The present study suggests that long term aerobic exercise has positive effects on systolic and diastolic blood pressure as well as heart rate of T2DM patients .


We observed significant differences in levels of BMI in two groups after intervention .


Intermittent preventive treatment in pregnancy ( IPTp ) with sulfadoxine-pyrimethamine ( SP ) is recommended by WHO to prevent malaria in African pregnant women .


The spread of SP parasite resistance has raised concerns regarding long-term use for IPT .


Mefloquine ( MQ ) is the most promising of available alternatives to SP based on safety profile , long half-life , and high efficacy in Africa .


We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women .


A total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin , Gabon , Mozambique , and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens .


The study arms were : ( 1 ) SP , ( 2 ) single dose MQ ( 15 mg/kg ) , and ( 3 ) split-dose MQ in the context of long lasting insecticide treated nets .


There was no difference on low birth weight prevalence ( primary study outcome ) between groups ( 360/2 ,778 [ 13.0 % ] ) for MQ group and 177/1 ,398 ( 12.7 % ) for SP group ; risk ratio [ RR ] , 1.02 ( 95 % CI 0.86-1 .22 ; p = 0.80 in the ITT analysis ) .


Women receiving MQ had reduced risks of parasitemia ( 63/1 ,372 [ 4.6 % ] in the SP group and 88/2 ,737 [ 3.2 % ] in the MQ group ; RR , 0.70 [ 95 % CI 0.51-0 .96 ] ; p = 0.03 ) and anemia at delivery ( 609/1 ,380 [ 44.1 % ] in the SP group and 1,110 / 2743 [ 40.5 % ] in the MQ group ; RR , 0.92 [ 95 % CI 0.85-0 .99 ] ; p = 0.03 ) , and reduced incidence of clinical malaria ( 96/551 .8 malaria episodes person/year [ PYAR ] in the SP group and 130/1 ,103.2 episodes PYAR in the MQ group ; RR , 0.67 [ 95 % CI 0.52-0 .88 ] ; p = 0.004 ) and all-cause outpatient attendances during pregnancy ( 850/557 .8 outpatients visits PYAR in the SP group and 1,480 / 1,110.1 visits PYAR in the MQ group ; RR , 0.86 [ 0.78-0 .95 ] ; p = 0.003 ) .


There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups .


Tolerability was poorer in the two MQ groups compared to SP .


The most frequently reported related adverse events were dizziness ( ranging from 33.9 % to 35.5 % after dose 1 ; and 16.0 % to 20.8 % after dose 2 ) and vomiting ( 30.2 % to 31.7 % , after dose 1 and 15.3 % to 17.4 % after dose 2 ) with similar proportions in the full and split MQ arms .


The open-label design is a limitation of the study that affects mainly the safety assessment .


Women taking MQ IPTp ( 15 mg/kg ) in the context of long lasting insecticide treated nets had similar prevalence rates of low birth weight as those taking SP IPTp .


MQ recipients had less clinical malaria than SP recipients , and the pregnancy outcomes and safety profile were similar .


MQ had poorer tolerability even when splitting the dose over two days .


These results do not support a change in the current IPTp policy .


ClinicalTrials.gov NCT 00811421 ; Pan African Clinical Trials Registry PACTR 2010020001429343 Please see later in the article for the Editors ' Summary .


We studied whether suppressed secretion of the orexigenic peptide ghrelin might be involved in the anorexigenic effects of nicotine .


Fifty healthy non-smokers chewed gums containing 2mg nicotine , or no nicotine in a double-blind randomised crossover design in two independent studies .


Plasma nonacylated ghrelin was not significantly affected by nicotine after 30 and 60min .


Increased blood pressure and decreased appetite ratings confirmed a biological nicotine effect .


These results do not support a key role of peripheral ghrelin secretion in weight changes related to smoking or smoking cessation , but do not rule out that central nervous system ghrelin is involved .


External thermal support is critical for preterm or ill infants due to altered thermoregulation .


Incubators are the gold standard for long-term support and have been adopted successfully in many countries .


Alternatives such as radiant warmers , blankets and others are often used as standard of care ( SoC ) in resource-limited settings when infants are otherwise not in Kangaroo Mother Care ( KMC ) .


In this pilot study , we evaluate the feasibility of a conductive thermal mattress ( CTM ) using phase change materials as a low-cost warmer .


We conducted a prospective multicentre open-label randomised controlled trial to determine non-inferiority of this CTM to SoC warming practices in low birthweight infants .


The primary outcome was maintenance of axillary temperature .


We equally randomised 160 infants to CTM or SoC .


The latter cohort continued to receive warmth by radiant warmers ( n = 48 ) , blankets ( n = 18 ) , warmed cradles ( n = 7 ) or KMC ( n = 7 ) before , during and subsequent to the study .


CTM was deemed non-inferior since warmed babies had higher axillary temperature compared with SoC ( mean increase 0.110.03 C SEM ; p < 0.001 ) .


Post hoc comparison to radiant warmers alone showed that CTM led to a higher axillary temperature ( mean increase by 0.140.03 C SEM ; p < 0.001 ) .


Short-term use of CTM compared with radiant warmers and other modes of warming is non-inferior to SoC and efficacious in maintaining body temperature .


No adverse effects were reported .


An extended multinational trial , preferably one that demonstrates longer-term thermoregulation , is warranted .


