The primary outcome was a self-reported improvement in self-management of their conditions in 69 % of participants , with another 22.2 % reporting that their confidence to self-manage had improved .


There was an improvement in all measures at 9 months .


The program resulted in improvements in lifestyle and confidence in self-management for Vietnam veterans , a cohort difficult to engage in healthy behaviors .


Most participants were also accompanied by their partners .


The program is a valuable resource for providing self-management education to veterans with alcohol dependency and various chronic conditions and needs to be considered in the suite of rehabilitation programs available to Defense Force personnel , veterans , and their partners .


The objectives of the studies reported here were to determine the relative bioavailability of linagliptin and metformin when administered in a fixed-dose combination ( FDC ) tablet with and without food , and to investigate the relative bioavailability of linagliptin and metformin FDC tablets from two treatment batches with different dissolution behavior .


These studies were open-label , single-dose , randomized , two-way crossover trials .


After an overnight fast , healthy volunteers received an FDC tablet once ( with/without food in the food-effect study ; or from one of two batches with differing dissolution behavior in the tablet-dissolution study ) .


On a separate visit , following a washout period of 35 days , participants received the alternative treatment .


In the food-effect study the primary endpoints were maximum measured concentration in plasma ( C ( max ) ) for linagliptin and metformin , area under the plasma concentration-time curve from 0 to 72 hours ( AUC ( 0-72 ) ) for linagliptin and from 0 to infinity ( AUC ( 0-inf ) ) for metformin .


In the tablet-dissolution study the primary endpoints were Cmax for both analytes , AUC ( 0-72 ) for linagliptin , and from 0 to the time of the last quantifiable data point ( AUC ( 0-t ) ) for metformin .


The administration of the FDC tablet with food had no influence on the relative bioavailability of linagliptin and metformin with regard to the extent of exposure as determined by AUC ( 0-72 ) ( linagliptin ) and AUC ( 0-inf ) ( metformin ) compared with FDC tablet administration while fasting .


After food intake , peak plasma concentrations of linagliptin were slightly lowered ( from 4.99 to 4.56 nmol L ) , but the 90 % confidence interval ( CI ) of the geometric mean test/reference ratio was still located within the generally applied bioequivalence acceptance limits of 80 - 125 % .


The median time from dosing to the maximum concentration of linagliptin in plasma ( t ( max ) ) was similar under both conditions .


Administration with food reduced the rate of absorption of metformin indicated by a prolongation in median tmax ( from 2 to 4 hours ) and a decrease in Cmax by ~ 18 % .


There were no notable differences between the two treatment groups with respect to safety and tolerability .


In the tablet-dissolution study , bioequivalence was demonstrated between linagliptin/metformin FDC tablets with normal and slower dissolution characteristics .


For both linagliptin and metformin , the 90 % CI of all pharmacokinetic ( PK ) parameters were well within the bioequivalence acceptance limits of 80 - 125 % .


Tablets from both batches were well tolerated with no unexpected adverse events .


Food did not have a relevant impact on the bioavailability of linagliptin from the FDC tablet .


The effect of food on the metformin component was comparable to that previously demonstrated .


Furthermore , differences in tablet-dissolution characteristics did not have an impact on the bioavailability of linagliptin or metformin from the FDC tablet .


Social factors play an important role in quitting smoking in the general population , but relatively little is known about social influences on smoking cessation efforts among individuals with serious mental illness who suffer disproportionately high rates of smoking .


This study examined social factors as predictors of using smoking cessation treatment among adults with serious mental illness .


We conducted a secondary analysis of data from a randomized study comparing two versions of a motivational decision support system for smoking cessation treatment including 124 smokers with schizophrenia or severe mood disorders .


Hierarchical logistic regression with blocked entry of theoretically linked predictor variables was used to model two types of social influences ( explicit and implicit ) as predictors of using cessation group therapy or smoking cessation medication .


Approximately 31 % of participants initiated smoking cessation treatment during the 2-month follow-up .


Hierarchical logistic regression analyses revealed that over and above demographic and personal factors , implicit social influences ( others ' approval of treatment ) significantly predicted use of smoking cessation medication , while explicit social influences ( smoking with others ) significantly predicted use of cessation group therapy .


For people with serious mental illness , social factors appear to influence use of smoking cessation treatment above and beyond personal factors and may be specific to the type of treatment .


These data support the need to further explore the role of social factors as potential leverage points for engagement in smoking cessation treatments in this population .


To evaluate 8-year weight losses achieved with intensive lifestyle intervention ( ILI ) in the Look AHEAD ( Action for Health in Diabetes ) study .


Look AHEAD assessed the effects of intentional weight loss on cardiovascular morbidity and mortality in 5,145 overweight/obese adults with type 2 diabetes , randomly assigned to ILI or usual care ( i.e. , diabetes support and education [ DSE ] ) .


The ILI provided comprehensive behavioral weight loss counseling over 8 years ; DSE participants received periodic group education only .


All participants had the opportunity to complete 8 years of intervention before Look AHEAD was halted in September 2012 ; 88 % of both groups completed the 8-year outcomes assessment .


ILI and DSE participants lost ( mean SE ) 4.7 % 0.2 % and 2.1 0.2 % of initial weight , respectively ( P < 0.001 ) at year 8 ; 50.3 % and 35.7 % , respectively , lost 5 % ( P < 0.001 ) , and 26.9 % and 17.2 % , respectively , lost 10 % ( P < 0.001 ) .


Across the 8 years ILI participants , compared with DSE , reported greater practice of several key weight-control behaviors .


These behaviors also distinguished ILI participants who lost 10 % and kept it off from those who lost but regained .


Look AHEAD 's ILI produced clinically meaningful weight loss ( 5 % ) at year 8 in 50 % of patients with type 2 diabetes and can be used to manage other obesity-related co-morbid conditions .


Intraocular pressure is increased during laparoscopic surgeries performed in a steep Trendelenburg position .


This study compared the effects of propofol with those of sevoflurane on intraocular pressure in patients undergoing robot-assisted laparoscopic radical prostatectomy in a 30 Trendelenburg position .


Sixty-six patients were randomly allocated to a maintenance anesthetic consisting of remifentanil and sevoflurane ( Sevoflurane Group ) or remifentanil and propofol ( Propofol Group ) .


Intraocular pressure ( IOP ) was measured at nine predefined time points , including baseline ( T0 ) , five minutes after establishing pneumoperitoneum ( T2 ) , 30min after establishing the Trendelenburg position with pneumoperitoneum ( T3 ) , five minutes after returning to the horizontal position ( T4 ) , and immediately after tracheal extubation ( T6 ) .


The primary outcome was the change in intraocular pressure from T0 to T3 .


The results of linear mixed model analysis showed that intraocular pressure differed between the two groups ( P = 0.0039 ) .


At T3 , the mean ( SD ) IOP was greater in the Sevoflurane Group [ 23.5 ( 4.3 ) mmHg ] than in the Propofol Group [ 19.9 ( 3.8 ) mmHg ] ( P = 0.0019 ) .


At T2 and T6 , IOP was also greater in the Sevoflurane Group than in the Propofol Group ( P = 0.038 and P = 0.009 , respectively ) .


There was a statistically significant increase in intraocular pressure from baseline to T3 ( pneumoperitoneum and steep Trendelenberg ) in the Sevoflurane Group [ 6.0 ( 5.0 ) mmHg ; P < 0.001 ] but not in the Propofol Group [ 2.1 ( 5.1 ) mmHg ; P = 0.136 ] .


None of the patients experienced ocular complications .


Intraocular pressure increases after pneumoperitoneum and the steep Trendelenburg position are established .


This increase is less with propofol than with sevoflurane anesthesia .


This trial was registered at ClinicalTrials.gov : NCT01744262 .


Enhancing exercise adherence over the longer term is an important goal in self-management of knee osteoarthritis ( OA ) .


Following an initial period of more intensive exercise supervision , this study investigated whether 2 additional physiotherapy visits improved outcomes with continued home exercise over a subsequent 24-week period .


A total of 78 people with medial knee OA ( mean SD age 62.1 6.9 years , mean SD body mass index 29.4 4.0 kg/m ( 2 ) , and radiographic disease severity 19 % mild , 49 % moderate , and 32 % severe ) who completed a 12-week physiotherapist-supervised exercise trial were randomly allocated to 2 30-minute physiotherapy booster sessions ( delivered by 8 physiotherapists in private clinics ) or no booster sessions for the subsequent 24 weeks .


All participants were asked to continue home exercises 4 times weekly .


Primary outcomes were change in pain , using a 100-mm visual analog scale , and self-reported physical function , measured using the Western Ontario McMaster Universities Osteoarthritis Index .


Participants and physiotherapists were unblinded to group allocation , although participants were blinded to the study hypothesis .


A total of 74 participants ( 95 % ) completed the trial .


There was no significant difference between groups for change in pain ( mean difference [ 95 % confidence interval ( 95 % CI ) ] 0.7 mm [ -9.4 , 8.0 ] ; P = 0.88 ) or physical function ( -0.3 units [ 95 % CI -4.0 , 3.5 ] ; P = 0.88 ) .


The mean SD percentage of home exercise sessions completed was 56 % 34 % in the booster group and 51 % 37 % in the control group ( P > 0.05 ) .


Two booster sessions with a physiotherapist did not influence pain or physical function outcomes , or measures of home exercise adherence .


These findings suggest other more effective strategies are needed to maximize longer-term adherence with the aim to achieve greater improvements in clinical outcomes from exercise in this patient population .


Heart failure is a prevalent health problem associated with costly hospital readmissions .


Transitional care programs have been shown to reduce readmissions but are costly to implement .


Evidence regarding the effectiveness of telemonitoring in managing the care of this chronic condition is mixed .


The objective of this randomized controlled comparative effectiveness study is to evaluate the effectiveness of a care transition intervention that includes pre-discharge education about heart failure and post-discharge telephone nurse coaching combined with home telemonitoring of weight , blood pressure , heart rate , and symptoms in reducing all-cause 180-day hospital readmissions for older adults hospitalized with heart failure .


A multi-center , randomized controlled trial is being conducted at six academic health systems in California .


A total of 1,500 patients aged 50years and older will be enrolled during a hospitalization for treatment of heart failure .


Patients in the intervention group will receive intensive patient education using the ` teach-back ' method and receive instruction in using the telemonitoring equipment .


Following hospital discharge , they will receive a series of nine scheduled health coaching telephone calls over 6months from nurses located in a centralized call center .


The nurses also will call patients and patients ' physicians in response to alerts generated by the telemonitoring system , based on predetermined parameters .


The primary outcome is readmission for any cause within 180days .


Secondary outcomes include 30-day readmission , mortality , hospital days , emergency department ( ED ) visits , hospital cost , and health-related quality of life .


BEAT-HF is one of the largest randomized controlled trials of telemonitoring in patients with heart failure , and the first explicitly to adapt the care transition approach and combine it with remote telemonitoring .


The study population also includes patients with a wide range of demographic and socioeconomic characteristics .


Once completed , the study will be a rich resource of information on how best to use remote technology in the care management of patients with chronic heart failure .


ClinicalTrials.gov # NCT01360203 .


