial on 85 patients undergoing elective PCI was performed .


The intervention group ( n = 41 ) received 1200 mg pentoxifylline in divided doses plus the standard treatment before PCI , while the control group ( n = 44 ) received the standard treatment .


For assessing myocardial damage during PCI , the levels of CK-MB and troponin-I were measured at baseline , 8 , and 24 h after the procedure .


Then , patients were followed up for a 1-month period regarding the major adverse cardiac effect .


Comparing with the control group , no significant change of CK-MB at 8 ( p = 0.315 ) and 24 h ( p = 0.896 ) after PCI was documented in pentoxifylline group .


Similarly , no significant change was found in troponin-I at 8 ( p = 0.141 ) and 24 h ( p = 0.256 ) after PCI .


This study could not support the pretreatment with pentoxifylline in the prevention of PMI in patients undergoing elective PCI .


However , the trend was toward the potential benefit of pentoxifylline .


Hospital admissions for acute decompensated heart failure ( ADHF ) are frequent and are accompanied by high percentages of mortality and readmissions .


Brain natriuretic peptide ( BNP ) and the inactive N-terminal fragment of its precursor proBNP ( NT-proBNP ) are currently the best predictors of prognosis in heart failure ( HF ) patients .


In the setting of chronic HF , studies that performed guidance of therapy by NT-proBNP have had only limited success .


For patients with ADHF , retrospective studies have shown that a reduction in NT-proBNP of 30 % during admission is a significant predictor of HF readmissions and mortality .


These data suggest a role for NT-proBNP guidance in the setting of ADHF admissions .


The PRIMA II is an investigator-initiated , multicenter , randomized , controlled , prospective 2-arm trial that investigates the impact of inhospital guidance for ADHF treatment by a predefined NT-proBNP target ( > 30 % reduction during admission ) on the reduction of readmission and mortality rates within 180 days .


Consenting ADHF patients with NT-proBNP levels of > 1,700 ng/L are eligible .


After achieving clinical stability , a total of 340 patients are randomized to either NT-proBNP-guided or conventional treatment ( 1:1 ) .


The primary end point is dual , that is , a composite of all-cause mortality and readmission for HF in 180 days and the number of days alive out of hospital in 180 days .


Secondary end points are readmissions and/or mortality in 180 days , cost effectiveness of hospitalization days in 180 days , readmissions and mortality in 90 days , and quality of life .


The PRIMA II trial aims at providing scientific evidence for the use of NT-proBNP-guided therapy compared with conventional treatment in patients admitted for ADHF .


We aimed to examine the effects of topical hypothermia on inflammatory markers in patients undergoing coronary artery bypass surgery .


Fifty patients undergoing isolated coronary artery bypass surgery were included the study .


They were randomised to two groups .


Mild hypothermic cardiopulmonary bypass ( 28-32C ) was performed on both groups using standardised anaesthesiology and surgical techniques .


Furthermore , topical cooling with 4C saline was performed on patients in group I.


We recorded peri-operative and intra-operative results of blood samples , pre-operative and postoperative outcomes of electrocardiography and echocardiography , diaphragm levels on X-ray , and the necessity of positive inotropic medication and intra-aortic balloon pump ( IABP ) .


Time-dependent changes in blood samples were compared between the two groups .


The changes on complement 3 ( C3 ) and TNF - levels were more significant in group I than group II ( p < 0.05 and p < 0.001 , respectively ) .


Spontaneous restoration rate of sinus rhythm was higher in group II than group I ( 80 vs 32 % , p < 0.01 ) .


Atrial fibrillation was seen in six patients in group I and one patient in group II ( p < 0.05 ) .


IABP was performed on four patients ( 16 % ) in group I ( p < 0.05 ) .


Diaphragmatic paralysis was seen in seven patients in group I but not in group II ( p < 0.01 ) .


Partial pericardiotomy rates were compared within the groups but there was no statistically significant difference ( p > 0.05 ) .


One patient in group I died on the 18th postoperative day , but operative mortality rate was not statistically significant between the two groups ( p > 0.05 ) .


Topical hypothermia had a negative impact on inflammatory markers and postoperative morbidities .


Bedaquiline ( Sirturo , TMC207 ) , a diarylquinoline that inhibits mycobacterial ATP synthase , has been associated with accelerated sputum-culture conversion in patients with multidrug-resistant tuberculosis , when added to a preferred background regimen for 8 weeks .


In this phase 2b trial , we randomly assigned 160 patients with newly diagnosed , smear-positive , multidrug-resistant tuberculosis to receive either 400 mg of bedaquiline once daily for 2 weeks , followed by 200 mg three times a week for 22 weeks , or placebo , both in combination with a preferred background regimen .


The primary efficacy end point was the time to sputum-culture conversion in liquid broth .


Patients were followed for 120 weeks from baseline .


Bedaquiline reduced the median time to culture conversion , as compared with placebo , from 125 days to 83 days ( hazard ratio in the bedaquiline group , 2.44 ; 95 % confidence interval , 1.57 to 3.80 ; P < 0.001 by Cox regression analysis ) and increased the rate of culture conversion at 24 weeks ( 79 % vs. 58 % , P = 0.008 ) and at 120 weeks ( 62 % vs. 44 % , P = 0.04 ) .


On the basis of World Health Organization outcome definitions for multidrug-resistant tuberculosis , cure rates at 120 weeks were 58 % in the bedaquiline group and 32 % in the placebo group ( P = 0.003 ) .


The overall incidence of adverse events was similar in the two groups .


There were 10 deaths in the bedaquiline group and 2 in the placebo group , with no causal pattern evident .


The addition of bedaquiline to a preferred background regimen for 24 weeks resulted in faster culture conversion and significantly more culture conversions at 120 weeks , as compared with placebo .


There were more deaths in the bedaquiline group than in the placebo group .


( Funded by Janssen Pharmaceuticals ; TMC207-C208 ClinicalTrials.gov number , NCT00449644 . )


The conventional sequence when using supraglottic airway devices is insertion , cuff inflation and fixation .


Our hypothesis was that a tighter fit of the cuff and tip could be achieved with a consequently lower incidence of air leak , better separation of gastrointestinal and respiratory tracts and less airway morbidity if the device were first affixed and the cuff then inflated .


Our clinical review board approved the study ( public registry number DRKS00003174 ) .


An LMA Supreme was inserted into 184 patients undergoing lower limb arthroscopy in propofol-remifentanil anaesthesia who were randomly assigned to either the control ( inflation then fixation ; n = 92 ) or study group ( fixation then inflation ; n = 92 ) .


The cuff was inflated to 60 cmH2O .


The patients ' lungs were ventilated in pressure-controlled mode with 5 cmH2O PEEP , Pmax to give 6mlkg-1 tidal volume , and respiratory rate adjusted to end-tidal CO2 of 4.8 and 5.6 kPa .


Correct cuff and tip position were determined by leak detection , capnometry trace , oropharyngeal leak pressure , suprasternal notch test , and lube-tube test .


Bowl and cuff position and the presence of glottic narrowing were assessed by fiberscopic examination .


Postoperative dysphagia , hoarseness and sore throat were assessed with a questionnaire .


Ventilatory impairment was defined as a tidal volume < 6mlkg-1 with Pmax at oropharyngeal leak pressure , glottic narrowing was defined as an angle between the vocal cords under 16 degrees .