Clinical Trials Registry of India ( CTRI/2010/091 / 002916 and CTRI/2011/04 / 001696 ) .


Schizophrenia is one of the most serious forms of mental illness among people being treated in psychiatric clinics in developing and developed countries .


Providing care for people diagnosed with schizophrenia can be stressful for their caregivers .


Psycho-educational interventions may improve patients ' and primary caregivers ' knowledge of schizophrenia and impact positively on patients ' physical and psychological outcomes and primary caregivers ' burden of care and quality of life .


Studies thus far have shown that these interventions may improve patients ' and caregivers ' outcomes , but the quality of included randomized controlled trials ( RCTs ) is poor and it is difficult to draw firm conclusions as to the effectiveness of such interventions on patients and primary caregivers ' outcomes , hence the current study .


A randomized controlled trial in four outpatient mental health clinics in Jordan comparing psycho-educational interventions in the form of six booklets every fortnight , with treatment as usual in people diagnosed with schizophrenia and their primary caregivers .


The primary outcome for participants is knowledge of Schizophrenia ; secondary outcomes for patients are positive and negative symptoms of schizophrenia and relapse rate , while secondary outcomes for primary caregivers are burden of care and quality of life .


All measures are assessed at baseline , immediately post-intervention and at three months follow-up .


This randomized control trial , conducted in Jordan among people living with schizophrenia and their primary caregivers , will assess the effect of psycho-educational interventions on knowledge of Schizophrenia , patients ' positive and negative symptoms and quality of life , and caregivers ' burden of care .


Current Controlled Trials ISRCTN78084871 .


Exercise has been shown to improve clinical measures of strength , balance and mobility , and in some cases , has improved symptoms of tremor and rigidity in people with Parkinson 's disease ( PD ) .


However , to date , no research has examined whether improvements in trunk control can remedy deficits in dynamic postural stability in this population .


The proposed randomised controlled trial aims to establish whether a 12-week exercise programme aimed at improving dynamic postural stability in people with PD ; ( 1 ) is more effective than education ; ( 2 ) is more effective when training frequency is increased ; and ( 3 ) provides greater long-term benefits than education .


Forty-five community-dwelling individuals diagnosed with idiopathic PD with a falls history will be recruited .


Participants will complete baseline assessments including tests of cognition , vision , disease severity , fear of falling , mobility and quality of life .


Additionally , participants will complete a series of standing balance tasks to evaluate static postural stability , while dynamic postural control will be measured during walking using head and trunk-mounted three-dimensional accelerometers .


Following baseline testing , participants will be randomly-assigned to one of three intervention groups , who will receive either exercise once per week , exercise 3 days/week , or education .


Participants will repeat the same battery of tests conducted at baseline after the 12-week intervention and again following a further 12-week sustainability period .


This study has the potential to show that low-intensity and progressive trunk exercises can provide a non-invasive and effective means for maintaining or improving postural stability for people with PD .


Importantly , if the programme is noted to be effective , it could be easily performed by patients within their home environment or under the guidance of available allied health professionals .


The protocol for this study is registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12613001175763 ) .


To compare the results of transperitoneal laparoscopic vs retroperitoneoscopic simple nephrectomy for benign renal diseases in a prospective randomized design .


In this study between January 2009 and August 2013 , 31 patients underwent transperitoneal laparoscopic nephrectomy and 31 retroperitoneoscopic nephrectomy after randomization .


The 2 groups were compared for the visual pain score on the first and second postoperative days as the primary end point of the study .


Complications were recorded and graded using Dindo-modified Clavien classification of surgical complications .


Secondary objectives were to compare each of the operative techniques in terms of duration of surgery , complication rates , and postoperative convalescence .


Statistical analysis was performed with SPSS version 16.0 with P < .05 considered statistically significant .


The difference in the visual pain score ( 4.9 vs 2.7 on day 1 ; 3.2 vs 1.1 on day 2 ) and the tramadol requirements ( 167.3 vs 132.8 mg ) were statistically significant and more in the transperitoneal laparoscopic nephrectomy .


The hospital stay and convalescence were significantly lower in retroperitoneoscopic group .


Three patients in transperitoneal laparoscopic nephrectomy group and 2 patients in retroperitoneoscopic group required conversion .


Mean time to normal activities wassignificantly less in retroperitoneal laparoscopic nephrectomy group ( 16.73.5 vs 9.344.9 days ; P = .0001 ) .


Although both transperitoneal laparoscopic and retroperitoneoscopic simple nephrectomy are feasible options for nonfunctioning kidneys due to benign renal diseases in adults , retroperitoneal laparoscopic nephrectomy is associated with significantly less pain , less analgesic requirement , shorter hospital stay , and short convalescence as compared with transperitoneal laparoscopic approach .


Breathlessness is common in advanced cancer .


The Breathlessness Intervention Service ( BIS ) is a multi-disciplinary complex intervention theoretically underpinned by a palliative care approach , utilising evidence-based non-pharmacological and pharmacological interventions to support patients with advanced disease .


We sought to establish whether BIS was more effective , and cost-effective , for patients with advanced cancer and their carers than standard care .


A single-centre Phase III fast-track single-blind mixed-method randomised controlled trial ( RCT ) of BIS versus standard care was conducted .


Participants were randomised to one of two groups ( randomly permuted blocks ) .


