A single random biopsy increased the detection of high-grade disease when no lesions were visualized at colposcopy .


The absolute risks of disease associated with the random biopsy were highest for women positive for genotype 16 or 18 .


Our study supports performing a random biopsy in women undergoing colposcopy without visible lesions , particularly in those positive for HPV 16 or 18 .


: II .


Pain and potential adverse events ( AE ) remain challenges for patients being treated with calcium hydroxylapatite ( CaHA ; Radiesse ) , especially CaHA not mixed with an anesthetic .


The blunt cannula may provide more comfortable and lower risk delivery of CaHA for nasolabial folds ( NLF ) correction .


This 30-day pilot study was designed to compare the effectiveness and safety of standard needles with that of blunt cannulas for CaHA application .


Twenty patients with moderate to severe NLF received split-face injections of CaHA mixed with 2 % lidocaine using a cannula for one NLF and needle for the other NLF .


At day 0 , patients evaluated pain ; the treating investigator evaluated changes in NLF depth .


At 0 , 3 , 7 , 14 , and 30days , the investigator evaluated AEs and NLF correction .


Patients recorded AEs in daily dairies .


After initial treatment , patients experienced greater pain and displayed increased erythema and swelling in the needle-treated side .


At days 3 and 7 , patients displayed greater instances of bruising , redness , and swelling in the needle-treated sides .


At day 30 , 19 patients showed slightly better correction in the cannula-treated sides .


The blunt cannula provided advantages in mitigation of pain and AEs , with a degree of correction similar to needle .


The addition of blunt cannulas to the clinical setting may be appropriate .


The aim of the study was to investigate the effects of the early initiation of passive and active range of motion exercises following arthroscopic rotator cuff repair .


The study included 40 patients who underwent arthroscopic rotator cuff repair .


Patients were quasi-randomly assigned into accelerated ( ACCEL ) protocol ( n = 19 ) and slow ( SLOW ) protocol ( n = 21 ) groups .


Patients in both groups were treated with the same protocol .


Active range of motion was begun at the 3rd week in the ACCEL group and the 6th week in the SLOW group .


Range of motion was recorded at postoperative weeks 3 , 5 , 8 , 12 , and 24 .


While active range of motion for all measurements improved across weeks , there were no differences between groups , with the exception of active total elevation which was greater at all time point measurements in the ACCEL group ( p < 0.05 ) .


The early initiation of passive and gentle controlled active motion exercise following rotator cuff repairs does not appear to affect range of motion in the first 6 postoperative months .


The safety of the manual treatment techniques such as spinal manipulation has been discussed and there is a need for more information about potential adverse events after manual therapy .


The aim of this randomized controlled trial was to investigate differences in occurrence of adverse events between three different combinations of manual treatment techniques used by manual therapists ( i.e. chiropractors , naprapaths , osteopaths , physicians and physiotherapists ) for patients seeking care for back and/or neck pain .


In addition women and men were compared regarding the occurrence of adverse events .


Participants were recruited among patients , ages 18-65 , seeking care at the educational clinic of the Scandinavian College of Naprapathic Manual Medicine in Stockholm .


The patients ( n = 767 ) were randomized to one of three treatment arms 1 ) manual therapy ( i.e. spinal manipulation , spinal mobilization , stretching and massage ) ( n = 249 ) , 2 ) manual therapy excluding spinal manipulation ( n = 258 ) and 3 ) manual therapy excluding stretching ( n = 260 ) .


Treatments were provided by students in the seventh semester of total eight .


Adverse events were measured with a questionnaire after each return visit and categorized in to five levels ; 1 ) short minor , 2 ) long minor , 3 ) short moderate , 4 ) long moderate and 5 ) serious adverse events , based on the duration and/or severity of the event .


Generalized estimating equations were used to examine the association between adverse event and treatments arms .


The most common adverse events were soreness in muscles , increased pain and stiffness .


No differences were found between the treatment arms concerning the occurrence of adverse event .


Fifty-one percent of patients , who received at least three treatments , experienced at least one adverse event after one or more visits .


Women more often had short moderate adverse events ( OR = 2.19 ( 95 % CI : 1.52-3 .15 ) ) , and long moderate adverse events ( OR = 2.49 ( 95 % CI : 1.77-3 .52 ) ) compared to men .


Adverse events after manual therapy are common and transient .


Excluding spinal manipulation or stretching do not affect the occurrence of adverse events .


The most common adverse event is soreness in the muscles .


Women reports more adverse events than men .


This trial was registered in a public registry ( Current Controlled Trials ) ( ISRCTN92249294 ) .


Surgical resection is the only curative treatment for gastric cancer .


However , the overall prognosis of gastric adenocarcinoma is poor and advanced disease may even make surgical treatment impossible .


It has been theoretically proposed that administration of chemotherapy before surgical resection may down-stage the disease state and facilitate resectability especially in locally-advanced tumors .


We wanted to assess the effect of administration of neoadjuvant chemotherapy on tumor resectability in patients with locally-advances gastric adenocarcinoma .


During a randomized-controlled trial , we divided 60 patients with locally-advanced gastric adenocarcinoma into two groups of neoadjuvant chemotherapy and surgery ( case ) versus surgery alone ( control ) .


Because of patient dropouts , we analyzed the results for 22 and 29 patients in case and control groups respectively .


The study period was March 21 , 2011 to March 20 , 2014 .


A non-randomized set of 23 patients were also added to the control group ( Multi-center analysis ) .


The analysis was repeated for non-randomized patients ( 22 case patients versus 52 control patients ) .


The mean age of patients in case and control groups was 58.39.1 and 59.78.7 years of age respectively ( p > 0.05 ) .


Male to female ratio was 15/7 and 41/11 in case and control groups respectively ( p > 0.05 ) .


In Randomized patients , 19 patients ( 86.4 % ) were resectable in case group ; while 16 patients ( 55.2 % ) were resectable in control group ( p < 0.05 ) .


Multicenter analysis also revealed resectability in 19 patients ( 86.4 % ) and 31 patients ( 59.6 % ) of case and control groups respectively ( p < 0.05 ) .


We conclude that neoadjuvant chemotherapy could increase tumor resectability rate in patients with locally-advanced gastric adenocarcinoma .


However , further studies are necessary to confirm the effect of this modality on patients ' overall survival .


This study was designed to evaluate and compare the efficacy and safety of nebulized dexmedetomidine , nebulized ketamine , and the combination of these drugs for premedication in pediatric outpatient dental surgeries .


A prospective , randomized , double-blinded study was conducted in the Alexandria Main University Hospital after approval of the Medical Ethics Committee .


Informed written consent was obtained from the patient 's parents .


Sixty children classified as ASA physical status I and II and aged 3 to 6 years were enrolled in the study .


Patients were randomly categorized into 3 equal groups .


Group K was premedicated with nebulized ketamine ( 2 mg/kg ) , group D was premedicated with nebulized dexmedetomidine ( 2 g/kg ) , and group DK was premedicated with combined nebulized dexmedetomidine and ketamine ( 1 g/kg + 1 mg/kg ) .


The primary end point was the level of sedation when the child was first seen in the operating room 30 minutes after sedation .


The secondary end points were tolerance of mask induction , hemodynamic changes , analgesia , sedation at emergence , and wake-up behavior .


Studied groups were comparable as regards demographic data ( age , weight , sex , and ASA physical status , all P > 0.226 ) and patients ' acceptance of drugs ( P = 0.968 ) .


Level of sedation at 30 minutes was significantly greater in group DK than in either group K ( P = 0.003 ) or group D ( P = 0.009 ) .


Group DK had the briefest recovery times , followed in order by group K and group D with progressively longer recovery times .


Recovery times were significantly briefer in group DK than in either group K ( P = 0.039 ) or group D ( P < 0.001 ) .


Group DK had significantly briefer discharge times than group D ( P < 0.001 ) .


Postoperative analgesia was significantly better in group DK compared with group K ( P = 0.008 ) .


A nebulized combination of low-dose ketamine and dexmedetomidine produced more satisfactory sedation and provided a smoother induction of general anesthesia than nebulized ketamine or dexmedetomidine alone , with more rapid recovery and no significant side effects .


Maternal nutritional status is an important predictor of infant birthweight .


Most previous attempts to improve birthweight through multiple micronutrient supplementation have been initiated after women are pregnant .


Interventions to improve maternal nutritional status prior to conception may be more effective in preventing low birthweight and improving other infant health outcomes .


To compare the effects of maternal supplementation with animal-source food from preconception to term or from mid-gestation to term with routine prenatal care on birthweight , the prevalence of preterm births , intrauterine growth restriction , and infant growth during the first 12 months of life and on maternal nutrient status and the incidence of maternal and infant infections .


Young women from 29 rural communes in northwestern Vietnam were recruited when they registered to marry and were randomized to one of three interventions : animal-source food supplement 5 days per week from marriage to term ( approximately 13 months ) , animal-source food supplement 5 days per week from 16 weeks of gestation to term ( approximately 5 months ) , or routine prenatal care without supplementalfeeding .


Data on infant birthweight and gestational age , maternal and infant anthropometry , micronutrient status , and infections in the infant and mother were collected at various time points .


In a preliminary study of women of reproductive age in this area of Vietnam , 40 % of the women were underweight ( body mass index < 18.5 ) and anemic .


About 50 % had infections .


Rice was the dietary staple , and nutrient-rich , animal-source foods were rarely consumed by women .


Iron , zinc , vitamin A , folate , and vitamin B12 intakes were inadequate in about 40 % of the women .


The study is still ongoing , and further data are not yet available .


The results of this study will provide important data regarding whether improved intake of micronutrient-rich animal-source foods that are locally available and affordable before and during pregnancy improves maternal and infant health and development .


This food-based approach may have global implications regarding how and when to initiate sustainable nutritional interventions to improve maternal and infant health .


Suvorexant , an orexin receptor antagonist , improves sleep in healthy subjects ( HS ) and patients with insomnia .


We compared the electroencephalographic ( EEG ) power spectral density ( PSD ) profile of suvorexant with placebo using data from a phase 2 trial in patients with insomnia .


We also compared suvorexant 's PSD profile with the profiles of other insomnia treatments using data from 3 HS studies .


Phase 2 trial -- randomized , double-blind , two-period ( 4 w per period ) crossover .


HS studies -- randomized , double-blind , crossover .


Sleep laboratories .


Insomnia patients ( n = 229 ) or HS ( n = 124 ) .


Phase 2 trial -- suvorexant 10 mg , 20 mg , 40 mg , 80 mg , placebo ; HS study 1 -- suvorexant 10 mg , 50 mg , placebo ; HS study 2 -- gaboxadol 15 mg , zolpidem 10 mg , placebo ; HS study 3 -- trazodone 150 mg , placebo .


The PSD of the EEG signal at 1-32 Hz of each PSG recording during nonrapid eye movement ( NREM ) and rapid eye movement ( REM ) sleep were calculated .


The day 1 and day 28 PSD profiles of suvorexant at all four doses during NREM and REM sleep in patients with insomnia were generally flat and close to 1.0 ( placebo ) at all frequencies .


