Antibody responses in infants born to women receiving Tdap during pregnancy were not different following the fourth dose of DTaP .


This preliminary assessment did not find an increased risk of adverse events among women who received Tdap vaccine during pregnancy or their infants .


For secondary outcomes , maternal immunization with Tdap resulted in high concentrations of pertussis antibodies in infants during the first 2 months of life and did not substantially alter infant responses to DTaP .


Further research is needed to provide definitive evidence of the safety and efficacy of Tdap immunization during pregnancy .


clinicaltrials.gov Identifier : NCT00707148 .


To investigate the effects of Huangqi injection on the infection factors in children with acute lymphoblastic leukemia ( ALL ) during remission induction chemotherapy .


Ninety-one children with ALL were divided into treatment ( n = 47 ) and control groups ( n = 44 ) by a randomized double-blind method .


During remission induction chemotherapy , the treatment group was given Huangqi injection ( 0.5 mL/kgd ) for 35 days , while an equal volume of normal saline was used instead in the control group ; the other supportive care was the same for the two groups .


After remission induction chemotherapy , the incidence of infection , duration of infection , white blood cell and neutrophil counts , site of infection , and positive rate of pathogenic bacteria in secretion were compared between the two groups .


Four cases in the treatment group dropped out of the study due to allergic reaction .


After remission induction chemotherapy , compared with the control group , the treatment group had a significantly lower incidence of infection ( P < 0.05 ) , a shorter duration of infection at any site ( P < 0.05 ) , a higher neutrophil count after chemotherapy ( P < 0.05 ) , and lower incidence rates of respiratory tract infection , urinary tract infection , blood infection , and skin and soft tissue infections ( P < 0.05 ) .


Gram-negative bacteria were the main pathogens .


Among the infected children , the positive rate of pathogenic bacteria in secretion was significantly lower in the treatment group than in the control group ( P < 0.05 ) .


Huangqi injection may reduce bone marrow suppression caused by chemotherapy drugs and increase neutrophil count during remission induction chemotherapy to reduce the incidence and duration of infection in children with ALL .


This study sought to determine whether outcomes for transfemoral ( TF ) transcatheter aortic valve replacement ( TAVR ) differ between the randomized controlled trial ( RCT ) and the subsequent NRCA ( Nonrandomized Continued Access ) registry of the PARTNER ( Placement of AoRTic TraNscathetER Valves ) trial .


The PARTNER RCT demonstrated that TAVR with the Edwards Sapien valve ( Edwards Lifesciences , Irvine , California ) is noninferior to surgery in high-risk patients and superior to standard therapy for inoperable patients .


The inclusion and exclusion criteria , data collection , monitoring , and core laboratories were the same for the RCT and NRCA registry .


Baseline characteristics , procedural results , and 1-year outcomes were compared between patients undergoing TF-TAVR as part of the RCT and as part of the NRCA registry .


In the RCT , 415 patients underwent TF-TAVR , whereas in the NRCA , 1,023 patients did .


At 30 days , death , cardiac death , stroke , and transient ischemic attacks were not different in the NRCA registry than in the RCT .


Major vascular complications ( 8.0 % vs. 15.7 % , p < 0.0001 ) and major bleeding ( 6.8 % vs. 15.3 % , p < 0.0001 ) were significantly lower in the NRCA registry .


At 1 year , death rates were significantly lower in the NRCA cohort ( 19.0 % vs. 25.3 % , p = 0.009 ) and cardiac death tended to be lower ( 8.4 % vs. 11.1 % , p = 0.12 ) .


Stroke or transient ischemic attack ( 6.2 % vs. 8.7 % , p = 0.10 ) and stroke alone ( 5.0 % vs. 7.1 % , p = 0.13 ) also tended to be lower .


The large NRCA registry demonstrates further improvement in procedural and longer-term outcomes after TF-TAVR when compared with the favorable results from the PARTNER RCT .


( THE PARTNER TRIAL : Placement of AoRTic TraNscathetER Valve Trial ; NCT00530894 ) .


Three small retrospective studies have suggested that patients undergoing continuous androgen deprivation ( CAD ) have superior survival and time to progression if lower castrate levels of testosterone ( < 0.7 nmol/L ) are achieved .


Evidence from prospective large studies has been lacking .


The PR-7 study randomly assigned patients experiencing biochemical failure after radiation therapy or surgery plus radiation therapy to CAD or intermittent androgen deprivation .


The relationship between testosterone levels in the first year and cause-specific survival ( CSS ) and time to androgen-independent progression in men in the CAD arm was evaluated using Cox regression .


There was a significant difference in CSS ( P = .015 ) and time to hormone resistance ( P = .02 ) among those who had first-year minimum nadir testosterone 0.7 , > 0.7 to 1.7 , and 1.7 nmol/L .


Patients with first-year nadir testosterone consistently > 0.7 nmol/L had significantly higher risks of dying as a result of disease ( 0.7 to 1.7 nmol/L : hazard ratio [ HR ] , 2.08 ; 95 % CI , 1.28 to 3.38 ; > 1.7 nmol/L : HR , 2.93 ; 95 % CI , 0.70 to 12.30 ) and developing hormone resistance ( 0.7 to 1.7 nmol/L : HR , 1.62 ; 95 % CI , 1.20 to 2.18 ; 1.7 nmol/L : HR , 1.90 ; 95 % CI , 0.77 to 4.70 ) .


Maximum testosterone 1.7 nmol/L predicted for a higher risk of dying as a result of disease ( P = .02 ) .


Low nadir serum testosterone ( ie , < 0.7 mmol/L ) within the first year of androgen-deprivation therapy correlates with improved CSS and duration of response to androgen deprivation in men being treated for biochemical failure undergoing CAD .


Despite vaccination , residents of long-term-care facilities ( LTCFs ) remain at high risk of influenza-related morbidity and mortality .


More-effective vaccine options for this population are needed .


We conducted a single-blinded , randomized , controlled trial comparing high-dose ( HD ) to standard-dose ( SD ) inactivated influenza vaccine ( IIV ) in 205 frail , elderly residents of LTCFs during the 2011-2012 and 2012-2013 influenza seasons .


Hemagglutination inhibition ( HI ) antibody titers were measured at baseline and 30 and 180 days following vaccination .


A total of 187 subjects ( 91 % ) completed the study .


The mean age was 86.7 years .


Geometric mean titers ( GMTs ) were significantly higher ( P < .05 ) at day 30 for HD recipients , compared with SD recipients , for all comparisons except influenza A ( H1N1 ) during 2012-2013 ( the HD formulation was noninferior to the SD formulation for influenza A [ H1N1 ] during 2012-2013 ) .


GMTs for HD and SD recipients during 2011-2012 were as follows : influenza A ( H1N1 ) , 78 ( 95 % confidence interval [ CI ] , 45-136 ) and 27 ( 95 % CI , 17-44 ) , respectively ; influenza A ( H3N2 ) , 26 ( 95 % CI , 17-40 ) and 10 ( 95 % CI , 7-15 ) , respectively ; and influenza B , 26 ( 95 % CI , 19-35 ) and 14 ( 95 % CI , 11-18 ) , respectively .


During 2012-2013 , GMTs for HD and SD recipients were as follows : influenza A ( H1N1 ) , 46 ( 95 % CI , 33-63 ) and 50 ( 95 % CI , 37-67 ) ; influenza A ( H3N2 ) , 23 ( 95 % CI , 18-31 ) and 14 ( 95 % CI , 11-18 ) , respectively ; and influenza B , 26 ( 95 % CI , 21-32 ) and 17 ( 95 % CI , 14-22 ) , respectively .


GMTs were significantly higher at day 180 for HD recipients , compared with SD recipients , for influenza A ( H3N2 ) in both years ( P < .001 ) .


Among frail , elderly residents of LTCFs , HD influenza vaccine produced superior responses for all strains except influenza A ( H1N1 ) in 2012-2013 .


NCT01654224 .


Preoperative radiotherapy ( RT ) is widely used to downstage rectal tumours , but the rate of recurrence varies significantly .


Therefore , new biomarkers are needed for better treatment and prognosis .


It has been shown that astrocyte elevated gene-1 ( AEG-1 ) is a key mediator of migration , invasion , and treatment resistance .


Our aim was to analyse the AEG-1 expression in relation to RT in rectal cancer patients and to test its radiosensitising properties .


The AEG-1 expression was examined by immunohistochemistry in 158 patients from the Swedish clinical trial of RT. .


Furthermore , we inhibited the AEG-1 expression by siRNA in five colon cancer cell lines and measured the survival after irradiation by colony-forming assay .


The AEG-1 expression was increased in the primary tumours compared with the normal mucosa independently of the RT ( P < 0.01 ) .


High AEG-1 expression in the primary tumour of the patients treated with RT correlated independently with higher risk of distant recurrence ( P = 0.009 ) and worse disease-free survival ( P = 0.007 ) .


Downregulation of AEG-1 revealed a decreased survival after radiation in radioresistant colon cancer cell lines .


The AEG-1 expression was independently related to distant recurrence and disease-free survival in rectal cancer patients with RT and could therefore be a marker to discriminate patients for distant relapse .


To evaluate the long-term effects of percutaneous tibial nerve stimulation ( PTNS ) on quality of life in women with chronic pelvic pain .


Thirty-three women with chronic pelvic pain were randomized into PTNS ( n = 16 ) or control ( n = 17 ) groups .


In PTNS group , weekly PTNS in 30-min sessions for 12 weeks was performed whereas the control group received no stimulation .


Present pain intensity-visual analog scale ( PPI-VAS ) , short-form McGill pain questionnaire ( SF-MPQ ) , and SF-36 were used at baseline , 12-week , and 6-month follow-up for the evaluation of pain intensity and quality of life .


Two women ( 12.5 % ) were cured , 7 ( 43.8 % ) were much improved , 6 ( 37.5 % ) were the same and 1 ( 6.3 % ) was worse after PTNS .


Two women ( 11.8 % ) were improved , 10 ( 58.8 % ) were the same , and 5 ( 29.4 % ) were worse in the control group .


Mean PPI-VAS of PTNS group at baseline , 12 weeks , and 6 months was 8.4 1.1 , 3.8 3.5 and 4.5 3.7 , respectively .


There was a significant improvement in PPI-VAS scores of PTNS group whereas no change was observed in the control group .


There was a slight increase in the PPI-VAS scores of the PTNS group at 6-month , but the difference was not statistically significant .


There was significant improvement in all domains of SF-MPQ and SF-36 in PTNS group with continuing effects at 6 months whereas no significant change was observed in the control group .


PTNS is a minimally invasive treatment method that leads to decrease in pain severity and improvement in quality of life in women with chronic pelvic pain with effects continuing at 6 months .


Antibiotics used to reduce nasal colonization by Staphylococcus aureus in patients before admission are inappropriate for carriage reduction on a regular basis within a hospital community .


Effective nonantibiotic alternatives for daily use in the nares will allow reduction of this bacterial source to be addressed .


Our study tested the effectiveness of a nonantibiotic , alcohol-based antiseptic in reducing nasal bacterial carriage in health care professionals ( HCPs ) at an urban hospital center .


HCPs testing positive for vestibular S aureus colonization were treated 3 times during the day with topical antiseptic or control preparations .


Nasal S aureus and total bacterial colonization levels were determined before and at the end of a 10-hour workday .


Seventy-eight of 387 HCPs screened ( 20.2 % ) tested positive for S aureus infection .


Of 39 subjects who tested positive for S aureus infection who completed the study , 20 received antiseptic and 19 received placebo treatment .