The incidence of incorrect device position ( 18 % vs. 21 % ) , failed ventilation ( 10 % vs. 9 % ) , leak pressure ( 24.8 vs. 25.2 cmH2O , p = 0.63 ) , failed lube-tube test ( 16.3 % vs. 17.6 % ) and glottic narrowing ( 19.3 % vs. 14.1 % , p = 0.35 ) was similar in both groups ( control vs. study , resp . )


When glottic narrowing occurred , it was more frequently associated with ventilatory impairment in the control group ( 77 % vs. 39 % ; p = 0.04 ) .


Airway morbidity was more common in the control group ( 33 % vs. 19 % ; p < 0.05 ) .


Altering the sequence of cuff inflation and device fixation does not affect device position , oropharyngeal leak pressures or separation of gastrointestinal and respiratory tracts .


It reduces the incidence of glottic narrowing with impaired ventilation and also perioperative airway morbidity .


A prophylactic human papillomavirus ( HPV ) vaccine targeting oncogenic HPV types in addition to HPV-16 and -18 may broaden protection against cervical cancer .


Two Phase I/II , randomized , controlled studies were conducted to compare the immunogenicity and safety of investigational tetravalent HPV L1 virus-like particle ( VLP ) vaccines , containing VLPs from two additional oncogenic genotypes , with the licensed HPV-16 / 18 AS04-adjuvanted vaccine ( control ) in healthy 18-25 year-old women .


In one trial ( NCT00231413 ) , subjects received control or one of 6 tetravalent HPV-16 / 18/31/45 AS04 vaccine formulations at months ( M ) 0,1,6 .


In a second trial ( NCT00478621 ) , subjects received control or one of 5 tetravalent HPV-16 / 18/33/58 vaccines formulated with different adjuvant systems ( AS04 , AS01 or AS02 ) , administered on different schedules ( M0 ,1,6 or M0 ,3 or M0 ,6 ) .


One month after the third injection ( Month 7 ) , there was a consistent trend for lower anti-HPV-16 and -18 geometric mean antibody titers ( GMTs ) for tetravalent AS04-adjuvanted vaccines compared with control .


GMTs were statistically significantly lower for an HPV-16 / 18/31/45 AS04 vaccine containing 20/20/10 / 10 g VLPs for both anti-HPV-16 and anti-HPV-18 antibodies , and for an HPV-16 / 18/33/58 AS04 vaccine containing 20/20/20 / 20 g VLPs for anti-HPV-16 antibodies .


There was also a trend for lower HPV-16 and -18 - specific memory B-cell responses for tetravalent AS04 vaccines versus control .


No such trends were observed for CD4 ( + ) T-cell responses .


Immune interference could not always be overcome by increasing the dose of HPV-16 / 18 L1 VLPs or by using a different adjuvant system .


All formulations had acceptable reactogenicity and safety profiles .


Reactogenicity in the 7-day post-vaccination period tended to increase with the introduction of additional VLPs , especially for formulations containing AS01 .


HPV-16 and -18 antibody responses were lower when additional HPV L1 VLPs were added to the HPV-16 / 18 AS04-adjuvanted vaccine .


Immune interference is a complex phenomenon that can not always be overcome by changing the antigen dose or adjuvant system .


In a multicenter , double-blind , randomized , parallel-group , placebo-controlled , single-dose study ( n = 1555 ) , a fixed combination of acetaminophen 500mg , acetylsalicylic acid 500mg , and caffeine 130mg ( AAC ) was compared with ibuprofen 400mg ( IB ) and placebo ( PLA ) for acute treatment of migraine .


An exploratory post-hoc analysis compared AAC with IB and PLA in the subset of patients with severe pain at baseline ( n = 660 ) .


At most time points , AAC and IB relieved the pain and associated symptoms of severe migraine significantly better than PLA ( p0 .05 ) .


AAC was significantly superior to IB for pain relief at 45 minutes and at one , two , three , and four hours postdose ( p < 0.04 ) ; pain intensity difference from one hour through three hours ( p < 0.05 ) ; headache response at two hours ( p = 0.04 ) ; functional disability reduced to little or none at three hours ( p = 0.013 ) ; freedom from phonophobia at three hours ( p = 0.04 ) and photophobia at 15 minutes postdose ( p = 0.03 ) ; and use of rescue medication ( p = 0.018 ) .


AAC patients also reported meaningful pain relief 16 minutes faster than IB patients ( 132 minutes vs 148 minutes , p = 0.026 ) .


In patients with severe baseline migraine pain , AAC and IB are significantly more effective than PLA , and AAC provides significantly faster and more effective pain relief than IB .


Determine whether MRI activity 6 months after treatment initiation in the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study ( CHAMPS ) predicted progression to clinically definite multiple sclerosis ( CDMS ) over the subsequent 30 months in intramuscular interferon beta-1a ( IM IFN-1a ) - treated patients vs placebo-treated patients .


CHAMPS patients were randomized to once-weekly IM IFN-1a 30 g or placebo for up to 36 months .


MRI was performed every 6 months until CDMS confirmation .


Patient groups were defined based on new T2 and/or Gd + lesions at 6 months .


Thirteen IM IFN-1a patients ( 6.7 % ) and 24 placebo patients ( 12.6 % ) developed CDMS prior to month 6 and did not undergo the 6-month MRI .


At 6 months , 29.7 % of IM IFN-1a-treated patients vs 40.9 % of placebo-treated patients were defined as having high MRI activity levels ( 2 new T2 and/or 2 Gd + lesions ) .


In this subgroup , estimated cumulative probabilities of CDMS were similar between groups ( HR = 0.88 [ 0.44-1 .77 ] , p = 0.7227 ) .


A significant treatment response was seen for patients with < 2 new T2 and < 2 Gd + lesions at 6 months ( HR = 0.39 [ 0.19-0 .82 ] , p = 0.0120 ) .


MRI scans 6 months after IM IFN-1a initiation in CIS patients predict early treatment non-response .


Standardized scanning and monitoring may facilitate early disease management .


Blood loss and blood substitution are associated with higher morbidity after major abdominal surgery .


During major liver resection low local venous pressure decreases blood loss .


Ambiguity persists concerning the impact of local venous pressure on blood loss during open radical cystectomy .


We determined the association between intraoperative blood loss and pelvic venous pressure as well as factors affecting pelvic venous pressure .


In this single center , double-blind , randomized trial pelvic venous pressure was measured in 82 patients in a norepinephrine-low volume group and in 81 controls with liberal hydration .


As secondary analysis patients from each arm were stratified into subgroups with pelvic venous pressure less than 5 mm Hg , or 5 or greater as measured after cystectomy , which is the optimal cutoff for identifying patients with relevant blood loss according to the Youden index .


Median blood loss was 800 ml ( range 300 to 1,600 ) in 55 of 163 patients ( 34 % ) with pelvic venous pressure less than 5 mm Hg and 1,200 ml ( range 400 to 3,000 ) in 108 of 163 ( 66 % ) with pelvic venous pressure 5 mm Hg or greater ( p < 0.0001 ) .


Pelvic venous pressure less than 5 mm Hg was measured in 42 of 82 patients ( 51 % ) in the norepinephrine-low volume group and in 13 of 81 controls ( 16 % ) ( p < 0.0001 ) .


Pelvic venous pressure decreased significantly after removing abdominal packing and abdominal lifting in each group at all time points , that is at the beginning and end of pelvic lymph node dissection , and the end of cystectomy ( p < 0.0001 ) .