The day 1 PSD profile of suvorexant in HS was similar to that in insomnia patients .


In contrast , the other three drugs had distinct PSD profiles in HS that differed from each other .


Suvorexant at clinically effective doses had limited effects on power spectral density compared with placebo in healthy subjects and in patients with insomnia , in contrast to the three comparison insomnia treatments .


These findings suggest the possibility that antagonism of the orexin pathway might lead to improvements in sleep without major changes in the patient 's neurophysiology as assessed by electroencephalographic .


Novel interventions tailored to blue collar workers are needed to reduce the disparities in smoking rates among occupational groups .


The main objective of this study was to evaluate the efficacy and usage of the Web-enhanced `` Tobacco Tactics '' intervention targeting operating engineers ( heavy equipment operators ) compared to the `` 1-800-QUIT-NOW '' telephone line .


Operating engineers ( N = 145 ) attending one of 25 safety training sessions from 2010 through 2012 were randomized to either the Tobacco Tactics website with nurse counseling by phone and access to nicotine replacement therapy ( NRT ) or to the 1-800-QUIT-NOW telephone line , which provided an equal number of phone calls and NRT .


The primary outcome was self-reported 7-day abstinence at 30-day and 6-month follow-up .


The outcomes were compared using chi-square tests , t tests , generalized mixed models , and logistic regression models .


The average age was 42 years and most were male ( 115/145 , 79.3 % ) and white ( 125/145 , 86.2 % ) .


Using an intent-to-treat analysis , the Tobacco Tactics website group showed significantly higher quit rates ( 18/67 , 27 % ) than the 1-800-QUIT NOW group ( 6/78 , 8 % ) at 30-day follow-up ( P = .003 ) , but this difference was no longer significant at 6-month follow-up .


There were significantly more positive changes in harm reduction measures ( quit attempts , number of cigarettes smoked per day , and nicotine dependence ) at both 30-day and 6-month follow-up in the Tobacco Tactics group compared to the 1-800-QUIT-NOW group .


Compared to participants in the 1-800-QUIT NOW group , significantly more of those in the Tobacco Tactics website group participated in the interventions , received phone calls and NRT , and found the intervention helpful .


The Web-enhanced Tobacco Tactics website with telephone support showed higher efficacy and reach than the 1-800-QUIT-NOW intervention .


Longer counseling sessions may be needed to improve 6-month cessation rates .


Clinicaltrials.gov NCT01124110 ; http://clinicaltrials.gov/ct2/show/NCT01124110 ( Archived by WebCite at http://www.webcitation.org/6TfKN5iNL ) .


The National Lung Screening Trial ( NLST ) showed that screening with low-dose computed tomography ( CT ) as compared with chest radiography reduced lung-cancer mortality .


We examined the cost-effectiveness of screening with low-dose CT in the NLST .


We estimated mean life-years , quality-adjusted life-years ( QALYs ) , costs per person , and incremental cost-effectiveness ratios ( ICERs ) for three alternative strategies : screening with low-dose CT , screening with radiography , and no screening .


Estimations of life-years were based on the number of observed deaths that occurred during the trial and the projected survival of persons who were alive at the end of the trial .


Quality adjustments were derived from a subgroup of participants who were selected to complete quality-of-life surveys .


Costs were based on utilization rates and Medicare reimbursements .


We also performed analyses of subgroups defined according to age , sex , smoking history , and risk of lung cancer and performed sensitivity analyses based on several assumptions .


As compared with no screening , screening with low-dose CT cost an additional $ 1,631 per person ( 95 % confidence interval [ CI ] , 1,557 to 1,709 ) and provided an additional 0.0316 life-years per person ( 95 % CI , 0.0154 to 0.0478 ) and 0.0201 QALYs per person ( 95 % CI , 0.0088 to 0.0314 ) .


The corresponding ICERs were $ 52,000 per life-year gained ( 95 % CI , 34,000 to 106,000 ) and $ 81,000 per QALY gained ( 95 % CI , 52,000 to 186,000 ) .


However , the ICERs varied widely in subgroup and sensitivity analyses .


We estimated that screening for lung cancer with low-dose CT would cost $ 81,000 per QALY gained , but we also determined that modest changes in our assumptions would greatly alter this figure .


The determination of whether screening outside the trial will be cost-effective will depend on how screening is implemented .


( Funded by the National Cancer Institute ; NLST ClinicalTrials.gov number , NCT00047385 . )


We evaluated the use of tamsulosine versus placebo for management of ureteral stent discomfort .


This prospective and randomized study was realized in the Department of Urology of three university hospital .


The participation was proposed at all patient having indication to receive an ureteral stent except for cancer .


The evaluation of the tolerance used two validate questionnaires : Ureteral Stent Symptom Questionnaire ( USSQ ) and IPSS completed by each patient the day of the insertion , next day , one week later and the day before and after the removal .


The main assessment criterion was the question `` global quality of life '' one week after the stent insertion .


Seventy-nine patients were randomized between June , 2010 and October , 2012 .


Despite phone reminders only 38 ( 48.1 % ) were complete questionnaires .


Out of 39 , 18 patients in the tamsulosine group and out of 40 , 20 in the phloroglucinol group .


The majority of the patients ( 92 % ) were included for stone disease .


There is not significant difference between the 2 groups using the USSQ and IPSS at day +1 , day +7 , pre-ablation and day +1 ablation .


A significant improvement of the scores was noted to day +1 by the ablation of the JJ in 2 groups .


Our study did not show superiority of tamsulosine versus placebo in the improvement of the tolerance of ureteral stent .


2 .


Permissive hypercapnia is a ventilatory strategy used to prevent lung injury in ventilated extremely low birth weight ( ELBW , birth weight 1,000 g ) infants .


However , there is retrospective evidence showing that high CO2 is associated with brain injury .


The objective of this study was to compare brain white matter development at term-equivalent age in ELBW infants randomized to hypercapnic vs. normocapnic ventilation during the first week of life and in healthy non-ventilated term newborns .


Twenty-two ELBW infants from a randomized controlled trial were included in this study ; 11 received hypercapnic ( transcutaneous PCO2 [ tcPCO2 ] 50-60 mmHg ) ventilation and 11 normocapnic ( tcPCO2 35-45 mmHg ) ventilation during the first week of life while still intubated .


In addition , ten term healthy newborns served as controls .


Magnetic resonance imaging ( MRI ) with diffusion tensor imaging ( DTI ) was performed at term-equivalent age for the ELBW infants and at approximately 2 weeks of age for the control infants .


White matter injury on conventional MRI was graded in the ELBW and control infants using a scoring system adopted from literature .


Tract-based spatial statistics ( TBSS ) was used to evaluate for differences in DTI measured fractional anisotropy ( FA , spatially normalized to a customized template ) among the ELBW and term control infants .


Conventional MRI white matter scores were not different ( 7.31.7 vs. 6.91.4 , P = 0.65 ) between the hypercapnic and normocapnic ELBW infants .


TBSS analysis did not show significant differences ( P < 0.05 , corrected ) between the two ELBW infant groups , although before multiple comparisons correction , hypercapnic infants had many regions with lower FA and no regions with higher FA ( P < 0.05 , uncorrected ) compared to normocapnic infants .


When compared to the control infants , normocapnic ELBW infants had a few small regions with significantly lower FA , while hypercapnic ELBW infants had more widespread regions with significantly lower FA ( P < 0.05 , fully corrected for multiple comparisons ) .


Normocapnic ventilation vs. permissive hypercapnia may be associated with improved white matter development at term-equivalent age in ELBW infants .


This effect , however , was small and was not apparent on conventional MRI .


Further research is needed using larger sample sizes to assess if permissive hypercapnic ventilation in ELBW infants is associated with worse white matter development .


Antidepressants are effective in adults with pain-related functional gastrointestinal disorders .


We investigated the effectiveness of citalopram in the treatment of childhood functional abdominal pain ( FAP ) .


Children with FAP , based on the Rome III criteria ( n = 115 , aged 6-18 years ) , were randomized to receive either citalopram 20 mg/day or placebo for 4 weeks .


Treatment response was defined as 2 point reduction in the 6-point Faces pain rating scale or ` no pain ' .


Depression , anxiety , somatization , and physician-rated global severity and improvement were also evaluated .


Patients were followed up for 8 weeks after medication period .


Eighty-six patients completed the medication ( 43 in each group ) .


Response rate in the citalopram and placebo groups based on per-protocol ( intention-to-treat ) analysis was 55.8 % ( 40.6 % ) and 39.5 % ( 30.3 % ) at week 4 ( p = 0.097 [ 0.169 ] ) and 72.0 % ( 52.5 % ) and 53.4 % ( 41.0 % ) at week 12 ( p = 0.059 [ 0.148 ] ) , respectively .


In per-protocol analysis , more reduction was observed in pain ( F = 3.84 , p = 0.024 ) and global severity scores ( F = 4.12 , p = 0.021 ) in the citalopram group compared with the placebo group over the study period .


Such differences were not present in the intention-to-treat analysis .


No difference was found between the two groups regarding change in depression , anxiety , or somatization score over the study .


Overall , we found a trend toward the effectiveness of citalopram in the treatment of children with FAP .


Trials with longer treatment duration in larger samples of patients are required in this regard .


Noninvasive continuous positive airway pressure ( CPAP ) is usually applied with a nasal or facial mask to treat mild acute respiratory failure ( ARF ) in infants .


A pediatric helmet has now been introduced in clinical practice to deliver CPAP .


This study compared treatment failure rates during CPAP delivered by helmet or facial mask in infants with respiratory syncytial virus-induced ARF .


In this multicenter randomized controlled trial , 30 infants with respiratory syncytial virus-induced ARF were randomized to receive CPAP by helmet ( n = 17 ) or facial mask ( n = 13 ) .


The primary endpoint was treatment failure rate ( defined as due to intolerance or need for intubation ) .


Secondary outcomes were CPAP application time , number of patients requiring sedation , and complications with each interface .


Compared with the facial mask , CPAP by helmet had a lower treatment failure rate due to intolerance ( 3/17 [ 17 % ] vs 7/13 [ 54 % ] , P = .009 ) , and fewer infants required sedation ( 6/17 [ 35 % ] vs 13/13 [ 100 % ] , P = .023 ) ; the intubation rates were similar .


In successfully treated patients , CPAP resulted in better gas exchange and breathing pattern with both interfaces .


No major complications due to the interfaces occurred , but CPAP by mask had higher rates of cutaneous sores and leaks .


These findings confirm that CPAP delivered by helmet is better tolerated than CPAP delivered by facial mask and requires less sedation .


In addition , it is safe to use and free from adverse events , even in a prolonged clinical setting .


TG4040 is a modified vaccinia Ankara ( MVA ) virus that expresses the hepatitis C virus ( HCV ) proteins NS3 , NS4 , and NS5B .


We performed a phase II open-label study to determine the efficacy , safety , and immunotherapeutic properties of TG4040 in combination with pegylated interferon -2 a and ribavirin ( PEG-IFN/RBV ) in patients with chronic HCV infection .