A total of 67 patients referred to BIS were randomised ( intervention arm n = 35 ; control arm n = 32 received BIS after a two-week wait ) ; 54 completed to the key outcome measurement .


The primary outcome measure was a 0 to 10 numerical rating scale for patient distress due to breathlessness at two-weeks .


Secondary outcomes were evaluated using the Chronic Respiratory Questionnaire , Hospital Anxiety and Depression Scale , Client Services Receipt Inventory , EQ-5D and topic-guided interviews .


BIS reduced patient distress due to breathlessness ( primary outcome : -1.29 ; 95 % CI -2.57 to -0.005 ; P = 0.049 ) significantly more than the control group ; 94 % of respondents reported a positive impact ( 51/53 ) .


BIS reduced fear and worry , and increased confidence in managing breathlessness .


Patients and carers consistently identified specific and repeatable aspects of the BIS model and interventions that helped .


How interventions were delivered was important .


BIS legitimised breathlessness and increased knowledge whilst making patients and carers feel ` not alone ' .


BIS had a 66 % likelihood of better outcomes in terms of reduced distress due to breathlessness at lower health/social care costs than standard care ( 81 % with informal care costs included ) .


BIS appears to be more effective and cost-effective in advanced cancer than standard care .


RCT registration at ClinicalTrials.gov NCT00678405 ( May 2008 ) and Current Controlled Trials ISRCTN04119516 ( December 2008 ) .


To evaluate the efficacy and tolerability of armodafinil in patients with excessive sleepiness following mild or moderate closed traumatic brain injury ( TBI ) .


Randomized , placebo-controlled , double-blind trial followed by open-label extension .


40 US centers .


Adults with closed TBI ( N = 117 ) , Glasgow Coma Scale score > 8 at time of injury ; baseline Epworth Sleepiness Scale ( ESS ) 10 ; sleep latency < 8 minutes on multiple sleep latency test ( MSLT ) ; and Clinical Global Impression-Severity of Illness ( CGI-S ) score 4 for excessive sleepiness .


Patients received armodafinil ( 50 , 150 , or 250 mg/day ) or placebo for 12 weeks followed by an optional 12-month open-label extension .


Outcomes included MSLT , ESS , Clinical Global Impression-Change ( CGI-C ) , TBI-Work Instability Scale ( TBI-WIS ) , CGI-S , and tolerability .


The study was terminated early due to low enrollment .


Patients receiving 250 mg armodafinil showed significant improvement in sleep latency from baseline to final visit versus placebo ( +7.2 minutes vs. +2.4 minutes ; p = 0.0010 ) .


CGI-C ratings were much / very much improved in approximately 50 % of patients receiving 150 and 250 mg armodafinil , compared to 38 % on placebo .


ESS and TBI-WIS scores were not significantly different between groups .


In the open-label extension ( N = 49 ) , patients demonstrated gradual improvement in ESS , TBI-WIS , and CGI-S scores up to 48 weeks post-baseline .


Armodafinil was generally well tolerated , with headache the most common adverse event in both double-blind and open-label portions .


Armodafinil 250 mg significantly improved sleep latency in patients with excessive sleepiness associated with mild or moderate TBI .


Efficacy and tolerability of armodafinil were sustained throughout the open-label extension .


NCT00893789 , NCT00983437 .


Is it possible to reach performance equality between boys and girls in a science class ?


Given the stereotypes targeting their groups in scientific domains , diagnostic contexts generally lower girls ' performance and non-diagnostic contexts may harm boys ' performance .


The present study tested the effectiveness of a mastery-oriented assessment , allowing both boys and girls to perform at an optimal level in a science class .


Participants were 120 boys and 72 girls ( all high-school students ) .


Participants attended a science lesson while expecting a performance-oriented assessment ( i.e. , an assessment designed to compare and select students ) , a mastery-oriented assessment ( i.e. , an assessment designed to help students in their learning ) , or no assessment of this lesson .


In the mastery-oriented assessment condition , both boys and girls performed at a similarly high level , whereas the performance-oriented assessment condition reduced girls ' performance and the no-assessment condition reduced boys ' performance .


One way to increase girls ' performance on a science test without harming boys ' performance is to present assessment as a tool for improving mastery rather than as a tool for comparing performances .


Traumatic brain injury ( TBI ) is a major public health problem recently , however , no intervention showing convincing efficacy .


Therapeutic hypothermia with a relatively long duration ( more than 48 h ) , as a promising treatment measure , might improve the patient outcome following severe TBI .


The LTH-1 trial is a prospective , nationwide multicenter , randomized , controlled clinical trial to examine the efficacy and safety of long-term mild hypothermia in adult patients after severe traumatic brain injury .


A total of 300 consecutive patients will be recruited from 15 large neurosurgical centers in China .


The eligible patient will be randomized to receive either long-term mild hypothermia ( 34-35 C ) for 5 days , or normothermia ( 36-37 C ) .


Additionally , a standardized management protocol will be used in all patients .


The primary end point is the neurological outcome 6 months post-injury on the Glasgow Outcome Scale .


The secondary outcomes include GOS score at one month post-injury , mortality during six months after injury , length of ICU and hospital stay , intracranial pressure control and Glasgow Coma Scale score during the hospital stay and frequency of complications during the six-month follow-up period .


Long-term hypothermia is recommended by most recent studies and its efficacy urgently needs to be established in randomized controlled settings .