No correlation was detected between pelvic venous pressure and central venous pressure .


Blood loss was significantly decreased in patients with low pelvic venous pressure .


Factors affecting pelvic venous pressure were fluid management and abdominal packing .


Survivors of breast cancer may experience deterioration of physical function .


This is important because poor physical function may be associated with premature mortality , injurious falls , bone fracture , and disability .


We conducted a post hoc analysis to explore the potential efficacy of slowly progressive weight lifting to reduce the incidence of physical function deterioration among survivors of breast cancer .


Between October 2005 and August 2008 , we conducted a single-blind , 12-month , randomized controlled trial of twice-per-week slowly progressive weight lifting or standard care among 295 survivors of nonmetastatic breast cancer .


In this post hoc analysis of data from the Physical Activity and Lymphedema Trial , we examined incident deterioration of physical function after 12 months , defined as a 10-point decrease in the physical function subscale of the Medical Outcomes Short-Form 36-item questionnaire .


The proportion of participants who experienced incident physical function deterioration after 12 months was 16.3 % ( 24/147 ) in the control group and 8.1 % ( 12/148 ) in the weight lifting group ( relative risk , 0.49 ; 95 % CI , 0.25 to 0.96 ; P = .04 ) .


No serious or unexpected adverse events occurred that were related to weight lifting .


Slowly progressive weight lifting compared with standard care reduced the incidence of physical function deterioration among survivors of breast cancer .


These data are hypothesis generating .


Future studies should directly compare the efficacy of weight lifting with other modalities of exercise , such as brisk walking , to appropriately inform the development of a confirmatory study designed to preserve physical function among survivors of breast cancer .


To evaluate the effect of intracameral lidocaine anesthesia on macular thickness and macular ganglion cell-inner plexiform layer ( GC-IPL ) thickness following uneventful phacoemusification in healthy subjects .


This is a prospective , randomized and double - masked study .


One hundred eyes of 74 consecutive patients were randomized to receive intracameral preservative-free lidocaine 1 % ( intracameral lidocaine group ) or intracameral injection of balanced salt solution ( sham injection group ) at the time of the phacoemulsification surgery .


Preoperative and postoperative macular thickness analyses with spectral domain optical coherence tomography ( SD-ODT ) were performed and the results between the two groups were compared .


Postoperatively , both the central foveal thickness ( CFT ) and the thickness of perifoveal macula were significantly improved in both groups ( p < 0.001 ) .


There was no statistically significant difference between CFT and the inner and outer macular zone thicknesses of the two groups at any follow-up time .


In both groups , GC-IPL thickness was significantly increased at the first week and first month visits ( p < 0.001 ) .


There was no statistically significant difference between GC-IPL thickness measurements of the two groups at any follow-up time .


The current study demonstrated that supplementary intracameral lidocaine 1 % did not cause more macular thickening than the intracameral sham injection during a follow-up period of 3months .


The present study also showed a tendency for a transient increase in high definition SD-OCT-based GC-IPL thickness measurements within a few months following cataract surgery under both intracameral lidocaine anesthesia and intracameral sham injection .


In the current analysis due to the mechanism of effect , we evaluated the treatment benefit of duloxetine 40 mg comparing with paroxetine 20 mg , based on its effects on personal distress and interpersonal difficulty related to ejaculation , perceived control over ejaculation , and satisfaction with sexual intercourse , as well as the patient-reported global impression of change in premature ejaculation ( PE ) and the effect on intravaginal ejaculatory latency times ( IELT ) in men with premature ejaculation .


The study included 80 married male patients diagnosed with lifelong PE .


A total of 80 patients were randomly distributed into two groups of 40 patients each .


Group 1 patients received 40 mg duloxetine once a day for a month .


Group 2 patients received 20 mg paroxetine once a day for a month .


International index of erectile function questionnaire ( IIEF ) and IELT and PE profile were recorded before and after treatment .


Comparing the groups ' mean treatment IELT , there was no difference between groups .


The IELT increase from baseline to treatment was 117 % in the duloxetine group ( P < 0.001 ) and 126 % in the paroxetine group ( P < 0.001 ) .


There was no statistical difference between two groups in terms of IELT increase ( P > 0.05 ) .


Also , there was no statistically significant difference between two groups at baseline IIEF to treatment IIEF scores .


All PEP measures improved significantly with duloxetine and paroxetine groups ( P < 0.001 ) .


We think that duloxetine is safe and effective for the treatment for premature ejaculation .


Dietary supplements are widely used by cancer survivors .


However , health effects among older cancer survivors are unclear .


We used the Iowa Women 's Health Study , a prospective cohort study with 2,118 postmenopausal women with a confirmed cancer diagnosis ( 1986-2002 ) , to evaluate the association between postdiagnosis dietary supplement use assessed in 2004 and subsequent all-cause mortality .


Risk of death was evaluated using multivariable-adjusted Cox proportional hazards regression .


We performed stratified analyses by diet quality score , dietary micronutrient intake , and perceived general health .


Through 2010 , 608 deaths were identified .


Approximately 85 % of the cancer survivors used dietary supplements .


Overall supplement use and multivitamin use were not associated with mortality .


Iron supplement use was associated with 39 % higher risk of death [ 95 % confidence interval ( CI ) , 1.09-1 .77 ] .


This association was stronger among survivors with deteriorating general health .


Folic acid supplement use was associated with higher risk of death , only among survivors reporting low-quality diets ( HR , 2.33 ; 95 % CI , 1.33-4 .08 ; P interaction = 0.006 ) .


Multivitamin use and using a greater number of supplements was associated with a trend towards higher mortality only among those with poor diet quality .


Using vitamin E supplements in combination with multivitamin was associated with lower risk of death only among survivors with higher dietary vitamin E intake ( HR , 0.61 ; 95 % CI , 0.39-0 .94 ; P interaction = 0.02 ) .


Postdiagnosis supplement use was associated with higher mortality among older female cancer survivors with poor general health and/or poor dietary intake .


The association between postdiagnosis dietary supplement use and mortality may differ by diet quality and health status among older female cancer survivors .


This post hoc analysis assessed the efficacy of desvenlafaxine 50 mg/day for treating major depressive disorder in perimenopausal versus postmenopausal women enrolled in a 10-week , double-blind , placebo-controlled study .


Perimenopausal and postmenopausal women ( 40-70 y ) diagnosed with major depressive disorder were randomly assigned to receive desvenlafaxine 50 mg/day or placebo .


Changes from baseline in the primary efficacy variable ( 17-item Hamilton Rating Scale for Depression [ HAM-D17 ] score , week 8 ) and in other secondary efficacy variables ( Sheehan Disability Scale and Menopause Rating Scale ) were analyzed using analysis of covariance with treatment , region , and baseline in the model .


Clinical Global Impressions-Improvement Scale was analyzed with the Cochran-Mantel-Haenszel test .


Response and remission rates were evaluated using logistic regression with treatment , region , and baseline HAM-D17 in the model .


Of 426 women ( desvenlafaxine , n = 216 ; placebo , n = 210 ) included in this analysis , 135 ( 32 % ) were perimenopausal and 291 ( 68 % ) were postmenopausal at baseline .


In both subgroups , improvement from baseline in HAM-D17 scores was significantly greater for desvenlafaxine 50 mg/day than for placebo .


Menopause status and time since menopause did not significantly affect HAM-D17 total score .