Treatment-naive patients with HCV genotype 1 infection were assigned randomly to 1 of thefollowing groups : PEG-IFN/RBV for 48 weeks ( group A , n = 31 ) , PEG-IFN/RBV for 4 weeks followed by PEG-IFN/RBV for 44 weeks with 6 injections of TG4040 ( group B , n = 63 ) , or TG4040 for 12 weeks ( 7 injections ) followed by PEG-IFN/RBV for 48 weeks with 6 injections of TG4040 ( group C , n = 59 ) .


The primary end point was complete early virologic response ( cEVR ) , defined as HCV-RNA level less than10 IU/mL after 12 weeks of PEG-IFN/RBV treatment .


In group C , 64.2 % of evaluable patients achieved cEVR , compared with 30.0 % in group A and 45.9 % in group B ( P = .0003 for group C vs A ) .


A higher percentage of patients achieved a sustained virologic response 24 weeks after therapy ended in group C ( 58.2 % ) than in groups A ( 48.4 % ) or B ( 50.8 % ) .


HCV - and MVA-specific T-cell responses were observed predominantly in group C.


As expected , most patients given injections of TG4040 developed anti-MVA antibodies .


The combination of TG4040 and PEG-IFN/RBV was reasonably well tolerated .


However , PEG-IFN-associated thrombocytopenia developed in 3 patients who carried the class II HLA allele DRB01 * 04 .


A higher percentage of patients with chronic HCV infection who received immunotherapy with TG4040 followed by TG4040 and PEG-IFN/RBV achieved a cEVR compared with patients who received only PEG-IFN/RBV therapy .


These findings show that immunotherapies that activate T cells are effective in patients with chronic HCV infection .


ClinicalTrials.gov number , NCT01055821 .


We aimed to identify doses of mirogabalin ( DS-5565 ) providing clinically meaningful efficacy with manageable side effects for treatment of diabetic peripheral neuropathic pain ( DPNP ) .


Adults ( 18 years ) with type 1 or 2 diabetes , HbAc 10 % at screening , and DPNP for 6 months were eligible for study participation .


Subjects ( n = 452 ) were randomized ( 2:1:1:1:1:1:1 ratio ) to placebo , dose-ranging mirogabalin ( 5 , 10 , 15 , 20 , and 30 mg/day ) , or pregabalin ( 300 mg/day ) for 5 weeks .


The primary end point was weekly change in average daily pain score ( ADPS ; 0 to 10 numeric rating scale ) from baseline to week 5 ( minimally meaningful effect , 1.0-point decrease versus placebo ) .


ANCOVA was conducted using last observation carried forward , and treatment effect least squares ( LS ) means were provided for each contrast .


Safety assessments included adverse events ( AEs ) , clinical laboratory tests , and electrocardiograms .


LS mean differences in change in ADPS from baseline to week 5 versus placebo were -0.22 , -0.53 , -0.94 , -0.88 , and -1.01 for the mirogabalin 5 - , 10 - , 15 - , 20 - , and 30-mg/day treatment groups , respectively , and -0.05 in the pregabalin group ( P < 0.05 versus placebo for mirogabalin 15 , 20 , and 30 mg/day ) .


Most frequent AEs ( n = 277 ) were primarily mild to moderate dizziness ( 9.4 % ) , somnolence ( 6.1 % ) , and headache ( 6.1 % ) ; otherwise , mirogabalin was well tolerated .


Mirogabalin 15 , 20 , and 30 mg/day had statistically significant reductions in ADPS versus placebo , and mirogabalin 30 mg/day also met the criteria of minimally meaningful effect .


Mirogabalin may be a promising new treatment option for patients with DPNP .


Flexible fiber-optic bronchoscope-guided orotracheal intubation is a valuable technique with demonstrated benefits in the management of difficult airways .


Despite its popularity with anesthesia providers , the technique is not fail-safe and airway-related complications secondary to failed intubation attempts remain an important problem .


We sought to determine the effect of incorporating lingual traction on the success rate of fiber-optic bronchoscope-guided intubation in patients with anticipated difficult airways .


In this prospective , randomized , cohort study , we enrolled 91 adult patients with anticipated difficult airways scheduled for elective surgery to undergo fiber-optic bronchoscope-guided orotracheal intubation alone or with lingual traction by an individual anesthesiologist after induction of general anesthesia and neuromuscular blockade .


A total of 78 patients were randomized : 39 patients to the fiber-optic bronchoscope-guided intubation with lingual traction group and 39 patients to the fiber-optic bronchoscope-guided intubation alone group .


The primary endpoint was the rate of successful first attempt intubations .


The secondary outcome was sore throat grade on post-operative day 1 .


Fiber-optic intubation with lingual traction compared to fiber-optic intubation alone resulted in a higher success rate ( 92.3 vs. 74.4 % , ( 2 ) = 4.523 , p = 0.033 ) and greater odds for successful first attempt intubation ( OR 4.138 , 95 % CI 1.041-16 .444 , p = 0.044 ) .


Sore throat severity on post-operative day 1 was not significantly different but trended towards worsening grades with lingual traction .


In this study , lingual traction was shown to be a valuable maneuver for facilitating fiber-optic bronchoscope-guided intubation in the management of patients with anticipated difficult airways .


Levels of physical activity ( PA ) in UK children are much lower than recommended and novel approaches to its promotion are needed .


The Children , Parents and Pets Exercising Together ( CPET ) study is the first exploratory randomised controlled trial ( RCT ) to develop and evaluate an intervention aimed at dog-based PA promotion in families .


CPET aimed to assess the feasibility , acceptability and potential efficacy of a theory-driven , family-based , dog walking intervention for 9-11 year olds .


Twenty-eight families were allocated randomly to either receive a 10-week dog based PA intervention or to a control group .


Families in the intervention group were motivated and supported to increase the frequency , intensity and duration of dog walking using a number of behaviour change techniques .


Parents in the intervention group were asked to complete a short study exit questionnaire .


In addition , focus groups with parents and children in the intervention group , and with key stakeholders were undertaken .


The primary outcome measure was 10 week change in total volume of PA using the mean accelerometer count per minute ( cpm ) .


Intervention and control groups were compared using analysis of covariance .


Analysis was performed on an intention to treat basis .


Twenty five families were retained at follow up ( 89 % ) and 97 % of all outcome data were collected at baseline and follow up .


Thirteen of 14 ( 93 % ) intervention group parents available at follow up completed the study exit questionnaire and noted that study outcome measures were acceptable .


There was a mean difference in child total volume of PA of 27 cpm ( 95 % CI -70 , 123 ) and -3 cpm ( 95 % CI -60 , 54 ) for intervention and control group children , respectively .


This was not statistically significant .


Approximately 21 % of dog walking time for parents and 39 % of dog walking time for children was moderate-vigorous PA. .


The acceptability of the CPET intervention and outcome measures was high .


Using pet dogs as the agent of lifestyle change in PA interventions in children and their parents is both feasible and acceptable , but did not result in a significant increase in child PA in this exploratory trial .


ISRCTN85939423 .


The aim of this study was to assess the prognostic performance of C-terminal provasopressin ( copeptin ) , midregional pro-adrenomedullin ( MR-proADM ) , and midregional pro-atrial natriuretic peptide ( MR-proANP ) in a large prospective cohort of patients with non-ST-segment elevation acute coronary syndrome ( NSTE-ACS ) .


Copeptin , MR-proADM , and MR-proANP are emerging biomarkers of hemodynamic stress that have been associated with adverse cardiovascular ( CV ) outcomes in heart failure ( HF ) and stable ischemic disease .


We measured copeptin , MR-proADM , and MR-proANP concentrations in 4,432 patients with NSTE-ACS who were randomized to treatment with ranolazine or placebo in the MERLIN-TIMI 36 ( Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis In Myocardial Infarction 36 ) trial and followed up for 1 year .


A high concentration ( quartile 4 vs. quartiles 1 to 3 ) of each biomarker identified an increased risk of CV death or HF ( copeptin : 13.2 % vs. 5.0 % , p < 0.001 ; MR-proADM : 15.8 % vs. 4.1 % , p < 0.001 ; MR-proANP : 17.7 % vs. 3.5 % , p < 0.001 ) as well as CV death , HF , and myocardial infarction individually ( all p 0.001 ) .


After adjustment for important covariates , each biomarker remained associated with CV death or HF at 1 year ( adjusted hazard ratio : copeptin , 1.71 ; MR-proADM , 1.96 ; MR-proANP , 2.20 ; all p 0.001 ) .


These biomarkers improved prognostic discrimination and patient re-classification for CV death or HF at 1 year ( all categorical NRI > 10 % , p < 0.001 ) , and maintained independent association with composite CV death or HF when concurrently assessed in a model with clinical indicators plus BNP , cTnI , ST2 , PAPP-A , and MPO ( each p0 .01 ) [ corrected ] .


Copeptin , MR-proADM , and MR-proANP are complementary prognostic markers for CV death and HF in patients with NSTE-ACS that perform as well as or better than established and other emerging biomarkers and warrant further investigation of application for therapeutic decision making .


( Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes ; NCT00099788 ) .


Glutamine rate of appearance ( Ra ) may be used as an estimate of endogenous glutamine production .


Recently a technique employing a bolus injection of isotopically labeled glutamine was introduced , with the potential to allow for multiple assessments of the glutamine Ra over time in critically ill patients , who may not be as metabolically stable as healthy individuals .


Here the technique was used to evaluate the endogenous glutamine production in critically ill patients in the fed state with and without exogenous glutamine supplementation intravenously .


Mechanically ventilated patients ( n = 11 ) in the intensive care unit ( ICU ) were studied on two consecutive days during continuous parenteral feeding .


To allow the patients to be used as their own controls , they were randomized for the reference measurement during basal feeding without supplementation , before or after the supplementation period .


Glutamine Ra was determined by a bolus injection of 13C-glutamine followed by a period of frequent sampling to establish the decay-curve for the glutamine tracer .


Exogenous glutamine supplementation was given by intravenous infusion of a glutamine containing dipeptide , L-alanyl-L-glutamine , 0.28 g/kg during 20 hours .


A 14 % increase of endogenous glutamine Ra was seen at the end of the intravenous supplementation period as compared to the basal measurements ( P = 0.009 ) .


The bolus injection technique to measure glutamine Ra to estimate the endogenous production of glutamine in critically ill patients was demonstrated to be useful for repetitive measurements .


The hypothesized attenuation of endogenous glutamine production during L-alanyl-L-glutamine infusion given as a part of full nutrition was not seen .


The purpose of this study was to evaluate the effect of the use of preoperative breast MRI on surgical and long-term outcomes among women with early-stage breast cancer undergoing breast conservation therapy .


A retrospective review yielded the cases of 174 women with stage 0 , I , or II breast cancer who underwent preoperative MRI between 2000 and 2004 .


A control group of 174 patients who did not undergo preoperative MRI before breast conservation therapy was matched by age , histopathologic finding , stage , and surgeon .