The LTH-1 trial , together with other ongoing studies , will present more evidence for optimal use of hypothermia in severe TBI patients .


RESTORE was a randomized , partially placebo-controlled exploratory study evaluating multiple sclerosis ( MS ) disease activity during a 24-week interruption of natalizumab .


Eligible patients were relapse-free through the prior year on natalizumab and had no gadolinium-enhancing lesions on screening brain MRI .


Patients were randomized 1:1:2 to continue natalizumab , to switch to placebo , or to receive alternative immunomodulatory therapy ( other therapies : IM interferon -1 a [ IM IFN -- 1a ] , glatiramer acetate [ GA ] , or methylprednisolone [ MP ] ) .


During the 24-week randomized treatment period , patients underwent clinical and MRI assessments every 4 weeks .


Patients ( n = 175 ) were randomized to natalizumab ( n = 45 ) , placebo ( n = 42 ) , or other therapies ( n = 88 : IM IFN -- 1a , n = 17 ; GA , n = 17 ; MP , n = 54 ) .


Of 167 patients evaluable for efficacy , 49 ( 29 % ) had MRI disease activity recurrence : 0/45 ( 0 % ) natalizumab , 19/41 ( 46 % ) placebo , 1/14 ( 7 % ) IM IFN -- 1a , 8/15 ( 53 % ) GA , and 21/52 ( 40 % ) MP .


Relapse occurred in 4 % of natalizumab patients and in 15 % -29 % of patients in the other treatment arms .


MRI disease activity recurred starting at 12 weeks ( n = 3 at week 12 ) while relapses were reported as early as 4-8 weeks ( n = 2 in weeks 4-8 ) after the last natalizumab dose .


Overall , 50/167 patients ( 30 % ) , all in placebo or other-therapies groups , restarted natalizumab early because of disease activity .


MRI and clinical disease activity recurred in some patients during natalizumab interruption , despite use of other therapies .


This study provides Class II evidence that for patients with MS taking natalizumab who are relapse-free for 1 year , stopping natalizumab increases the risk of MS relapse or MRI disease activity as compared with continuing natalizumab .


The efficacy of botulinum neurotoxin type A after prolonged storage at room temperature is currently unknown .


This randomized , double-blinded , split-face study investigated the impact of postreconstitution 25C storage for 1 week on the clinical efficacy of incobotulinumtoxinA in the treatment of lateral canthus lines .


Twenty-one participants with at least mild to moderate crow 's feet at maximum contraction on the Crow 's Feet Grading Scale ( CFGS ) underwent injection to each lateral canthus area with 10 U of freshly reconstituted and room temperature-stored product and followed for 4 months .


Responders were defined as those demonstrating at least a 1-point improvement on their CFGS score .


At each visit ( 2 weeks and 1 , 2 , 3 , and 4 months ) , there was no statistical difference in the rate of responders between the fresh and the stored products .


In addition , the percentage of responders displaying a 2-point versus a 1-point improvement and response longevity did not statistically differ between both products for the entire 4-month study duration .


Prolonged storage of incobotulinumtoxinA at room temperature does not appear to significantly alter its efficacy or longevity in the treatment of dynamic lateral canthus lines .


The aim of this study was to evaluate the safety and tolerability of sitagliptin 100 mg/day in elderly patients with type 2 diabetes .


A post hoc pooled analysis of 25 randomized , double-blind , parallel group clinical studies with results available as of 1 December 2011 .


Multicenter , international clinical trials .


Patients with type 2 diabetes aged 65 years or older .


Patients were randomized to sitagliptin 100 mg/day ( n = 1,261 ) or a comparator ( n = 1,185 ) for 12 weeks to 2 years .


In each study , investigators reported serious and non-serious adverse events that occurred during the study , and serious adverse events occurring within 14 days following the last dose of study drug .


This analysis used patient-level data from each study to assess the exposure-adjusted incidence rates of specific adverse events that occurred following initiation of study drug .


Summary measures of adverse events overall were similar between the sitagliptin and non-exposed ( active comparator or placebo ) groups , except for higher incidences of deaths and drug-related adverse events in the non-exposed group .


Incidence rates of specific adverse events were generally similar between the two groups , with the exception of hypoglycemia .


A lower incidence rate of hypoglycemia was observed in the sitagliptin group compared with the non-exposed group [ 7.0 vs. 14.3 per 100 patient-years ; difference -7.6 ( 95 % CI -11.2 to -4.3 ] ) , primarily due to greater use of sulfonylureas in the non-exposed group .


In this pooled safety analysis of elderly patients with type 2 diabetes , treatment with sitagliptin 100 mg/day was generally well tolerated for up to 2 years .


nab-Paclitaxel ( nab-P ) is approved , in the United States , in combination with carboplatin for the first-line treatment of advanced non-small-cell lung cancer , based on a randomized phase 3 trial of nab-P plus carboplatin ( nab-P/C ) versus solvent-based paclitaxel plus carboplatin ( sb-P/C ) .


This trial revealed a higher overall response rate ( 33 % versus 25 % ; p = 0.005 ) and longer , but not statistically significant , overall and progression-free survival for nab-P/C versus sb-P/C .


In addition , nab-P/C demonstrated lower rates of grade 3 or higher peripheral neuropathy , myalgia , arthralgia , and neutropenia but higher rates of anemia and thrombocytopenia .