The drug-placebo difference in Sheehan Disability Scale scores was significant in perimenopausal women ( -9.3 vs. -5.1 , P < 0.001 ) but not in postmenopausal women ( -8.8 vs. -8.1 ) .


Menopause Rating Scale and Clinical Global Impressions-Improvement Scale scores were significantly improved with desvenlafaxine in postmenopausal women .


Desvenlafaxine 50 mg/day is effective in treating depression in both perimenopausal and postmenopausal women .


Placebo response on measures of functional impairment is lower in perimenopausal women than in postmenopausal women , resulting in a greater apparent treatment benefit with desvenlafaxine among perimenopausal women .


Large-scale randomized clinical trials are needed to assess the role of Roux-en-Y gastric bypass ( RYGB ) in treating patients with type 2 diabetes mellitus ( T2DM ) .


Recruitment challenges must be understood .


One hundred twenty participants were needed for a prospective randomized controlled trial investigating treatments for hyperglycemia and cardiovascular disease risk factors in patients with T2DM .


The trial had two arms-intensive medical management plus a rigorous lifestyle intervention ( LS/IMM ) versus LS/IMM with RYGB .


Medical inclusion criteria included glycosylated hemoglobin ( HbA1c ) 8.0 % while under the care of a physician and body mass index ( BMI ) 30.0-39 .9 kg/m ( 2 ) .


Another inclusion criterion was expressed willingness to accept randomization and participate fully .


Varied recruitment strategies were employed at four academic hospitals in the USA and Taiwan , including referrals , mass media , direct mail to patients drawn from a practice-based database , and direct mail to commercial mailing lists .


Between February 2008 and December 2011 , 2,648 candidates were phone-screened and 240 were screened on site ; 120 participants were eventually randomized .


Impediments included stringent medical inclusion criteria and a lack of equipoise ( i.e. , strong beliefs or preferences ) among patients and their personal community-based physicians .


To meet timeline requirements , the upper limit for BMI was increased from 34.9 to 39.9 kg/m ( 2 ) and an additional site was added .


We successfully recruited 120 participants with poorly controlled T2DM and mild to moderate obesity .


Participants had to be willing to accept randomization to either surgical or nonsurgical treatments .


Recruitment took 4 years .


The aim of this study was to evaluate the effects of pre-warmed ( approximately 41 C ) intravenous fluids ( IV ) on perioperative hypothermia and postoperative shivering in female patients undergoing short , ambulatory urological surgery under monitored anesthesia care ( MAC ) .


Patients between the ages of 35 and 80 years were randomly assigned to either the pre-warmed ( n = 27 ) or the room temperature ( n = 26 ) group .


According to group allocation , either pre-warmed IV fluids that had been stored in a warming cabinet for at least 8 h or room temperature IV fluids were administered intraoperatively up to approximately 600-700 ml , including a bolus infusion of 10 ml/kg within 20 min .


Perioperative core temperatures at the tympanic membrane , postoperative shivering , subjective thermal comfort , and the use of forced-air warming interventions in the post-anesthesia care unit ( PACU ) were recorded .


Mean core temperatures were significantly higher in the pre-warmed group than they were in the room temperature group after 10 ml/kg preload fluid was administered , at the end of the operation , and on admission to the PACU ( p = 0.004 , p = 0.02 , and p = 0.008 , respectively ) .


The incidence of hypothermia ( < 36 C ) was significantly lower in the pre-warmed group ( n = 4 ) than in the room temperature group ( n = 11 , p = 0.035 ) upon PACU admission .


The postoperative shivering incidence was also significantly lower in the pre-warmed group ( n = 2 ) than in the room temperature group ( n = 8 , p = 0.039 ) .


Infusion of pre-warmed IV fluid improved the postoperative recovery profile by decreasing hypothermia and shivering in female patients undergoing short , ambulatory urological surgery under MAC .


Studies have indicated a blood pressure ( BP ) - lowering effect of milk-derived peptides in non-diabetic individuals , but the cardiometabolic effects of such peptides in patients with type 2 diabetes ( T2D ) are not known .


We investigated the effect of milk fermented with Lactobacillus helveticus on BP , glycaemic control and cardiovascular risk factors in T2D .


A randomised , double-blinded , prospective , placebo-controlled study .


In one arm of a factorial study design , 41 patients with T2D were randomised to receive 300 ml milk fermented with L. helveticus ( Cardi04 yogurt ) ( n = 23 ) or 300 ml artificially acidified milk ( placebo yogurt ) ( n = 18 ) for 12 weeks .


BPs were measured over 24-h , and blood samples were collected in the fasting state and during a meal test before and after the intervention .


Cardi04 yogurt did not reduce 24-h , daytime or nighttime systolic or diastolic BPs compared with placebo ( P > 0.05 ) .


Daytime and 24-h heart rate ( HR ) were significantly reduced in the group treated by Cardi04 yogurt compared with the placebo group ( P < 0.05 for both ) .


There were no differences in HbA1c , plasma lipids , C-reactive protein , plasminogen activator inhibitor-1 , tumour necrosis factor alpha , tissue-type plasminogen activator : Ag , and von Willebrand factor : Ag between the groups .


The change in fasting blood glucose concentration differed significantly between the two groups with a larger increase in the placebo group ( P < 0.05 ) .


Ingestion of milk fermented with L. helveticus compared with placebo for 12 weeks did not significantly reduce BP in patients with T2D .


Our finding of lower HRs and fasting plasma glucose levels in T2D patients during ingestion of fermented milk needs further validation .


Suboptimal virologic response to nucleos ( t ) ide analogs may represent a significant risk factor for resistance development in patients with chronic hepatitis B virus infection ; treatment options have not been well studied .


We evaluated long-term efficacy and safety of tenofovir alone and in combination with emtricitabine in a prospective , placebo-controlled trial in patients who remained viremic on adefovir therapy .


Hepatitis B e antigen-positive and - negative patients with hepatitis B virus DNA 1000 copies/ml despite up to 96 weeks of adefovir were randomized to double-blind tenofovir or emtricitabine/tenofovir for 168 weeks .


Patients with hepatitis B virus DNA 400 copies/ml ( 69IU/ml ) at or after week 24 could switch to open-label emtricitabine/tenofovir .


Overall , 90/105 ( 86 % ) patients ( 46/53 tenofovir and 44/52 emtricitabine/tenofovir ) completed the 168-week study period , including 74/105 ( 70 % ) patients ( 35/53 tenofovir and 39/52 emtricitabine/tenofovir ) who completed the study on their initial randomized treatment .


Long-term viral suppression ( hepatitis B virus DNA < 400 copies/ml ) was maintained at week 168 in 84 % and 82 % of patients receiving either emtricitabine/tenofovir combination or tenofovir monotherapy , respectively ( non-completer equal to failure analysis ) .


Baseline viral load as well as the presence of lamivudine and/or adefovir resistance-associated mutations at baseline had no impact on long-term treatment response .


No resistance to tenofovir was observed through 168 weeks .


Both treatments had a favorable safety profile .


Tenofovir monotherapy is as effective as emtricitabine/tenofovir combination therapy in maintaining long-term viral suppression in patients with a suboptimal response to adefovir , and is well tolerated in this population .


To investigate the effectiveness of a school based intervention to increase physical activity , reduce sedentary behaviour , and increase fruit and vegetable consumption in children .


Cluster randomised controlled trial .


60 primary schools in the south west of England .