Features compared included breast density , presence of mammographically occult disease , margin status , lymph node involvement , lymphovascular invasion , extensive intraductal component , hormone receptor status , and use of adjuvant therapy .


Outcomes , including rates of reexcision , ipsilateral recurrence , and disease-free survival , were compared by Kaplan-Meier methods and the log-rank test .


Patients referred for preoperative breast MRI were more likely to have extremely dense breasts ( 28 % vs 6 % , p < 0.0001 ) and mammographically occult cancer ( 24 % vs 9 % , p = 0.0003 ) .


The two groups had identical rates of final negative margins , lymph node involvement , lymphovascular invasion , extensive intraductal component status , positive hormone receptor results , and systemic adjuvant therapy .


Fewer patients in the preoperative MRI group needed reexcision ( 29 % vs 45 % , p = 0.02 ) .


The median follow-up period after treatment was 8 years .


There was no significant difference in locoregional recurrence ( p = 0.33 ) or disease-free survival ( p = 0.73 ) rates between the two groups .


Reexcision rates among patients with early breast cancer undergoing conservation therapy were lower among women who underwent preoperative breast MRI .


There was no statistically significant effect of the use of preoperative MRI on rates of locoregional recurrence or disease-free survival .


Pulmonary rehabilitation ( PR ) is an evidence-based intervention in patients with chronic obstructive pulmonary disease ( COPD ) which improves the exercise capacity and quality of life ( QoL ) .


We studied 60 patients after an episode of acute exacerbation of COPD ( AECOPD ) .


They were randomised to receive conventional treatment without pulmonary rehabilitation ( CTWPR ) ( n = 30 ) or , standard treatment plus a 12-week post-exacerbation pulmonary rehabilitation ( PEPR ) programme in addition .


Assessment of exercise capacity by six minute walk test ( 6MWT ) and QoL measured by St George 's Respiratory Questionnaire ( SGRQ ) were carried out initially and at the end of three months .


The baseline characteristics of both the groups were found to be similar .


There was a statistically significant increase in the six minute walk distance ( 6MWD ) ( increase by 37.9 meters , p < 0.001 ) and a significant decline in the total SGRQ score ( by 3.8 units p < 0.001 ) in the PEPR group compared to CTWPR group .


Early pulmonary rehabilitation in patients with an AECOPD has significant benefits on the QoL and exercise capacity .


A phase IIa study investigated efficacy and safety/tolerability of ascending doses of mavrilimumab ( anti-granulocyte-macrophage colony-stimulating factor receptor [ GM-CSFR ] monoclonal antibody ) in adult subjects with moderate to severe rheumatoid arthritis from Japan and Europe .


Findings from the Japanese population are presented .


Fifty-one subjects received mavrilimumab ( 10-100 mg ) or placebo subcutaneously every other week for 12 weeks , followed by a 12-week follow-up period .


The primary endpoint was the proportion of subjects achieving a Disease Activity Score using 28 joints ( DAS28 ) - C-reactive protein ( CRP ) response ( decrease > 1.2 from baseline ) .


Secondary endpoints included DAS28-CRP remission , Health Assessment Questionnaire Disability Index ( HAQ-DI ) and American College of Rheumatology ( ACR ) response .


By Week 12 , more mavrilimumab - versus placebo-treated subjects achieved a DAS28-CRP response ( 50.0 % vs. 23.5 % , p = 0.081 ) ; a significant response was seen in the 30 mg and 100 mg dose groups ( both 75.0 % vs. 23.5 % , p = 0.028 ) .


The 100 mg group also demonstrated statistically significant HAQ-DI and ACR20 responses at Week 12 .


Results were generally consistent between Japanese and European populations .


Overall , adverse events ( AEs ) were mild to moderate in intensity with one serious AE of pneumonia , considered possibly treatment-related .


A rapid and clinically meaningful response was seen in subjects treated with GM-CSFR blockade with mavrilimumab , supporting further investigation of mavrilimumab for the treatment of RA in Japanese subjects .


We compared the antiinflammatory and cardioprotective effects of the two most common regimens of corticosteroid administration in pediatric cardiac surgical procedures : a single dose delivered either at anesthesia induction or by cardiopulmonary bypass ( CPB ) prime .


Forty-five children , aged between 1 and 18 months and undergoing ventricular septal or atrioventricular septal defect correction , were randomized in double-blind fashion into three groups .


The anesthesia induction group received 30 mg/kg methylprednisolone intravenously after anesthesia induction , and the CPB-prime group received 30 mg/kg methylprednisolone by CPB circuit .


The placebo group received saline solution .


Plasma concentrations of methylprednisolone , interleukin ( IL ) -6 , IL-8 and IL-10 , and troponin were measured at anesthesia induction before the study drug , 30 minutes on CPB , after patients were weaned from CPB , and 6 hours after cessation of CPB .


Equally high methylprednisolone concentrations were detected in both methylprednisolone groups , but the measured peak concentration occurred earlier in the induction group .


Significantly lower IL-8 concentrations were observed just after patients were weaned from and 6 hours after CPB in the anesthesia induction group compared with the placebo ( p = 0.002 , p = 0.001 ) and prime groups ( p = 0.003 , p = 0.006 ) .


Significant reductions of troponin were detected in both methylprednisolone groups compared with placebo ( induction , p = 0.001 ; prime , p = 0.002 ) 6 hours after patients were weaned from CPB .


Methylprednisolone administration at anesthesia induction was superior in terms of antiinflammatory action .


Methylprednisolone administration in CPB-prime only a few minutes before aortic cross-clamping and cardioplegia resulted in mean troponin reductions similar to those of administration at anesthesia induction .


Corticosteroids may have direct cardioprotective properties , as reported in experimental studies .


To determine whether the postoperative administration of tryptophan would be beneficial for elderly adults undergoing surgery who are at risk of developing postoperative delirium .


Randomized , double-blind , placebo-controlled trial .


Denver Veterans Affairs Medical Center .


Individuals aged 60 and older undergoing major elective operations requiring a postoperative intensive care unit ( ICU ) admission ( n = 325 ) .


L-tryptophan , 1g orally three times a day or placebo was started after surgery and continued for up to 3days postoperatively .


Delirium and its motor subtypes were measured using the Confusion Assessment Method-Intensive Care Unit ( CAM-ICU ) and the Richmond Agitation and Sedation Scale .


The primary outcome for between-group comparison was the incidence of excitatory ( mixed and hyperactive ) postoperative delirium .


The secondary outcomes for comparison were the incidence and duration of overall postoperative delirium .


The overall incidence of postoperative delirium was 39 % ( 95 % confidence interval = 34-44 % ) ( n = 116 ) .


Seventeen percent of participants in the tryptophan group and 9 % in the placebo group had excitatory delirium ( P = .18 ) , and the duration of excitatory delirium was 3.31.7 days for tryptophan and 3.11.9 days for placebo ( P = .74 ) .


Forty percent of participants in the tryptophan group and 37 % in the placebo group had overall delirium ( P = .60 ) , and the duration of overall delirium was 2.91.8 days for tryptophan and 2.41.6 days for placebo ( P = .17 ) .


Postoperative tryptophan supplementation in older adults undergoing major elective operations requiring postoperative ICU admission did not reduce the incidence or duration of postoperative excitatory delirium or overall delirium .


Optimizing vancomycin dosing may help eradicate bacteria while avoiding resistance .


The guidelines recommend loading doses ; however , there are no data to demonstrate that this may result in a more rapid achievement of therapeutic troughs .


To evaluate the percentage of troughs reaching therapeutic levels at 12 , 24 , and 36 hours following an initial vancomycin dose of 30 mg/kg compared with 15 mg/kg .


This prospective , randomized study was performed in a community academic medical center .


Patients who were to receive vancomycin in the emergency department were randomized to an initial traditional dose of 15 mg/kg or a 30-mg/kg loading dose followed by 15 mg/kg every 12 hours for 3 doses .


Patients weighing > 120 kg or with creatinine clearances < 50 mL/min were excluded .


In total , 99 patients were enrolled ; 12 hours after the initial dose of vancomycin , there was a significantly greater proportion of patients reaching target trough levels of 15 mg/L among the patients who received a loading dose as compared with a traditional dose ( 34 % vs 3 % , P < 0.01 ) .


This trend continued at 24 hours but was not statistically significant .


At 36 hours , there was no difference in the percentage of patients reaching target levels between the 2 groups .


No statistically significant difference in nephrotoxicity or adverse events among the 2 groups was demonstrated .


A loading dose of 30 mg/kg of vancomycin achieved a higher percentage of therapeutic levels at 12 hours when compared with the traditional dose of 15 mg/kg , without increased nephrotoxicity or adverse events .


United States pediatric guidelines recommend that childhood obesity counseling be conducted in the primary care setting .


Primary care-based interventions can be effective in improving health behaviors , but also costly .


The purpose of this study was to evaluate the cost of a primary care-based obesity prevention intervention targeting children between the ages of two and six years who are at elevated risk for obesity , measured against usual care .


High Five for Kids was a cluster-randomized controlled clinical trial that aimed to modify children 's nutrition and TV viewing habits through a motivational interviewing intervention .


We assessed visit-related costs from a societal perspective , including provider-incurred direct medical costs , provider-incurred equipment costs , parent time costs and parent out-of-pocket costs , in 2011 dollars for the intervention ( n = 253 ) and usual care ( n = 192 ) groups .


We conducted a net cost analysis using both societal and health plan costing perspectives and conducted one-way sensitivity and uncertainty analyses on results .


The total costs for the intervention group and usual care groups in the first year of the intervention were $ 65,643 ( 95 % CI [ $ 64,522 , $ 66,842 ] ) and $ 12,192 ( 95 % CI [ $ 11,393 , $ 13,174 ] ) .


The mean costs for the intervention and usual care groups were $ 259 ( 95 % CI [ $ 255 , $ 264 ] ) and $ 63 ( 95 % CI [ $ 59 , $ 69 ] ) per child , respectively , for a incremental difference of $ 196 ( 95 % CI [ $ 191 , $ 202 ] ) per child .


Children in the intervention group attended a mean of 2.4 of a possible 4 in-person visits and received 0.45 of a possible 2 counseling phone calls .


Provider-incurred costs were the primary driver of cost estimates in sensitivity analyses .


High Five for Kids was a resource-intensive intervention .


Further studies are needed to assess the cost-effectiveness of the intervention relative to other pediatric obesity interventions .


To investigate the efficacy of letrozole for delaying bone maturation and increasing predicted adult height in boys with idiopathic central precocious puberty ( ICPP ) who have a bone age above 13 years and a short stature , and its adverse effects .


Twenty ICPP boys with a bone age above 13 years and a short stature were randomly divided into letrozole treatment ( n = 10 ) and control groups ( n = 10 ) .


The letrozole treatment group received oral letrozole [ 2.5 mg / ( m ( 2 ) d ) , Qd ] for 6 months , while the control group received no treatment and was observed periodically .