Chemosaturation with percutaneous hepatic perfusion ( PHP ; Hepatic CHEMOSAT ( ) Delivery System ; Delcath Systems Inc , USA ) is a minimally invasive , repeatable regional therapy for unresectable hepatic metastases .


It uses a system of catheters and filters to isolate hepatic venous blood from the systemic circulation , allowing delivery of high-dose chemotherapy to the hepatic artery .


Effluent hepatic venous blood is filtered before being returned to the systemic circulation , thereby reducing exposure to chemotherapy .


We describe our experiences with chemosaturation-PHP at 2 European centers .


14 patients presented unresectable hepatic metastases from solid tumors ; 13 received 1-3 sessions of chemosaturation-PHP .


Melphalan 2.0 ( n = 1 ) or 3.0 ( n = 12 ) mg/kg was given as a 30-minute infusion into the hepatic artery .


12 patients were evaluable for tumor response .


One complete ( cholangiocarcinoma , n = 1 ) and 6 partial responses ( ocular , n = 3 or cutaneous melanoma , n = 3 ) were observed , 5 patients had stable disease ( ocular melanoma , n = 3 ; breast cancer , n = 1 ; gastric cancer , n = 1 ) .


Mild to moderate filter-related toxicity ( i.e. thrombocytopenia , anemia ) was observed immediately post-procedure .


Grade 3/4 melphalan-related pancytopenia developed after 1-2 weeks .


All hematological events were managed effectively with transfusions and/or other supportive measures .


The new high-efficiency filter showed milder toxicity and faster recovery .


In one case , chemosaturation-PHP was abandoned prematurely due to heparin-induced vaginal bleeding , and one patient died due to retroperitoneal hemorrhage from heparin anti-coagulation .


Chemosaturation-PHP for non-resectable liver metastases is a feasible treatment option when performed by an experienced multi-disciplinary team .


It may be a promising regional therapy for patients with no effective treatment options .


The perspectives and experiences of trial staff are increasingly being investigated as these can be used to improve recruitment , adherence to trial protocols and support given to future staff .


We interviewed staff working on a type 1 diabetes trial in order to aid interpretation of trial findings , inform recommendations for the rollout of the treatments investigated and provide recommendations for the conduct of future trials .


However , our interviews uncovered aspects of trial work erstwhile unrecognised or underreported in the trials literature , and it is these which form the focus of this paper .


In-depth interviews were conducted with ( n = 18 ) staff , recruited from seven centres , who were involved in recruitment and trial delivery .


Data were analysed thematically .


Alongside logistical and practical issues which made trial work challenging , staff often talked spontaneously and at length about how trial work had affected them emotionally .


Staff not only described the emotional stresses arising from having to meet recruitment targets and from balancing research roles with clinical responsibilities , they also discussed having to emotionally manage patients and their colleagues .


The emotional aspects of trial work particularly came to the fore when staff notified patients about their treatment allocation .


On such occasions , staff described having to employ emotional strategies to pre-empt and manage potential patient disappointment and anger .


Staff also described having to manage their own emotions when patients withdrew from the trial or were not randomised to the treatment arm which , in their clinical judgment , would have been in their best interests .


To help address the emotional challenges they encountered , staff highlighted a need for more practical , emotional and specialist psychological support .


More attention should be paid to the emotional aspects of trial work to help ensure trial staff are adequately supported .


Such support could comprise : increased training for staff to improve their own and patients ' understandings of randomization , role-play to develop techniques to manage patient anger and disappointment , sharing of good practice , formalised team support with psychological input and access to specialist psychological support to troubleshoot complex emotional and ethical issues .


Motion sickness is an unpleasant physiological state that may be controlled via nonpharmacological methods .


Controlled breathing has been shown to maximize parasympathetic nervous system ( PNS ) tone and may have the ability to decrease motion sickness symptoms .


The effects of slow diaphragmatic breathing ( DB ) in a motion sickness-inducing environment were examined within motion sickness susceptible individuals .


Subjects ( N = 43 ) were assigned randomly to either an experimental group trained in slow DB or a control group breathing naturally at a normal pace .


The experimental group was trained using a digital video that helped them pace their diaphragmatic breathing at six breaths/min .


During the study , subjects viewed a virtual reality ( VR ) experience of a boat in rough seas for 10 min .


Motion sickness ratings along with heart rate and respiration rate were collected before , during , and after the VR experience .


Results indicated that the experimental group was able to decrease their breathing to eight breaths/min during the VR experience .


This breathing rate was significantly slower than those in the control group .


We found that DB subjects , compared to those in the control group , displayed significantly greater heart rate variability and reported feeling less motion sickness during exposure to the VR experience than those in the control group .


Results indicate possible benefits of using slow DB techniques in a motion sickness inducing environment .


The sore throat pain model has been conducted by different clinical investigators to demonstrate the efficacy of acute analgesic drugs in single-dose randomized clinical trials .


The model used here was designed to study the multiple-dose safety and efficacy of lozenges containing flurbiprofen at 8.75 mg .


Adults ( n = 198 ) with moderate or severe acute sore throat and findings of pharyngitis on a Tonsillo-Pharyngitis Assessment ( TPA ) were randomly assigned to use either flurbiprofen 8.75 mg lozenges ( n = 101 ) or matching placebo lozenges ( n = 97 ) under double-blind conditions .


Patients sucked one lozenge every three to six hours as needed , up to five lozenges per day , and rated symptoms on 100-mm scales : the Sore Throat Pain Intensity Scale ( STPIS ) , the Difficulty Swallowing Scale ( DSS ) , and the Swollen Throat Scale ( SwoTS ) .


Reductions in pain ( lasting for three hours ) and in difficulty swallowing and throat swelling ( for four hours ) were observed after a single dose of the flurbiprofen 8.75 mg lozenge ( P < 0.05 compared with placebo ) .


After using multiple doses over 24 hours , flurbiprofen-treated patients experienced a 59 % greater reduction in throat pain , 45 % less difficulty swallowing , and 44 % less throat swelling than placebo-treated patients ( all P < 0.01 ) .


There were no serious adverse events .


Utilizing the sore throat pain model with multiple doses over 24 hours , flurbiprofen 8.75 mg lozenges were shown to be an effective , well-tolerated treatment for sore throat pain .


Other pharmacologic actions ( reduced difficulty swallowing and reduced throat swelling ) and overall patient satisfaction from the flurbiprofen lozenges were also demonstrated in this multiple-dose implementation of the sore throat pain model .


This trial was registered with ClinicalTrials.gov , registration number : NCT01048866 , registration date : January 13 , 2010 .


The aim of this randomized trial was to compare short-term postoperative complications of laparoscopic transabdominal preperitoneal ( TAPP ) and Lichtenstein tension free hernia repair .


A total of 120 patients who went inguinal hernia repair at Shahid Sadoughi university training hospital from April 2011 to August 2013 were randomized into two TAPP ( N. = 60 ) and Lichtenstein ( N. = 60 ) repair group .


Follow-up occurred within 6 weeks .


The postoperative assessments included pain score ( VAS ) , hematoma/seroma , urinary retention , wound infection incidence , and duration of hospital stay .


Pain was the most common symptoms in both groups .


The TAPP group patients significantly had experienced less postoperative pain than the Lichtenstein group in all moments ( P < 0.05 ) .


TAPP group had lower incidence of hematoma ( TAPP , 6.6 % vs. Lichtenstein 13.3 % ; P = 0.67 ) , seroma ( TAPP 10 % vs. Lichtenstein 13.3 % ; P = 1.00 ) , and infection ( TAPP 0 vs. Lichtenstein 1.6 % ; P = 0.67 ) .


However , no differences between the 2 groups were found in terms of postoperative complications .


In TAPP group mean of hospital stay significantly was less than Lichtenstein group ( TAPP , 8.132.19 vs. Lichtenstein , 13.151.5 days ; P < 0.001 ) .


The laparoscopic TAPP repair is safer and less complicated approach to inguinal hernia repair .


The two main short-term advantages of the laparoscopic TAPP repair with the tension free Lichtenstein repair were less postoperative pain and earlier return to the normal life activities .


No difference was seen in overall complications .


To assess whether bipolar transurethral resection of the prostate ( B-TURP ) using the TURis system has a similar level of efficacy and safety to that of the traditional monopolar transurethral resection of the prostate ( M-TURP ) , and to evaluate the impact of the TURis system on postoperative urethral stricture rates over a 36-month follow-up period .


A total of 136 patients with benign prostatic obstruction were randomised to undergo either B-TURP using the TURis system or conventional M-TURP , and were regularly followed for 36 months after surgery .


The primary endpoint was safety , which included the long-term complication rates of postoperative urethral stricture .


The secondary endpoint was the follow-up measurement of efficacy .


In peri-operative findings , no patient in either treatment group presented with transurethral resection syndrome , and the decline in levels of haemoglobin and hematocrit were similar .


The mean operation time was significantly extended in the TURis treatment group compared with the M-TURP group ( 79.5 vs 68.6 min ; P = 0.032 ) and postoperative clot retention was more likely to be seen after M-TURP ( P = 0.044 ) .


Similar efficacy findings were maintained throughout 36 months , but a significant difference in postoperative urethral stricture rates between groups was detected ( 6.6 % in M-TURP vs 19.0 % in TURis ; P = 0.022 ) .


After stratifying patients according to prostate volume , there was no significant difference between the two treatment groups with regard to urethral stricture rates in patients with a prostate volume 70mL ( 3.8 % in M-TURP vs 3.8 % in TURis ) , but in the TURis group there was a significantly higher urethral stricture rate compared with the M-TURP group in patients with a prostate volume > 70mL ( 20 % in TURis vs 2.2 % in M-TURP ; P = 0.012 ) .


Furthermore , the mean operation time for TURis was significantly longer than for M-TURP for the subgroup of patients with a prostate volume > 70mL ( 99.6 vs 77.2 min ; P = 0.011 ) , but not for the subgroup of patients with a prostate volume 70mL .


The TURis system seems to be as efficacious and safe as conventional M-TURP except that there was a higher incidence of urethral stricture in patients with larger preoperative prostate volumes .


The gadolinium-based MRI contrast agent gadobenate dimeglumine has nearly twice the MR relaxivity of gadopentetate dimeglumine at 1.5 T.


The purpose of this study was to determine whether a lower dose ( 0.1 mmol/kg ) of gadobenate dimeglumine can be used to obtain delayed-enhancement MR images comparable to those obtained with a standard dose ( 0.2 mmol/kg ) of gadopentetate dimeglumine .


In this blinded randomized crossover study , 20 patients with known myocardial infarction underwent two separate delayed-enhancement MRI examinations after receiving 0.1 mmol/kg gadobenate dimeglumine and 0.2 mmol/kg gadopentetate dimeglumine ( random administration ) .


The conspicuity of lesion enhancement 5 , 10 , and 20 minutes after contrast administration was quantified as relative enhancement ratio ( RER ) .


With either gadolinium-based contrast agent , damaged myocardium had higher signal intensity than normal remote myocardium ( RER > 4 ) on delayed-enhancement MR images , and the blood RER declined over time after contrast administration .


The blood RER was not significantly higher for gadobenate dimeglumine than for gadopentetate dimeglumine at 5 and 10 minutes .


Nevertheless , there was a larger reduction in blood RER for gadobenate dimeglumine than for gadopentetate dimeglumine between 5 and 10 minutes and between 10 and 20 minutes .