Primary school children who were in school year 4 ( age 8-9 years ) at recruitment and baseline assessment , in year 5 during the intervention , and at the end of year 5 ( age 9-10 ) at follow-up assessment .


The Active for Life Year 5 ( AFLY5 ) intervention consisted of teacher training , provision of lesson and child-parent interactive homework plans , all materials required for lessons and homework , and written materials for school newsletters and parents .


The intervention was delivered when children were in school year 5 ( age 9-10 years ) .


Schools allocated to control received standard teaching .


The pre-specified primary outcomes were accelerometer assessed minutes of moderate to vigorous physical activity per day , accelerometer assessed minutes of sedentary behaviour per day , and reported daily consumption of servings of fruit and vegetables .


60 schools with more than 2221 children were recruited ; valid data were available for fruit and vegetable consumption for 2121 children , for accelerometer assessed physical activity and sedentary behaviour for 1252 children , and for secondary outcomes for between 1825 and 2212 children for the main analyses .


None of the three primary outcomes differed between children in schools allocated to the AFLY5 intervention and those allocated to the control group .


The difference in means comparing the intervention group with the control group was -1.35 ( 95 % confidence interval -5.29 to 2.59 ) minutes per day for moderate to vigorous physical activity , -0.11 ( -9.71 to 9.49 ) minutes per day for sedentary behaviour , and 0.08 ( -0.12 to 0.28 ) servings per day for fruit and vegetable consumption .


The intervention was effective for three out of nine of the secondary outcomes after multiple testing was taken into account : self reported time spent in screen viewing at the weekend ( -21 ( -37 to -4 ) minutes per day ) , self reported servings of snacks per day ( -0.22 ( -0.38 to -0.05 ) ) , and servings of high energy drinks per day ( -0.26 ( -0.43 to -0.10 ) ) were all reduced .


Results from a series of sensitivity analyses testing different assumptions about missing data and from per protocol analyses produced similar results .


The findings suggest that the AFLY5 school based intervention is not effective at increasing levels of physical activity , decreasing sedentary behaviour , and increasing fruit and vegetable consumption in primary school children .


Change in these activities may require more intensive behavioural interventions with children or upstream interventions at the family and societal level , as well as at the school environment level .


These findings have relevance for researchers , policy makers , public health practitioners , and doctors who are involved in health promotion , policy making , and commissioning services .


Trial registration Current Controlled Trials ISRCTN50133740 .


Central venous catheter ( CVC ) - related thrombosis and infections are frequently occurring complications in patients with hematological malignancies .


At present , heparin is most often used as a locking solution .


Trisodium citrate ( TSC ) had been shown to be a very effective antimicrobial catheter locking in hemodialysis patients .


We performed a prospective randomized phase III multicenter trial to determine the efficacy of TSC as a locking solution compared to heparin in preventing CVC-related thrombosis and infections in patients with hematological malignancies .


Thirty-four episodes of CVC-related bloodstream infections ( CVC-BSI ) occurred in the 108 patients who were randomized to locking with heparin compared with 35 episodes in the 99 patients who were randomized to locking with TSC ( P = 0.654 ) .


We did find seven times more CVC-BSI with gram-negative rods in CVCs locked with heparin ( P = 0.041 ) .


The cumulative incidence of symptomatic thrombosis was 10 % in the heparin group and 5 % in the TSC group ( hazard ratio 0.525 ; 95 % confidence interval 0.182-1 .512 ) .


This study shows that locking with TSC in patients with hematological malignancies significantly reduced the incidence of CVC-BSI with gram-negative rods .


However , the incidence of CVC-BSI with coagulase-negative staphylococcus or CVC-related thrombosis was not reduced by TSC locking .


C-reactive protein ( CRP ) binds to damaged cells , activates the classical complement pathway , is elevated in multiple inflammatory conditions , and provides prognostic information on risk of future atherosclerotic events .


It is controversial , however , as to whether inhibiting CRP synthesis would have any direct anti-inflammatory effects in humans .


A placebo-controlled study was used to evaluate the effects of ISIS 329993 ( ISIS-CRPR x ) on the acute-phase response after endotoxin challenge in 30 evaluable subjects .


Healthy adult males were randomly allocated to receive 6 injections over a 22-day period of placebo or active therapy with ISIS 329993 at 400 - or 600-mg doses .


Eligible subjects were subsequently challenged with a bolus of endotoxin ( 2 ng/kg ) .


Inflammatory and hematological biomarkers were measured before and serially after the challenge .


ISIS-CRPR x was well tolerated with no serious adverse events .


Median CRP levels increased more than 50-fold from baseline 24 hours after endotoxin challenge in the placebo group .


In contrast , the median increase in CRP levels was attenuated by 37 % ( 400 mg ) and 69 % ( 600 mg ) in subjects pretreated with ISIS-CRPR x ( P < 0.05 vs. placebo ) .


All other aspects of the acute inflammatory response were similar between treatment groups .


Pretreatment of subjects with ISIS-CRPR x selectively reduced the endotoxin-induced increase in CRP levels in a dose-dependent manner , without affecting other components of the acute-phase response .


These data demonstrate the specificity of antisense oligonucleotides and provide an investigative tool to further define the role of CRP in human pathological conditions .


We recently reported that epithelial-mesenchymal transition ( EMT ) is active in the airways in chronic obstructive pulmonary disease ( COPD ) , suggesting presence of an active profibrotic and promalignant stroma .


With no data available on potential treatment effects , we undertook a blinded analysis of inhaled corticosteroids ( ICS ) effects versus placebo on EMT markers in previously obtained endobronchial biopsies in COPD patients , as a `` proof of concept '' study .


Assessment of the effects of inhaled fluticasone propionate ( FP ; 500 g twice daily for 6 months ) versus placebo in 34 COPD patients ( 23 on fluticasone propionate and eleven on placebo ) .


The end points were epidermal growth factor receptor ( EGFR ; marker of epithelial activation ) and the biomarkers of EMT : reticular basement membrane ( Rbm ) fragmentation ( `` hallmark '' structural marker ) , matrix metalloproteinase-9 ( MMP-9 ) cell expression , and S100A4 expression in basal epithelial and Rbm cells ( mesenchymal transition markers ) .


Epithelial activation , `` clefts/fragmentation '' in the Rbm , and changes in the other biomarkers all regressed on ICS , at or close to conventional levels of statistical significance .


From these data , we have been able to nominate primary and secondary end points and develop power calculations that would be applicable to a definitive prospective study .


Although only a pilot `` proof of concept '' study , this trial provided strong suggestive support for an anti-EMT effect of ICS in COPD airways .


A larger and fully powered prospective study is now indicated as this issue is likely to be extremely important .


Such studies may clarify the links between ICS use and better clinical outcomes and protection against lung cancer in COPD .


The Radiation Reduction During Cardiac Catheterization Using Real-Time Monitoring study sought to examine the effect of a radiation detection device that provides real-time operator dose reporting through auditory feedback ( Bleeper Sv ; Vertec Scientific Ltd ; Berkshire , UK ) on patient dose and operator exposure during cardiac catheterization .


Between January 2012 and May 2014 , 505 patients undergoing coronary angiography , percutaneous coronary intervention , or both were randomized to use ( n = 253 ) or no use ( n = 252 ) of the Bleeper Sv radiation monitor .


Operator radiation exposure was measured in both groups using a second , silent radiation exposure monitoring device .