This report analyzes patient and physician assessment of symptoms within this trial .


Patients completed the taxane subscale of the Functional Assessment of Cancer Therapy questionnaire , which focuses on taxane toxicity , including peripheral neuropathy and neurotoxicity .


Mean baseline scores and changes from baseline are reported .


Physicians also graded the severity of neuropathy at each patient visit using National Cancer Institute Common Toxicity Criteria .


Patients receiving nab-P/C reported significantly less worsening of peripheral neuropathy ( p < 0.001 ) , pain ( p < 0.001 ) , and hearing loss ( p = 0.002 ) .


Patient-reported edema was similar between the two treatment arms .


In agreement with patient-reported symptoms , the results of a per-treatment cycle physician assessment of peripheral neuropathy also favored nab-P/C over sb-P/C ( p < 0.001 ) .


In this trial of patients receiving first-line treatment for advanced non-small-cell lung cancer , nab-P/C was associated with statistically and clinically significant reductions in patient-reported neuropathy , neuropathic pain in the hands and feet , and hearing loss compared with sb-P/C .


Inhaled long-acting beta2 agonists used alone and in combination with an inhaled corticosteroid reduce the risk of exacerbations in patients with stable COPD .


However , the relative efficacy of these agents in preventing recurrent exacerbations in those recovering from an initial episode is not known .


This study compared the rate of COPD exacerbations over the 26 weeks after an initial exacerbation in patients receiving the combination of fluticasone propionate and salmeterol ( FP/SAL ) or SAL alone .


Patients ( n = 639 ) aged 40 years were randomized to either twice-daily inhaled FP/SAL 250/50 g or SAL 50 g. Primary , and secondary , endpoints were rates of recurrent severe , and moderate/severe , exacerbations of COPD .


Lung function , health outcomes and levels of biomarkers of systemic inflammation were also assessed .


There was no statistically significant treatment difference in rates of recurrent severe exacerbations ( treatment ratio 0.92 [ 95 % CI : 0.58 , 1.45 ] ) and moderate/severe exacerbations ( 0.82 [ 0.64 , 1.06 ] ) between FP/SAL and SAL in the intent-to-treat population .


Pre-dose morning FEV1 change from baseline was greater ( 0.10 L [ 0.04 , 0.16 ] ) with FP/SAL than SAL .


No treatment difference was seen for other endpoints including patient-reported health outcomes and biomarker levels for the full cohort .


No significant treatment difference between FP/SAL and SAL was seen in COPD exacerbation recurrence for the complete cohort .


Treatment benefit with FP/SAL over SAL ( treatment ratio 0.68 [ 0.47 , 0.97 ] ) was seen in patients having FEV130 % and prior exposure to ICS .


No unexpected safety issues were identified with either treatment .


Patients with the most severe COPD may be more refractory to treatment .


ClinicalTrials.gov ( identifier NCT01110200 ) .


This study was funded by GlaxoSmithKline ( study number ADC113874 ) .


To evaluate the efficacy of internal application of Qigui Mixture ( QM ) and external application of Qigui Huoxue Lotion ( QHL ) in treating type 2 diabetic peripheral neuropathy ( DNP ) patients of qi-yin deficiency complicated phlegm-dampness blocking collaterals syndrome ( QYD-PDBCS ) , and to primarily discuss its mechanism .


Totally 62 DPN patients of QYD-PDBCS were randomly assigned to the treatment group ( 31 cases ) and the control group ( 31 cases ) .


All patients received routine comprehensive therapy .


Patients in the control group took Mecobalamine Tablet , 500 microg each time , 3 times per day .


Patients in the treatment group additionally took QM , 200 mL per day , twice daily .


Besides , they had foot bath in QHL 10 - 15 min every evening for 3 months .


The efficacy was assessed by Chinese medical symptom integrals and Toronto clinical scoring system ( TCSS ) before treatment , 2 and 3 months after treatment .


The nerve conduction velocity was determined ; the serum levels of total antioxidant capacity ( T - AOC ) , malondialdehyde ( MDA ) , and superoxide dismutase ( SOD ) were detected 2 and 3 months after treatment .


The total effective rates of Chinese medical symptom integrals and TCSS score were obviously higher in the treatment group than in the control group ( P < 0.05 ) .


The nerve conduction velocity was significantly improved in the treatment group , when compared with before treatment ( P < 0.01 ) .


There was statistical difference in the nerve conduction velocity difference of right median nerve motor branch , bilateral tibial nerve motor branches , bilateral common peroneal nerve motor branches , bilateral ulnar nerve sensory branches , and left tibial nerve sensory branch ( P < 0.05 ) .


Compared with before treatment , serum levels of T-AOC and SOD significantly increased , and the level of MDA decreased significantly in the treatment group after 2 and 3 months of treatment ( P < 0.01 ) .


But only the SOD level increased significantly in the control group ( P < 0.01 ) .


There was no statistical difference in increased T-AOC level between the two groups after 2 months of treatment ( P > 0.05 ) , but there was statistical difference in increased SOD level and decreased MDA level ( P < 0.05 ) .


There was statistical difference in increased T-AOC and SOD levels and decreased MDA level between the two groups after 3 months of treatment ( P < 0.05 ) .


No adverse reaction occurred during the therapeutic course .