The volumes of enhancement were similar for gadobenate dimeglumine ( 13.6 8.8 cm ( 3 ) ) and gadopentetate dimeglumine ( 13.5 8.9 cm ( 3 ) ) ( p = 0.98 ) .


The mean difference in Bland-Altman analysis for delayed-enhancement volume between the agents was 0.1 cm ( 3 ) .


Qualitatively and quantitatively , delayed-enhancement MR images of ischemic myocardium obtained with 0.1 mmol/kg gadobenate dimeglumine are comparable to those obtained with 0.2 mmol/kg gadopentetate dimeglumine 5 , 10 , and 20 minutes after contrast administration .


The ocular vestibular-evoked myogenic potential ( oVEMP ) test yields the same information as the rotational test in sleep-deprived subjects as evidenced by increased vestibulo-ocular reflex ( VOR ) asymmetry .


However , the duration of sleep deprivation ( 12 h ) and testing time required for the oVEMP test are shorter than for the rotational test .


This study utilized the oVEMP test in sleep-deprived subjects to investigate the effect of short-duration sleep deprivation on the VOR system .


Twenty healthy resident physicians underwent oVEMP and cervical VEMP ( cVEMP ) tests twice in a randomized order ; one test battery was performed after a normal sleep , and the other was performed after a night duty at the emergency service , which meant a state of 12 h sleep deprivation .


All 20 subjects had clear oVEMPs regardless of whether testing was performed after a normal sleep or 12 h sleep deprivation condition .


Significant differences were not identified between the two sleep conditions in terms of characteristic parameters , i.e. latencies and amplitude of oVEMPs .


However , the mean asymmetry ratio after sleep deprivation ( 20 13 % ) was significantly larger than that after normal sleep ( 8 12 % ) .


Conversely , the cVEMP parameters did not differ significantly between the two sleep conditions .


Peer-led interventions to improve chronic disease self-management can improve health outcomes but are not widely used .


Therefore , we tested a peer-led hypertension self-management intervention delivered at regular meetings of community veterans ' organizations .


We randomized 58 organizational units ( `` posts '' ) of veterans ' organizations in southeast Wisconsin to peer-led vs. professionally delivered self-management education .


Volunteer peer leaders at peer-led posts delivered monthly presentations regarding hypertension self-management during regular post meetings .


Volunteer post representatives at seminar posts encouraged post members to attend 3 didactic seminars delivered by health professionals at a time separate from the post meeting .


Volunteers in both groups encouraged members to self-monitor using blood pressure cuffs , weight scales , and pedometers .


Our primary outcome was change in systolic blood pressure ( SBP ) at 12 months .


We measured SBP in 404 participants at baseline and in 379 participants at 12 months .


SBP decreased significantly ( 4.4 mm Hg ; P < 0.0001 ) overall ; the decrease was similar in peer-led and seminar posts ( 3.5 mm Hg vs. 5.4 mm Hg ; P = 0.24 ) .


Among participants with uncontrolled BP at baseline , SBP decreased by 10.1 mm Hg from baseline to 12 months but was again similar in the 2 groups .


This pattern was also seen at 6 months and with diastolic blood pressure .


Our peer-led educational intervention was not more effective than didactic seminars for SBP control .


Although peer-led educational programs have had important impacts in a number of studies , we did not find our intervention superior to a similar intervention delivered by healthcare professionals .


ClinicalTrials.gov NCT00571038 .


Pritelivir , an inhibitor of the viral helicase-primase complex , exhibits antiviral activity in vitro and in animal models of herpes simplex virus ( HSV ) infection .


We tested the efficacy and safety of pritelivir in otherwise healthy persons with genital HSV-2 infection .


We randomly assigned 156 HSV-2-positive persons with a history of genital herpes to receive one of four doses of oral pritelivir ( 5 , 25 , or 75 mg daily , or 400 mg weekly ) or placebo for 28 days .


Participants obtained daily swabs from the genital area for HSV-2 testing , which was performed with a polymerase-chain-reaction assay .


Participants also maintained a diary of genital signs and symptoms .


The primary end point was the rate of genital HSV shedding .


HSV shedding among placebo recipients was detected on 16.6 % of days ; shedding among pritelivir recipients was detected on 18.2 % of days among those receiving 5 mg daily , 9.3 % of days among those receiving 25 mg daily , 2.1 % of days among those receiving 75 mg daily , and 5.3 % of days among those receiving 400 mg weekly .


The relative risk of viral shedding with pritelivir , as compared with placebo , was 1.11 ( 95 % confidence interval [ CI ] , 0.65 to 1.87 ) with the 5-mg daily dose , 0.57 ( 95 % CI , 0.31 to 1.03 ) with the 25-mg daily dose , 0.13 ( 95 % CI , 0.04 to 0.38 ) with the 75-mg daily dose , and 0.32 ( 95 % CI , 0.17 to 0.59 ) with the 400-mg weekly dose .


The percentage of days with genital lesions was also significantly reduced , from 9.0 % in the placebo group to 1.2 % in both the group receiving 75 mg of pritelivir daily ( relative risk , 0.13 ; 95 % CI , 0.02 to 0.70 ) and the group receiving 400 mg weekly ( relative risk , 0.13 ; 95 % CI , 0.03 to 0.52 ) .


The rate of adverse events was similar in all groups .


Pritelivir reduced the rates of genital HSV shedding and days with lesions in a dose-dependent manner in otherwise healthy men and women with genital herpes .


( Funded by AiCuris ; ClinicalTrials.gov number , NCT01047540 . )


To test the hypothesis that the simultaneous administration of GLP-1 and insulin may increase their vasodilatory , antiinflammatory , and antioxidant action in type 2 diabetes .


In two groups of persons with type 2 diabetes , two sets of experiments were performed .


The first group had two normoglycemic-normoinsulinemic clamps with or without GLP-1 and two normoglycemic-hyperinsulinemic clamps with or without GLP-1 .


The second group had two hyperglycemic-normoinsulinemic clamps and two hyperglycemic-hyperinsulinemic clamps with or without GLP-1 .


During the normoglycemic-hyperinsulinemic clamp , flow-mediated dilatation ( FMD ) increased , while soluble intercellular adhesion molecule ( sICAM-1 ) , plasma 8-iso-prostaglandin F2 ( 8-iso-PGF2 ) , nitrotyrosine , and interleukin ( IL ) -6 decreased compared with normoglycemic-normoinsulinemic clamp .


Similar results were obtained with the infusion of GLP-1 during the normoglycemic-normoinsulinemic clamp .


The combination of hyperinsulinemia and GLP-1 in normoglycemia was accompanied by a further FMD increase and sICAM-1 , 8-iso-PGF2 , nitrotyrosine , and IL-6 decrease .


During the hyperglycemic-normoinsulinemic clamp , FMD significantly decreased , while sICAM-1 , 8-iso-PGF2 , nitrotyrosine , and IL-6 significantly increased .


When hyperglycemia was accompanied by hyperinsulinemia or by the simultaneous infusion of GLP-1 , these phenomena were attenuated .


The simultaneous presence of hyperinsulinemia and GLP-1 had an increased beneficial effect .


Our results show that the combination of insulin and GLP-1 is more effective than insulin or GLP-1 alone in improving endothelial dysfunction , inflammation , and oxidative stress in type 2 diabetes .


Examine the effect of an early intervention programme on cognitive outcome at 7 and 9years in children with birth weight ( BW ) < 2000g .


A randomised controlled trial of a modified version of the Mother-Infant Transaction Program .


A single tertiary neonatal unit .


146 infants were randomised into a preterm control group ( 74 ) or a preterm intervention group ( 72 ) .


The intervention consisted of eight sessions shortly before discharge and four home visits by specially trained nurses focusing on the infants ' unique characteristics , temperament , developmental potential and the interaction between infants and parents .


Outcomes were assessed with the Wechsler Intelligence Scale for Children ( WISC-III ) .


Mean BWs were 1396 ( 429 ) g in the intervention group and 1381 ( 436 ) g in the control group .


After adjusting for the possible clustering effects of twin pairs and maternal education , there were no significant differences in WISC-III scores at age 7 or 9 .


The mean difference was 4.1 points ( 95 % CI -1.5 to 9.8 points ) in favour of the intervention group at 7years and 2.2 points ( 95 % CI -3.4 to 7.6 points ) at 9years .


At 7years , a 6.8 points difference in the Verbal Comprehension Index ( 95 % CI 0.5 to 13.0 points ) was found in favour of the intervention group .


Loss to follow-up at age 7 and 9 was 11 % and 14 % , respectively .


This intervention programme did not have a sustained significant effect on overall cognitive outcomes in preterm children at age 7 and 9 .


The trial has been registered at http://www.clinicaltrials.gov ( identifier NCT00222456 ) .


Local analgesia through wound catheters is used as a part of multimodal analgesia .


The efficacy of continuous subfascial wound infusion compared to epidural analgesia is unknown for abdominal hysterectomy and bilateral salpingo-oophorectomy ( TAH-BSO ) via Pfannenstiel incision .


The aim of this study was to compare the aforementioned two methods in this type of surgery for postoperative morphine consumption , acute and persistent postsurgical pain .


Fifty patients enrolled in the study were randomly allocated to receive continuous 10 mL/h levobupivacaine either via subfascial ( Group S ) or epidural ( Group E ) catheter for 48 h postoperatively .


In Group S 0.25 % levobupivacaine was used for the first six hours and 0.125 % thereafter , whereas Group E received 0.125 % levobupivacaine throughout the study period .


Cumulative morphine consumption , static and dynamic pain , gastrointestinal recovery , ambulation , patient satisfaction , hospital stay , as well as pain at 2nd and 6th months were evaluated .


Group S was superior to Group E regarding cumulative morphine consumption ( 16.87.2 mg and 28.710.3 mg respectively , P < 0.001 ; mean difference -11.9 with 95 % CI of the difference -17.1 to -6.7 ) and pain relief .


Patient satisfaction was higher in Group S compared to Group E ( P = 0.006 ) .


Less postoperative vomiting was observed in Group S. No difference was detected in length of hospital stay and persistent postsurgical pain incidence .


Wound analgesia via subfascial catheter with continuous levobupivacaine infusion decreases postoperative morphine consumption and increases patient satisfaction compared to epidural analgesia with no difference in persistent postsurgical pain following TAH-BSO via Pfannenstiel incision .


This study evaluates the effects of an intervention performed by youth health care professionals on child health behaviors .


The intervention consisted of offering healthy lifestyle counseling to parents of overweight ( not obese ) 5-year-old children .


Effects of the intervention on the child having breakfast , drinking sweet beverages , watching television and playing outside were evaluated .


Data were collected with the ` Be active , eat right ' study , a cluster randomized controlled trial among nine youth health care centers in the Netherlands .


Parents of overweight children received lifestyle counseling according to the intervention protocol in the intervention condition ( n = 349 ) and usual care in the control condition ( n = 288 ) .


Parents completed questionnaires regarding demographic characteristics , health behaviors and the home environment at baseline and at 2-year follow-up .


Cluster adjusted regression models were applied ; interaction terms were explored .


The population for analysis consisted of 38.1 % boys ; mean age 5.8 [ sd 0.4 ] years ; mean BMI SDS 1.9 [ sd 0.4 ] .