Mean patient age was 658 years , most patients ( 99 % ) were men , and 30 % had prior coronary artery bypass graft surgery .


Baseline clinical characteristics were similar in the 2 study groups .


Radial access was used in 18 % and chronic total occlusion percutaneous coronary intervention constituted 7 % of the total procedures .


Median procedure time was 17 ( 12-27 ) minutes for diagnostic angiography , 42 ( 28-70 ) minutes for percutaneous coronary intervention , and 27 ( 14-51 ) minutes in the overall study population , with similar distribution between the study groups .


First ( 9 [ 4-17 ] versus 14 [ 7-25 ] Sv ; P < 0.001 ) and second ( 5 [ 2-10 ] versus 7 [ 4-14 ] Sv ; P < 0.001 ) operator radiation exposure was significantly lower in the Bleeper Sv group .


Use of the device did not result in a significant reduction in patient radiation dose .


The effect of the Bleeper Sv device on operator radiation exposure was consistent among various study subgroups .


Use of a real-time radiation monitoring device that provides auditory feedback can significantly reduce operator radiation exposure during cardiac catheterization .


http://www.clinicaltrials.gov .


Unique identifier : NCT01510353 .


Aerobic exercise training is a recognized approach for improving functional capacity in COPD .


People with greater disease severity often have difficulty achieving higher aerobic exercise training intensity .


The effects of resistance training prior to aerobic training were examined to determine if this sequential approach was associated with greater gains in functional status than aerobic training alone or concurrent aerobic and resistance training .


Patients were randomized to : 1 ) sequential resistance then aerobic training ( RT-then-AT ) ( 8 weeks resistance training followed by 8 weeks aerobic exercise training ) , 2 ) control group ( CE-then-AT + RT ) ( 8 weeks of ` sham ' training followed by 8 weeks concurrent aerobic and resistance training ) , 3 ) control group ( CE-then-AT ) ( 8 weeks ` sham ' training followed by 8 weeks aerobic training ) .


Outcomes were assessed at study entry , after week 8 , and after week 16 : aerobic exercise performance ; muscle strength and endurance .


75 patients completed training : FEV1 % pred 40 10 , VO ( 2peak ) % predicted , 71 22 , fat-free mass index 19.5 3.1 .


RT-then-AT had greater acquisition of peripheral muscle endurance than CE-then-AT + RT and CE-then-AT , but improvements in aerobic exercise performance were similar .


Improvements in muscle strength were similar between RT-then-AT and CE-then-AT + RT. .


Sarcopenia was associated with poorer attendance , and lower aerobic and resistance training volumes .


Although the sequential approach to resistance and aerobic training yielded a greater increase in muscle endurance and higher resistance training volume compared to concurrent resistance and aerobic training , other training outcomes were similar between the two groups , thus the sequential approach is not clearly superior to the concurrent approach in severe COPD .


ClinicalTrials.gov Identifier : NCT01058213 .


The association between epicardial adipose tissue ( EAT ) volume and coronary artery disease ( CAD ) severity was evaluated , independent of traditional risk factors and coronary artery calcium ( CAC ) scores , in patients with diabetes type 2 ( DM-2 ) using cardiac computed tomography angiography ( CTA ) .


A multivariate analysis was utilized to assess for an independent association after calculating EAT volume , CAD severity , and calcium scores in 92 patients with DM-II from the CTRAD study .


We graded CAD severity as none ( normal coronaries ) , mild-moderate ( < 70 % stenosis ) , and severe ( 70 % or greater stenosis ) .


A total of 39 ( 42.3 % ) asymptomatic patients with diabetes did not have CAD ; 30.4 % had mild/moderate CAD ; and 27.1 % had severe CAD .


Mean EAT volume was highest in patients with severe CAD ( 143.14 cm ( 3 ) ) as compared to mild/moderate CAD ( 112.7 cm ( 3 ) ) , and no CAD ( 107.5 cm ( 3 ) ) ( p = 0.003 ) .


After adjustment of clinical risk factors , notably , CAC score , multivariate regression analysis showed EAT volume was an independent predictor of CAD severity in this sample ( odds ratio 11.2 , 95 % confidence interval 1.7-73 .8 , p = 0.01 ) .


Increasing EAT volume in asymptomatic patients with DM-II is associated with presence of severe CAD , independent of BMI and CAC , as well as traditional risk factors .


To evaluate the efficacy and safety of mite allergen specific immunotherapy ( SIT ) in treating children with allergic asthma .


A total of 136 patients with mite allergy were recruited into the study .


They were randomly divided into two groups : SIT group ( n = 66 ) and ST ( symptomatic therapy ) group ( n = 70 ) .


They were investigated of SIT with standardized allergen vaccine or no SIT only symptomatic therapy respectively .


Therapeutic evaluation index includes : asthma symptoms score , drug score , skin prick test , pulmonary function , serum specificity IgE ( sIgE ) and the new sensitization was also assessed .


Local and systemic adverse reactions were used to evaluate the clinical safety .


Clinical symptom scores , drug scores , Lung function , and skin test result all improved significantly after the treatment with SIT compared to ST group ( P < 0.01 ) .


SIT groups do not have new sensitization and no fatal systemic reactions occurred .


The standardized dust mite allergen specific immunotherapy is efficacious and safe to Children with allergic asthma .


SIT can reduce house dust mites skin sensitivity and prevent new allergen appeared .


No-rinse disposable wash gloves are increasingly implemented in health care to replace traditional soap and water bed baths without proper evaluation of ( cost ) effectiveness .


To compare bed baths for effects on skin integrity and resistance against bathing and costs .


Cluster randomized trial .


Fifty six nursing home wards in the Netherlands .


Participants : Five hundred adult care-dependent residents and 275 nurses from nursing home wards .


The experimental condition ` washing without water ' consists of a bed bath with disposable wash gloves made of non-woven waffled fibers , saturated with a no-rinse , quickly vaporizing skin cleaning and caring lotion .


The control condition is a traditional bed bath using soap , water , washcloths and towels .


Both conditions were continued for 6 weeks .


Outcome measures were prevalence of skin damage distinguished in two levels of severity : any skin abnormality/lesion and significant skin lesions .


Additional outcomes : resistance during bed baths , costs .


Any skin abnormalities/lesions over time decreased slightly in the experimental group , and increased slightly in the control group , resulting in 72.7 % vs 77.6 % of residents having any skin abnormalities/lesions after 6 weeks , respectively ( p = 0.04 ) .


There were no differences in significant skin lesions or resistance after 6 weeks .


Mean costs for bed baths during 6 weeks per resident were estimated at 218.30 ( 95 % CI 150.52-286 .08 ) in the experimental group and 232.20 ( 95 % CI : 203.80-260 .60 ) in the control group ( difference 13.90 ( 95 % CI : -25.61 -53.42 ) .


Washing without water mildly protects from skin abnormalities/lesions , costs for preparing and performing bed baths do not differ from costs for traditional bed bathing .


Thus , washing without water can be considered the more efficient alternative .


The aim of this study is to investigate the effectiveness of preemptive thoracic epidural analgesia ( TEA ) comparing conventional postoperative epidural analgesia on thoracotomy .


Forty-four patients were randomized in to two groups ( preemptive : Group P , control : Group C ) .


Epidural catheter was inserted in all patients preoperatively .


In Group P , epidural analgesic solution was administered as a bolus before the surgical incision and was continued until the end of the surgery .