The internal application of QM and external application of QHL combined with Mecobalamine in treating DPN was safe and effective , with more significant efficacy than using Mecobalamine alone .


Its mechanism might be associated with resistance to oxidative stress .


To compare the effectiveness and costs of telephone-only approach to in-person plus telephone for delivering an evidence-based , coordinated care management program for dementia .


We randomized 151 patient-caregiver dyads from an underserved predominantly Latino community to two arms that shared a care management protocol but implemented in different formats : in-person visits at home and/or in the community plus telephone and mail , versus telephone and mail only .


We compared between-arm caregiver burden and care-recipient problem behaviors ( primary outcomes ) and patient-caregiver dyad retention , care quality , health care utilization , and costs ( secondary outcomes ) at 6 - and 12-months follow-up .


Care quality improved substantially over time in both arms .


Caregiver burden , care-recipient problem behaviors , retention , and health care utilization did not differ across arms but the in-person program cost more to deliver .


Dementia care quality improved regardless of how care management was delivered ; large differences in effectiveness or cost offsets were not detected .


Elevated circulating levels of the protein galectin-3 , a mediator of fibrogenesis , have previously been associated with adverse outcomes in heart failure ( HF ) patients and appear to modify response to certain pharmacologic therapies .


This study investigated the relationship between galectin-3 level and clinical outcomes in HF patients randomized to implantable cardioverter defibrillator ( ICD-only ) or cardiac resynchronization therapy ( CRT-D ) .


Plasma galectin-3 concentrations were measured in 654 New York Heart Association functional class I/II patients participating in the MADIT-CRT trial .


A heterogeneity of response was detected between pre-implantation galectin-3 and randomization group ( CRT-D or ICD-only ) on the primary MADIT-CRT trial end point of nonfatal HF event or death ( P = .045 ) .


Among patients with baseline galectin-3 levels in the top quartile of the distribution , CRT-D was associated with a 65 % reduction in risk of the primary end point ( hazard ratio [ HR ] 0.35 , 95 % confidence interval [ CI ] 0.19-0 .67 ) , whereas among patients with lower baseline galectin-3 values CRT-D was associated with a 25 % decrease in risk ( HR 0.75 , 95 % CI .


0.51-1 .11 ) .


Baseline galectin-3 level also was observed to be an independent predictor of the primary end point ( multivariable adjusted HR per log unit increase : 1.55 ; 95 % CI 1.01-2 .38 ; P = .043 ) .


Elevated galectin-3 was found to be an independent predictor of adverse HF outcome in patients with mildly symptomatic HF .


A significant interaction of device randomization group with pre-implantation galectin-3 level was detected , with HF patients with the highest baseline galectin-3 levels deriving a disproportionately larger benefit from CRT-D .


Although mitral regurgitation ( MR ) results in left ventricular ( LV ) volume overload , right ventricular ( RV ) function may also be impaired .


We investigated the influence of short-term beta-blockade on RV function in patients with moderate-severe MR.


Twenty-six patients were randomised in a cross-over design to receive two weeks of beta-blockade or placebo .


Echocardiography was performed at baseline and at the end of the treatment periods .


Measurements included : RV ejection fraction ( RVEF ) tricuspid annular motion and Tei index .


No differences in mean RVEF ( 64.0 6.0 v 67.0 8.0 % , p = 0.3 ) , tricuspid annular motion ( 13.5 3.0 v 14.7 2.9 cm/s , p = 0.5 ) , or median Tei index ( 0.61 ( 0.54 , 0.88 ) v 0.59 ( 0.54 , 0.74 ) , p = 0.8 ) were observed between placebo and metoprolol , despite significantly longer cardiac time intervals .


Tei index under both conditions was significantly reduced .


Short-term treatment with a beta-blocker did not influence RV function in these patients .


Interestingly , the RV Tei index was high suggesting significant RV dysfunction despite normal RVEF .


A parallel-group randomized controlled trial ( RCT ) was conducted to evaluate the effect of combining the interscalene brachial plexus block ( IBPB ) with Intravenous-inhalation combined anesthesia to isolated Intravenous-inhalation anesthesia in the upper extremity fractures surgery of elderly patients .


One hundred elderly patients who underwent upper extremity surgery were randomly assigned to received isolated Intravenous-inhalation combined anesthesia ( group CI , n = 50 ) and IBPB associated with Intravenous-inhalation combined anesthesia ( group NB , n = 50 ) .


Associated side effects , recovery time after operation , as well as the dose of intraoperative vasoactive agents and auxiliary drugs were noted .


The two groups were not significantly different in gender ( P = 0.539 ) , ages ( P = 0.683 ) and weight ( P = 0.212 ) .


Five patients ( 10 % ) in the group NB and 17 patients ( 34 % ) in the group CI suffered from preoperative hypotension ( P = 0.004 ) .


Besides , lower incidence of other adverse effects such as mental stress , incision pain and hypertension were also found in the group NB ; however , the differences were not statistically significant ( P > 0.05 ) .


The consumption of general anesthetics in the group NB was significantly less than that of the group CI ( propofol , P = 0.004 ; lsoflurane , P < 0.001 ) , and the recovery time of the group NB was significantly shorter than that of the group CI ( P = 0.020 ) .


Combining IBPB with Intravenous-inhalation combined anesthesia in elderly patients hold a greater potential for upper extremity fractures surgery due to its improved clinical effectiveness and fewer side effects .