Antiseptic treatment reduced S aureus colony forming units from baseline by 99 % ( median ) and 82 % ( mean ) ( P < .001 ) .


Total bacterial colony forming units were reduced by 91 % ( median ) and 71 % ( mean ) ( P < .001 ) .


Nasal application of a nonantibiotic , alcohol-based antiseptic was effective in reducing S aureus and total bacterial carriage , suggesting the usefulness of this approach as a safe , effective , and convenient alternative to antibiotic treatment .


The pharmacokinetics of nifedipine as a tocolytic agent has not been studied in great detail in pregnant women and has instead focused on immediate release tablets and gastrointestinal therapeutic system ( GITS ) tablets .


The aim of this study was to determine nifedipine slow-release half-life and distribution volume in pregnant women and to compare these with pharmacokinetic parameters of nifedipine in non-pregnant subjects described in the literature .


This is a study parallel to a trial studying women with threatened preterm labor between 26 + 0 and 32 + 2 weeks after initial tocolysis and a completed course of corticosteroids , who were randomly allocated to maintenance nifedipine ( slow-release tablets 20 mg 4 times daily ) or placebo .


Exclusion criteria for the pharmacokinetic study were contra-indications for nifedipine , impaired liver function , and concomitant intake of inhibitors or inducers of the cytochrome P450 3A4 isoenzyme .


Blood samples for measuring nifedipine plasma concentrations were drawn at t = 0 , t = 12 hours , t = 24 hours , t = 48 hours , t = 72 hours , t = 7 days , and t = 9 days .


Pharmacokinetic parameters were estimated using iterative two-stage Bayesian population pharmacokinetic analysis by MWPharm software .


The study was designed to establish a correlation between body weight and nifedipine plasma level .


The pharmacokinetic parameters of nifedipine slow-release tablets were determined from the data of 8 pregnant women .


Nifedipine slow-release had a half-life of 2 - 5 hours , a mean distribution volume of 6.2 1.9 L/kg ( calculated while using a fixed biological availability of 0.45 taken from the literature due to lack of intravenous data in this population ) compared to a half-life of 6 - 11 hours , and a distribution volume of 1.2 - 1.3 L/kg described in non-pregnant subjects in the literature .


None of the women delivered during study medication .


Study medication was continued for the duration of the pharmacokinetic study ( 9 days ) in all women .


A correlation between nifedipine plasma levels and maternal body weight was not demonstrated .


This may have been caused by lack of power .


Pregnant subjects in this study , using nifedipine slow-release tablets , showed a larger volume of distribution and a shorter elimination half-life than for non-pregnant subjects as published in the literature .


Impairment of the mucosal barrier plays an important role in the pathophysiology of acute pancreatitis .


The myosin IXB ( MYO9B ) gene and the two tight-junction adaptor genes , PARD3 and MAGI2 , have been linked to gastrointestinal permeability .


Common variants of these genes are associated with celiac disease and inflammatory bowel disease , two other conditions in which intestinal permeability plays a role .


We investigated genetic variation in MYO9B , PARD3 and MAGI2 for association with acute pancreatitis .


Five single nucleotide polymorphisms ( SNPs ) in MYO9B , two SNPs in PARD3 , and three SNPs in MAGI2 were studied in a Dutch cohort of 387 patients with acute pancreatitis and over 800 controls , and in a German cohort of 235 patients and 250 controls .


Association to MYO9B and PARD3 was observed in the Dutch cohort , but only one SNP in MYO9B and one in MAGI2 showed association in the German cohort ( p < 0.05 ) .


Joint analysis of the combined cohorts showed that , after correcting for multiple testing , only two SNPs in MYO9B remained associated ( rs7259292 , p = 0.0031 , odds ratio ( OR ) 1.94 , 95 % confidence interval ( 95 % CI ) 1.35-2 .78 ; rs1545620 , p = 0.0006 , OR 1.33 , 95 % CI 1.16-1 .53 ) .


SNP rs1545620 is a non-synonymous SNP previously suspected to impact on ulcerative colitis .


None of the SNPs showed association to disease severity or etiology .


Variants in MYO9B may be involved in acute pancreatitis , but we found no evidence for involvement of PARD3 or MAGI2 .


More than 70 % of patients with resistant hypertension have obstructive sleep apnea ( OSA ) .


However , there is little evidence about the effect of continuous positive airway pressure ( CPAP ) treatment on blood pressure in patients with resistant hypertension .


To assess the effect of CPAP treatment on blood pressure values and nocturnal blood pressure patterns in patients with resistant hypertension and OSA .


Open-label , randomized , multicenter clinical trial of parallel groups with blinded end point design conducted in 24 teaching hospitals in Spain involving 194 patients with resistant hypertension and an apnea-hypopnea index ( AHI ) of 15 or higher .


Data were collected from June 2009 to October 2011 .


CPAP or no therapy while maintaining usual blood pressure control medication .


The primary end point was the change in 24-hour mean blood pressure after 12 weeks .


Secondary end points included changes in other blood pressure values and changes in nocturnal blood pressure patterns .


Both intention-to-treat ( ITT ) and per-protocol analyses were performed .


A total of 194 patients were randomly assigned to receive CPAP ( n = 98 ) or no CPAP ( control ; n = 96 ) .


The mean AHI was 40.4 ( SD , 18.9 ) and an average of 3.8 antihypertensive drugs were taken per patient .


Baseline 24-hour mean blood pressure was 103.4 mm Hg ; systolic blood pressure ( SBP ) , 144.2 mm Hg ; and diastolic blood pressure ( DBP ) , 83 mm Hg .


At baseline , 25.8 % of patients displayed a dipper pattern ( a decrease of at least 10 % in the average nighttime blood pressure compared with the average daytime blood pressure ) .


The percentage of patients using CPAP for 4 or more hours per day was 72.4 % .


When the changes in blood pressure over the study period were compared between groups by ITT , the CPAP group achieved a greater decrease in 24-hour mean blood pressure ( 3.1 mm Hg [ 95 % CI , 0.6 to 5.6 ] ; P = .02 ) and 24-hour DBP ( 3.2 mm Hg [ 95 % CI , 1.0 to 5.4 ] ; P = .005 ) , but not in 24-hour SBP ( 3.1 mm Hg [ 95 % CI , -0.6 to 6.7 ] ; P = .10 ) compared with the control group .


Moreover , the percentage of patients displaying a nocturnal blood pressure dipper pattern at the 12-week follow-up was greater in the CPAP group than in the control group ( 35.9 % vs 21.6 % ; adjusted odds ratio [ OR ] , 2.4 [ 95 % CI , 1.2 to 5.1 ] ; P = .02 ) .


There was a significant positive correlation between hours of CPAP use and the decrease in 24-hour mean blood pressure ( r = 0.29 , P = .006 ) , SBP ( r = 0.25 ; P = .02 ) , and DBP ( r = 0.30 , P = .005 ) .


Among patients with OSA and resistant hypertension , CPAP treatment for 12 weeks compared with control resulted in a decrease in 24-hour mean and diastolic blood pressure and an improvement in the nocturnal blood pressure pattern .


Further research is warranted to assess longer-term health outcomes .


clinicaltrials.gov Identifier : NCT00616265 .


Tools to predict death or spontaneous survival are necessary to inform liver transplantation ( LTx ) decisions in pediatric acute liver failure ( PALF ) , but such tools are not available .


Recent data suggest that immune/inflammatory dysregulation occurs in the setting of acute liver failure .


We hypothesized that specific , dynamic , and measurable patterns of immune/inflammatory dysregulation will correlate with outcomes in PALF .


We assayed 26 inflammatory mediators on stored serum samples obtained from a convenience sample of 49 children in the PALF study group ( PALFSG ) collected within 7 days after enrollment .


Outcomes were assessed within 21 days of enrollment consisting of spontaneous survivors , non-survivors , and LTx recipients .


Data were subjected to statistical analysis , patient-specific Principal Component Analysis ( PCA ) , and Dynamic Bayesian Network ( DBN ) inference .


Raw inflammatory mediator levels assessed over time did not distinguish among PALF outcomes .


However , DBN analysis did reveal distinct interferon-gamma-related networks that distinguished spontaneous survivors from those who died .


The network identified in LTx patients pre-transplant was more like that seen in spontaneous survivors than in those who died , a finding supported by PCA .


The application of DBN analysis of inflammatory mediators in this small patient sample appears to differentiate survivors from non-survivors in PALF .


Patterns associated with LTx pre-transplant were more like those seen in spontaneous survivors than in those who died .


DBN-based analyses might lead to a better prediction of outcome in PALF , and could also have more general utility in other complex diseases with an inflammatory etiology .


Treatment of patients with prostate cancer has evolved considerably in the last decade , especially in terms of minimization of the negative impacts on erectile function and continence to ensure good quality of life for treated patients .


New surgical devices , such as dissectors and hemostatic scalpels , allow precise definition of the surgical field with finer dissection of the anatomic structures , with subsequent reductions in operative times and better oncologic and functional outcomes .


Although monopolar scissors ( MS ) are still widely used , radiofrequency ( RF ) and ultrasound ( US ) scalpels have been introduced recently in laparoscopic radical prostatectomy ( LRP ) .


Despite the widespread use of these scalpels , however , few studies have compared these devices in terms of oncologic and functional outcomes after radical prostatectomy .


The present study aimed to prospectively assess the impact of MS , RF , and US scalpels on margin status at apex , and recovery of urinary continence and erectile function in patients undergoing extraperitoneal LRP .


A total of 150 men were prospectively enrolled between September 2009 and April 2013 and postoperatively evaluated for continence and clinical factors .


There were no differences in terms of operative times ( P = 0.9433 ) , blood loss ( P = 0.9681 ) , apical margin positivity ( P = 0.3965 ) or postoperative hospital stay ( P = 0.9257 ) among the groups .


Moreover , no differences in the functional outcome scores , as evaluated by the International Consultation on Incontinence self-administered Questionnaire , at 1 , 3 , and 6 months postsurgery were observed .


Our study represents the first evaluation of continence recovery in LRP with respect to different devices used for prostatic apex dissection .


We found that the oncologic , functional , and operative outcomes were similar between these different devices during LRP , with no scalpel demonstrating superiority in continence recovery .


This study was to determine any significant difference between the incidence of infectious morbidity with the use of a 24 hour antibiotics regimen compared to a 7-day course of antibiotics following elective caesarean section using a cheap and easily available combination of Ampicillin/Cloxacillin and Metronidazole .


Two hundred patients planned to have elective caesarean section for various indications and who satisfied the inclusion criteria were enrolled in the study in two groups of 100 patients each between the period of January to June 2010 .


Patients were randomized to receive either Ampiclox as 4 intravenous doses of 1g stat and 500 mg each 6 hourly and Metronidazole as 3 intravenous doses of 500 mg each 8 hourly both for 24 hours or same combination intravenously for 48 hours and subsequent oral use for 5 days .


The mean maternal age , parity , gestational age and indication for caesarean section were similar in the two groups of participants .


There was no statistical difference in the incidence of febrile morbidity ( 17 % / 18 % , p = 0.852 ) , urinary tract infection ( 6 % / 4 % , p = 0.196 ) , wound infection ( 4 % / 3 % , p = 0.056 ) and endometritis ( 3 % / 2 % , p = 0.367 ) .


The mean cost of antibiotics per patient ( N730 / $ 4.65 ) in the short term prophylaxis group was half that of the long term prophylaxis group ( N1 , 540 / $ 9.81 ) .