There were no significant differences in the number of minutes of outside play or television viewing a day between children in the intervention and the control condition .


Also , the odds ratio for having breakfast daily or drinking two or less glasses of sweet beverages a day showed no significant differences between the two conditions .


Additional analyses showed that the odds ratio for drinking less than two glasses of sweet beverages at follow-up compared with baseline was significantly higher for children in both the intervention ( p < 0.001 ) and the control condition ( p = 0.029 ) .


Comparison of the children in the two conditions showed that the intervention does not contribute to a change in health behaviors .


Further studies are needed to investigate opportunities to adjust the intervention protocol , such as integration of elements in the regular well-child visit .


The intervention protocol for youth health care may become part of a broader approach to tackle childhood overweight and obesity .


Current Controlled Trials ISRCTN04965410 .


Current practice in the delivery of caloric intake ( DCI ) in patients with severe acute kidney injury ( AKI ) receiving renal replacement therapy ( RRT ) is unknown .


We aimed to describe calorie administration in patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy ( RENAL ) study and to assess the association between DCI and clinical outcomes .


We performed a secondary analysis in 1456 patients from the RENAL trial .


We measured the dose and evolution of DCI during treatment and analyzed its association with major clinical outcomes using multivariable logistic regression , Cox proportional hazards models , and time adjusted models .


Overall , mean DCI during treatment in ICU was low at only 10.99 Kcal/kg/day for non-survivors and 119 Kcal/kg/day for survivors .


Among patients with a lower DCI ( below the median ) 334 of 729 ( 45.8 % ) had died at 90-days after randomization compared with 316 of 727 ( 43.3 % ) patients with a higher DCI ( above the median ) ( P = 0.34 ) .


On multivariable logistic regression analysis , mean DCI carried an odds ratio of 0.95 ( 95 % confidence interval ( CI ) : 0.91-1 .00 ; P = 0.06 ) per 100 Kcal increase for 90-day mortality .


DCI was not associated with significant differences in renal replacement ( RRT ) free days , mechanical ventilation free days , ICU free days and hospital free days .


These findings remained essentially unaltered after time adjusted analysis and Cox proportional hazards modeling .


In the RENAL study , mean DCI was low .


Within the limits of such low caloric intake , greater DCI was not associated with improved clinical outcomes .


ClinicalTrials.gov number , NCT00221013 .


To develop a clinically valid interactive level 2 screening assessment for autism spectrum disorders ( ASD ) in toddlers that is brief , easily administered , and scored by clinicians .


We describe the development , training , standardization , and validation of the Rapid Interactive Screening Test for Autism in Toddlers ( RITA-T ) with ASD-specific diagnostic instruments .


The RITA-T can be administered and scored in 10 minutes .


We studied the validity of the RITA-T to distinguish between toddlers with ASD from toddlers with developmental delay ( DD ) / non-ASD in an early childhood clinic .


We also evaluated the test 's performance in toddlers with no developmental concerns .


We identified a cutoff score based on sensitivity , specificity , and positive predictive value of the RITA-T that best differentiates between ASD and DD/non-ASD .


A total of 61 toddlers were enrolled .


RITA-T scores were correlated with ASD-specific diagnostic tools ( r = 0.79 ; P < .01 ) and ASD clinical diagnoses ( r = 0.77 ; P < .01 ) .


Mean scores were significantly different in subjects with ASD , those with DD/non-ASD , and those with no developmental concerns ( 20.8 vs 13 vs 10.6 , respectively ; P < .0001 ) .


At a cutoff score of > 14 , the RITA-T had a sensitivity of 1.00 , specificity of 0.84 , and positive predictive value of 0.88 for identifying ASD risk in a high-risk group .


The RITA-T is a promising new level 2 interactive screening tool for improving the early identification of ASD in toddlers in general pediatric and early intervention settings and allowing access to treatment .


Despite the great variety of mammaplasty techniques , outcome assessment remains a challenging issue .


The authors devised an objective method to evaluate mammary symmetry based on statistical analysis of objective manual breast measurements and validated the method by applying it to results of a randomized controlled trial on the correction of breast asymmetry .


Sixty consecutive patients with hypoplastic breasts and small-volume asymmetry were enrolled in the study and randomly assigned to 1 of 2 groups .


One group received a fixed-volume implant in 1 breast and an adjustable-volume implant in the other .


The other group received 2 fixed-volume implants of different sizes .


The differences in specific breast and chest measurements , obtained before surgery and during follow-up , were analyzed statistically with the Wilcoxon signed rank test .


Correction of the asymmetry resulted in the reduction of the differences between left and right values for each specific breast measurement .


Placement of an adjustable implant on 1 side yielded better symmetry than placement of 2 fixed-volume prostheses of different sizes .


Patient and physician satisfaction was high for both groups .


This objective analysis of clinical parameters enables comparing results for different patients in large clinical trials and for the same patient at different follow-up periods .


3 .


The safety and effectiveness of automated glycemic management have not been tested in multiday studies under unrestricted outpatient conditions .


In two random-order , crossover studies with similar but distinct designs , we compared glycemic control with a wearable , bihormonal , automated , `` bionic '' pancreas ( bionic-pancreas period ) with glycemic control with an insulin pump ( control period ) for 5 days in 20 adults and 32 adolescents with type 1 diabetes mellitus .


The automatically adaptive algorithm of the bionic pancreas received data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon .


Among the adults , the mean plasma glucose level over the 5-day bionic-pancreas period was 138 mg per deciliter ( 7.7 mmol per liter ) , and the mean percentage of time with a low glucose level ( < 70 mg per deciliter [ 3.9 mmol per liter ] ) was 4.8 % .


After 1 day of automatic adaptation by the bionic pancreas , the mean ( SD ) glucose level on continuous monitoring was lower than the mean level during the control period ( 13313 vs. 15930 mg per deciliter [ 7.40.7 vs. 8.81.7 mmol per liter ] , P < 0.001 ) and the percentage of time with a low glucose reading was lower ( 4.1 % vs. 7.3 % , P = 0.01 ) .


Among the adolescents , the mean plasma glucose level was also lower during the bionic-pancreas period than during the control period ( 13818 vs. 15727 mg per deciliter [ 7.71.0 vs. 8.71.5 mmol per liter ] , P = 0.004 ) , but the percentage of time with a low plasma glucose reading was similar during the two periods ( 6.1 % and 7.6 % , respectively ; P = 0.23 ) .


The mean frequency of interventions for hypoglycemia among the adolescents was lower during the bionic-pancreas period than during the control period ( one per 1.6 days vs. one per 0.8 days , P < 0.001 ) .


As compared with an insulin pump , a wearable , automated , bihormonal , bionic pancreas improved mean glycemic levels , with less frequent hypoglycemic episodes , among both adults and adolescents with type 1 diabetes mellitus .


( Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others ; ClinicalTrials.gov numbers , NCT01762059 and NCT01833988 . )


The study aim was to establish the threshold of stretching volume for flexibility enhancement during physical education lessons in secondary school children .


Subjects were 239 tenth grade children randomly assigned to four groups ( boys 107 , girls 132 , mean age 15.1 0.4 ) .


Children involved in after-school sports were not included in the study .


Physical education lessons were performed twice a week for 45 minutes in duration .


The intervention lasted for five weeks comprising 10 physical education lessons .


Flexibility was determined from sit and reach test before and after intervention .


Subjects in group 1 performed standard `` sit and reach '' test of four trials in every physical education lesson ; in group 2 received one stretching exercise of four repetitions ; group 3 received four stretching exercises of four repetitions ; in group 4 no stretching was performed .


Flexibility improvement in group 3 were the greatest ( 21.6 % ; P < 0.05 ) , smaller in group 2 ( 12.6 % , P < 0.05 ) and smallest in 1 group ( 5.1 % , P < 0.05 ) , while control group changes were insignificant ( 1.7 % , P > 0.05 ) .


The main finding was that single flexibility test performed twice a week for five weeks was sufficient stimulus to increase range of motion in secondary school children .


Stretching exercises provides exceptional prospects to achieve youths ' improvement since schoolchildren are very sensitive to flexibility training .


In this phase II study , patients with stage IIIB/IV non-small-cell lung cancer were randomly assigned ( 1:1:1 ) to receive LY293111 ( 200 mg twice daily [ 200 LY293111 ] or 600 mg twice daily [ 600 LY293111 ] ) or placebo for 7 days , followed by concurrent cisplatin ( 75 mg/m2 ; day 1 ) and gemcitabine ( 1250 mg/m2 ; days 1 and 8 ) , every 21 days.The primary endpoint was progression-free survival , ( PFS ) , with 75 % power to detect 33 % improvement compared with placebo ( 5 months ) .


Of 200 randomized patients , 195 were treated .


Demographics were well balanced across treatment arms : 65 % of the patients were men ; median age was 62 years ; 85 % had stage IV disease ; and patients had an Eastern Cooperative Oncology Group performance status of 0 ( 36 % ) or 1 ( 64 % ) .


The most frequent study drug-related toxicities were nausea , vomiting , and fatigue .


Response rates were similar across treatment arms ( 200 LY293111 : 20 % ; 600 LY293111 : 25 % ; placebo : 31 % ) .


Median PFS ( 95 % confidence interval ) was not significantly different across treatment arms ( 200 LY293111 : 4.6 months [ 3.2-5 .0 ] ; 600 LY293111 : 5.6 months [ 4.1-6 .8 ] ; placebo : 6.0 months [ 5.2-7 .5 ] ) .


LY293111 combined with gemcitabine-cisplatin did not increase median PFS compared with placebo plus gemcitabine-cisplatin in patients with non-small-cell lung cancer .


The alginate-antacid , Gaviscon Double Action ( Gaviscon DA ; Reckitt Benckiser , Slough , UK ) suppresses reflux after meals by creating a gel-like barrier that caps and displaces the acid pocket distal to the oesophago-gastric junction .


The effect of Gaviscon DA on reflux and dyspepsia symptoms has not yet been demonstrated with a modern trial design .


A pilot study to assess the efficacy and safety of Gaviscon DA compared with matched placebo for decreasing upper gastrointestinal symptoms in symptomatic gastro-oesophageal reflux disease ( GERD ) patients .


A randomised , double-blind , parallel group study was performed in 110 patients with symptoms of GERD .


Patients received Gaviscon DA or placebo tablets for 7 consecutive days .


The primary endpoint compared the change in overall Reflux Disease Questionnaire ( RDQ ) symptom score ( combined heartburn/regurgitation/dyspepsia ) .


Secondary endpoints assessed individual dimensions , GERD dimension ( heartburn and regurgitation ) and overall treatment evaluation ( OTE ) .


There was a greater decrease in overall RDQ symptom score in the Gaviscon DA group compared with the placebo group ( Least Squares Mean difference -0.55 ; P = 0.0033 ) , and for each of the dimensions independently .


Patients in the Gaviscon DA group evaluated their overall treatment response higher than patients in the placebo group [ mean ( standard deviation ) OTE 4.1 ( 2.44 ) vs. 1.9 ( 3.34 ) ; P = 0.0005 ] .


No differences in the incidence of adverse events were observed between treatment groups .