Bone age , growth rate , height standard deviation ( SD ) score , predicted adult height SD score , sexual maturity , and levels of follicle-stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , dehydroepiandrosterone , testosterone ( T ) , estradiol ( E2 ) , progesterone ( P ) , and androstenedione ( ASD ) were measured .


The letrozole-related adverse reactions were evaluated .


After 6 months of treatment , both groups had a significantly increased bone age , but the letrozole group had a significantly slowed increase in bone age compared with the control group ( 13.82 0.23 years vs 14.47 0.30 years ; P < 0.05 ) ; compared with the control group , the letrozole group had a significantly increased predicted adult height SD score ( -1.69 0.26 vs -1.91 0.35 ; P < 0.05 ) and a significantly increased T level ( 4.9 0.9 nmol/L vs 4.4 0.8 nmol/L ; P < 0.05 ) .


There was no significant difference in testicular volume between the two groups .


The treatment led to no significant changes in growth rate , Tanner stage , and levels of FSH , LH , P , E2 and ASD in the two groups , and there was no significant difference in these indices between the two groups .


No adverse reactions were observed during letrozole treatment .


Letrozole delays bone maturation and increases predicted adult height in ICPP boys with a bone age above 13 years and a short stature , and it causes no obvious adverse reactions .


In percutaneous nephrolithotomy ( PCNL ) , placement of the access tract into the kidney is an important aspect of the procedure and is responsible for the steep learning curve associated with the operation .


The aim of the current prospective randomized trial was to assess the duration of radiation exposure along with the safety and efficacy of PCNL done by a trainee , utilizing either ultrasonography ( US ) or fluoroscopic guidance to obtain access .


Sixty-four patients with 3cm renal calculi undergoing single-tract PCNL by trainee urologists ( experience of < 25 PCNL 's ) were randomized into US - and fluoroscopic-guided access groups ( 32 in each ) .


In Group 1 ( US guided ) , puncture was done using a 3.5 / 5MHz US probe with a puncture attachment , whereas the triangulation technique with biplanar C-arm fluoroscopy was utilized in group 2 ( fluoroscopic guided ) .


Patient demographics , stone parameters , intraoperative characteristics , fluoroscopy durations , and postoperative outcomes were analyzed .


Both groups were comparable as far as patient and stone characteristics were concerned .


The fluoroscopy exposure during the puncture phase ( T2 ) and overall ( T ) was significantly lower in the US group at 9.020.8 vs 43.834.8 , ( p < 0.0001 ) and 204.384 vs 239.977.5 , ( p = 0.04 ) .


Six patients in group1 required fluoroscopic adjustment ( p = 0.03 ) .


All other intra - and postoperative parameters were similar in both the groups .


Both ultrasound and fluoroscopic guidance for renal access are equally safe and feasible in the hands of a trainee urologist .


Total fluoroscopy duration and exposure time during puncture were both significantly less in the ultrasound group .


Expertise in fluoroscopic-guided access is essential for a novice to effectively achieve access in all possible situations .


Hangeshashinto ( TJ-14 , a Kampo medicine ) , which reduces the level of prostaglandin E2 and affects the cyclooxygenase activity , alleviates chemotherapy-induced oral mucositis ( COM ) .


We conducted a randomized comparative trial to investigate whether TJ-14 prevents and controls COM in patients with gastric cancer .


We randomly assigned patients with gastric cancer who developed moderate-to-severe oral mucositis ( CTCAE v4 .0 grade 1 ) during any cycle of chemotherapy to receive either TJ-14 or a placebo as a double-blind trial .


The patients received a placebo or TJ-14 for 2-6 weeks according to the chemotherapy regimen from the beginning of the next course of chemotherapy .


The primary end point was the incidence of grade 2 oral mucositis in the protocol treatment course , and the secondary end points were the time to disappearance of oral mucositis and the incidence of adverse events .


Following the key opening of the blinding protocol , we analyzed 91 eligible patients ( TJ-14 : 45 , placebo : 46 ) using a `` per protocol set '' analysis .


The incidence of grade 2 COM was 40.0 % in the TJ-14 group and 41.3 % in the placebo group ( p = 0.588 ) .


The median duration of grade 2 COM was 14 days in the TJ-14 group and 16 days in the placebo group ( p = 0.894 ) .


Meanwhile , the median duration of any grade of COM was 9 days in the TJ-14 group and 17 days in the placebo group among the patients who developed grade 1 symptoms during the screening cycle [ hazard ratio 0.60 ; 95 % CI ( 0.23-1 .59 ) , p = 0.290 ] .


Although TJ-14 treatment did not reduce the incidence of 2 COM in the patients who developed mucositis during chemotherapy for gastric cancer , a trend was observed in which TJ-14 reduced the risk of COM in the patients who developed grade 1 COM during the screening cycle .


Further , phase III studies with a larger sample size are needed to clarify the protective effects of TJ-14 for COM .


Genetic information , typically communicated in-person by genetic counselors , can be challenging to comprehend ; delivery of this information online -- as is becoming more common -- has the potential of increasing these challenges .


To address the impact of the mode of delivery of genomic risk information , 300 individuals were recruited from the general public and randomized to receive genomic risk information for type 2 diabetes mellitus in-person from a board-certified genetic counselor or online through the testing company 's website .


Participants were asked to indicate their genomic risk and overall lifetime risk as reported on their test report as well as to interpret their genomic risk ( increased , decreased , or same as population ) .


For each question , 59 % of participants correctly indicated their risk .


Participants who received their results in-person were more likely than those who reviewed their results on-line to correctly interpret their genomic risk ( 72 vs. 47 % , p = 0.0002 ) and report their actual genomic risk ( 69 vs. 49 % , p = 0.002 ) .


The delivery of personal genomic risk through a trained health professional resulted in significantly higher comprehension .


Therefore , if the online delivery of genomic test results is to become more widespread , further evaluation of this method of communication may be needed to ensure the effective presentation of results to promote comprehension .


A high prevalence of hyperandrogenism has been reported in women with type 1 diabetes ( T1D ) .


Metformin has been used as a therapeutic agent in patients with polycystic ovarian syndrome and in T1D patients without hyperandrogenism .


This study sought to determine the effect of metformin on hyperandrogenism and ovarian function in adolescents with T1D .


We recruited 24 girls with T1D .


The participants had hyperandrogenism and displayed suboptimal metabolic control .


The patients were enrolled in a randomized , double-blind , placebo-controlled trial .


One group received metformin ( 850 mg bid ) and the other group received a placebo .


Treatment was administered for 9 months .


Ovulation , steroids and gonadotropin levels were evaluated .


Metformin treatment was associated with decreases in testosterone , free androgen index , androstenedione , 17-OH progesterone and estradiol levels .


The girls who were treated with placebo showed stable steroid , gonadotropin and sex hormone-binding globulin levels during the analysis .


No differences were observed in the Ferriman-Gallwey scores , ovulation rates , HbA1c levels or daily insulin doses of the girls treated with metformin compared with the placebo group .


Treating hyperandrogenic T1D adolescents with metformin significantly decreased the serum androgens compared to the placebo , but metformin therapy did not significantly affect clinical parameters , such as hirsutism , ovulation and metabolic control .


To explore the dynamics of aggregation of platelets and erythrocytes , their deformity and computed morphodensitometric parameters in patients with chronic cerebral ischemia , stages I and II , treated with cerebrolysin .


We examined 300 patients , including 87 men and 213 women , aged from 30 to 55 years .


Patients were randomized by disease stage and treatment ( standard treatment with or without cerebrolysin ) .


The dynamics of neurological and emotional status as well as cognitive functions and results of laboratory studies were assessed .


Along with the total positive effect of cerebrolysin on the clinical picture , additional mechanisms of its action ( antiaggregant , antihypoxic and membranotropic ) improved the erythrocyte morphodensitometric parameters , hemostatic , hemorheological and blood gas transport characteristics , in particular on the microcirculatory level .


The Secondary Prevention of Small Subcortical Stroke trial ( SPS3 ) recruited participants meeting clinical and radiological criteria for symptomatic lacunes .


Individuals randomized to dual antiplatelet therapy with clopidogrel and aspirin had an unanticipated increase in all-cause mortality compared with those assigned to aspirin .


We investigated the factors associated with mortality in this well-characterized population .


We identified independent predictors of mortality among baseline demographic and clinical factors by Cox regression analysis in participants of the SPS3 trial .


Separately , we examined the effect on mortality of nonfatal bleeding during the trial .


During a mean follow-up of 3.6 years , the mortality rate was 1.78 % per year for the 3020 participants ( mean age , 63 years ) .


Significant independent predictors of mortality at study entry were age , diabetes mellitus , history of hypertension , systolic blood pressure ( hazard ratio [ HR ] , 1.3 per 20 mm Hg increase ) , serum hemoglobin < 13 g/dL ( HR , 1.6 ) , renal function ( HR , 1.3 per estimated glomerular filtration rate decrease of 20 mL/min ) , and body mass index ( HR , 1.8 per 10 kg/m2 decrease ) .


Participants with ischemic heart disease ( P = 0.01 for interaction ) and normotensive/prehypertensive participants ( P = 0.03 for interaction ) were at increased risk if assigned to dual antiplatelet therapy .


Nonfatal major hemorrhage increased mortality in both treatment arms ( HR , 4.5 ; 95 % confidence interval , 3.1-6 .6 ; P < 0.001 ) .


Unexpected interactions between assigned antiplatelet therapy and each of ischemic heart disease and normal/prehypertensive status accounted for increased mortality among patients with recent lacunar stroke given dual antiplatelet therapy .


Despite extensive exploratory analyses , the mechanisms underlying these interactions are uncertain .


http://www.SPS3ClinicalTrials.gov .


Unique identifier : NCT00059306 .


To investigate the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with Type2 diabetes mellitus inadequately controlled by a combination of metformin and pioglitazone .


This was a multi-centre , phase3 , randomized , double-blind , placebo-controlled study comparing linagliptin 5mg once daily ( n = 183 ) and placebo ( n = 89 ) as add-on to metformin and pioglitazone .


The primary endpoint was the change from baseline in glycated haemoglobin ( HbA1c ) after 24weeks .


The placebo-corrected adjusted mean ( se ) change in HbA1c from baseline to 24weeks was -6 ( 1 ) mmol/mol [ -0.57 ( 0.13 ) % ] ( P < 0.0001 ) .


In patients with baseline HbA1c 53mmol/mol ( 7.0 % ) , 32.4 % of patients in the linagliptin group and 13.8 % in the placebo group achieved HbA1c < 53mmol/mol ( 7.0 % ) ( odds ratio2 .94 ; P = 0.0033 ) .


The placebo-corrected adjusted mean ( se ) change from baseline in fasting plasma glucose at week24 was -0.57 ( 0.26 ) mmol/l [ -10.4 ( 4.7 ) mg/dl ] ( P = 0.0280 ) .


The incidence of serious adverse events was 2.2 % with linagliptin and 3.4 % with placebo .


Investigator-defined hypoglycaemia occurred in 5.5 % of the linagliptin group and 5.6 % of the placebo group .


No meaningful changes in mean body weight were noted for either group .