There was no difference in the incidence of infection related morbidity when short term prophylactic antibiotics was used at elective caesarean section compared to long term prophylactic antibiotics .


Inferior scapular notching following reverse shoulder arthroplasty is due to mechanical impingement and , in some studies , has been associated with poorer functional scores , lower patient satisfaction , and more limited shoulder motion .


We aimed to test the hypothesis that inferior positioning of the center of rotation with eccentric glenosphere designs decreases the adduction deficit before impingement occurs and improves clinical outcome .


A randomized , controlled , double-blinded trial was performed .


According to the results of a power analysis , fifty patients undergoing reverse shoulder arthroplasty for the diagnosis of cuff tear arthropathy were randomized intraoperatively to receive either a concentric or eccentric glenosphere .


The glenoid baseplate was positioned flush to the inferior border of the glenoid before the glenosphere was then attached .


Notching was assessed using an anteroposterior radiograph , and clinical outcome was assessed using the visual analog pain scale score , shoulder function rating , American Shoulder and Elbow Surgeons score , and Oxford shoulder score .


Active forward elevation and external rotation were assessed .


The outcome assessor was blinded to the treatment group .


The mean follow-up period for the groups was forty-three and forty-seven months .


Patient demographics and preoperative scores were similar between the groups .


At the time of the final follow-up , four patients ( 14.8 % ) in the concentric group had developed inferior scapular notching ( two with Nerot grade I and two with Nerot grade II ) , ranging in size from 1.1 to 7.4 mm , compared with one patient ( 4.3 % ; Nerot grade I ) in the eccentric group ( p = 0.36 ) .


No notching occurred in any patient with glenoid overhang of > 3.5 mm .


No significant difference between the groups was seen with respect to functional outcome scores , patient satisfaction , or shoulder motion .


There were no differences in notching rates or clinical outcomes between concentric and eccentric glenospheres following reverse shoulder arthroplasty .


Inferior glenosphere overhang of > 3.5 mm , however , prevented notching .


This may be achieved with a modified surgical technique , but eccentric glenospheres provide an additional option .


Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence .


Couples-based HIV counseling and testing ( CHCT ) is a proven strategy to reduce the risk of HIV transmission between partners , but uptake of CHCT is low .


We describe the study design of a randomized controlled trial ( RCT ) aimed to increase participation in CHCT and reduce sexual risk behavior for HIV among heterosexual couples in rural KwaZulu-Natal , South Africa .


We hypothesize that the rate of participation in CHCT will be higher and sexual risk behavior will be lower in the intervention group as compared to the control .


Heterosexual couples ( N = 350 couples , 700 individuals ) are being recruited to participate in a randomized trial of a couples-based intervention comprising two group sessions ( one mixed gender , one single gender ) and four couples ' counseling sessions .


Couples must have been in a relationship together for at least 6 months .


Quantitative assessments are conducted via mobile phones by gender-matched interviewers at baseline , 3 , 6 , and 9 months post-randomization .


Intervention content is aimed to improve relationship dynamics , and includes communication skills and setting goals regarding CHCT .


The Uthando Lwethu ( ` our love ' ) intervention is the first couples-based intervention to have CHCT as its outcome .


We are also targeting reductions in unprotected sex .


CHCT necessitates the testing and mutual disclosure of both partners , conditions that are essential for improving subsequent outcomes such as disclosure of HIV status , sexual risk reduction , and improving treatment outcomes .


Thus , improving rates of CHCT has the potential to improve health outcomes for heterosexual couples in a rural area of South Africa that is highly impacted by HIV .


The results of our ongoing clinical trial will provide much needed information regarding whether a relationship-focused approach is effective in increasing rates of participation in CHCT .


Our intervention represents an attempt to move away from individual-level conceptualizations , to a more integrated approach for HIV prevention .


Study Name : Couples in Context : An RCT of a Couples-based HIV Prevention InterventionClinicalTrials.gov identifier : NCT01953133.South African clinical trial registration number : DOH-27-0212-3937 .


In this post-hoc analysis , we determined the influence of single nucleotide polymorphisms in host candidate immune genes on the outcome of drug resistant malaria in Cameroon .


Human DNA from 760 patients from a previous clinical trial was subjected to mass spectrometry-based single nucleotide polymorphism ( SNP ) genotyping .


Allele frequencies of candidate immune genes were calculated for 62 SNPs on 17 human chromosomes for their possible involvement in clearance of drug-resistant parasites with the triple mutations of pfcrt76T , pfmdr86Y , and pfmdr1246Y ( TY ) and pfdhfr51I , pfdhfr59R , pfdhfr108N , and pfdhps437G ( IRNG ) which were determined by dotblot or PCR-restriction analysis .


Differences in SNP frequencies and association analysis were carried out by comparing Chi-square odds ratios ( ORs ) and stratified by Mantel-Haenzel statistics .


An adjusted P value ( OR ) < 00008 was considered significant .


Post-treatment drug failure rates were amodiaquine ( 364 % ) ; sulpadoxine/pyrimethamine-amodiaquine combination ( 154 % ) ; and sulphadoxine/pyrimethamine ( 181 % ) .


SNPs in IL22 , IL-4R1 , and CD36 appeared to have been associated with clearance of resistant parasites [ p = 0017 , OR ( C allele ) :144 , 95 % CI ( OR ) : 106-195 ] ; [ P = 0014 , OR = 131 , 95 % CI ( OR ) : 107-183 ] ; [ P = 57810 ( -5 ) , OR = 027 , 95 % CI ( OR ) : 013-054 ] , respectively , with high fever ( > 39C for 48 hours ) [ IL-22 , P = 001 , OR = 15 , 95 % CI ( OR ) : 18-21 ] and also in high frequency among the Fulani participants [ P = 0006 , OR = 183 , 95 % CI ( OR ) : 111-308 ) ] .


The CD36-1264 null allele was completely absent in the northern population .


Independent association of SNPs in IL22 and IL-4 with clearance of amodiaquine - and sulphadoxine/pyrimethamine-resistant parasites did not reach statistical significance , but may suggest that not all drug-resistant mutants are adversely affected by the same immune-mediated mechanisms of clearance .


We validated the metabolic syndrome ( MetS ) score by confirmatory factor analysis ( CFA ) in children , middle-aged men , and older women and men and by investigating the relationships of the MetS score to incident type 2 diabetes , myocardial infarction , and cardiovascular and overall death in middle-aged men .


We assessed the core features of MetS , calculated the MetS score using z scores for waist circumference , insulin , glucose , triacylglycerols , HDL-cholesterol and blood pressure , and carried out CFA to investigate whether MetS represents a single entity in population samples of 491 children , 1,900 middle-aged men , 614 older women and 555 older men from Finland .


We also followed-up incident type 2 diabetes for 11 years and other outcomes for 17-18 years in middle-aged men .


We carried out second-order CFAs in which the MetS was represented by a second-order latent variable underlying four latent variables characterised by abdominal obesity , insulin resistance , dyslipidaemia and raised blood pressure in different age groups .


These second-order factors and factors derived from first-order CFA using previously proposed models were strongly associated with a composite MetS score in all age groups ( r = 0.84-0 .94 ) and similarly predicted type 2 diabetes , cardiovascular outcomes and mortality in middle-aged men .


The risk of type 2 diabetes , myocardial infarction , cardiovascular death and overall death increased 3.67 - , 1.38 - , 1.56 - and 1.44-fold , respectively , for a 1 SD increase in the MetS score .


The MetS can be described as a single entity in all age groups .


The MetS score is a valid tool for research evaluating cardiometabolic risk in different age groups .


Further research is needed to define cut-off points for risk estimation in clinical practice .


Insufficient use of behavioral theory to understand health care workers ' ( HCWs ) hand hygiene compliance may result in suboptimal design of hand hygiene interventions and limit effectiveness .


Previous studies examined HCWs ' intended , rather than directly observed , compliance and/or focused on just 1 behavioral model .


This study examined HCWs ' explanations of noncompliance in `` real time '' ( immediately after observation ) , using a behavioral theory framework , to inform future intervention design .


HCWs were directly observed and asked to explain episodes of noncompliance in `` real-time . ''


Explanations were recorded , coded into 12 behavioral domains , using the Theory Domains Framework , and subdivided into themes .


Over two-thirds of 207 recorded explanations were explained by 2 domains .


These were `` Memory/Attention/Decision Making '' ( 87 , 44 % ) , subdivided into 3 themes ( memory , loss of concentration , and distraction by interruptions ) , and `` Knowledge '' ( 55 , 26 % ) , with 2 themes relating to specific hand hygiene indications .


No other domain accounted for more than 18 ( 9 % ) explanations .


An explanation of HCW 's `` real-time '' explanations for noncompliance identified `` Memory/Attention/Decision Making '' and `` Knowledge '' as the 2 behavioral domains commonly linked to noncompliance .


This suggests that hand hygiene interventions should target both automatic associative learning processes and conscious decision making , in addition to ensuring good knowledge .


A theoretical framework to investigate HCW 's `` real-time '' explanations of noncompliance provides a coherent way to design hand hygiene interventions .


Western industrialised nations face a large increase in the number of older people .


People over the age of 60 years account for almost half of the 16.8 million hospital admissions in England from 2009 to 2010 .


During 2009-10 , respiratory infections accounted for approximately 1 in 30 hospital admissions and 1 in 20 of the 51.5 million bed-days .


To determine the diagnostic accuracy and clinical effectiveness and cost-effectiveness of rapid molecular and near-patient diagnostic tests for influenza , respiratory syncytial virus ( RSV ) and Streptococcus pneumoniae infections in comparison with traditional laboratory culture .


We carried out a randomised controlled trial ( RCT ) to evaluate impact on prescribing and clinical outcomes of point-of-care tests ( POCTs ) for influenza A and B and pneumococcal infection , reverse transcriptase-polymerase chain reaction ( RT-PCR ) tests for influenza A and B and RSV A and B , and conventional culture for these pathogens .


We evaluated diagnostic accuracy of POCTs for influenza and pneumococcal infection , RT-PCR for influenza and sputum culture for S. pneumoniae using samples collected during the RCT .


We did a systematic review and meta-analysis of POCTs for influenza A and B.


We evaluated ease and speed of use of each test , process outcomes and cost-effectiveness .


There was no evidence of association between diagnostic group and prescribing or clinical outcomes .


Using PCR as ` gold standard ' , Quidel Influenza A+B POCT detected 24.4 % [ 95 % confidence interval ( CI ) 16.0 % to 34.6 % ] of influenza infections ( specificity 99.7 % , 95 % CI 99.2 % to 99.9 % ) ; viral culture detected 21.6 % ( 95 % CI 13.5 % to 31.6 % ; specificity 99.8 % , 95 % CI 99.4 % to 100 % ) .


Using blood culture as ` gold standard ' , BinaxNOW pneumococcal POCT detected 57.1 % ( 95 % CI 18.4 % to 90.1 % ) of pneumococcal infections ( specificity 92.5 % ; 95 % CI 90.6 % to 94.1 % ) ; sputum culture detected 100 % ( 95 % CI 2.5 % to 100 % ; specificity 97.2 % , 95 % CI 94.3 % to 98.9 % ) .


Overall , pooled estimates of sensitivity and specificity of POCTs for influenza from the literature were 74 % ( 95 % CI 67 % to 80 % ) and 99 % ( 95 % CI 98 % to 99 % ) , respectively .