Chronic heart failure , is increasing due to the aging population and improvements in heart disease detection and management .


The prevalence is estimated at ~ 10 % of the French general practice patient population over 59 years old .


The primary objective of this study is to improve the quality of life for heart failure patients though a complex intervention involving patient and general practitioner ( GP ) education in primary care .


A randomised , cluster controlled trial , stratified over 4 areas of the Auvergne region in France comparing intervention and control groups .


The inclusion criteria are : patients older than 50 years with New York Heart Association ( NYHA ) stage I , II , or III heart failure , with reduced ejection fraction or with preserved ejection fraction .


Heart failure should be confirmed by the patient 's cardiologist according to the European Society of Cardiology guidelines criteria .


The exclusion criteria include : severe cognitive disorders , living in an institution , participating in another clinical trial , having NYHA stage IV heart failure , or a lack of French language skills .


The complex intervention consists of training at the GP practice with an interactive 2-day workshop to provide a patient 's education programme .


GPs are trained to perform case management , lifestyle counselling and motivational interviewing , to educate patients on the main topics including clinical alarm signs , physical activity , diet and cardiovascular risk factors .


The patients ' education sessions are scheduled at 1 , 4 , 7 , 10 , 13 and 19 months following the start of the trial .


The primary outcome to be assessed is the impact on the quality of life as determined using two questionnaires : the Minnesota Living with Heart Failure Questionnaire and SF-36 .


To detect a difference in the mean quality of life at 19 months , we anticipate studying a minimum of 400 patients from 80 GPs .


This trial will provide insight into the effectiveness of a complex intervention to educate patients with heart failure including a 2-day GP workshop and patients ' education programme in the setting of a GP consultation to improve the quality of life in patients with chronic heart failure .


This complex intervention tool could be used during initial and further medical training .


ETIC is a cluster-randomised , controlled trial registered on ClinicalTrials.gov [ NCT01065142 , 2010 , Feb 8 ] and the French drug agency [ Agence Nationale de Scurit du Mdicament et des produits de sant ; registration number : 2009-A01142-55 , on March 5th , 2010 ] .


Enterocolitis ( EC ) is the most common and serious postoperative complication of Hirschsprung 's disease ( HD ) .


Probiotics potentially play a protective role in maintaining intestinal mucosal integrity .


Based on the beneficial effects of probiotics , we hypothesized that oral probiotics could decrease the incidence and severity of Hirschsprung 's disease-associated enterocolitis ( HAEC ) .


We conducted a prospective , multicenter , randomized , and controlled trial to assess whether oral probiotics could decrease the incidence and severity of HAEC .


HD patients were randomly assigned into the control group and probiotic-treated group .


All children in probiotic-treated group were fed with probiotics per day for 4weeks .


In next 3months , the incidence and severity of HAEC were analyzed .


The peripheral blood T lymphocyte subsets and cytokines , including TNF - , IFN - , IL-6 , and IL-10 , were analyzed by flow cytometry and enzyme immunoassay ( EIA ) .


Compared with the control group , the incidence of HAEC in the probiotic-treated group was significantly diminished .


The severity of EC was also remarkably decreased .


Furthermore , probiotics balanced T lymphocyte subsets .


Moreover , pro-inflammatory cytokines TNF - , IFN - , and IL-6 were significantly decreased and anti-inflammatory cytokine IL-10 was notably increased in probiotic-treated group .


Probiotics not only significantly diminished the incidence but also decreased the severity of HAEC .


Moreover , our study revealed that probiotics decreased pro-inflammatory cytokine and increased anti-inflammatory cytokine and furthermore balanced T lymphocytes ( registered with ClinicalTrials.gov , NCT number : NCT01934959 ) .


Renal impairment increases the risk of stroke and bleeding in patients with atrial fibrillation .


In the Randomized Evaluation of Long-Term Anticoagulant Therapy ( RELY ) trial , dabigatran , with 80 % renal elimination , displayed superiority over warfarin for prevention of stroke and systemic embolism in the 150-mg dose and significantly less major bleeding in the 110-mg dose in 18 113 patients with nonvalvular atrial fibrillation .


This prespecified study investigated these outcomes in relation to renal function .


Glomerular filtration rate was estimated with the Cockcroft-Gault , Chronic Kidney Disease Epidemiology Collaboration ( CKD-EPI ) , and Modification of Diet in Renal Disease ( MDRD ) equations in all randomized patients with available creatinine at baseline ( n = 17 951 ) , and cystatin C-based glomerular filtration rate was estimated in a subpopulation with measurements available ( n = 6190 ) .


A glomerular filtration rate 80 , 50 to < 80 , and < 50 mL/min was estimated in 32.6 % , 47.6 % , and 19.8 % and in 21.6 % , 59.6 % , and 18.8 % of patients based on Cockcroft-Gault and CKD-EPI , respectively .


Rates of stroke or systemic embolism , major bleeding , and all-cause mortality increased as renal function decreased .


The rates of stroke or systemic embolism were lower with dabigatran 150 mg and similar with 110 mg twice daily compared with warfarin , without significant heterogeneity in subgroups defined by renal function ( interaction P > 0.1 for all ) .


For the outcome of major bleeding , there were significant interactions between treatment and renal function according to CKD-EPI and MDRD equations , respectively ( P < 0.05 ) .