Postoperative patient controlled epidural analgesia infusion pumps were prepared for all patients .


Respiratory rates ( RR ) were recorded .


Patient 's analgesia was evaluated with visual analog scale at rest ( VASr ) and coughing ( VASc ) .


Number of patient 's demands from the pump , pump 's delivery , and additional analgesic requirement were also recorded .


RR in Group C was higher than in Group P at postoperative 1st and 2nd hours .


Both VASr and VASc scores in Group P were lower than in Group C at postoperative 1st , 2nd , and 4th hours .


Patient 's demand and pump 's delivery count for bolus dose in Group P were lower than in Group C in all measurement times .


Total analgesic requirements on postoperative 1st and 24th hours in Group P were lower than in Group C.


We consider that preemptive TEA may offer better analgesia after thoracotomy .


and purpose Participant recruitment is central to all clinical trials .


Any delay in recruitment affects the completion and ultimate success of the trial .


We report our experience with patient screening and randomization in CombiRx , which may inform the design of other trials .


CombiRx was a multicenter , phase III , double-blind , randomized clinical trial comparing the combined use of interferon beta-1a and glatiramer acetate to either agent alone in patients with relapsing-remitting multiple sclerosis ( RRMS ) .


This trial was launched in January 2005 in 69 centers in the United States and Canada under a co-operative agreement with the National Institute of Neurological Disorders and Stroke ( NINDS ) .


The goal was to recruit 1000 patients over 1.5 years after a 6-month start-up period .


Instead , the investigators required 4.25 years to enroll 1008 patients .


During this trial , we assessed the effectiveness of various recruitment strategies , utility of rescreening prior screen failures , and potential factors and strategies used in study conduct , research , and infrastructure , all of which affected recruitment of participants and ultimately time to completion of CombiRx .


We particularly were interested in the variability in time to site initiation between academic centers and private practice sites .


Physicians who were directly involved in the medical care of patients with RRMS were the primary source of patients recruited to CombiRx .


A flexible study design that allowed for rescreening of the initial screen failures after a period of time was useful due to the relapsing/remitting course of the disease .


Academic centers took longer to implement the trial than the private practice centers , but once sites were approved for enrollment , there was no important difference in the number of participants enrolled .


The CombiRx trial was conducted during a period when multiple new medications were being tested , thus affecting the pace of recruitment and limiting ability to generalize our experiences .


However , the lessons we learned about process are relevant .


Participants can be enrolled successfully in a clinical trial for RRMS , but factors affecting the time to achieve the requirements needed to start screening can be unpredictable and problematic .


Prospective planning by the sponsors and investigators , use of central institutional review boards ( IRBs ) , master trial agreements and secure remote desktop access to the trial database may expedite trial implementation and participant recruitment .


A good scientific research question with flexible study design and active involvement of the clinicians are important factors driving recruitment .


Clinical trials can be implemented successfully both in private practices and at academic centers , a consideration when selecting sites .


Primary health care in Tanzania is provided at two types of health units , the dispensary and the health centre .


Theoretically , primary health workers ( with knowledge of primary eye care [ PEC ] ) are ideally placed to identify people in need of eye care services .


In Tanzania , they are expected to be able to identify , treat , or correctly refer a number of eye conditions including cataract , trauma , presbyopia , and the ` red eye ' .


They are also expected to be able to measure visual acuity correctly and to educate the community about prevention .


The objective was to determine the effect of enhanced supervision of health workers on PEC knowledge and skills in Kilimanjaro Region , Tanzania .


This was a quasi-experimental , cluster randomized intervention study of an enhanced supervisory method compared to a routine supervisory method ; 36 dispensaries were randomly allocated into the two groups .


Health workers based at government dispensaries in Mwanga District .


Participants were interviewed pre and post intervention and the information was recorded using a standardized pretested questionnaire .


Mean scores of knowledge in healthcare workers was higher in the intervention group ( score = 6.43 , 80.4 % improvement ) compared to the non-intervention group ( score = 4.71 , 58.9 % improvement ) .


The ability to describe and demonstrate vision testing was better ( score = 1.8 ) in the enhanced supervision group compared to the routine supervision group ( score = 0.88 , P = 0.03 ) .


There was a high level of attrition ( 24 % ) within one year from the time of baseline survey , especially amongst clinical officers ( 44 % ) .


During the pilot study , enhanced supervision improved PEC knowledge and skills of health workers compared to health workers with routine supervision .


Training in PEC needs revision to become more practicum-based .


There is need to revise supervision guidelines ( to be skills-based ) and the supervision skills of district eye coordinators ( DECs ) need to be enhanced .


There is a huge need to improve governance ( accountability and rule of law ) of health staff .


To assess differences between manual wheelchairs and 3 pushrim-activated power-assisted wheelchairs ( PAPAWs ) : Servomatic A and B and E-motion .


Repeated measures .


Rehabilitation hospital .


Volunteers with spinal cord injuries ( N = 52 ) .


Ten subjects propelled the wheelchairs on a dynamometer , 46 evaluated each wheelchair on indoor and outdoor courses , and 10 evaluated their ability to transfer themselves and their wheelchairs into and out of their car .


Oxygen consumption per unit time ( Vo2 ) and heart rate were measured during propulsion on the dynamometer .


Wheelchair efficiency on the indoor and outdoor courses was evaluated on the basis of heart rate , completion time , handrim push frequency , and patient satisfaction .


On the dynamometer , decreases in Vo2 and heart rate were similar with the 3 PAPAWs compared with manual wheelchairs .


On the outdoor course , heart rate was significantly decreased by PAPAWs compared with manual wheelchairs and patient satisfaction was better with Servomatic devices than with the E-motion device .


Indoors , the course completion time was longer with the E-motion wheelchair than with other wheelchairs in the overall population , and handrim push frequency was higher with the E-motion wheelchair than with other wheelchairs in the subgroup with T12 to L1 injuries .


Car transfer ability was lower with PAPAWs than with manual wheelchairs .


Differences exist across PAPAWs .


Compared with E-motion , the 2 Servomatic PAPAWs were easier to use outdoors , and difficulty transferring into/out of the car was similarly increased with all 3 PAPAWs .


Bipolar disorders ( BD ) are among the most severe mental disorders with first clinical signs and symptoms frequently appearing in adolescence and early adulthood .


The long latency in clinical diagnosis ( and subsequent adequate treatment ) adversely affects the course of disease , effectiveness of interventions and health-related quality of life , and increases the economic burden of BD .


Despite uncertainties about risk constellations and symptomatology in the early stages of potentially developing BD , many adolescents and young adults seek help , and most of them suffer substantially from symptoms already leading to impairments in psychosocial functioning in school , training , at work and in their social relationships .


We aimed to identify subjects at risk of developing BD and investigate the efficacy and safety of early specific cognitive-behavioural psychotherapy ( CBT ) in this subpopulation .


EarlyCBT is a randomised controlled multi-centre clinical trial to evaluate the efficacy and safety of early specific CBT , including stress management and problem solving strategies , with elements of mindfulness-based therapy ( MBT ) versus unstructured group meetings for 14weeks each and follow-up until week 78 .


Participants are recruited at seven university hospitals throughout Germany , which provide in - and outpatient care ( including early recognition centres ) for psychiatric patients .


Subjects at high risk must be 15 to 30years old and meet the combination of specified affective symptomatology , reduction of psychosocial functioning , and family history for ( schizo ) affective disorders .