Linagliptin as add-on therapy to metformin and pioglitazone produced significant and clinically meaningful improvements in glycaemic control , without an additional risk of hypoglycaemia or weight gain ( Clinical Trials Registry No : NCT 00996658 ) .


The study aimed at comparing the effectiveness and maternal satisfaction of oral misoprostol with vaginal misoprostol for induction of labor at term .


A randomized controlled trial of 140 term pregnant women at the University of Nigeria Teaching Hospital Enugu , Nigeria , was conducted from April 2011 to May 2012 .


The women were equally randomized into two groups ( A and B ) to receive oral and vaginal misoprostol , respectively .


The vaginal route reduced the mean induction-vaginal delivery interval by four-and-half hours ( 20.7 12.1 vs. 16.2 10.4 ; mean difference : 4.50 , 95 % CI 0.63-0 .82 ; p = 0.02 ) .


Furthermore , the mean dose of misoprostol required to achieve induction of labor and the mean duration of oxytocin augmentation when indicated were significantly less in the vaginal group than in the oral group ( 2.5 1.3 vs. 2.0 1.1 ; mean difference : 0.50 , 95 % CI 0.10-0 .90 ; p = 0.02 and 4.6 3.2 vs. 3.4 3.1 ; mean difference : 1.20 , 95 % CI 0.15-0 .23 ; p = 0.03 respectively ) .


However , neonatal complications and maternal satisfaction were similar between the two groups .


Both routes of administration are effective in the induction of labor at term and have comparable maternal satisfaction .


However , the vaginal route has the added advantage of shorter induction-delivery interval among others , and thus should be highly considered when induction of labor is indicated at term .


The incidence of acute kidney injury ( AKI ) is increasing globally and it is much more common than end-stage kidney disease .


AKI is associated with high mortality and cost of hospitalisation .


Studies of treatments to reduce this high mortality have used differing renal replacement therapy ( RRT ) modalities and have not shown improvement in the short term .


The reported long-term outcomes of AKI are variable and the effect of differing RRT modalities upon them is not clear .


We used the prolonged follow-up of a large clinical trial to prospectively examine the long-term outcomes and effect of RRT dosing in patients with AKI .


We extended the follow-up of participants in the Randomised Evaluation of Normal vs. Augmented Levels of RRT ( RENAL ) study from 90 days to 4 years after randomization .


Primary and secondary outcomes were mortality and requirement for maintenance dialysis , respectively , assessed in 1,464 ( 97 % ) patients at a median of 43.9 months ( interquartile range [ IQR ] 30.0-48 .6 months ) post randomization .


A total of 468/743 ( 63 % ) and 444/721 ( 62 % ) patients died in the lower and higher intensity groups , respectively ( risk ratio [ RR ] 1.04 , 95 % CI 0.96-1 .12 , p = 0.49 ) .


Amongst survivors to day 90 , 21 of 411 ( 5.1 % ) and 23 of 399 ( 5.8 % ) in the respective groups were treated with maintenance dialysis ( RR 1.12 , 95 % CI 0.63-2 .00 , p = 0.69 ) .


The prevalence of albuminuria among survivors was 40 % and 44 % , respectively ( p = 0.48 ) .


Quality of life was not different between the two treatment groups .


The generalizability of these findings to other populations with AKI requires further exploration .


Patients with AKI requiring RRT in intensive care have high long-term mortality but few require maintenance dialysis .


Long-term survivors have a heavy burden of proteinuria .


Increased intensity of RRT does not reduce mortality or subsequent treatment with dialysis .


www.ClinicalTrials.govNCT00221013 .


The incidence of non-alcoholic fatty liver disease ( NAFLD ) is increasing dramatically affecting up to 30 % of the population worldwide .


At present , treatment options are limited and pharmacological management of NAFLD has had disappointing results .


Some of the best available evidence to improve NAFLD concerns lifestyle modification .


To detect the degree of weight reduction needed to improve the markers of hepatic function and insulin resistance in type-2 diabetics with NAFLD .


One hundred type-2 diabetic male patients with NAFLD were included into this study and divided into two equal groups .


Group ( A ) received aerobic exercise training in addition to diet regimen .


Group ( B ) received no treatment intervention .


There was a 26.99 % , 40.8 % , 33.81 % , 32.73 % , 37.8 % and 15 % reduction in mean values of Alkaline Phosphatase ( ALP ) , Alanine Aminotransferase ( ALT ) , Aspartate Aminotransferase ( AST ) , Gamma - Glutamyltransferase ( GGT ) and Homeostasis Model Assessment-Insulin Resistance-index ( HOMA-IR ) and BMI respectively in group ( A ) at the end of the study .


While there were significant differences between mean levels of the investigated parameters in group ( A ) and group ( B ) after treatment .


About 15 % reduction in BMI is effective to improve the liver condition and insulin resistance in type-2 diabetics with NAFLD .


Major depressive disorder ( MDD ) is a prevalent and severe disorder .


Although effective treatments for MDD are available , many patients remain untreated , mainly because of insufficient treatment capacities in the health care system .


Resulting waiting periods are often associated with prolonged suffering and impairment as well as a higher risk of chronification .


Web-based interventions may help to alleviate these problems .


Numerous studies provided evidence for the efficacy of web-based interventions for depression .


The aim of this study is to evaluate a new web-based guided self-help intervention ( GET.ON-Mood Enhancer-WL ) specifically developed for patients waiting to commence inpatient therapy for MDD .


In a two-armed randomised controlled trial ( n = 200 ) , the web-based guided intervention GET.ON-Mood Enhancer-WL in addition to treatment as usual ( TAU ) will be compared with TAU alone .


The intervention contains six modules ( psycho education , behavioural activation I & II , problem solving I & II , and preparation for subsequent inpatient depression therapy ) .


The participants will be supported by an e-coach , who will provide written feedback after each module .


Inclusion criteria include a diagnosis of MDD assessed with a structured clinical interview [ SCID ] and a waiting period of at least three weeks before start of inpatient treatment .


The primary outcome is observer-rated depressive symptom severity ( HRSD24 ) .


Further ( explorative ) questions include whether remission will be achieved earlier and by more patients during inpatient therapy because of the web-based preparatory intervention .


If GET.ON-Mood Enhancer-WL is proven to be effective , patients may start inpatient therapy with reduced depressive symptom severity , ideally leading to higher remission rates , shortened inpatient therapy , reduced costs , and decreased waiting times .


German Clinical Trial Registration ( DRKS ) : DRKS00004708 .


Development of obesity after heart transplantation ( HT ) is a common complication , largely attributed to immunosuppressive therapy .


The objective of this study is to compare the incidence of development of obesity after HT , according to the calcineurin inhibitor ( CNI ) used ( cyclosporine [ CsA ] vs tacrolimus [ Tac ] ) .


We studied 101 consecutive HT patients from November 2006 to December 2010 .


A diagnosis of overweight-obesity was made by a body mass index of 25 kg/m ( 2 ) , which was assessed before HT and at 1 year after HT .


Patients were randomly assigned to the administration of CsA or Tac by a simple randomization method using a computer program ( 56 % received CsA and 44 % Tac ) .


Of the 101 patients , 77 % were men , and ischemic heart disease was the most common indication for HT .


At baseline , there were no differences in weight between groups treated with CsA or Tac .


The mean weight for each group was 71.5 12 and 75 14 kg , respectively ( P = .2 ) .


The weight increase was greater among CsA patients : after HT , the weight gain was 6.9 11 kg in the CsA group , whereas a minimal weight loss of 0.03 14 kg ( P = .008 ) was experienced in the group treated with Tac .


The multivariate analysis showed that only CsA treatment was an independent predictor of development of obesity 1 year after HT ( odds ratio , 3.84 ; 95 % CI , 1.04-14 .21 ; P = .01 ) .


Weight gain after HT may be related to the CNI used and CsA seems to be the CNI that produces the greatest increase .


To examine whether greater exposure to resin-based composite materials , which may intra-orally release bisphenol A ( BPA ) , is associated with worse renal function outcomes in children .


Prospective multi-centre study .


Community health dental clinics in Boston and Maine from 1997-2005 .


Subjects and methods Five hundred and thirty-four New England Children 's Amalgam Trial participants aged six to ten years were randomised to treatment with amalgam or resin-based composite restorations over five years of follow-up .


Restorations were placed according to treatment arm , and sealants placed per standard of care .


Cumulative composite exposure was calculated using surface-years ( each treated surface weighted by number years present ) .


Urinary excretion of albumin , gamma-glutamyl transpeptidase ( gamma-GT ) , and N-acetyl -- D-glucosaminidase ( NAG ) were available for 417 children .


Analysis of covariance showed no association between exposure to dental composites , polyacid-modified compomer , or flowable composite dental sealants and preventative resin restorations with levels of renal function .


There was no association between composite materials and thresholds indicating renal damage in logistic regression models .


This study found no harmful associations between dental composite materials and renal function in children .


Therefore , concerns about renal function need not be a consideration in the choice of dental restoration material or placement of preventative dental sealants .


The Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts .


The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital .


We aimed to assess the clinical outcomes of the Organ Care System compared with standard cold storage of human donor hearts for transplantation .


We did this prospective , open-label , multicentre , randomised non-inferiority trial at ten heart-transplant centres in the USA and Europe .


Eligible heart-transplant candidates ( aged > 18 years ) were randomly assigned ( 1:1 ) to receive donor hearts preserved with either the Organ Care System or standard cold storage .


Participants , investigators , and medical staff were not masked to group assignment .


The primary endpoint was 30 day patient and graft survival , with a 10 % non-inferiority margin .


We did analyses in the intention-to-treat , as-treated , and per-protocol populations .


This trial is registered with ClinicalTrials.gov , number NCT00855712 .


Between June 29 , 2010 , and Sept 16 , 2013 , we randomly assigned 130 patients to the Organ Care System group ( n = 67 ) or the standard cold storage group ( n = 63 ) .


30 day patient and graft survival rates were 94 % ( n = 63 ) in the Organ Care System group and 97 % ( n = 61 ) in the standard cold storage group ( difference 28 % , one-sided 95 % upper confidence bound 88 ; p = 045 ) .


Eight ( 13 % ) patients in the Organ Care System group and nine ( 14 % ) patients in the standard cold storage group had cardiac-related serious adverse events .


Heart transplantation using donor hearts adequately preserved with the Organ Care System or with standard cold storage yield similar short-term clinical outcomes .


The metabolic assessment capability of the Organ Care System needs further study .


TransMedics .


Interactions between calcium and vitamin D may have implications for the regulation of serum 25-hydroxyvitamin D [ 25 ( OH ) D ] and its catabolism and , consequently , the vitamin D dietary requirement .


We investigated whether different calcium intakes influenced serum 25 ( OH ) D and indexes of vitamin D activation and catabolism during winter and in the context of both adequate and inadequate vitamin D intakes .