Median intervals from specimen collection to test result were 15 minutes [ interquartile range ( IQR ) 10-23 minutes ) for Quidel Influenza A+B POCT , 20 minutes ( IQR 15-30 minutes ) for BinaxNOW pneumococcal POCT , 50.8 hours ( IQR 44.3-92 .6 hours ) for semi-nested conventional PCR , 29.2 hours ( IQR 26-46 .9 hours ) for real-time PCR , 629.6 hours ( IQR 262.5-846 .7 hours ) for culture of influenza and 84.4 hours ( IQR 70.7-137 .8 hours ) and 71.4 hours ( IQR 69.15-84 .0 hours ) for culture of S. pneumoniae in blood and sputum , respectively .


Both POCTs were rated straightforward and undemanding ; blood culture was moderately complex and all other tests were complex .


Costs and quality-adjusted life-years ( QALYs ) of each diagnostic strategy were similar .


Incrementally , PCR was most cost-effective ( 78.3 % probability at a willingness to pay of 20,000 / QALY ) .


Few patients were admitted within a timescale conducive to treatment with a neuraminidase inhibitor according to National Institute for Health and Care Excellence guidance .


The accuracy study was limited by inadequate gold standards .


All tests had limitations .


We found no evidence that POCTs for influenza or S. pneumoniae , or PCR for influenza or RSV influenced antimicrobial prescribing or clinical outcomes .


The total costs and QALYs of each diagnostic strategy were similar , although , incrementally , PCR was the most cost-effective strategy .


The analysis does not support routine use of POCTs for either influenza or pneumococcal antigen for adults presenting with acute cardiopulmonary conditions , but suggests that conventional viral culture for clinical diagnosis should be replaced by PCR .


Current Controlled Trials ISRCTN21521552 .


This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol .


18 , No. 36 .


See the NIHR Journals Library website for further project information .


Elastic resistance bands ( ERB ) combined with proprioceptive neuromuscular facilitation ( PNF ) are often used in resistance muscle training programs , which have potential effects on peripheral muscle strength .


However , the effects of the combination of ERB and PNF on respiratory muscle strength warrant further investigation .


The assessment of the effects of PNF combined with ERB on respiratory muscle strength .


Twenty healthy , right-handed females were included .


Subjects were randomized to either the resistance training program group ( TG , n = 10 ) or the control group ( CG , n = 10 ) .


Maximal expiratory pressure ( MEP ) and inspiratory pressure ( MIP ) were measured before and after four weeks of an upper extremity resistance training program .


The training protocol consisted of upper extremity PNF combined with ERB , with resistance selected from 1 repetition maximum protocol .


PNF combined with ERB showed significant increases in MIP and MEP ( p < 0.05 ) .


In addition , there were significant differences between the TG and CG regarding MIP ( p = 0.01 ) and MEP ( p = 0.04 ) .


PNF combined with ERB can have a positive impact on respiratory muscle strength .


These results may be useful with respect to cardiopulmonary chronic diseases that are associated with reduced respiratory muscle strength .


To examine the performance of T2-weighted ( T2W ) and diffusion-weighted ( DW ) magnetic resonance imaging ( MRI ) for detecting the index tumour in patients with prostate cancer and to examine the agreement between MRI and histology when assessing tumour volume ( TV ) and overall tumour burden .


The study included 199 consecutive patients with biopsy confirmed prostate cancer randomised to MRI before radical prostatectomy from December 2009 to July 2012 .


MRI-detected tumours ( MRTs ) were ranked from 1 to 3 according to decreasing volume and were compared with histologically detected tumours ( HTs ) ranked from 1 to 3 , with HT 1 = index tumour .


Whole-mount section histology was used as a reference standard .


The TVs of true-positive MRTs ( MRTVs 1-3 ) were compared with the TVs found by histology ( HTVs 1-3 ) .


All tumours were registered on a 30-sector map and by classifying each sector as positive/negative , the rate of true-positive and - negative sectors was calculated .


The detection rate for the HT 1 ( index tumour ) was 92 % ; HT 2 , 45 % ; and HT 3 , 37 % .


The MRTV 1-3 vs the HTV 1-3 were 2.8 mL vs 4.0 mL ( index tumour , P < 0.001 ) , 1.0 mL vs 0.9 mL ( tumour 2 , P = 0.413 ) , and 0.6 mL vs 0.5 mL ( tumour 3 , P = 0.492 ) .


The rate of true-positive and - negative sectors was 50 % and 88 % , = 0.39 .


A combination of T2W and DW MRI detects the index tumour in 92 % of cases , although MRI underestimates both TV and tumour burden compared with histology .


Heart rate variability ( HRV ) is a marker of autonomic dysfunction severity .


The effects of physical training on HRV indexes in Chagas heart disease ( CHD ) are not well established .


To evaluate the changes in HRV indexes in response to physical training in CHD .


Patients with CHD and left ventricular ( LV ) dysfunction , physically inactive , were randomized either to the intervention ( IG , N = 18 ) or control group ( CG , N = 19 ) .


The IG participated in a 12-week exercise program consisting of 3 sessions/week .


Mean age was 49.5 8 years , 59 % males , mean LVEF was 36.3 7.8 % .


Baseline HRV indexes were similar between groups .


From baseline to follow-up , total power ( TP ) : 1653 ( IQ 625 - 3418 ) to 2794 ( 1617 - 4452 ) ms , p = 0.02 ) and very low frequency power : 586 ( 290 - 1565 ) to 815 ( 610 - 1425 ) ms , p = 0.047 ) increased in the IG , but not in the CG .


The delta ( post - pre ) HRV indexes were similar : SDNN 11.5 30.0 vs. 3.7 25.1 ms. p = 0.10 ; rMSSD 2 ( 6 - 17 ) vs. 1 ( 21 - 9 ) ms. p = 0.43 ; TP 943 ( 731 - 3130 ) vs. 1780 ( 921 - 2743 ) Hz .


p = 0.46 ; low frequency power ( LFP ) 1.0 ( 150 - 197 ) vs. 60 ( 111 - 146 ) Hz .


p = 0.85 ; except for high frequency power , which tended to increase in the IG : 42 ( 133 - 92 ) vs. 79 ( 61 - 328 ) Hz .


p = 0.08 ) .


In the studied population , the variation of HRV indexes was similar between the active and inactive groups .


Clinical improvement with physical activity seems to be independent from autonomic dysfunction markers in CHD .


There is co-morbidity between parental depression and childhood conduct disorder .


The Incredible Years ( IY ) parenting programmes reduce both conduct disorder in children and depression in their parents .


Recent U.K. and Ireland trials of the effectiveness and cost-effectiveness of IY parenting programmes have assessed children 's health and social care service use , but little is known about the programme 's impact on parental service use .


This paper explores whether an above clinical cut-off score on the Beck Depression Inventory II ( BDI II ) is associated with high or low parental health and social care service use in high-risk families receiving the IY Basic Programme .


This is a secondary analysis of a subsample ( N = 119 ) from the first U.K. community-based randomised controlled trial of the 12-week IY Basic Programme ( N = 153 ) .


Parents with children at risk of developing conduct disorder were randomised to receive the programme or to a waiting-list control group .


BDI II total and BDI II clinical depression cut-off scores were compared to frequencies and costs of parents ' service use , at baseline , six , twelve and eighteen months post-baseline for the intervention group and at baseline and six months post-baseline for the control group .


Intervention group parents who scored above the clinical cut-off on the BDI II at baseline used more health and social care services than those who scored below at baseline , six and eighteen months .


Significant reductions in service use frequencies were found for the intervention group only .


Parents with higher levels or depression used more health and social care service and parenting programmes have been shown to reduce parental depression and also health and social service use .


However , further exploration of depressed parents ' service use and the cost implications for publically funded health and social care services is needed .


In the late 1990s , the use of high-dose chemotherapy ( HDCT ) and stem-cell rescue held promise for patients with advanced and poor prognosis germ-cell tumors ( GCT ) .


We started a randomized phase II trial to assess the efficacy of sequential HDCT compared with cisplatin , etoposide , and bleomycin ( PEB ) .


Patients were randomly assigned to receive four cycles of PEB every 3 weeks or two cycles of PEB followed by a high-dose sequence ( HDS ) comprising HD-cyclophosphamide ( 7.0 g/m ( 2 ) ) , 2 courses of cisplatin and HD-etoposide ( 2.4 g/m ( 2 ) ) with stem-cell support , and a single course of HD-carboplatin [ area under the curve ( AUC ) 27 mg/ml min ] with autologous stem-cell transplant .


Postchemotherapy surgery was planned on responding residual disease in both arms .


The primary end point was progression-free survival ( PFS ) .


The study was designed to detect a 30 % improvement of 5-year PFS ( from 40 % to 70 % ) , with 80 % power and two-sided at 5 % .


From December 1996 to March 2007 , 85 patients were randomized : 43 in PEB and 42 in HDS arm .


Median follow-up was 114.2 months [ interquartile range ( IQR ) : 87.7-165 .8 ] .


Complete or partial response with normal markers ( PRm - ) were obtained in 28 ( 65.1 % ) and 29 ( 69.1 % ) patients , respectively .


Five-year PFS was 55.8 % [ 95 % confidence interval ( CI ) 42.8-72 .8 ] and 54.8 % ( 95 % CI 41.6 % -72.1 % ) in PEB and HDS arm , respectively ( log-rank test P = 0.726 ) .


Five-year overall survival was 62.8 % ( 95 % CI 49.9-79 .0 ) and 59.3 % ( 95 % CI 46.1-76 .3 ) .


One toxic death ( PEB arm ) was recorded .


The study failed to meet the primary end point .


Furthermore , survival estimates of conventional-dose chemotherapy higher than expected should be accounted for and will likely limit further improvements in the first-line setting .


CLINICALTRIALS.GOV : NCT02161692 .


Osteochondral lesions of the talus ( OLT ) frequently occur after ankle sprains in young patients participating in sports activities .


These injuries may lead to chronic pain , joint swelling , and finally osteoarthritis , therefore , surgical repair is frequently needed .


A collagen scaffold seeded with bone marrow-derived cells ( BMDCs ) harvested from patient 's iliac crest and implanted into the OLT through a single arthroscopic procedure has been recently proposed as an effective treatment option .


Nevertheless , BMDCs , embedded in an inflammatory environment , tend to differentiate toward a fibroblast phenotype with a consequential loss of mechanical characteristics .


Biophysical stimulation with pulsed electromagnetic fields ( PEMFs ) has been shown to promote anabolic chondrocyte activity , stimulate proteoglycan synthesis , and reduce the release of the most relevant pro-inflammatory cytokines .


The aim of this randomized controlled trial was to evaluate the effects of PEMFs on clinical outcome in patients who underwent BMDCs transplantation for OLT .


Thirty patients affected by grade III and IV Outerbridge OLT underwent BMDCs transplantation .


After surgery , patients were randomly assigned to either experimental group ( PEMFs 4 hours per day for 60 days starting within 3 days after operation ) or control group .


Clinical outcome was evaluated with ( American Orthopaedic Foot and Ankle Society ) AOFAS score , Visual Analog Scale ( VAS ) , and Short Form-36 ( SF-36 ) .


Significantly higher AOFAS score was recorded in the experimental group both at 6 or 12 months follow-up .


At 60 days and 6 and 12 months follow-up , significant lower pain was observed in the experimental group .


No significant difference was found in SF-36 between groups .


A superior clinical outcome was found in the experimental group with more than 10 points higher AOFAS score at final follow-up .


Biophysical stimulation started soon after surgery aided patient recovery leading to pain control and a better clinical outcome with these improvements lasting more than 1 year after surgery .