Primary efficacy endpoints are differences in psychosocial functioning and defined affective symptomatology at 14weeks between groups .


Secondary endpoints include the above mentioned endpoints at 7 , 24 , 52 and 78weeks and the change within groups compared to baseline ; perception of , reaction to and coping with stress ; and conversion to full BD .


To our knowledge , this is the first study to evaluate early specific CBT in subjects at high risk for BD .


Structured diagnostic interviews are used to map the risk status and development of disease .


With our study , the level of evidence for the treatment of those young patients will be significantly raised .


WHO International Clinical Trials Platform ( ICTRP ) , identifier : DRKS00000444 , date of registration : 16 June 2010 .


A primary goal of acute ischemic stroke ( AIS ) management is to maximize perfusion in the affected region and surrounding ischemic penumbra .


However , interventions to maximize perfusion , such as flat head-of-bed ( HOB ) positioning , are currently prescribed empirically .


Bedside monitoring of cerebral blood flow ( CBF ) allows the effects of interventions such as flat HOB to be monitored and may ultimately be used to guide clinical management .


Cerebral perfusion was measured during HOB manipulations in 17 patients with unilateral AIS affecting large cortical territories in the anterior circulation .


Simultaneous measurements of frontal CBF and arterial flow velocity were performed with diffuse correlation spectroscopy and transcranial Doppler ultrasound , respectively .


Results were analyzed in the context of available clinical data and a previous study .


Frontal CBF , averaged over the patient cohort , decreased by 17 % ( P = 0.034 ) and 15 % ( P = 0.011 ) in the ipsilesional and contralesional hemispheres , respectively , when HOB was changed from flat to 30 .


Significant ( cohort-averaged ) changes in blood velocity were not observed .


Individually , varying responses to HOB manipulation were observed , including paradoxical increases in CBF with increasing HOB angle .


Clinical features , stroke volume , and distance to the optical probe could not explain this paradoxical response .


A lower HOB angle results in an increase in cortical CBF without a significant change in arterial flow velocity in AIS , but there is variability across patients in this response .


Bedside CBF monitoring with diffuse correlation spectroscopy provides a potential means to individualize interventions designed to optimize CBF in AIS .


Trastuzumab ( Herceptin ( ) ) is a humanized monoclonal antibody targeting the human epidermal growth factor receptor 2 ( HER2 ) and is used in the treatment of HER2-overexpressing breast and gastric cancer .


FTMB is being developed as a biosimilar of trastuzumab .


In this combined dose-escalation and bioequivalence study of parallel design , the pharmacokinetic profile of FTMB was compared with Herceptin ( ) .


Healthy male volunteers received single doses of 0.5 , 1.5 , 3.0 or 6.0 mg/kg FTMB , or placebo , in consecutive dose-escalation cohorts to assess the safety profile .


Thereafter , the 6 mg/kg cohort was expanded to establish bioequivalence between FTMB ( Test ) and Herceptin ( ) ( Reference ) based on an acceptance interval of 80.0-125 .0 % .


In total , 118 subjects were enrolled in the study .


The mean area under the concentration-time curve from time zero to infinity ( AUC ) was 1,609 gday/mL ( Test ) and 1,330 gday/mL ( Reference ) .


The log-transformed geometric mean Test/Reference ( T/R ) ratio for AUC was 89.6 % ( 90 % confidence interval [ CI ] 85.1-94 .4 ) , demonstrating bioequivalence .


For the secondary endpoint , the maximum concentration observed ( Cmax ) , the geometric mean T/R ratio was 89.4 % ( 90 % CI 83.4-95 .9 ) .


Non-linear , target-mediated pharmacokinetics were also observed .


Adverse events other than the documented side effects of Herceptin ( ) ( fever , influenza-like illness , and fatigue ) did not occur .


No signs of cardiotoxicity were observed .


This bioequivalence study with a trastuzumab biosimilar in healthy male volunteers demonstrated bioequivalence of FTMB with Herceptin ( ) .


FTMB was well tolerated in doses up to 6 mg/kg .


Non-linear target elimination was also observed in the pharmacokinetic profile of trastuzumab .


Nutritional insults and conditions during fetal life and infancy influence subsequent growth and body composition of children .


Effects of maternal food and micronutrient supplementation and exclusive breastfeeding counseling on growth of offspring aged 0-54 months and their body composition at 54 months of age were studied .


In the MINIMat trial ( ISRCTN16581394 ) in Matlab , Bangladesh , pregnant women were randomized to early ( around 9 weeks ) or usual invitation ( around 20 weeks ) to food supplementation and to one of the three daily micronutrient supplements : 30-mg Fe and 400-g folic acid ( Fe30F ) , 60-mg Fe and 400-g folic acid ( Fe60F ) , and multiple micronutrient supplements ( MMS ) .


The supplements were also randomized to exclusive breastfeeding ( EBF ) counseling or to usual health messages .


No differences in background characteristics were observed among the intervention groups .


There was also no differential effect of prenatal interventions on birthweight or birthlength .


Early food supplementation reduced the level of stunting from early infancy up to 54 months of age among boys ( average difference - 6.5 % units , 95 % confidence interval [ CI ] 1.7-11 .3 , p = 0.01 ) but not among girls ( average difference - 2.4 % units , 95 % CI -2.2 -7.0 , p = 0.31 ) .


MMS resulted in more stunting compared to standard Fe60F ( average difference - 4.8 % units , 95 % CI 0.8-8 .9 , p = 0.02 ) .


Breastfeeding counseling prolonged the duration of EBF ( difference - 35 days , 95 % CI 30.6-39 .5 , p < 0.001 ) .


Neither pregnancy interventions nor breastfeeding counseling influenced the body composition of children at 54 months of age .


Early food supplementation during pregnancy reduced the occurrence of stunting among boys aged 0-54 months , while prenatal MMS increased the proportion of stunting .


Food and micronutrient supplementation or EBF intervention did not affect body composition of offspring at 54 months of age .


The effects of prenatal interventions on postnatal growth suggest programming effects in early fetal life .


Limited evidence suggests that dietary interventions may offer a promising approach for migraine .


The purpose of this study was to determine the effects of a low-fat plant-based diet intervention on migraine severity and frequency .


Forty-two adult migraine sufferers were recruited from the general community in Washington , DC , and divided randomly into two groups .


This 36-week crossover study included two treatments : dietary instruction and placebo supplement .


Each treatment period was 16 weeks , with a 4-week washout between .


During the diet period , a low-fat vegan diet was prescribed for 4 weeks , after which an elimination diet was used .


Participants were assessed at the beginning , midpoint , and end of each period .


Significance was determined using student 's t-tests .


Worst headache pain in last 2 weeks , as measured by visual analog scale , was initially 6.4 / 10 cm ( SD 2.1 cm ) , and declined 2.1 cm during the diet period and 0.7 cm during the supplement period ( p = 0.03 ) .


Average headache intensity ( 0-10 scale ) was initially 4.2 ( SD 1.4 ) per week , and this declined by 1.0 during the diet period and by 0.5 during the supplement period ( p = 0.20 ) .


Average headache frequency was initially 2.3 ( SD 1.8 ) per week , and this declined by 0.3 during the diet period and by 0.4 during the supplement period ( p = 0.61 ) .


The Patient 's Global Impression of Change showed greater improvement in pain during the diet period ( p < 0.001 ) .