A 15-wk winter-based , randomized , placebo-controlled , double-blind vitamin D intervention ( 20 g/d ) study was carried out in free-living men and women aged 50 y ( n = 125 ) who were stratified according to calcium intakes [ moderate-low ( < 700 mg/d ) or high ( > 1000 mg/d ) intake ] .


The serum 25 ( OH ) D concentration was the primary outcome , and serum calcium , parathyroid hormone ( PTH ) , 1,25-dihydroxyvitamin D [ 1,25 ( OH ) D ] , 24,25-dihydroxyvitamin D [ 24,25 ( OH ) D ] , the ratio of 24,25 ( OH ) D to 25 ( OH ) D , vitamin D-binding protein , and free 25 ( OH ) D were exploratory outcomes .


A repeated-measures ANOVA showed there was no significant ( P = 0.2 ) time vitamin D treatment calcium intake grouping interaction effect on the mean serum 25 ( OH ) D concentration over the 15-wk intervention period .


Serum 25 ( OH ) D concentrations increased ( P 0.005 ) and decreased ( P 0.002 ) in vitamin D and placebo groups , respectively , and were of similar magnitudes in subjects with calcium intakes < 700 mg/d ( and even < 550 mg/d ) compared with > 1000 mg/d .


The response of serum PTH , 1,25 ( OH ) D , 24,25 ( OH ) D , the ratio of 24,25 ( OH ) D to 25 ( OH ) D , and free 25 ( OH ) D significantly differed in vitamin D and placebo groups but not by calcium intake grouping .


We found no evidence of a vitamin D sparing effect of high calcium intake , which has been referred to by some authors as `` vitamin D economy . ''


Thus , recent dietary vitamin D requirement estimates will cover the vitamin D needs of even those individuals who have inadequate calcium intakes .


A recent Cochrane Review showed that early robotic training of the upper limb in stroke survivors can be more effective than other interventions when improving activities of daily living involving the arm function is the aim of therapy .


We tested for efficacy of the study a protocol which involved the use of the NeReBot therapy in partial substitution of standard upper limb rehabilitation in post-acute stroke patients .


In this dose-matched , randomized controlled clinical trial , 34 hemiparetic participants with movement against gravity in shoulder , elbow , and wrist muscle groups were enrolled within 15 days of the onset of stroke .


All participants received a total daily rehabilitation treatment for 120 minutes , 5 days per week for 5 weeks .


The control group received standard therapy for the upper limb .


The experimental group received standard therapy ( 65 % of exercise time ) associated with robotic training ( 35 % of exercise time ) .


Muscle tone ( Modified Ashworth Scale ) , strength ( Medical Research Council ) , and synergism ( Fugl-Meyer motor scores ) were measured at impairment level , whereas dexterity ( Box and Block Test and Frenchay Arm Test ) and activities of daily living ( Functional Independence Measure ) were measured at activity level .


All assessments were performed at baseline , at the end of therapy ( time T1 ) , at 3 months ( time T2 ) , and at 7 months ( time T3 ) after entry .


All between-group analyses were tested using nonparametric test with Bonferroni 's adjustments for multiple testing .


No significant between-group differences were found with respect to demographic characteristics , motor , dexterity , and ADLs at baseline , postintervention ( T1 ) and at follow-up ( T2 and T3 ) .


The robot therapy by NeReBot did not lead to better outcomes compared with conventional inpatient rehabilitation .


Preventing smoking initiation among adolescents is crucial to reducing tobacco-caused death and disease .


This study focuses on the effectiveness of a Web-based computer-tailored smoking prevention intervention aimed at adolescents .


The intent of the study was to describe the intervention characteristics and to show the effectiveness and results of a randomized controlled trial .


We hypothesized that the intervention would prevent smoking initiation among Dutch secondary school students aged 10-20 years and would have the largest smoking prevention effect among the age cohort of 14-16 years , as smoking uptake in that period is highest .


The intervention consisted of a questionnaire and fully automated computer-tailored feedback on intention to start smoking and motivational determinants .


A total of 89 secondary schools were recruited via postal mail and randomized into either the computer-tailored intervention condition or the control condition .


Participants had to complete a Web-based questionnaire at baseline and at 6-month follow-up .


Data on smoking initiation were collected from 897 students from these schools .


To identify intervention effects , multilevel logistic regression analyses were conducted using multiple imputation .


Smoking initiation among students aged 10-20 years was borderline significantly lower in the experimental condition as compared to the control condition 6 months after baseline ( OR 0.25 , 95 % CI 0.05-1 .21 , P = .09 ) .


Additional analyses of the data for the 14-16 year age group showed a significant effect , with 11.5 % ( 24/209 ) of the students in the control condition reporting initiation compared to 5.7 % ( 10/176 ) in the experimental condition ( OR 0.22 , 95 % CI 0.05-1 .02 , P = .05 ) .


No moderation effects were found regarding gender and educational level .


The findings of this study suggest that computer-tailored smoking prevention programs are a promising way of preventing smoking initiation among adolescents for at least 6 months , in particular among the age cohort of 14-16 years .


Further research is needed to focus on long-term effects .


International Standard Randomized Controlled Trial Number ( ISRCTN ) : 77864351 ; http://www.controlled-trials.com/ISRCTN77864351 ( Archived by WebCite at http://www.webcitation.org/6BSLKSTm5 ) .


Endoscopic biliary sphincterotomy and stone removal is the standard of care for choledocholithiasis , with a success rate of > 90 % .


For stones 25 mm diameter , mechanical lithotripsy , extracorporeal shock wave lithotripsy , electrohydraulic lithotripsy , and laser lithotripsy can be used .


In the case of failure , the next step is surgery .


In elderly patients and in patients with an elevated surgical risk , stenting is the only treatment modality .


In these cases the aim is to avoid the onset of acute obstructive cholangitis .


The aim of the current study was to evaluate the best management of plastic stents in patients with biliary duct stones who were unfit for surgery and in whom previous endoscopic therapy had failed .


Patients who were high surgical risks and in whom stone clearance was not possible due to the number and sizes of stones were included .


Between March 2008 and September 2010 all patients were treated with endoscopic plastic biliary stenting at four tertiary care referral centers in Italy .


Patients were randomly assigned to two groups : in Group A ( n = 39 ) plastic stents were changed every 3 months or sooner if symptoms appeared ; in Group B plastic stents were changed on demand at the onset of symptoms , and ultrasonography and blood samples were performed every 3 months to check for signs of cholestasis and inflammation .


The primary outcome was the rate of cholangitis .


The secondary outcome was the rate of stone clearance after a period of stenting .


A total of 78 patients were included in the study ( 43M/35F ; mean age 76 years ) .


Acute cholangitis occurred in 3 patients from Group A and in 14 patients from Group B ( P = 0.03 ) .


Mortality related to cholangitis occurred in one patient from Group A and three patients from Group B ( P = n.s. ) .


The mean follow-up was 13.5 months ( range 2-23 ) .


Stone clearance after long term stenting occurred in 24 patients from Group A ( 61.5 % ) and in 21 patients from group B ( 53.8 % ) ( P = n.s. ) .


In patients with bile duct stones who were treated with biliary plastic stents , the best stent management to avoid cholangitis was stent changing at defined intervals ( every 3 months in the current study ) .


The data confirmed that plastic biliary stenting may decrease stone size with a high percentage of subsequent total stone clearance .


Previous analyses from a randomized trial in women aged 24-45 have shown the quadrivalent HPV vaccine to be efficacious in the prevention of infection , cervical intraepithelial neoplasia ( CIN ) and external genital lesions ( EGL ) related to HPV 6/11/16 / 18 through 4 years .


In this report we present long term follow-up data on the efficacy , safety and immunogenicity of the quadrivalent HPV vaccine in adult women .


Follow-up data are from a study being conducted in 5 sites in Colombia designed to evaluate the long-term immunogenicity , effectiveness , and safety of the qHPV vaccine in women who were vaccinated at 24 to 45 years of age ( in the original vaccine group during the base study [ n = 684 ] ) or 29 to 50 years of age ( in the original placebo group during the base study [ n = 651 ] ) .


This analysis summarizes data collected as of the year 6 post-vaccination visit relative to day 1 of the base study ( median follow-up of 6.26 years ) from both the original base study and the Colombian follow-up .


There were no cases of HPV 6/11/16 / 18-related CIN or EGL during the extended follow-up phase in the per-protocol population .


Immunogenicity persists against vaccine-related HPV types , and no evidence of HPV type replacement has been observed .


No new serious adverse experiences have been reported .


Vaccination with qHPV vaccine provides generally safe and effective protection from HPV 6 - , 11 - , 16 - , and 18-related genital warts and cervical dysplasia through 6 years following administration to 24-45 year-old women .


Clinicaltrials.govNCT00090220 .


To evaluate whether trabectedin as first-line chemotherapy for advanced/metastatic soft tissue sarcoma prolongs progression-free survival ( PFS ) , compared to doxorubicin and , in the phase IIb part here , to select the most appropriate trabectedin treatment schedule ( 3-hour or 24-hour infusion ) in terms of safety , convenience and efficacy .


In this randomised multicentre prospective dose-selection phase IIb superiority trial , 133 patients were randomised between doxorubicin ( n = 43 ) , trabectedin ( 3-hour infusion , T3h ) ( n = 47 ) and trabectedin ( 24-hour infusion , T24h ) ( n = 43 ) .


PFS was defined as time from random assignment until objective progression by response evaluation criteria in solid tumours ( RECIST 1.1 ) , a global deterioration of the health status requiring discontinuation of the treatment , or death from any cause .


The study was terminated due to lack of superiority in both trabectedin treatment arms as compared to the doxorubicin control arm .


Median PFS was 2.8 months in the T3h arm , 3.1 months in the T24h arm and 5.5 months in the doxorubicin arm .


No significant improvements in PFS were observed in the trabectedin arms as compared to the doxorubicin arm ( T24h versus doxorubicin : hazard ratio ( HR ) 1.13 , 95 % confidence interval ( CI ) 0.67-1 .90 , P = .675 ; T3h versus doxorubicin : HR 1.50 , 95 % CI 0.91-2 .48 , P = .944 ) .


Only one toxic death occurred in the T3h arm , but treatment had to be stopped due to toxicity in 7 ( 15.2 % ) ( T3h ) , 8 ( 19.5 % ) ( T24h ) and 1 ( 2.5 % ) doxorubicin patients .


Doxorubicin continues to be the standard treatment in eligible patients with advanced/metastatic soft-tissue sarcoma ( STS ) .


Trabectedin 1.5 mg/m ( 2 ) / 24-hour infusion is the overall proven approach to delivering this agent in the second-line setting for patients with advanced or metastatic STS .


Esophageal cancer is among the most common gastrointestinal cancers for which the main treatment is surgery .


This study was undertaken to analyze the results of Botox injection in preventing gastric stasis in these patients .


60 patients with esophageal cancer in the middle and lower third parts were included in our study between 2010 and 2011 , and were randomly divided into two groups .


In group A , 30 patients underwent pyloroplasty , and in group B , injection of botulinum toxin into the pyloric sphincter muscle was used in 30 patients .


The mean age of these patients was 6110.7 years and the male/female ratio was 33:27 .