Gaviscon DA decreases reflux and dyspeptic symptoms in GERD patients compared with matched placebo and has a favourable benefit-risk balance .


Larger scale clinical investigations of medications targeting the acid pocket are warranted .


( EudraCT , 2012-002188-84 ) .


Polysomnography defines the pathophysiology of obstructive sleep apnea syndrome ( OSAS ) but does not predict some important comorbidities or their response to adenotonsillectomy .


We assessed whether OSAS symptoms , as reflected on the Sleep-Related Breathing Disorders Scale of the Pediatric Sleep Questionnaire ( PSQ ) , may offer clinical predictive value .


Baseline and 7-month follow-up data were analyzed from 185 participants ( aged 5-9 years with polysomnographically confirmed OSAS ) in the surgical treatment arm of the multicenter Childhood Adenotonsillectomy Trial .


Associations were assessed between baseline PSQ or polysomnographic data and baseline morbidity ( executive dysfunction , behavior , quality of life , sleepiness ) or postsurgical improvement .


At baseline , each 1-SD increase in baseline PSQ score was associated with an adjusted odds ratio that was 3 to 4 times higher for behavioral morbidity , 2 times higher for reduced global quality of life , 6 times higher for reduced disease-specific quality of life , and 2 times higher for sleepiness .


Higher baseline PSQ scores ( greater symptom burden ) also predicted postsurgical improvement in parent ratings of executive functioning , behavior , quality of life , and sleepiness .


In contrast , baseline polysomnographic data did not independently predict these morbidities or their postsurgical improvement .


Neither PSQ nor polysomnographic data were associated with objectively assessed executive dysfunction or improvement at follow-up .


PSQ symptom items , in contrast to polysomnographic results , reflect subjective measures of OSAS-related impairment of behavior , quality of life , and sleepiness and predict their improvement after adenotonsillectomy .


Although objective polysomnography is needed to diagnose OSAS , the symptoms obtained during an office visit can offer adjunctive insight into important comorbidities and likely surgical responses .


Adherence to evidence-based cardiovascular ( CV ) medications after an acute myocardial infarction ( MI ) is low after the first 6 months .


The use of fixed-dose combinations ( FDC ) has been shown to improve treatment adherence and risk factor control .


However , no previous randomized trial has analyzed the impact of a polypill strategy on adherence in post-MI patients .


The cross-sectional FOCUS ( Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention ) study ( Phase 1 ) aimed to elucidate factors that interfere with appropriate adherence to CV medications for secondary prevention after an acute MI .


Additionally , 695 patients from Phase 1 were randomized into a controlled trial ( Phase 2 ) to test the effect of a polypill ( containing aspirin 100 mg , simvastatin 40 mg , and ramipril 2.5 , 5 , or 10 mg ) compared with the 3 drugs given separately on adherence , blood pressure , and low-density lipoprotein cholesterol , as well as safety and tolerability over a period of 9 months of follow-up .


In Phase 1 , a 5-country cohort of 2,118 patients was analyzed .


Patients were randomized to either the polypill or 3 drugs separately for Phase 2 .


Primary endpoint was adherence to the treatment measured at the final visit by the self-reported Morisky-Green questionnaire ( MAQ ) and pill count ( patients had to meet both criteria for adherence at the in-person visit to be considered adherent ) .


In Phase 1 , overall CV medication adherence , defined as an MAQ score of 20 , was 45.5 % .


In a multivariable regression model , the risk of being nonadherent ( MAQ < 20 ) was associated with younger age , depression , being on a complex medication regimen , poorer health insurance coverage , and a lower level of social support , with consistent findings across countries .


In Phase 2 , the polypill group showed improved adherence compared with the group receiving separate medications after 9 months of follow-up : 50.8 % versus 41 % ( p = 0.019 ; intention-to-treat population ) and 65.7 % versus 55.7 % ( p = 0.012 ; per protocol population ) when using the primary endpoint , attending the final visit with MAQ = 20 and high pill count ( 80 % to 110 % ) combined , to assess adherence .


Adherence also was higher in the FDC group when measured by MAQ alone ( 68 % vs. 59 % , p = 0.049 ) .


No treatment difference was found at follow-up in mean systolic blood pressure ( 129.6 mmHg vs. 128.6 mmHg ) , mean low-density lipoprotein cholesterol levels ( 89.9 mg/dl vs. 91.7 mg/dl ) , serious adverse events ( 23 vs. 21 ) , or death ( 1 , 0.3 % in each group ) .


For secondary prevention following acute MI , younger age , depression , and a complex drug treatment plan are associated with lower medication adherence .


Meanwhile , adherence is increased in patients with higher insurance coverage levels and social support .


Compared with the 3 drugs given separately , the use of a polypill strategy met the primary endpoint for adherence for secondary prevention following an acute MI .


( Fixed Dose Combination Drug [ Polypill ] for Secondary Cardiovascular Prevention [ FOCUS ] ; NCT01321255 ) .


The presence of entrapped lung changes the appropriate management of malignant pleural effusion from pleurodesis to insertion of an indwelling pleural catheter .


No methods currently exist to identify entrapped lung prior to effusion drainage .


Our objectives were to develop a method to identify entrapped lung using tissue movement and deformation ( strain ) analysis with ultrasonography and compare it to the existing technique of pleural elastance ( PEL ) .


Prior to drainage , 81 patients with suspected malignant pleural effusion underwent thoracic ultrasound using an echocardiogram machine .


Images of the atelectatic lower lobe were acquired during breath hold , allowing motion and strain related to the cardiac impulse to be analyzed using motion mode ( M mode ) and speckle-tracking imaging , respectively .


PEL was measured during effusion drainage .


The gold-standard diagnosis of entrapped lung was the consensus opinion of two interventional pulmonologists according to postdrainage imaging .


Participants were randomly divided into development and validation sets .


Both total movement and strain were significantly reduced in entrapped lung .


Using data from the development set , the area under the receiver-operating curves for the diagnosis of entrapped lung was 0.86 ( speckle tracking ) , 0.79 ( M mode ) , and 0.69 ( PEL ) .


Using respective cutoffs of 6 % , 1 mm , and 19 cm H2O on the validation set , the sensitivity/specificity was 71 % / 85 % ( speckle tracking ) , 50 % / 85 % ( M mode ) , and 40 % / 100 % ( PEL ) .


This novel ultrasound technique can identify entrapped lung prior to effusion drainage , which could allow appropriate choice of definitive management ( pleurodesis vs indwelling catheter ) , reducing the number of interventions required to treat malignant pleural effusion .


Oral care is important for oral and systemic health , especially for elderly institutionalized individuals and compromised patients .


However , conventional mechanical plaque control is often difficult for these patients because of the pain or the risk of aspiration .


Although antimicrobial photodynamic therapy ( aPDT ) , which is considered an alternative or adjunct to mechanical approaches , has potential application as a less stressful method of daily plaque control , no clinical application of this technique has been reported .


We investigated the inhibitory effect of a combination of toluidine blue O ( TBO ) , and a red light-emitting diode ( LED ) on dental plaque formation in healthy volunteers .


The optimal concentration of TBO was determined in preliminary in vitro experiments to evaluate the bactericidal effect of aPDT on Streptococcus oralis and to clarify its safety in fibroblast cells .


To survey the mechanism of TBO-mediated aPDT , the quality and quantity of reactive oxygen species ( ROS ) generated during aPDT were also examined using electron spin resonance ( ESR ) spectroscopy .


Subsequently , the inhibitory effect of aPDT on dental plaque formation was investigated in eleven subjects as a clinical pilot study .


The right or left mandibular premolars were randomly assigned to the treatment ( with aPDT ) or control ( without aPDT ) groups .


In total , aPDT was applied six times ( twice per day ) to the teeth in the test group over a period of four days .


On the fourth day , the study concluded and the analyses were performed .


A combination of 500 or 1000 g/ml TBO and LED irradiation for 20 s significantly decreased the number of colony forming units of Streptococcus oralis .


The cytotoxicity of aPDT was comparable to that of standard antiseptics used in the oral cavity .


Hydroxyl radicals were detected by ESR analysis , but singlet oxygen was not .


A randomized controlled trial demonstrated that aPDT with 1000 g/ml TBO and red LED irradiation significantly suppressed dental plaque formation without harming teeth or the surrounding tissues .


aPDT has the potential to be a promising novel technical modality for dental plaque control .


This trial was registered with University Hospital Medical Information Network Clinical Trials Registry ( number UMIN000012504 ) .


Familial amyloid polyneuropathy , a lethal genetic disease caused by aggregation of variant transthyretin , induces progressive peripheral nerve deficits and disability .


Diflunisal , a nonsteroidal anti-inflammatory agent , stabilizes transthyretin tetramers and prevents amyloid fibril formation in vitro .


To determine the effect of diflunisal on polyneuropathy progression in patients with familial amyloid polyneuropathy .


International randomized , double-blind , placebo-controlled study conducted among 130 patients with familial amyloid polyneuropathy exhibiting clinically detectable peripheral or autonomic neuropathy at amyloid centers in Sweden ( Ume ) , Italy ( Pavia ) , Japan ( Matsumoto and Kumamoto ) , England ( London ) , and the United States ( Boston , Massachusetts ; New York , New York ; and Rochester , Minnesota ) from 2006 through 2012 .


Participants were randomly assigned to receive diflunisal , 250 mg ( n = 64 ) , or placebo ( n = 66 ) twice daily for 2 years .


The primary end point , the difference in polyneuropathy progression between treatments , was measured by the Neuropathy Impairment Score plus 7 nerve tests ( NIS +7 ) which ranges from 0 ( no neurological deficits ) to 270 points ( no detectable peripheral nerve function ) .


Secondary outcomes included a quality-of-life questionnaire ( 36-Item Short-Form Health Survey [ SF-36 ] ) and modified body mass index .


Because of attrition , we used likelihood-based modeling and multiple imputation analysis of baseline to 2-year data .


By multiple imputation , the NIS +7 score increased by 25.0 ( 95 % CI , 18.4-31 .6 ) points in the placebo group and by 8.7 ( 95 % CI , 3.3-14 .1 ) points in the diflunisal group , a difference of 16.3 points ( 95 % CI , 8.1-24 .5 points ; P < .001 ) .


Mean SF-36 physical scores decreased by 4.9 ( 95 % CI , -7.6 to -2.2 ) points in the placebo group and increased by 1.5 ( 95 % CI , -0.8 to 3.7 ) points in the diflunisal group ( P < .001 ) .


Mean SF-36 mental scores declined by 1.1 ( 95 % CI , -4.3 to 2.0 ) points in the placebo group while increasing by 3.7 ( 95 % CI , 1.0-6 .4 ) points in the diflunisal group ( P = .02 ) .


By responder analysis , 29.7 % of the diflunisal group and 9.4 % of the placebo group exhibited neurological stability at 2 years ( < 2-point increase in NIS +7 score ; P = .007 ) .


Among patients with familial amyloid polyneuropathy , the use of diflunisal compared with placebo for 2 years reduced the rate of progression of neurological impairment and preserved quality of life .


Although longer-term follow-up studies are needed , these findings suggest benefit of this treatment for familial amyloid polyneuropathy .


clinicaltrials.gov Identifier : NCT00294671 .


It has been known that ADH1B * 2 allele has a protective effect against the development of alcohol dependence .