Level II , prospective comparative study .


Asparaginase is a critical agent used to treat acute lymphoblastic leukemia ( ALL ) .


Pegaspargase ( SS-PEG ) , a pegylated form of Escherichia coli L-asparaginase with a succinimidyl succinate ( SS ) linker , is the first-line asparaginase product used in Children 's Oncology Group ( COG ) ALL trials .


Calaspargase pegol ( SC-PEG ) replaces the SS linker in SS-PEG with a succinimidyl carbamate linker , creating a more stable molecule .


COG AALL07P4 was designed to determine the pharmacokinetic and pharmacodynamic comparability of SC-PEG to SS-PEG in patients with newly diagnosed high-risk ( HR ) B-cell ALL .


A total of 165 evaluable patients were randomly assigned at a 2:1 ratio to receive SC-PEG at 2,100 ( SC-PEG2100 ; n = 69 ) or 2,500 IU/m ( 2 ) ( SC-PEG2500 ; n = 42 ) versus SS-PEG 2,500 IU/m ( 2 ) ( SS-PEG2500 ; n = 54 ) as part of an otherwise identical chemotherapy regimen .


The groups were similar demographically , except more female patients received SC-PEG2500 .


The mean half-life of plasma asparaginase activity for both SC-PEG doses was approximately 2.5 longer than that of SS-PEG2500 .


The total systemic exposure , as defined by induction area under the curve from time 0 to 25 days , was greater with SC-PEG2500 than with SS-PEG2500 or SC-PEG2100 .


The proportion of patients with plasma asparaginase activity 100 mIU/mL and 400 mIU/mL was higher in patients who received SC-PEG as compared with SS-PEG2500 .


After one dose of pegylated asparaginase on induction day 4 , plasma asparagine was undetectable for 11 days for SS-PEG2500 and 18 days for both SC-PEG groups .


SC-PEG2500 achieves a significantly longer period of asparaginase activity above defined thresholds and asparagine depletion compared with SS-PEG2500 and has a comparable toxicity profile in children with HR B-cell ALL .


The aim of this study was to confirm the cardioprotective effects of hypothermia using a combination of cold salineand endovascular cooling .


Hypothermia has been reported to reduce infarct size ( IS ) in patients with ST-segment elevation myocardial infarctions .


In a multicenter study , 120 patients with ST-segment elevation myocardial infarctions ( < 6 h ) scheduled to undergopercutaneous coronary intervention were randomized to hypothermia induced by the rapid infusion of600to 2,000 ml cold saline and endovascular cooling or standard of care .


Hypothermia was initiated before percutaneous coronary intervention and continued for 1 h after reperfusion .


The primary end point was IS as apercent of myocardium at risk ( MaR ) , assessed by cardiac magnetic resonance imaging at 4 2 days .


Mean times from symptom onset to randomization were 129 56 min in patients receiving hypothermia and 132 64min in controls .


Patients randomized to hypothermia achieved a core body temperature of 34.7 C before reperfusion , with a 9-min longer door-to-balloon time .


Median IS/MaR was not significantly reduced ( hypothermia : 40.5 % [ interquartile range : 29.3 % to 57.8 % ; control : 46.6 % [ interquartile range : 37.8 % to 63.4 % ] ; relative reduction 13 % ; p = 0.15 ) .


The incidence of heart failure was lower with hypothermia at 45 15 days ( 3 % vs. 14 % , p < 0.05 ) , with no mortality .


Exploratory analysis of early anterior infarctions ( 0 to 4 h ) found a reduction in IS/MaR of 33 % ( p < 0.05 ) and an absolute reduction of IS/left ventricular volume of 6.2 % ( p = 0.15 ) .


Hypothermia induced by cold saline and endovascular cooling was feasible and safe , and it rapidly reduced coretemperature with minor reperfusion delay .


The primary end point of IS/MaR was not significantly reduced .


Lower incidence of heart failure and a possible effect in patients with early anterior ST-segment elevation myocardial infarctions need confirmation .


( Efficacy of Endovascular Catheter Cooling Combined With Cold Saline for the Treatment of Acute Myocardial Infarction [ CHILL-MI ] ; NCT01379261 ) .


Physicians have a major influence on parental vaccine decisions .


We tested a physician-targeted communication intervention designed to ( 1 ) reduce vaccine hesitancy in mothers of infants seen by trained physicians and ( 2 ) increase physician confidence in communicating about vaccines .


We conducted a community-based , clinic-level , 2-arm cluster randomized trial in Washington State .


Intervention clinics received physician-targeted communications training .


We enrolled mothers of healthy newborns from these clinics at the hospital of birth .


Mothers and physicians were surveyed at baseline and 6 months .


The primary outcome was maternal vaccine hesitancy measured by Parental Attitudes on Childhood Vaccines score ; secondary outcome was physician self-efficacy in communicating with parents by using 3 vaccine communication domains .


We enrolled 56 clinics and 347 mothers .


We conducted intervention trainings at 30 clinics , reaching 67 % of eligible physicians ; 26 clinics were randomized to the control group .


Maternal vaccine hesitancy at baseline and follow-up changed from 9.8 % to 7.5 % in the intervention group and 12.6 % to 8.0 % in the control group .


At baseline , groups were similar on all variables except maternal race and ethnicity .


The intervention had no detectable effect on maternal vaccine hesitancy ( adjusted odds ratio 1.22 , 95 % confidence interval 0.47-2 .68 ) .


At follow-up , physician self-efficacy in communicating with parents was not significantly different between intervention and control groups .


This physician-targeted communication intervention did not reduce maternal vaccine hesitancy or improve physician self-efficacy .


Research is needed to identify physician communication strategies effective at reducing parental vaccine hesitancy in the primary care setting .


Physical therapy influences chronic pain by means of the specific ingredient of an intervention as well as contextual factors including the setting and therapeutic alliance ( TA ) between provider and patient .


The purpose of this study was to compare the effect of enhanced versus limited TA on pain intensity and muscle pain sensitivity in patients with chronic low back pain ( CLBP ) receiving either active or sham interferential current therapy ( IFC ) .


An experimental controlled study with repeated measures was conducted .


Participants were randomly divided into 4 groups : ( 1 ) AL ( n = 30 ) , which included the application of active IFC combined with a limited TA ; ( 2 ) SL ( n = 29 ) , which received sham IFC combined with a limited TA ; ( 3 ) AE ( n = 29 ) , which received active IFC combined with an enhanced TA ; and ( 4 ) SE ( n = 29 ) , which received sham IFC combined with an enhanced TA .


One hundred seventeen individuals with CLBP received a single session of active or sham IFC .


Measurements included pain intensity as assessed with a numerical rating scale ( PI-NRS ) and muscle pain sensitivity as assessed via pressure pain threshold ( PPT ) .


Mean differences on the PI-NRS were 1.83 cm ( 95 % CI = 14.3-20 .3 ) , 1.03 cm ( 95 % CI = 6.6-12 .7 ) , 3.13 cm ( 95 % CI = 27.2-33 .3 ) , and 2.22 cm ( 95 % CI = 18.9-25 .0 ) for the AL , SL , AE , and SE groups , respectively .


Mean differences on PPTs were 1.2 kg ( 95 % CI = 0.7-1 .6 ) , 0.3 kg ( 95 % CI = 0.2-0 .8 ) , 2.0 kg ( 95 % CI = 1.6-2 .5 ) , and 1.7 kg ( 95 % CI = 1.3-2 .1 ) , for the AL , SL , AE , and SE groups , respectively .


The study protocol aimed to test the immediate effect of the TA within a clinical laboratory setting .


The context in which physical therapy interventions are offered has the potential to dramatically improve therapeutic effects .


Enhanced TA combined with active IFC appears to lead to clinically meaningful improvements in outcomes when treating patients with CLBP .


Statins have multiple antiatherosclerotic effects , but can reduce blood plasma concentrations of minerals , including zinc .


As zinc possesses antiinflammatory and antioxidant effects , low zinc status can promote injuries or inadequate tissue repair in endothelial cells .


Metallothionein ( MT ) expression might modulate responses induced by statins in patients with atherosclerosis .


However , research regarding mineral status and the use of statins is scarce .


This study evaluated the effects of zinc supplementation on zinc status and expression of the zinc-dependent MT1F and MT2A genes in patients with atherosclerosis treated with rosuvastatin .


A double-blind , randomized clinical trial was performed with 54 participants treated with 10mg rosuvastatin for 4 months with or without zinc supplementation ( 30mg/day ) .


Diet , lipid profile , high-sensitivity reactive protein C ( hs-CRP ) , plasma and erythrocyte zinc concentrations , erythrocyte superoxide dismutase ( SOD ) activity , and MT1F and MT2A genes expression were analyzed before and after intervention .


Rosuvastatin therapy was effective in reducing low - and non-high-density lipoprotein , total cholesterol , triglycerides , and hs-CRP levels , independent of zinc supplementation .


Additionally , zinc treatment had no effect on SOD enzyme activity ( P = 0.201 ) , plasma ( P > 0.671 ) and erythrocyte ( P > 0.123 ) zinc concentrations , or the pattern of MT1F and MT2A genes expression ( P = 0.088 and P = 0.229 , respectively ) .


The effectiveness of rosuvastatin treatment is independent of the effects of zinc supplementation .


Moreover , rosuvastatin treatment did not have a significant impact on zinc status or MT1F and MT2A genes expression in patients with atherosclerosis .


A reduction of gynaecological adverse events has been reported in trials comparing aromatase inhibitors with tamoxifen as adjuvant treatment in postmenopausal women with early breast cancer , but there is a paucity of randomised studies specifically investigating their effects on the uterus .


We report here the results of a prospective phase III trial comparing the effects of tamoxifen and exemestane by transvaginal ultrasound ( TVUS ) .


Postmenopausal patients with ER + early breast cancer were randomised to receive tamoxifen 20 mg once daily or exemestane 25 mg once daily as adjuvant hormone therapy .


TVUS was performed at baseline and at 6 and 12 months to measure endometrial thickness ( ET ) and uterine volume ( UV ) .


A total of 123 women were randomised to tamoxifen ( n = 61 ) or exemestane ( n = 62 ) .


A significantly higher proportion of patients in the tamoxifen group had increased ET at 6 and 12 months from randomisation compared with the exemestane group ( 66.1 % and 64.3 % versus 12.1 % and 6.8 % , respectively ; P < 0.0001 ) .


Mean ET and UV also significantly increased with tamoxifen compared to exemestane at both time points ( P < 0.01 for all comparisons ) .


Tamoxifen is associated with endometrial thickening and increased uterine volume in a significant proportion of postmenopausal women with early breast cancer .


Our study confirms the lack of endometrial effects of exemestane , which may be of interest to patients and clinicians when choosing among adjuvant endocrine options for breast cancer .


To evaluate the efficacy of furazolidone-based triple and quadruple therapy in eradicating Helicobacter pylori ( H. pylori ) in a multi-center randomized controlled trial .


A total of 720 H. pylori positive patients with duodenal ulcer disease were enrolled at 10 different hospitals in Jiangxi province in China .


The patients were randomly assigned to four treatment groups as follows : patients in Groups 1 and 3 received rabeprazole ( 10 mg ) , amoxicillin ( 1000 mg ) and furazolidone ( 100 mg ) twice daily for 7 and 10 d , respectively ; patients in Groups 2 and 4 received rabeprazole ( 10 mg ) , bismuth ( 220 mg ) , amoxicillin ( 1000 mg ) and furazolidone ( 100 mg ) twice daily for 7 and 10 d , respectively .