Isotope scans 3 weeks after surgery showed that 5 patients in group A and 3 in group B had delayed gastric emptying ; there was no significant difference between the 2 groups , and the success rate of Botox injection was 90 % .


Considering the fact that there was no significant difference between pyloroplasty and Botox injection on gastric emptying after surgery , and given the need to use less-aggressive techniques and facilitate greater use of endoscopic methods , botulinum toxin injection may be used instead of pyloroplasty as a simple , effective , and complication-free method to prevent delayed gastric emptying .


Social support is associated with enhanced illness management and recovery in persons with mental illness , making it an important topic addressed through acute inpatient psychoeducational programs .


In addition , trust in the therapist may mediate clinical outcomes in this patient population .


To date , few studies have examined the effect of music-based psychoeducational programs on these variables .


The purpose of this study was to isolate and examine the component parts of a live educational music therapy intervention , and its effect on acute psychiatric inpatients ' perceived social support from significant others , family , and friends and trust in the therapist .


This study also explored whether trust in therapist varied across conditions , but did not examine it as a mediator for social support .


Participants ( N = 96 ) were cluster-randomized in a single-session posttest-only design to one of four conditions : live educational music therapy , recorded educational music therapy , education without music , or recreational music therapy without education .


Conditions were designed to isolate the following intervention components : live vs. recorded music , educational vs. non-educational content , and music vs. nonmusic modality .


Dependent measures were assessed post intervention via established self-report instruments evaluating perceived social support and trust in the therapist .


There were no significant between-group differences for social support or trust in therapist total scores .


However , subscale score analyses revealed two significant between-group differences : ( a ) participants in the Live Educational Music Therapy condition reported significantly higher perceived therapist competence compared with the Recorded Educational Music Therapy condition ; ( b ) participants in the Live Educational Music Therapy condition reported significantly higher perceived support from friends compared with the Recreational Music Therapy condition .


Live educational music therapy may be a way to heighten psychiatric inpatients ' perceived social support concerning friends and perceptions of the therapist 's competence .


The current results demonstrated differences between live and recorded music therapy in psychiatric music therapy and provide empirical support for competent musicianship .


Implications for clinical practice , limitations , and suggestions for future research are included .


Hyperventilation has been associated with adverse effects on lung function , symptoms , and well-being in asthma .


We examined whether raising end-tidal CO2 levels ( ie , Pco2 ) compared with slow breathing is associated with improvements in asthma control , including peak flow variability .


One hundred twenty patients with asthma were randomly assigned to capnometry-assisted respiratory training ( CART ) for raising Pco2 or slow breathing and awareness training ( SLOW ) for slowing respiratory rate .


Patients received five weekly sessions and completed bid homework exercises over 4 weeks .


Blinded assessments at baseline , posttreatment , 1 - and 6-month follow-up of asthma control , Pco2 , and diurnal peak flow variability were primary outcome measures .


Additionally , we measured pulmonary function ( spirometry , forced oscillation , exhaled nitric oxide , and methacholine challenge ) , symptoms , quality of life , and bronchodilator use .


Because the control group received active treatment , we expected improvements in asthma control in both groups but more pronounced benefits from CART .


Improvements were seen in 17 of 21 clinical indexes ( 81.0 % ) in both interventions , including the primary outcome variables asthma control ( d = 0.81 ) , peak flow variability ( d = 0.54 ) , quality of life , bronchodilator use , lung function , and airway hyperreactivity .


Most improvements were sustained across the 6-month follow-up .


Compared with slow breathing , CART showed greater increases in Pco2 ( d = 1.45 vs 0.64 for CART vs SLOW , respectively ) and greater reductions in respiratory impedance during treatment , less distress during methacholine challenge , and greater reduction in asthma symptoms at follow-up ( P < .05 ) .


Brief interventions aimed at raising Pco2 or slowing respiratory rate provide significant , sustained , and clinically meaningful improvements in asthma control .


Raising Pco2 was associated with greater benefits in aspects of lung function and long-term symptoms .


ClinicalTrials.gov ; No. : NCT00975273 ; URL : www.clinicaltrials.gov .


Selective serotonin reuptake inhibitors ( SSRIs ) are common treatments for patients with major depressive disorder ( MDD ) .


However , adverse effects of SSRIs on sexual function are common in the treatment of patients with MDD .


There is a discrepancy in the reported frequency of SSRI-induced sexual dysfunction .


On the other hand , there is also less evidence about sexual dysfunction with serotonin receptor antagonists and reuptake inhibitors ( SARIs ) .


Therefore , we aimed to assess sexual dysfunction in MDD patients who received fluoxetine , sertraline and trazodone .


In a single-blind , randomized , controlled trial in Kermanshah , Iran , during 2009-2010 , 195 patients who met the DSMIV-IR criteria for MDD were enrolled .


The patients completed the Hamilton Depression Rating Scale ( HAM-D ) and the sexual function questionnaire ( SFQ ) .


Eligible patients were allocated in three treatment groups ( receiving fluoxetine , sertraline or trazodone ) for 14 weeks randomly .


Measurement of HAMD was repeated in 4-week interval .


Analysis for comparing sexual dysfunction among three groups and men and women was performed .


There were 102 men and 93 women in the three groups receiving fluoxetine ( n = 64 ) , sertraline ( n = 67 ) and trazodone ( n = 64 ) .


There was no significant difference in the sexual dysfunction of the patients in the three groups at baseline ( P > .05 ) .


After treatment , both men and women who had received fluoxetine had the most impairment in desire/drive items ( 43 % -51 % and 44 % -50 % , respectively ) , while patients receiving trazodone had the least impairment in these items ( 12 % -18 % and 23 % -24 % , respectively ) .


Trazodone was also induced with a lower rate of impairment in arousal/orgasm items in men ( 9 % -15 % ) compared with the other two drugs .


Compared with fluoxetine and trazodone , sertraline was associated with intermediate impairment in sexual function ( 39 % -42 % in desire/drive items and 32 % -39 % in arousal/orgasm items ) that was lower than that with fluoxetine and more than that with trazodone .


There were different rates of sexual dysfunction with different antidepressants drugs in under treated patients .


Compared with fluoxetine , and sertraline , trazodone was associated with the fewest sexual dysfunction .


Fluoxetine was also associated with more sexual dysfunction than sertraline .


Further research to better identify the differences among antidepressant drugs is recommended .


To evaluate the potential efficacy of buspirone as a relapse-prevention treatment for cocaine dependence .


A randomized , double-blind , placebo-controlled , 16-week pilot trial was conducted at 6 clinical sites between August 2012 and June 2013 .


Adult crack cocaine users meeting DSM-IV-TR criteria for current cocaine dependence who were scheduled to be in inpatient/residential substance use disorder ( SUD ) treatment for 12-19 days when randomized and planning to enroll in local outpatient treatment through the end of the active treatment phase were randomized to buspirone titrated to 60 mg/d ( n = 35 ) or placebo ( n = 27 ) .


All participants received psychosocial treatment as usually provided by the SUD treatment programs in which they were enrolled .


Outcome measures included maximum days of continuous cocaine abstinence ( primary ) , proportion of cocaine use days , and days to first cocaine use during the outpatient treatment phase ( study weeks 4-15 ) as assessed by self-report and urine drug screens .


There were no significant treatment effects on maximum continuous days of cocaine abstinence or days to first cocaine use .


In the female participants ( n = 23 ) , there was a significant treatment-by-time interaction effect ( = 15.26 , P < .0001 ) , reflecting an increase in cocaine use by those receiving buspirone , relative to placebo , early in the outpatient treatment phase .


A similar effect was not detected in the male participants ( n = 39 ; = 0.14 , P = .70 ) .


The results suggest that buspirone is unlikely to have a beneficial effect on preventing relapse to cocaine use and that buspirone for cocaine-dependent women may worsen their cocaine use outcomes .


ClinicalTrials.gov identifier : NCT01641159 .


People with intellectual disabilities ( ID ) have lower levels of physical activity and quality of life and they have a lot of barriers to face when taking part in physical activity .


Other problems are the poor adherence to physical activity such people have so this study is designed to improve adherence to physical activity for people with intellectual disabilities with the assistance of an application for smartphones .


The aim of the study will be to improve physical activity and physical condition after multimodal intervention and to analyse the promotion of adherence to physical activity through a multimodal intervention and an app intervention ( mHealth ) in people with ID .


A two-stage study will be conducted .


In stage 1 a multimodal intervention will take place will be done with physical activity and educational advice over eight weeks , two days a week .


Data will be measured after and before the intervention .


In stage 2 a randomized controlled trial will be conducted .


In the intervention group we will install an application to a smartphone ; this application will be a reminder to do a physical activity and they have to select whether they have or have n't done a physical activity every day .


This application will be installed for 18 weeks .


Data will be measured after and before the application is installed in two groups .


We will measure results 10 weeks later when the two groups do n't have the reminder .


The principal outcome used to measure the adherence to physical activity will be the International Physical Activity Questionnaire ; secondary outcomes will be a fun-fitness test and self-report survey about quality of life , self-efficacy and social support .


Samples will be randomized by sealed envelope in two groups , with approximately 20 subjects in each group .


It 's important to know that the therapist will be blinded and wo n't know the subjects of each group .


Offering people with ID a multimodal intervention and tool to increase the adherence to a physical activity may increase the levels of physical activity and quality of life .


Such a scheme , if beneficial , could be implemented successfully within public health sense .


ClinicalTrials.gov Identifier : NCT01915381 .


We report updated progression-free survival ( PFS ) and overall survival ( OS ) data from a trial that compared capecitabine plus oxaliplatin ( CapeOX ) versus S-1 plus oxaliplatin ( SOX ) for the first-line treatment of metastatic colorectal cancer .


This trial was a randomized , two-armed , non-inferiority phase 3 comparison of CapeOX ( capecitabine 1000 mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1 ) versus SOX ( S-1 40 mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1 ) .


The primary end point was to show non-inferiority of SOX relative to CapeOX in terms of PFS .


Thus , a follow-up exploratory analysis of PFS and OS was performed .


The intention to treat ( ITT ) population was comprised of 340 patients ( SOX arm : 168 and CapeOX arm : 172 ) .


The updated median PFS was 7.1 months ( 95 % CI 6.4-8 .0 ) in the SOX group and 6.3 months ( 95 % CI 4.9-6 .7 ) in the CapeOX group ( hazard ratio [ HR ] , 0.83 [ 0.66-1 .04 ] , p = .10 ) .


The median OS was 19.0 months ( 95 % CI 15.3-23 .0 ) in the SOX group and 18.4 months ( 95 % CI 14.1-20 .7 ) in the CapeOX group ( HR , 0.86 [ 0.68-1 .08 ] , p = .19 ) .


Subgroup analyses according to principal demographic factors such as sex , age , ECOG ( Eastern Cooperative Oncology Group ) performance status , primary tumor location , measurability , previous adjuvant therapy , number of metastatic organs , and liver metastases showed no interaction between any of these characteristics and the treatment .