However , the protection mechanism is still unknown .


We investigated whether ADH1B gene polymorphism affects ethanol ( EtOH ) metabolism .


In a parent study , we conducted a randomized crossover trials on 24 healthy male subjects who were selected by genotyping : 12 with ALDH2 * 1 / * 1 ( active form ) and 12 with ALDH2 * 1 / * 2 ( inactive form ) .


In the present study , the 24 subjects were reclassified into 2 groups of 11 with ADH1B * 1 / * 2 and 13 with ADH1B * 2 / * 2 according to the ADH1B genotypes .


Each subject was administered 1 of 3 doses of EtOH ( 0.25 , 0.5 , 0.75 g/kg ) or a placebo in 4 trials .


After the administration of alcohol , blood EtOH and acetaldehyde concentrations were measured 9 times over 4 hours .


In the case of EtOH , the area under the concentration-time curve from 0 to 4 hours ( AUC0-4 ) and the peak blood concentration of EtOH ( Cmax ) in subjects with ADH1B * 2 / * 2 were significantly higher than those in subjects with ADH1B * 1 / * 2 at all 3 dosages before stratifying by ALDH2 genotype .


However , after stratifying by ALDH2 genotype , a statistically significant difference between ADH1B * 2 / * 2 and ADH1B * 1 / * 2 was found only at the 0.5 g/kg dosage regardless of ALDH2 genotype .


In the case of acetaldehyde , the AUC0-4 and Cmax of acetaldehyde of ADH1B * 2 / * 2 after administration of 0.25 g/kg alcohol and the AUC0-4 of acetaldehyde of ADH1B * 2 / * 2 at 0.5 g/kg were significantly higher than corresponding values of ADH1B * 1 / * 2 only in the group of ALDH2 * 1 / * 2 .


Our findings indicate that the blood EtOH concentrations of ADH1B * 2 / * 2 group are higher than those of ADH1B * 1 / * 2 group regardless of ALDH2 genotype , and the blood acetaldehyde concentrations of ADH1B * 2 / * 2 are also higher than those of ADH1B * 1 / * 2 only in the ALDH2 * 1 / * 2 group .


To our knowledge , this is the first report to demonstrate the association of ADH1B * 2 allele with blood EtOH and acetaldehyde levels in humans , and these results suggest that higher blood EtOH and acetaldehyde concentrations in ADH1B * 2 / * 2 may constitute the mechanism of protection against alcoholism by ADH1B * 2 / * 2 .


Chronic kidney disease is associated with increased arterial stiffness even in the early stages and this is thought to be a key mediator in the pathophysiology of the increased cardiovascular risk associated with this condition .


The use of low-dose spironolactone has previously been shown to improve arterial stiffness and reduce left ventricular mass safely in early-stage chronic kidney disease in the context of careful monitoring at a university hospital .


However , the majority of patients with chronic kidney disease are managed by their general practitioners in the community .


It is not known whether similar beneficial effects can be achieved safely using spironolactone in the primary care setting .


The aim of this study is to determine whether low-dose spironolactone can safely lower arterial stiffness in patients with stage 3 chronic kidney disease in the primary care setting .


STOP-CKD is a multicentre , prospective , randomized , double-blind , placebo-controlled pilot trial of 240 adult patients with stage 3 chronic kidney disease recruited from up to 20 general practices in South Birmingham , England .


Participants will be randomly allocated using a secured web-based computer randomization system to receive either spironolactone 25mg once daily or a matching inactive placebo for 40weeks , followed by a wash-out period of 6weeks .


Investigators , outcome assessors , data analysts and participants will all be blinded to the treatment allocation .


The primary endpoint is improved arterial stiffness , as measured by carotid-femoral pulse wave velocity between baseline and 40weeks .


The secondary endpoints are incidence of hyperkalaemia , change in estimated glomerular filtration rate , change in urine albumin : creatinine ratio , change in brachial blood pressure , change in pulse waveform characteristics and overall tolerability of spironolactone .


An additional quality control study , aiming to compare the laboratory serum potassium results of samples processed via two methods ( utilizing routine transport or centrifugation on site before rapid transport to the laboratory ) for 100 participants and a qualitative research study exploring patients ' and general practitioners ' attitudes to research and the use of spironolactone in chronic kidney disease in the community setting will be embedded in this pilot study .


Current Controlled Trials ISRCTN80658312 .


Herpes simplex virus type 2 ( HSV-2 ) biomarkers are often used in adolescent sub-Saharan HIV prevention studies , but evaluations of test performance and disclosure outcomes are rare in the published literature .


Therefore , we investigated the proportion of ELISA-positive and indeterminate samples confirmed by western blot ( WB ) , the psychosocial response to disclosure and whether reports of sexual behaviour and HSV-2 symptoms are consistent with WB confirmatory results among adolescent orphans in Kenya .


In 2011 , 837 Kenyan orphan youth in grades 7 and 8 enrolled in an HIV prevention clinical trial with HSV-2 biomarker outcomes .


We used a modified algorithm for the Kalon HSV-2 ELISA to improve specificity ; positive and indeterminate results were WB tested .


We developed culturally sensitive protocols for disclosing positive results , and documented psychosocial responses , reports of sexual contact and HSV-2 symptoms .


28 adolescents ( 3.3 % ) were identified as HSV-2 seropositive , six as indeterminate .


Of these , 22 positive and all indeterminates were WB tested ; 20 and 5 , respectively , were confirmed positive .


Most youth reported moderate brief stress after disclosure ; 22 % reported longer and more severe distress .


Boys were more likely to be in the latter category .


Self-reported virginity was highly inconsistent with WB-confirmed positives .


The higher than manufacturer 's cut-off for Kalon ELISA modestly reduced the rate of false-positive test results , but also increased false negatives .


Investigators should consider the risk : benefit ratio in deciding whether or not to disclose HSV-2 results to adolescent participants under specific field conditions .


NCT01501864 .


We investigated and compared the effects of 2 different types of upper extremity exercise training on upper extremity function , strength , endurance , and ambulation in patients with early-stage Duchenne muscular dystrophy ( DMD ) .


The study group ( n = 12 ) exercised with an arm ergometer under the supervision of a physiotherapist , whereas the control group ( n = 12 ) underwent a strengthening range-of-motion ( ROM ) exercise program under the supervision of their families at home for 8 weeks .


Upper extremity functional performance , strength , endurance , and ambulatory status were assessed before and after the training .


Ambulation scores , endurance , and arm functions , as well as proximal muscle strength , were improved after the training in the study group ( P < 0.05 ) .


These results demonstrate that upper extremity training with an arm ergometer is more effective in preserving and improving the functional level of early-stage DMD patients compared to ROM exercises alone .


To evaluate whether follow-up of patients with obstructive sleep apnoea ( OSA ) undergoing CPAP treatment could be performed in primary care ( PC ) settings .


Non-inferiority , randomised , prospective controlled study .


Sleep unit ( SU ) at the University Hospital and in 8 PC units in Lleida , Spain .


Patients with OSA were randomised to be followed up at the SU or PC units over a 6-month period .


The primary outcome was CPAP compliance at 6months .


The secondary outcomes were Epworth Sleep Scale ( ESS ) score , EuroQoL , patient satisfaction , body mass index ( BMI ) , blood pressure and cost-effectiveness .


We included 101 patients in PC ( ( meanSD ) apnoea-hypopnoea index ( AHI ) 50.822.9 / h , age 56.211 years , 74 % male ) and 109 in the SU ( AHI 51.424.4 / h , age 55.811 years , 77 % male ) ) .


The CPAP compliance was ( mean ( 95 % CI ) 4.94 ( 4.47 to 5.5 ) vs 5.23 ( 4.79 to 5.66 ) h , p = 0.18 ) in PC and SU groups , respectively .


In the SU group , there were greater improvements in ESS scores ( mean change 1.79 , 95 % CI +0.05 to +3.53 , p = 0.04 ) and patient satisfaction ( -1.49 , 95 % CI -2.22 to -0.76 ) ; there was a significant mean difference in BMI between the groups ( 0.57 , 95 % CI +0.01 to +1.13 , p = 0.04 ) .


In the PC setting , there was a cost saving of 60 % , with similar effectiveness , as well as a decrease in systolic blood pressure ( -5.32 ; 95 % CI -10.91 to +0.28 , p = 0.06 ) .


For patients with OSA , treatment provided in a PC setting did not result in worse CPAP compliance compared with a specialist model and was shown to be a cost-effective alternative .


Clinical Trials NCT01918449 .


Japanese encephalitis ( JE ) is a vaccine-preventable acute disease .


We report the results of a phase 2/3 trial of JENVAC , a Vero cell-derived vaccine developed using an Indian strain of JE virus ( JEV ) .


JENVAC was administered in 2 doses 28 days apart , and immunogenicity was compared to that from a single dose of SA-14-14-2 , the only approved JE vaccine and regimen at the time in India .


After both the doses , seroconversion and seroprotection were > 90 % for JENVAC .


For SA-14-14-2 , seroconversion and seroprotection were 57.69 % and 77.56 % , respectively , on day 28 and 39.74 % and 60.26 % , respectively , on day 56 .


The geometric mean titers at day 28 and day 56 were 145.04 and 460.53 , respectively , for JENVAC and 38.56 and 25.29 , respectively , for SA-14-14-2 .


With a single dose of JENVAC , seroprotection titers lasted at least 12 months in > 80 % of the subjects .


Following receipt of 2 doses , 61.17 % of subjects retained seroprotection titers at 24 months , and immunogenicity criteria were higher than that for SA-14-14-2 at 12 , 18 , and 24 months each .


Sera from JENVAC subjects neutralized JEV genotypes I , II , III , and IV equally well .


Adverse events were not significantly different between the 2 vaccines .


JENVAC elicits long-lasting , broadly protective immunity .


CTRI/2011/07 / 001855 .


Experimental studies suggest that pretreatment with - agonists might prevent acute lung injury ( ALI ) .


To determine if in adult patients undergoing elective esophagectomy , perioperative treatment with inhaled - agonists effects the development of early ALI .


We conducted a randomized placebo-controlled trial in 12 UK centers ( 2008-2011 ) .


Adult patients undergoing elective esophagectomy were allocated to prerandomized , sequentially numbered treatment packs containing inhaled salmeterol ( 100 g twice daily ) or a matching placebo .


Patients , clinicians , and researchers were masked to treatment allocation .


The primary outcome was development of ALI within 72 hours of surgery .


Secondary outcomes were ALI within 28 days , organ failure , adverse events , survival , and health-related quality of life .


An exploratory substudy measured biomarkers of alveolar-capillary inflammation and injury .


A total of 179 patients were randomized to salmeterol and 183 to placebo .


Baseline characteristics were similar .


Treatment with salmeterol did not prevent early lung injury ( 32 [ 19.2 % ] of 168 vs. 27 [ 16.0 % ] of 170 ; odds ratio [ OR ] , 1.25 ; 95 % confidence interval [ CI ] , 0.71-2 .22 ) .


There was no difference in organ failure , survival , or health-related quality of life .


Adverse events were less frequent in the salmeterol group ( 55 vs. 70 ; OR , 0.63 ; 95 % CI , 0.39-0 .99 ) , predominantly because of a lower number of pneumonia ( 7 vs. 17 ; OR , 0.39 ; 95 % CI , 0.16-0 .96 ) .