The primary outcome measure was H. pylori eradication rate 4 wk after treatment by intention-to-treat and per protocol analysis , while the secondary outcome measures were symptom and sign changes at the end of treatment and 4 wk after the end of treatment , as well as the proportion of patients who developed adverse events .


The demographic data of the four groups were not significantly different .


Overall , 666 patients completed the scheme and were re-assessed with the ( 13 ) C-urea breath test .


The intention-to-treat analysis of the H. pylori eradication rates in Groups 1 , 2 , 3 and 4 were 74.44 % , 82.78 % , 78.89 % and 86.11 % , respectively .


The H. pylori eradication rate in Group 4 was significantly higher than that in Group 1 .


According to the per protocol analysis , the H. pylori eradication rates in Groups 1 , 2 , 3 and 4 were 81.21 % , 89.22 % , 85.54 % and 92.26 % , respectively .


The number of adverse events was 15 ( 8.3 % ) , 16 ( 8.9 % ) , 15 ( 8.3 % ) and 17 ( 9.4 % ) in Groups 1 , 2 , 3 and 4 , respectively , including dizziness , vomiting , diarrhea , nausea , skin rash , itchy skin , and malaise .


The symptoms were relieved without special treatment in all of the patients .


Both 7 - and 10-d quadruple furazolidone-based therapies achieve satisfactory H. pylori eradication rates .


Heart failure with preserved left ventricular ejection fraction ( HFpEF ) currently affects more than seven million Europeans and is the only cardiovascular disease increasing in prevalence and incidence .


No pharmacological agent has yet been shown to improve symptoms or prognosis .


The most promising way to improve pathophysiology and deprived exercise-tolerance in HFpEF patients seems to be exercise training , but the optimal approach and dose of exercise is still unknown .


The major objective of the optimising exercise training in prevention and treatment of diastolic heart failure study ( OptimEx-CLIN ) is to define the optimal dose of exercise training in patients with HFpEF .


In order to optimise adherence , supervision and economic aspects of exercise training a novel telemedical approach will be introduced and investigated .


In a prospective randomised multi-centre study , 180 patients with stable symptomatic HFpEF will be randomised ( 1:1:1 ) to moderate intensity continuous training , high intensity interval training , or a control group .


The training intervention includes three months supervised followed by nine months of telemedically monitored home-based training .


The primary endpoint is change in exercise capacity , defined as change in peak oxygen uptake ( VO2peak ) after three months , assessed by cardiopulmonary exercise testing .


Secondary endpoints include diastolic filling pressure ( E/e ' ) and further echocardiographic and cardiopulmonary exercise testing ( CPX ) parameters , biomarkers , quality of life and endothelial function .


Training sessions and physical activity will be monitored and documented throughout the study with accelerometers and heart rate monitors developed on a telemedical platform for the OptimEx-CLIN study .


Inclusion of patients started in July 2014 , first results are expected in 2017 .


The authors hypothesized that a muscle relaxant would have no meaningful difference in intubation conditions during nasal intubation under remifentanil and propofol anesthesia .


This parallel-group , double-blinded , randomized controlled trial included 44 patients who received saline ( S group ; n = 22 ) or rocuronium ( R group ; n = 22 ) .


In addition to remifentanil 0.5 g/kg per minute and propofol 5 mg/kg per hour , propofol 0.5 mg/kg was administered until loss of consciousness .


Nasal intubation was performed 10 minutes after administration of R or S 0.6 mg/kg .


Significant differences in intubation conditions and salivary amylase levels before and after intubation were tested ( P < .05 ) .


Vocal cord status ( P = .003 ) and response to intubation or cuff filling ( P = .008 ) were significantly different , but intubation conditions were not .


Salivary amylase level was significantly lower with R administration ( P = .022 ) .


No patient complained of postoperative throat pain and hoarseness .


Muscle relaxants during nasal intubation performed after bolus administration of propofol 0.9 mg/kg in addition to 10 minutes of remifentanil 0.5 g/kg per minute plus propofol 5 mg/kg per hour are unnecessary .


The aims of this study were to establish whether , in patients with gout , MPO is released from neutrophils and urate is oxidized to allantoin and if these effects are attenuated by allopurinol .


MPO , urate , allantoin and oxypurinol were measured in plasma from 54 patients with gout and 27 healthy controls .


Twenty-three patients had acute gout , 13 of whom were receiving allopurinol , and 31 had intercritical gout , 20 of whom were receiving allopurinol .


Ten additional gout patients had samples collected before and after 4 weeks of allopurinol .


Plasma MPO and its specific activity were higher ( P < 0.05 ) in patients with acute gout not receiving allopurinol compared with controls .


MPO protein in patients ' plasma was related to urate concentration ( r = 0.5 , P < 0.001 ) .


Plasma allantoin was higher ( P < 0.001 ) in all patient groups compared with controls .


In controls and patients not receiving allopurinol , allantoin was associated with plasma urate ( r = 0.62 , P < 0.001 ) and MPO activity ( r = 0.45 , P < 0.002 ) .


When 10 patients were treated with allopurinol , it lowered their plasma urate and allantoin ( P = 0.002 ) .


In all patients receiving allopurinol , plasma allantoin was related to oxypurinol ( r = 0.65 , P < 0.0001 ) .


Oxypurinol was a substrate for purified MPO that enhanced the oxidation of urate .


Increased concentrations of urate in gout lead to the release of MPO from neutrophils and the oxidation of urate .


Products of MPO and reactive metabolites of urate may contribute to the pathology of gout and hyperuricaemia .


At low concentrations , oxypurinol should reduce inflammation , but high concentrations may contribute to oxidative stress .


To propose a simple correction of body-mass index ( BMI ) based on self-reported weight and height ( reported BMI ) using gender , body shape perception and socioeconomic status in an adolescent population .


341 boys and girls aged 17-18 years were randomly selected from a representative sample of 2165 French adolescents living in Paris surveyed in 2010 .


After an anonymous self-administered pen-and-paper questionnaire asking for height , weight , body shape perception ( feeling too thin , about the right weight or too fat ) and socioeconomic status , subjects were measured and weighed .


BMI categories were computed according to Cole 's cut-offs .


Reported BMIs were corrected using linear regressions and ROC analyses and checked with cross-validation and multiple imputations to handle missing values .


Agreement between actual and corrected BMI values was estimated with Kappa indexes and Intraclass correlation coefficients ( ICC ) .


On average , BMIs were underreported , especially among girls .


Kappa indexes between actual and reported BMI were low , especially for girls : 0.56 95 % CI = [ 0.42-0 .70 ] for boys and 0.45 95 % CI = [ 0.30-0 .60 ] for girls .


The regression of reported BMI by gender and body shape perception gave the most balanced results for both genders : the Kappa and ICC obtained were 0.63 95 % CI = [ 0.50-0 .76 ] and 0.67 , 95 % CI = [ 0.58-0 .74 ] for boys ; 0.65 95 % CI = [ 0.52-0 .78 ] and 0.74 , 95 % CI = [ 0.66-0 .81 ] for girls .


The regression of reported BMI by gender and socioeconomic status led to similar corrections while the ROC analyses were inaccurate .


Using body shape perception , or socioeconomic status and gender is a promising way of correcting BMI in self-administered questionnaires , especially for girls .


Souvenaid is a nutraceutical compound thought to positively enhance synaptic function .


In line with this mechanism of action , Souvenaid has been shown to improve cognitive function in subjects with mild Alzheimer 's disease in randomized clinical trials .


To date , however , the potential of Souvenaid to improve cognitive functioning in subjects with other neurodegenerative conditions also characterized by synaptic loss has not been explored .


To evaluate the impact of Souvenaid on executive functions , social cognition and behavioral disturbances in subjects with the behavioral variant of frontotemporal dementia ( bv-FTD ) .


Twenty-six subjects with bv-FTD were enrolled in the study and randomized to Souvenaid ( 125 ml/day ) or placebo groups .


After 12 weeks , subjects were switched between the two groups .


All subjects , blinded to treatment , underwent clinical and cognitive evaluations at enrollment , after 12 weeks and after 24 weeks .


Treatment with Souvenaid was associated with a significant reduction of behavioral symptoms and an increase in Theory of Mind skills compared to placebo , which both returned to baseline when Souvenaid was discontinued .


Souvenaid did not have an effect on executive functions .


Our results provide evidence of the potential of Souvenaid therapy for the treatment of behavioral disturbances and social cognition skills in FTD .


Intracranial-pressure ( ICP ) monitoring is considered standard care for severe traumatic brain injury and is used frequently , but the efficacy of treatment based on monitoring in patients with hemorrhagic stroke has not been rigorously assessed .


In this study , we investigated the clinical value of ICP monitoring in patients with hemorrhagic stroke .


We conducted a randomized , unblinded , controlled trial in which 90 patients with hemorrhagic stroke were randomly assigned to ICP monitoring or a control group .


The primary outcome was a composite of incidence rate of hematoma enlargement and secondary brain herniation .


The secondary outcome was neurological status assessed using the Glasgow Outcome Scale scores at 6months post-onset .


Characteristics of the patients at baseline and outcome measurements were also compared between the two groups .


There was no significant between-group difference in the incidence of hematoma enlargement ( control group , 38.6 % vs. ICP monitoring group , 32.6 % ; P > 0.05 ) .


The incidence rate of secondary brain herniation in the ICP monitoring group was significantly lower compared with the control group ( 10.9 % vs. 20.5 % , P = 0.04 ) .


Six-month mortality was 6.5 % in the ICP group and 9.1 % in the control group ( P < 0.05 ) , and neurological outcome was better in the ICP group compared with the control group ( P < 0.05 ) .


The dynamic ICP value may be more sensitive and effective in preventing secondary brain herniation in patients with hemorrhagic stroke compared with guidance directed by clinical signs and radiological indicators .


To explore the pain control effect of lornoxicam on patients after nasal packing .


A total of 56 patients undergoing nasal packing between January 2011 and August 2011 were randomly divided into the treatment group and control group .


( 1 ) Treatment group : routinely given lornoxicam for injection 8 mg ( 2 ml ) , intravenous injection , twice a day ; ( 2 ) CONTROL GROUP : given saline 2 ml , intravenous injection , twice a day , other treatments are the same with the treatment group .


Visual analog scale was used to record the painful severity of nose and head at 3 , 6 , 12 , 24 and 48 h , and record the sleep quality score at 24 and 48 h.


The pain in nose and head and night sleeping in treatment group were all significantly better than that in control group .


The analgesic effect of lornoxicam in nasal packing is good , with no evident adverse reactions .


Noninvasive brain stimulation , including repetitive transcranial magnetic stimulation ( rTMS ) and transcranial direct current stimulation ( tDCS ) , have gained popularity in the stroke rehabilitation literature .


Little is known about the time course and duration of effects of noninvasive brain stimulation on corticospinal excitability in individuals with stroke .


We examined the aftereffects of a single session of high-frequency rTMS ( 5 Hz ) and anodal tDCS on corticospinal excitability in the same sample of participants with chronic stroke .


Ten individuals with chronic stroke participated in this randomized cross-over study .


Participants received 1 session of rTMS and 1 session of tDCS , with 1 week between sessions .


During the rTMS session , 5-Hz rTMS ( total of 1200 stimuli ) was administered to the ipsilesional primary motor cortex ( M1 ) .


For anodal tDCS , 1 mA of direct current was delivered to the ipsilesional M1 for 20 minutes .


Motor evoked potentials were measured before and after ( immediately , 15 minutes , 30 minutes , and 60 minutes ) each stimulation session .


Both 5-Hz rTMS and anodal tDCS significantly increased corticospinal excitability for 30 to 60 minutes after stimulation .


There was no statistically significant difference between the 2 stimulation techniques in their effects on motor evoked potentials .


No changes in measures of motor or cognitive performance were observed .


Both 5-Hz rTMS and anodal tDCS induced effects on corticospinal excitability in persons with chronic stroke lasting at least 1 hour after stimulation .


In the absence of concurrent motor practice , neither form of stimulation applied in a single session was associated the changes in motor performance .


These approaches to increased cortical excitability may be of value as adjuncts to training .


See Video ( Supplemental Digital Content 1 , http://links.lww.com/JNPT/A83 ) for more insights from the authors .


Postoperative infection after breast reduction surgery is a common complication , with the most commonly involved pathogen being Staphylococcus aureus .


Previous studies of antibiotic prophylaxis in breast reduction surgery have been inconclusive .


The aim of the present study was to clarify the role of prophylactic antibiotics in breast reduction surgery .


In total , 325 women were randomized to antibiotic prophylaxis [ with 2 g of cloxacillin intravenously ( IV ) or 600 mg of clindamycin IV ] ( intervention group ) or no antibiotic prophylaxis ( control group ) .


Follow-up was conducted at 1 and 2 weeks postoperatively .


Patients with signs of infections or other complications were followed up until resolution .


Patients who received antibiotic treatment within 30 days from surgery ( cloxacillin 750 mg or clindamycin 300 mg orally ) were considered having an infection and this was the main outcome variable .


All postoperative infections were also judged according to a graded scale .


In the intervention group , 26 ( 16.0 % ) patients were treated with antibiotic ; and in the control group , 32 ( 19.6 % ) patients were treated with antibiotics .


No difference was found between the groups ( relative risk , 0.82 ; 95 % confidence interval , 0.51-1 .31 ; P = 0.49 ) .


Twenty-two ( 14 % ) patients in the intervention group were classified to have a possible infection according to the scale compared to 27 ( 17 % ) in the control group .


No statistical difference was found ( relative risk , 0.81 ; 95 % confidence interval , 0.48-1 .37 ; P = 0.54 ) .


Prophylactic cloxacillin as a single-dose IV in breast reduction surgery does not reduce the incidence of postoperative infections .


Personalized medicine is the holy grail of medicine .


The EULAR recommendations for the management of rheumatoid arthritis ( RA ) support differential treatment between patients with baseline characteristics suggestive of a non-poor prognosis ( non-PP ) or poor prognosis ( PP ) ( presence of autoantibodies , a high inflammatory activity and damage on radiographs ) .


We aimed to determine which prognostic risk groups benefit more from initial monotherapy or initial combination therapy .


508 patients were randomized to initial monotherapy ( iMono ) or initial combination therapy ( iCombo ) .


Disease outcomes of iMono and iCombo were compared within non-PP or PP groups as determined on baseline characteristics


PP patients treated with iCombo after three months more often achieved ACR20 ( 70 % vs 38 % , P < 0.001 ) , ACR50 ( 48 % vs 13 % , P < 0.001 ) and ACR70 response ( 24 % vs 4 % , P < 0.001 ) than those treated with iMono , and had more improvement in HAQ ( median decrease 0.75 vs 0.38 , P < 0.001 ) .


After 1 year , differences in ACR20 response and DAS-remission remained ; PP patients treated with iCombo ( vs iMono ) had less radiographic progression ( median 0.0 vs 1.5 , P = 0.001 ) .


Since PP and non-PP patients benefit equally from iCombo through earlier clinical response and functional improvement than with iMono , we conclude that personalized medicine as suggested in the guidelines is not yet feasible .


The choice of treatment strategy should depend more on rapid relief of symptoms than on prognostic factors .


Netherlands Trial Register NTR262 ( registered 7 September 2005 ) and NTR265 ( 8 September 2005 ) .


The aim of this study was to evaluate the effect of knee position during wound closure ( flexed vs. extended ) in total knee arthroplasty on knee strength and function , as determined by knee society scores and isokinetic testing of extensor and flexor muscle groups .


In a prospective , randomized , double-blind trial , 29 patients were divided in two groups : for Group 1 patients , surgical closing was performed with the knee extended , and for Group 2 patients , the knee flexed at 90 .


All the patients were treated with the same anaesthesia method , surgical team , surgical technique , prosthesis type , and rehabilitation process .


American Knee Society Score values and knee flexion degrees were recorded .


Isokinetic muscle strength measurements of both knees in flexion and extension were taken using 60 and 180/s angular velocity .


The peak torque and total work values , isokinetic muscle strength differences , and total work difference values were calculated for surgically repaired and healthy knees .


No significant difference in the mean American Knee Society Score values and knee flexion degrees was observed between the two groups .


However , using isokinetic evaluation , a significant difference was found in the isokinetic muscle strength differences and total work difference of the flexor muscle between the two groups when patients were tested at 180/s .


Less loss of strength was detected in the isokinetic muscle strength differences of the flexor muscle in Group 2 ( -4.2 % ) than in Group 1 ( -23.1 % ) .


For patients undergoing total knee arthroplasty , post-operative flexor muscle strength is improved if the knee is flexed during wound closure .


II .


Patients with diabetes mellitus inject insulin in different regions of the body .


This study investigated the pharmacokinetic and pharmacodynamic properties of insulin degludec ( IDeg ) , a new-generation once-daily basal insulin with an ultra-long duration of action , after subcutaneous ( SC ) administration in different injection regions .


In this study , 20 healthy subjects received single SC doses of IDeg ( 0.4 U/kg ; separated by 13-21days ) in the thigh , abdomen and deltoid in a randomised , open-label , single-centre , single-dose , complete crossover trial .


Each dose was followed by a 24-h euglycaemic clamp and 120-h pharmacokinetic blood sampling .


The obtained pharmacokinetic/pharmacodynamic profiles were extrapolated to steady state by simulation using a pharmacokinetic/pharmacodynamic model .


Total IDeg exposure [ area under the IDeg serum concentration-time curve 0-120h after a single dose ( AUCIDeg,0-120h , SD ) ] and maximum serum concentration [ maximum IDeg serum concentration after a single dose ( C max , IDeg , SD ) ] were higher ( 6-7 and 23-27 % , respectively ) following a single SC dose in the deltoid or abdomen , compared with the thigh , as also observed with other insulin preparations .


No statistical difference was observed in these measures between deltoid and abdominal administration .


No pronounced differences were observed in the glucose-lowering effect of IDeg [ area under the glucose infusion rate ( GIR ) curve 0-24h after a single dose ( AUCGIR,0-24h , SD ) and maximum GIR after a single dose ( GIRmax , SD ) ] when injected in the thigh , abdomen or deltoid ( AUCGIR,0-24h , SD 2,572 , 2,833 and 2,960 mg/kg , respectively ) .


Simulated mean steady-state pharmacokinetic and pharmacodynamic profiles supported a flat and stable IDeg exposure and effect regardless of injection region , with comparable total glucose-lowering effects [ area under the GIR curve at steady state ( AUCGIR , , SS ) ] between the thigh , abdomen and deltoid .


These findings support administering IDeg SC in the thigh , upper arm or abdominal wall without affecting IDeg absorption or effect at steady state .


FVC outcomes in clinical trials on idiopathic pulmonary fibrosis ( IPF ) can be substantially influenced by the analytic methodology and the handling of missing data .


We conducted a series of sensitivity analyses to assess the robustness of the statistical finding and the stability of the estimate of the magnitude of treatment effect on the primary end point of FVC change in a phase 3 trial evaluating pirfenidone in adults with IPF .


Source data included all 555 study participants randomized to treatment with pirfenidone or placebo in the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis ( ASCEND ) study .


Sensitivity analyses were conducted to assess whether alternative statistical tests and methods for handling missing data influenced the observed magnitude of treatment effect on the primary end point of change from baseline to week 52 in FVC .


The distribution of FVC change at week 52 was systematically different between the two treatment groups and favored pirfenidone in each analysis .


The method used to impute missing data due to death had a marked effect on the magnitude of change in FVC in both treatment groups ; however , the magnitude of treatment benefit was generally consistent on a relative basis , with an approximate 50 % reduction in FVC decline observed in the pirfenidone group in each analysis .


Our results confirm the robustness of the statistical finding on the primary end point of change in FVC in the ASCEND trial and corroborate the estimated magnitude of the pirfenidone treatment effect in patients with IPF .


ClinicalTrials.gov ; No. : NCT01366209 ; URL : www.clinicaltrials.gov .


Children whose mothers had low thyroid hormone levels during pregnancy have been reported to have decreased cognitive function .


The reported research is part of the follow-on study of the Controlled Antenatal Thyroid Screening Study ( CATS I ) , a randomised controlled trial which investigated the impact of treated vs. untreated low thyroid hormone level in women during pregnancy with the primary outcome being the child 's IQ at age 3 .


No significant differences in IQ were found between the treated and untreated groups .


These children are now aged between 7 and 10 years and aspects of their cognitive functioning including their IQ are being reassessed as part of CATS II .


Cognitive assessments generate an IQ score and further tests administered will investigate long term memory function and motor coordination .


The aim is to complete the assessments with 40 % of the children born to mothers either in the treated or untreated low thyroid hormone groups ( n = 120 per group ) .


Also children born to mothers who had normal thyroid functioning during CATS I are being assessed for the first time ( n = 240 ) to provide a comparison .


Assessments are conducted either in the research facility or the participant 's home .


The study is designed to assess the cognitive functioning of children born to mothers with low thyroid hormone levels and normal thyroid functioning during pregnancy .


This is the largest study of its type and also is distinguishable in its longitudinal design .


The research has the potential to have a significant impact on public health policy in the UK ; universal screening of thyroid hormone levels in pregnancy may be the recommendation .


Unnecessary ventricular pacing in sinus node disease ( SND ) must be avoided .


To test the hypothesis that in SND , with or without 1st degree atrioventricular ( AV ) block , cumulative percent ventricular pacing ( cum % VP ) can be limited by low right atrial septal ( LRAS ) instead of right atrial appendage ( RAA ) pacing .


We studied 102 dual-chamber pacemaker recipients with SND .


The PQ interval on 12-lead electrocardiogram and the atrial paced to ventricular sensed interval ( Ap-Vs ) during LRAS and RAA pacing were measured and compared at implantation , 3 months and 1 year of follow-up .


Group 1 included 62 patients with baseline PQ interval < 200milliseconds during LRAS ( n = 28 ) versus RAA ( n = 34 ) pacing .


Group 2 included 40 patients with baseline PQ 200 milliseconds during LRAS ( n = 20 ) versus RAA ( n = 20 ) pacing .


cum % VP were measured at 3 months and 1 year .


The characteristics and AV conduction properties were similar and the Ap-Vs interval was significantly shorter in the LRAS than in the RAA pacing group up to 1 year ( 193 32 milliseconds vs. 220 27 milliseconds in Group 1 ; P = 0.003 , 222 41 milliseconds vs. 281 30 milliseconds in Group 2 ; P < 0.001 ) .


While cumulative percent atrial pacing was consistently similar , cum % VP was significantly smaller during LRAS than RAA pacing ( 1 1 % vs. 8 18 % in Group 1 ; P = 0.03 , 7 10 % vs. 48 38 % in Group 2 ; P < 0.001 ) .