Salmeterol reduced some biomarkers of alveolar inflammation and epithelial injury .


Perioperative treatment with inhaled salmeterol was well tolerated but did not prevent ALI .


Clinical trial registered with International Standard Randomized Controlled Trial Register ( ISRCTN47481946 ) and European Union database of randomized Controlled Trials ( EudraCT 2007-004096-19 ) .


To evaluate the clinical outcome of sonic endo-instruments in combination with Mtwo Ni-Ti files in root canal preparation of molars .


One hundred patients ( 118 first molars , 428 root canals ) were included in this study , they were randomly assigned into 2 groups ( n = 50 ) .


Group 1 was shaped with sonic endo-instruments in combination with Mtwo Ni-Ti files , while group 2 was treated with stainless-steel files , both groups were obturated with lateral condensation technique .


The time of root canal shaping , acute post-operative pain , the quality of the root canal filling and the success rate after 1 year were recorded and analyzed using SPSS 11.0 software package .


The average preparation time in group 1 was ( 5.30.6 ) min/canal and ( 12.70.9 ) min/canal in group 2 ( t = 100.89 , P < 0.001 ) .


The rate of acute postoperative pain was significantly lower X ( 2 ) = 4.87 , P < 0.05 , in group 1 ( 8.20 % ) than in group 2 ( 22.81 % ) ; in group 1 , 92.86 % root canals were filled adequately while only 78.92 % in group 2 , the difference was significant ( X ( 2 ) = 17.45 , P < 0.05 ) ; higher success rate ( X ( 2 ) = 3.95 , P < 0.05 ) after 1 year was achieved in group 1 ( 91.80 % ) compared with group 2 ( 78.95 % ) .


Compared with stainless-steel files , sonic endo instruments in combination with Mtwo Ni-Ti files in root canal preparation of molars seem more effective , cause less postoperative pain and offer higher success rates .


To determine which patients respond best to stereotactic radiotherapy ( SRT ) for neovascular age-related macular degeneration .


Participants ( n = 230 ) receiving intravitreal anti-vascular endothelial growth factor injections for neovascular age-related macular degeneration enrolled in a randomized , double-masked sham-controlled trial comparing 16 Gray , 24 Gray , or Sham SRT .


In a post hoc analysis , participants were grouped according to their baseline characteristics , to determine if these influenced SRT efficacy .


At 52 weeks , SRT was most effective for lesions 4 mm in greatest linear dimension and with a macular volume greater than the median value of 7.4 mm .


For 26 % of the participants with both these characteristics , SRT resulted in 55 % fewer ranibizumab injections ( 2.08 vs. 4.60 ; P = 0.0002 ) , a mean visual acuity change that was 5.33 letters superior to sham ( +2.18 vs. -3.15 letters ; P = 0.0284 ) , and a 71.1-m greater reduction in mean central subfield thickness ( -122.6 vs. -51.5 m ; P = 0.027 ) .


Other features associated with a positive response to SRT included pigment epithelial detachment and the absence of fibrosis .


Stereotactic radiotherapy is most effective for neovascular age-related macular degeneration lesions that are actively leaking at the time of treatment , and no larger than the 4-mm treatment zone .


To evaluate the efficacy of a stand-alone personalized normative feedback ( PNF ) intervention targeting misperceptions of gambling among college students .


Undergraduates ( N = 136 ; 55 % male ) who reported gambling in the past 30 days were recruited between September 2011 and March 2012 .


Using a randomized clinical trial design , participants were assigned to receive either PNF or an attention control task .


In addition to self-report , this study used 2 computer-based risk tasks framed as `` gambling opportunities '' to assess cognitive and behavioral change at 1 week post intervention .


After 1 week , participants receiving PNF showed a marked decrease in perception of other students ' gambling , and evinced lower risk-taking performance on 2 analog measures of gambling .


Changes in both self-reported perceived norms and analog gambling behavior suggest that a single , stand-alone PNF intervention may modify gambling among college students .


Whether it can impact gambling outside of the laboratory remains untested .


To evaluate interobserver agreement and time-trend in chest CT assessment of emphysema , airways , and interstitial abnormalities in a lung cancer screening cohort .


Visual assessment of baseline and fifth-year examination of 1990 participants was performed independently by two observers .


Results were standardised by means of an electronic score sheet ; kappa and time-trend analyses were performed .


Interobserver agreement was substantial in early emphysema diagnosis ; highly significant ( p < 0.001 ) time-trends in both emphysema presence and grading were found ( higher prevalence and grade of emphysema in late CT examinations ) .


Significant progression in emphysema was seen in continuous smokers , but not in former smokers .


Agreement on centrilobular emphysema subtype was substantial ; agreement on paraseptal subtype , moderate .


Agreement on panlobular and mixed subtypes was only fair .


Agreement was fair regarding airway analysis .


Interstitial abnormalities were infrequent in the cohort , and agreement on these was fair to moderate .


A highly significant time-trend was found regarding interstitial abnormalities , which were more frequent in late examinations .


Visual scoring of chest CT is able to characterise the presence , pattern , and progression of early emphysema .


Continuous smokers progress ; former smokers do not .


Substantial interobserver consistency in determining early-stage emphysema in low-dose CT. .


Longitudinal analyses show clear time-trends for emphysema presence and grading .


For continuous smokers , progression of emphysema was seen in all lung zones .


For former smokers , progression of emphysema was undetectable by visual assessment .


Onset and progression of interstitial abnormalities are visually detectable .


Aortic root management in type A acute aortic dissection is controversial .


This study compared outcomes of root replacement ( RR ) interventions versus more conservative root ( CR ) management .


Of 1,995 type A acute aortic dissection patients enrolled in the International Registry of Acute Aortic Dissection , 699 ( 35 % ) underwent RR interventions and 1,296 ( 65 % ) underwent CR management .


Independent predictors of hospital and 3-year survival were identified using multivariable logistic and Cox regression models .


Compared with CR patients , RR patients were younger ( 56.9 versus 62.3 years ; p = 0.023 ) and more likely to present with larger root diameter ( 4.7 cm versus 4.0 cm ; p < 0.001 ) , Marfan syndrome ( 8.7 % versus 2.5 % ; p < 0.001 ) , aortic insufficiency ( 64.0 % versus 50.3 % ; p < 0.001 ) , and hypotension , shock , or tamponade ( 33.0 % versus 26.5 % ; p = 0.003 ) .


Root replacement management did not increase hospital mortality ( propensity score-adjusted odds ratio , 1.14 ; p = 0.674 ) .


On Kaplan-Meier analysis , 3-year survival ( RR , 92.5 % 1.7 % versus CR , 91.6 % 1.3 % ; log-rank p = 0.623 ) and freedom from aortic root reintervention ( RR , 99.2 % 0.1 % versus CR ,99.3 % 0.1 % ; log-rank p = 0.770 ) were similar .


Only 2 patients ( 1 per group ) underwent follow-up root reintervention .


Propensity score-adjusted Cox regression excluded a relationship between root treatment and follow-up survival ( hazard ratio , 1.5 ; 95 % confidence interval , 0.502 to 5.010 ; p = 0.432 ) .


In type A acute aortic dissection patients more-extensive RR interventions are not associated withincreased hospital mortality .


This supports such anapproach in young patients and patients with connective tissue diseases and bicuspid aortic valves .


Excellent midterm survival and freedom from root reintervention in both groups suggest stable behavior of the nonreplaced aortic sinuses at 3 years .


Thus , pending studies with longer follow-up , the use of aggressive RR techniques can be determined by patient-specific and dissection-related factors .


To identify clinical conditions associated with a large increase ( spike ) in the heart rate characteristics index in very low birth weight ( VLBW ) infants .


Retrospective medical record review within a day of all large heart rate characteristics index spikes ( increase of 3 from the previous 5-day average ) in VLBW infants at a single center enrolled from 2007 to 2010 in a multicenter trial of heart rate characteristics monitoring .


In the trial , infants were randomized to having their heart rate characteristics index displayed to clinicians or not displayed .


Of 274 eligible infants , 224 large heart rate characteristics spikes occurred in 105 infants .


Thirty-three spikes were associated with surgery or procedures requiring anesthetic or anticholinergic medications , and infection-related conditions were the most common clinical association with the other spikes .


Of the first spikes in 47 infants randomized to conventional monitoring ( heart rate characteristics index not displayed to clinicians ) , 53 % were associated with suspected or proven infection .


Respiratory deterioration without suspected infection occurred with 34 % , and no association was identified in 13 % .


Infants randomized to having their heart rate characteristics index displayed were more likely to have antibiotics initiated around the time of a large heart rate characteristics index spike .


Sepsis , other infectious or systemic inflammatory conditions , respiratory deterioration , and surgical procedures are the most common clinical associations with a large increase in the heart rate characteristics index in VLBW infants .


This information may improve use of heart rate characteristics monitors in patients in the neonatal intensive care unit .


Small studies suggest peanut oral immunotherapy ( OIT ) might be effective in the treatment of peanut allergy .


We aimed to establish the efficacy of OIT for the desensitisation of children with allergy to peanuts .


We did a randomised controlled crossover trial to compare the efficacy of active OIT ( using characterised peanut flour ; protein doses of 2-800 mg/day ) with control ( peanut avoidance , the present standard of care ) at the NIHR/Wellcome Trust Cambridge Clinical Research Facility ( Cambridge , UK ) .


Randomisation ( 1:1 ) was by use of an audited online system ; group allocation was not masked .


Eligible participants were aged 7-16 years with an immediate hypersensitivity reaction after peanut ingestion , positive skin prick test to peanuts , and positive by double-blind placebo-controlled food challenge ( DBPCFC ) .


We excluded participants if they had a major chronic illness , if the care provider or a present household member had suspected or diagnosed allergy to peanuts , or if there was an unwillingness or inability to comply with study procedures .


Our primary outcome was desensitisation , defined as negative peanut challenge ( 1400 mg protein in DBPCFC ) at 6 months ( first phase ) .


Control participants underwent OIT during the second phase , with subsequent DBPCFC .


Immunological parameters and disease-specific quality-of-life scores were measured .


Analysis was by intention to treat .


Fisher 's exact test was used to compare the proportion of those with desensitisation to peanut after 6 months between the active and control group at the end of the first phase .


This trial is registered with Current Controlled Trials , number ISRCTN62416244 .


The primary outcome , desensitisation , was recorded for 62 % ( 24 of 39 participants ; 95 % CI 45-78 ) in the active group and none of the control group after the first phase ( 0 of 46 ; 95 % CI 0-9 ; p < 0001 ) .


84 % ( 95 % CI 70-93 ) of the active group tolerated daily ingestion of 800 mg protein ( equivalent to roughly five peanuts ) .


Median increase in peanut threshold after OIT was 1345 mg ( range 45-1400 ; p < 0001 ) or 255 times ( range 182-280 ; p < 0001 ) .


After the second phase , 54 % ( 95 % CI 35-72 ) tolerated 1400 mg challenge ( equivalent to roughly ten peanuts ) and 91 % ( 79-98 ) tolerated daily ingestion of 800 mg protein .


Quality-of-life scores improved ( decreased ) after OIT ( median change -161 ; p < 0001 ) .