Similar observations were made with or without left atrial ( LA ) enlargement .


Compared with RAA , LRAS pacing showed shorter AV interval in SND patients with or without 1st degree AV block and LA enlargement .


This beneficial effect persisted through 1-year follow-up , and decreased cum % VP significantly .


While prior preliminary studies have broadened our understanding of how repetitive transcranial magnetic stimulation ( rTMS ) improves language outcomes in stroke patients with nonfluent aphasia , the evidence base of the effectiveness of this method remains inadequate .


In this study , we aimed to strengthen the evidence that this approach improves language performance and to identify characteristics of patients predisposed to benefit most from this treatment .


Fifty-six stroke patients with nonfluent aphasia were randomly allocated to a real or a sham stimulation group : Group A ( n = 33 ) , who underwent 10 sessions of 1-Hz rTMS over the contralesional pars triangularis ( PTr ) , and Group B ( n = 23 ) , who received sham 1-Hz stimulation .


We performed the Picture Naming Test and the Concise Chinese Aphasia Test ( CCAT ) at the baseline , post-rTMS intervention , and at 3-month follow-up .


Group A showed significantly greater improvement than Group B in CCAT scoring ( P < .001 ) , object-naming accuracy ( P = .01 ) , and naming reaction time ( P = .004 ) .


The CCAT scoring and naming testing changes for Group A were persistent at 3 months following intervention ( P = .008 ) .


Patients who had a lower contralesional rest motor threshold ( rMT ) were predisposed to a favorable therapeutic outcome ( P = .006 ) , independent of aphasia type , severity , and duration .


The results of this study provide evidence that inhibitory rTMS , through downregulating the circuitry of the right pars triangularis ( PTr ) , achieves a persistent and broadly modulating effect , irrespective of aphasia severity and subtype .


Patients who show lower rMT in the right motor system would seem to benefit the most from inhibitory rTMS .


The aim of this study was to determine the pharmacokinetic profile of metronidazole ( Mtz ) tablet and to compare Mtz gel and tablet concentrations in both blood plasma and saliva .


In this randomized cross-over study with a 1-week washout period , 13 volunteers randomly received one ( a single oral dose of 750 mg Mtz ( Flagyl -- tablet ) and 2 ) 3 g of 15 % Mtz benzoate gel ( applied by using a dental tray ) .


The HPLC with ultraviolet detection was used to quantify plasma and saliva concentrations of Mtz .


The pharmacokinetic parameters ( PPs ) areas under the curves from 0 to 48 h ( AUC0-48 ) and from 0 to infinity ( AUC0 - ) , the maximum plasma concentration ( C ( max ) ) , the time to C ( max ) , volume of distribution and renal clearance were determined for Mtz tablet .


Considering the Mtz tablet , plasma showed higher Mtz concentration from 6 to 24 h after drug administration and the highest values concerning AUC0-48 h and AUC0 - than those obtained in saliva ( P < 0.05 ) .


No significant differences were observed between plasma and saliva concentrations for Mtz gel .


The study showed that some PPs were higher in plasma ( P < 0.05 ) than in saliva concerning Mtz tablet .


Gel formulation had similar Mtz bioavailability in plasma and saliva resulting in systemic absorption .


Therapy with tenofovir is associated with lower bone mineral density ( BMD ) , higher markers of bone turnover and increased fracture risk in HIV-infected adults .


Bone structural parameters generated by hip structural analysis may represent a separate measure of bone strength , but have not been assessed in HIV .


Dual-energy X-ray absorptiometry ( DXA ) scans from 254 HIV-infected adults randomised to simplify their existing dual nucleoside analogue reverse transcriptase inhibitor therapy to coformulated tenofovir-emtricitabine or abacavir-lamivudine were analysed using DXA-derived hip structural analysis software .


Hip structural parameters included femoral strength index , section modulus , cross-sectional area , and cross-sectional moment of inertia .


We used one-way ANOVA to test the relationship between nucleoside analogue type at baseline and structural parameters , multivariable analysis to assess baseline covariates associated with femoral strength index , and t-tests to compare mean change in structural parameters over 96 weeks between randomised groups .


Participants taking tenofovir at baseline had lower section modulus ( -107.3 mm2 , p = 0.001 ) , lower cross-sectional area ( -15.01 mm3 , p = 0.001 ) , and lower cross-sectional moment of inertia ( -2,036.8 mm4 , p = 0.007 ) than those receiving other nucleoside analogues .


After adjustment for baseline risk factors , the association remained significant for section modulus ( p = 0.008 ) and cross-sectional area ( p = 0.002 ) .


Baseline covariates significantly associated with higher femoral strength index were higher spine T-score ( p = 0.001 ) , lower body fat mass ( p < 0.001 ) , lower bone alkaline phosphatase ( p = 0.025 ) , and higher osteoprotegerin ( p = 0.024 ) .


Hip structural parameters did not change significantly over 96 weeks and none was significantly affected by treatment simplification to tenofovir-emtricitabine or abacavir-lamivudine .


In this population , tenofovir use was associated with reduced composite indices of bone strength as measured by hip structural analysis , but none of the structural parameters improved significantly over 96 weeks with tenofovir cessation .


ClinicalTrials.gov NCT00192634 .


We examined narrative discourse in amyotrophic lateral sclerosis ( ALS ) to assess the role of executive functioning in support of language and the neuroanatomical basis for such support .


We analyzed a semistructured speech sample in 26 patients with ALS and 19 healthy seniors for narrative discourse features of coherence .


Regression analyses related a measure of discourse coherence ( `` local connectedness '' ) to gray matter atrophy and reduced white matter fractional anisotropy .


Patients with ALS were impaired relative to controls on measures of discourse adequacy , including local connectedness and maintenance of the theme .


These discourse measures were related to measures of executive functioning but not to motor functioning .


Regressions related local connectedness to gray matter atrophy in ventral and dorsal prefrontal regions and to reduced fractional anisotropy in white matter tracts mediating projections between prefrontal regions .


Patients with ALS exhibit deficits in their ability to organize narrative discourse .


These deficits appear to be related in part to executive limitations .


Consistent with the hypothesis that ALS is a multisystem disorder , this deficit is related to disease in prefrontal regions .


In spite of the high occurrence of migraine headaches in school-age children , there are currently no approved and widely accepted pharmacologic agents for migraine prophylaxis in children .


Our previous open-label study in children revealed the efficacy of cinnarizine , a calcium channel blocker , in migraine prophylaxis .


A placebo-controlled trial was conducted to demonstrate the efficacy and safety of cinnarizine in the prophylaxis of migraine in children .


A double-blind , placebo-controlled , parallel-group study conducted in a tertiary medical center in Tehran , Iran .


Children ( 5-17 years ) who experienced migraines with and without aura , as defined on the basis of 2004 International Headache Society criteria , were recruited into the study .


Children were excluded if they had complicated migraine , epilepsy , or a history of use of migraine prophylactic agents .


Each participant was randomly assigned to receive cinnarizine ( a single 1.5 mg/kg/day dose in children weighing less than 30 kg and a single 50 mg dose in children weighing more than 30 kg , administered at bedtime ) or placebo .


The frequency , severity , and duration of headaches over the trial period were assessed and adverse effects were monitored .


A total of 68 children ( 34 in each group ) with migraine were enrolled and 62 participants completed the study .


After 3 months of taking cinnarizine or placebo , children in both groups experienced significantly reduced frequency , severity , and duration of headaches compared with baseline measurements ( P < 0.001 ) .


However , compared with 31.3 % of children in the placebo group , 60 % of children in the cinnarizine group reported more than 50 % reduction in monthly headache frequency ( P = 0.023 ) , suggesting that cinnarizine was significantly more effective than placebo in reducing the frequency of headaches .


No serious adverse effects of the medications were observed in the treated children , including no abnormal weight gain or extrapyramidal signs .


Our results indicate that the use of cinnarizine at doses administered in this study is effective and safe for prophylaxis of migraine headaches in children .


Among patients with HIV infection , changes in the kidney filtration marker cystatin C after initiation of antiretroviral therapy ( ART ) may be related to changes in body composition or biomarkers of inflammation .


ACTG A5224s was a substudy of A5202 , which randomly assigned ART-naive HIV-infected subjects to blinded abacavir/lamivudine ( ABC/3TC ) or tenofovir/emtricitabine ( TDF/FTC ) with open-label efavirenz ( EFV ) or ritonavir-boosted atazanavir .


This analysis explored changes in cystatin C from 0 to 96 weeks .


Of the 269 subjects , 85 % were male and 66 % white non-Hispanics ; baseline mean CD4 count was 236 cells per cubic millimeter and cystatin C was 0.89 mg/L .


Cystatin C decreased significantly within each arm ; however , ritonavir-boosted atazanavir attenuated the beneficial effects of ART on cystatin C compared to EFV .


Compared to ABC/3TC , TDF/FTC led to a marginally significant attenuation for percent change analyses only .


Higher baseline body mass index and HIV RNA were associated with larger reductions in cystatin C in multivariable models .


At baseline , cystatin C was positively correlated with high-sensitivity C-reactive protein ( Spearman r = 0.25 ) , interleukin 6 ( r = 0.34 ) , soluble intercellular adhesion molecule ( r = 0.36 ) , soluble vascular cell adhesion molecule ( r = 0.54 ) , tumor necrosis factor ( r = 0.57 ) , and soluble TNF - receptor I ( r = 0.70 , all P < 0.001 ) .


Reductions in cystatin C from 0 to 96 weeks correlated with reductions in all inflammatory biomarkers ( r = 0.39-0 .58 , P < 0.001 ) except for high-sensitivity C-reactive protein ( r = 0.01 , P = 0.89 ) and IL-6 ( r = 0.08 , P = 0.24 ) .


The beneficial effect of ART on cystatin C concentrations is attenuated by boosted ATV when compared to EFV .


Reductions in cystatin C after ART are associated with reductions in systemic inflammation .


We aimed to assess the effect of afatinib on overall survival of patients with EGFR mutation-positive lung adenocarcinoma through an analysis of data from two open-label , randomised , phase 3 trials .


Previously untreated patients with EGFR mutation-positive stage IIIB or IV lung adenocarcinoma were enrolled in LUX-Lung 3 ( n = 345 ) and LUX-Lung 6 ( n = 364 ) .


These patients were randomly assigned in a 2:1 ratio to receive afatinib or chemotherapy ( pemetrexed-cisplatin [ LUX-Lung 3 ] or gemcitabine-cisplatin [ LUX-Lung 6 ] ) , stratified by EGFR mutation ( exon 19 deletion [ del19 ] , Leu858Arg , or other ) and ethnic origin ( LUX-Lung 3 only ) .


We planned analyses of mature overall survival data in the intention-to-treat population after 209 ( LUX-Lung 3 ) and 237 ( LUX-Lung 6 ) deaths .


These ongoing studies are registered with ClinicalTrials.gov , numbers NCT00949650 and NCT01121393 .


Median follow-up in LUX-Lung 3 was 41 months ( IQR 35-44 ) ; 213 ( 62 % ) of 345 patients had died .


Median follow-up in LUX-Lung 6 was 33 months ( IQR 31-37 ) ; 246 ( 68 % ) of 364 patients had died .


In LUX-Lung 3 , median overall survival was 28.2 months ( 95 % CI 24.6-33 .6 ) in the afatinib group and 28.2 months ( 20.7-33 .2 ) in the pemetrexed-cisplatin group ( HR 0.88 , 95 % CI 0.66-1 .17 , p = 0.39 ) .