Side-effects were mild in most participants .


Gastrointestinal symptoms were , collectively , most common ( 31 participants with nausea , 31 with vomiting , and one with diarrhoea ) , then oral pruritus after 63 % of doses ( 76 participants ) and wheeze after 041 % of doses ( 21 participants ) .


Intramuscular adrenaline was used after 001 % of doses ( one participant ) .


OIT successfully induced desensitisation in most children within the study population with peanut allergy of any severity , with a clinically meaningful increase in peanut threshold .


Quality of life improved after intervention and there was a good safety profile .


Immunological changes corresponded with clinical desensitisation .


Further studies in wider populations are recommended ; peanut OIT should not be done in non-specialist settings , but it is effective and well tolerated in the studied age group .


MRC-NIHR partnership .


Surgery in the beach chair position ( BCP ) may reduce cerebral blood flow and oxygenation , resulting in neurological injuries .


The authors tested the hypothesis that a ventilation strategy designed to achieve end-tidal carbon dioxide ( E ' ( CO ) ) values of 40-42 mm Hg would increase cerebral oxygenation ( Sct ( O ) ) during BCP shoulder surgery compared with a ventilation strategy designed to achieve E ' ( CO ) values of 30-32 mm Hg .


Seventy patients undergoing shoulder surgery in the BCP with general anaesthesia were enrolled in this randomized controlled trial .


Mechanical ventilation was adjusted to maintain an E ' ( CO ) of 30-32 mm Hg in the control group and an E ' ( CO ) of 40-42 mm Hg in the study group .


Cerebral oxygenation was monitored continuously in the operating theatre using near-infrared spectroscopy .


Baseline haemodynamics and Sct ( O ) were obtained before induction of anaesthesia , and these values were then measured and recorded continuously from induction of anaesthesia until tracheal extubation .


The number of cerebral desaturation events ( CDEs ) ( defined as a 20 % reduction in Sct ( O ) from baseline values ) was recorded .


No significant differences between the groups were observed in haemodynamic variables or phenylephrine interventions during the surgical procedure .


Sct ( O ) values were significantly higher in the study 40-42 group throughout the intraoperative period ( P < 0.01 ) .


In addition , the incidence of CDEs was lower in the study 40-42 group ( 8.8 % ) compared with the control 30-32 group ( 55.6 % , P < 0.0001 ) .


Cerebral oxygenation is significantly improved during BCP surgery when ventilation is adjusted to maintain E ' ( CO ) at 40-42 mm Hg compared with 30-32 mm Hg .


ClinicalTrials.gov NCT01546636 .


Prognosis of unresectable glioblastoma ( GB ) remains poor , despite temozolomide ( TMZ ) - based chemoradiation .


Activity of bevacizumab ( BEV ) and irinotecan ( IRI ) has been reported in recurrent disease .


We evaluated BEV and IRI as neo-adjuvant and adjuvant treatment combined with TMZ-based chemoradiation for unresectable GB .


Patients with unresectable GB , age 18-70 , IK 50 were eligible .


The experimental arm ( BEV/IRI ) consisted of neo-adjuvant intravenous BEV , 10 mg/kg , and IRI , 125 mg/m ( 2 ) , every 2 weeks for four cycles before radiotherapy ( RT ) ( 60 Gy ) , concomitant oral TMZ , 75 mg/m ( 2 ) / day , and BEV , 10 mg/kg every 2 weeks .


Adjuvant BEV and IRI were given every 2 weeks for 6 months .


The control arm consisted of concomitant oral TMZ , 75 mg/m ( 2 ) / day during RT , and 150-200 mg/m ( 2 ) for 5 days every 28 days for 6 months .


The use of BEV was allowed at progression in the control arm .


Patients ( 120 ) were included from April 2009 to January 2011 .


The working hypothesis was that treatment would increase the progression-free survival at 6 month ( PFS-6 ) from 50 % to 66 % .


The primary objective was not achieved , and only 30 out of 60 patients were alive without progression at 6 months ( 50.0 % [ IC95 % ( 36.8 ; 63.1 ) ] in the BEV/IRI arm when 37 out of 60 patients were required according to the Fleming decision rules .


PFS-6 was 7.1 months in BEV/IRI versus 5.2 months in the control arm .


The median overall survival was not different between the two arms ( 11.1 months ) .


Main toxicities were three fatal intracranial bleedings , three bile duct or digestive perforations/infections ( 1 fatal ) , and six thrombotic episodes in the BEV/IRI arm , whereas there was one intracranial bleeding , two bile duct or digestive perforations/infections ( 1 fatal ) , and one thrombotic episode in the control arm .


Neo-adjuvant and adjuvant BEV/IRI , combined with TMZ-radiation , is not recommended for further evaluation in the first-line treatment of unresectable GB .


Clinical trial registered under EUDRACT number 2008-002775-28 ( NCT01022918 ) .


Physical therapists are well established as providers of treatments for common , painful , and disabling conditions , such as knee osteoarthritis ( OA ) .


Thus , they are well placed to deliver treatments that integrate physical and psychosocial elements .


Attention is usually given to outcomes of such programs , but few studies have examined the processes and outcomes of training physical therapists to deliver such treatments .


The aim of this study was to describe the processes in training physical therapists : ( 1 ) to deliver a standardized pain coping skills treatment and ( 2 ) to evaluate the effectiveness of that training .


This study was an analysis of data relating to therapist performance in a randomized clinical trial .


Eleven physical therapists were trained to deliver a 10-session pain coping skills training program for people with knee OA as part of a randomized controlled trial ( N = 222 ) .


The initial training was provided in a workshop format and included extensive , ongoing supervision by a psychologist and rigorous use of well-defined performance criteria to assess competence .


Adherence to the program , ratings of performance , and use of advanced skills were all measured against these criteria in a sample ( n = 74 , 10 % ) of the audio recordings of the intervention sessions .


Overall , the physical therapists achieved a very high standard of treatment delivery , with 96.6 % adherence to the program and mean performance ratings all in the satisfactory range .


These results were maintained throughout the intervention and across all sessions .


Only 10 % of the delivered sessions were analyzed , and the physical therapists who took part in the study were a self-selected group .


This study demonstrated that a systematic approach to training and accrediting physical therapists to deliver a standardized pain coping skills program can result in high and sustained levels of adherence to the program .


Training fidelity was achieved in this group of motivated clinicians , but the supervision provided was time intensive .


The data provide a promising indicator of greater potential for psychologically informed practice to be a feature of effective health care .


Venous thromboembolism ( VTE ) prophylaxis remains debated following trauma , and recommendations have not been established .


Although hyperfibrinogenemia is a marker of proinflammatory states , it also contributes to thrombus formation .


Postinjury hyperfibrinogenemia is common , but the effect of hyperfibrinogenemia on VTE prophylaxis has not been fully elucidated .


Therefore , we hypothesized that heparin is less effective for VTE prophylaxis following severe injury due to hyperfibrinogenemia .


In vitro studies evaluated thromboelastography ( TEG ) parameters in 10 healthy volunteers after the addition of fibrinogen concentrate and heparin .


Data from a recent randomized controlled trial , conducted at an academic level I trauma center surgical intensive care unit , were reviewed .


Critically injured patients were randomized to standard VTE prophylaxis ( 5,000 U low-molecular-weight heparin daily ) or TEG-guided prophylaxis ( up to 10,000 U low-molecular-weight heparin daily ) and were followed up for 5 days .


Analysis was performed to evaluate the relationship between fibrinogen levels , measures of anticoagulation , and TEG parameters .


In vitro studies revealed increased fibrinogen reversed the effects of heparin as measured by TEG .


Fifty patients were enrolled in the clinical study with 25 in each arm .


Thromboelastography parameters , fibrinogen , platelet count , and anti-Xa levels did not differ between groups despite treatment provided .


Fibrinogen levels increased over the 5-day study period ( 597 24.0 to 689.3 25.0 ) , as well as clot strength ( 9.8 0.4 to 14.5 0.6 ) , which had a significant correlation coefficient ( P < 0.01 ) .


Moreover , there was a moderate inverse correlation between fibrinogen level and the effect of heparin ( RF ) , which was significant on study days 1 and 3 , implicating hyperfibrinogenemia in heparin resistance .


Hypercoagulability and heparin resistance are common following trauma .


The preclinical and clinical relationships between fibrinogen levels and hypercoagulability implicate hyperfibrinogenemia as a potential factor in heparin resistance .


( Primary ) To establish the effect of antenatal group self-hypnosis for nulliparous women on intra-partum epidural use .


Multi-method randomised control trial ( RCT ) .


Three NHS Trusts .


Nulliparous women not planning elective caesarean , without medication for hypertension and without psychological illness .


Randomisation at 28-32 weeks ' gestation to usual care , or to usual care plus brief self-hypnosis training ( two 90-minute groups at around 32 and 35 weeks ' gestation ; daily audio self-hypnosis CD ) .


Follow up at 2 and 6 weeks postnatal .


Primary : epidural analgesia .


Secondary : associated clinical and psychological outcomes ; cost analysis .


Six hundred and eighty women were randomised .


There was no statistically significant difference in epidural use : 27.9 % ( intervention ) , 30.3 % ( control ) , odds ratio ( OR ) 0.89 [ 95 % confidence interval ( CI ) : 0.64-1 .24 ] , or in 27 of 29 pre-specified secondary clinical and psychological outcomes .


Women in the intervention group had lower actual than anticipated levels of fear and anxiety between baseline and 2 weeks post natal ( anxiety : mean difference -0.72 , 95 % CI -1.16 to -0.28 , P = 0.001 ) ; fear ( mean difference -0.62 , 95 % CI -1.08 to -0.16 , P = 0.009 ) [ Correction added on 7 July 2015 , after first online publication : ` Mean difference ' replaced ` Odds ratio ( OR ) ' in the preceding sentence . ]


Postnatal response rates were 67 % overall at 2 weeks .


The additional cost in the intervention arm per woman was 4.83 ( CI -257.93 to 267.59 ) .


Allocation to two-third-trimester group self-hypnosis training sessions did not significantly reduce intra-partum epidural analgesia use or a range of other clinical and psychological variables .


The impact of women 's anxiety and fear about childbirth needs further investigation .


The aim of this prospective randomized trial was to test the null hypothesis that there was no difference in the percentage of the fracture line of scaphoid waist fractures that demonstrated bridging bone on computed tomography ( CT ) 10 weeks after injury between patients treated in a below-elbow cast including or excluding the thumb .


A total of 62 patients with a CT or magnetic resonance image-confirmed nondisplaced or minimally displaced fracture of the scaphoid were enrolled in a prospective , multicenter , randomized trial comparing treatment in a below-elbow cast including or excluding the thumb .


There were 55 waist and 7 distal fractures ( owing to a miscommunication at 3 of the centers ) .


We adhered to intention-to-treat principles .


The primary outcome was the extent of union on CT performed after 10 weeks of cast treatment , expressed as a percentage of the fracture line that had bridging bone , determined by musculoskeletal radiologists blinded to treatment .


Secondary study outcomes included wrist motion ; grip strength ; the Mayo Modified Wrist Score ; the Disabilities of the Arm , Shoulder and Hand score ; a visual analog scale for pain ; and radiographic union at 6 months after injury .