The relative reduction in major bleeding with either dabigatran dose compared with warfarin was greater in patients with glomerular filtration rate 80 mL/min .


The efficacy of both dosages of dabigatran was consistent with the overall trial irrespective of renal function .


However , with the CKD-EPI and MDRD equations , both dabigatran dosages displayed significantly lower rates of major bleeding in patients with glomerular filtration rate 80 mL/min .


http://www.clinicaltrials.gov .


Unique identifier : NCT00262600 .


To determine the prognostic and predictive value of intrinsic subtyping by using immunohistochemical ( IHC ) biomarkers for ipsilateral breast relapse ( IBR ) in participants in an early breast cancer randomized trial of tamoxifen with or without breast radiotherapy ( RT ) .


IHC analysis of estrogen receptor , progesterone receptor , human epidermal growth factor receptor 2 ( HER2 ) , cytokeratin 5/6 , epidermal growth factor receptor , and Ki-67 was conducted on 501 of 769 available blocks .


Patients were classified as luminal A ( n = 265 ) , luminal B ( n = 165 ) , or high-risk subtype ( luminal HER2 , n = 22 ; HER2 enriched , n = 13 ; basal like , n = 30 ; or triple-negative nonbasal , n = 6 ) .


Median follow-up was 10 years .


Classification by subtype was prognostic for IBR ( 10-year estimates : luminal A , 5.2 % ; luminal B , 10.5 % ; high-risk subtypes , 21.3 % ; P < .001 ) .


Luminal subtypes seemed to derive less benefit from RT ( luminal A hazard ratio [ HR ] , 0.40 ; luminal B HR , 0.51 ) than high-risk subtypes ( HR , 0.13 ) ; however , the overall subtype-treatment interaction term was not significant ( P = .26 ) .


In an exploratory analysis of women with clinical low-risk ( age older than 60 years , T1 , grade 1 or 2 ) luminal A tumors ( n = 151 ) , 10-year IBR was 3.1 % versus 11.8 % for the high-risk cohort ( n = 341 ; P = .0063 ) .


Clinical low-risk luminal A patients had a 10-year IBR of 1.3 % with tamoxifen versus 5.0 % with tamoxifen plus RT ( P = .42 ) .


Multivariable analysis showed that RT ( HR , 0.31 ; P < .001 ) , clinical risk group ( HR , 2.2 ; P = .025 ) , and luminal A subtype ( HR , 0.25 ; P < .001 ) were significantly associated with IBR .


IHC subtyping was prognostic for IBR but was not predictive of benefit from RT. .


Further studies may validate the exploratory finding of a low-risk luminal A group who may be spared breast RT. .


Dry skin reflects a skin barrier defect which can lead to atopic dermatitis .


Little is known about the distinct effects of emollient use in children with dry skin and atopic predisposition .


We investigated the effects of daily application of pressed ice plant juice ( PIPJ ) - based emollients and petrolatum-based emollients .


Children aged 2-6 years with dry skin and atopic predisposition were randomized into 2 groups : group 1 received emollients containing PIPJ and natural lipids , while group 2 received petrolatum-based emollients .


Skin condition and biophysical properties of the skin barrier were assessed at inclusion and weeks 4 , 12 and 16 .


Skin condition improved significantly in all children .


Comparing the groups , children treated with emollients containing PIPJ showed significantly higher stratum corneum hydration values and significantly lower transepidermal water loss values at week 16 on the forearm and forehead .


A significant decrease in skin pH was noted in group 2 on the forearm and forehead ; group 1 showed a stable course .


Early intervention with emollients in children with dry skin condition and atopic predisposition may improve their skin condition during daily emollient application .


PIPJ-based formulations may be helpful to maintain skin barrier integrity .


In 2010 a Cochrane review confirmed that folic acid ( FA ) supplementation prevents the first - and second-time occurrence of neural tube defects ( NTDs ) .


At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital malformations ( CMs ) or the risk of a specific and selected group of them , namely cardiac defects and oral clefts .


Furthermore , the effects on the prevention of prematurity , foetal growth retardation and pre-eclampsia are unclear.Although the most common recommendation is to take 0.4 mg/day , the problem of the most appropriate dose of FA is still open.The aim of this project is to assess the effect a higher dose of peri-conceptional FA supplementation on reducing the occurrence of all CMs .


Other aims include the promotion of pre-conceptional counselling , comparing rates of selected CMs , miscarriage , pre-eclampsia , preterm birth , small for gestational age , abruptio placentae .


This project is a joint effort by research groups in Italy and the Netherlands .


Women of childbearing age , who intend to become pregnant within 12months are eligible for the studies .


Women are randomly assigned to receive 4mg of FA ( treatment in study ) or 0.4 mg of FA ( referent treatment ) daily .


Information on pregnancy outcomes are derived from women-and-physician information.We foresee to analyze the data considering all the adverse outcomes of pregnancy taken together in a global end point ( e.g. : CMs , miscarriage , pre-eclampsia , preterm birth , small for gestational age ) .


A total of about 1,000 pregnancies need to be evaluated to detect an absolute reduction of the frequency of 8 % .


Since the sample size needed for studying outcomes separately is large , this project also promotes an international prospective meta-analysis .


The rationale of these randomized clinical trials ( RCTs ) is the hypothesis that a higher intake of FA is related to a higher risk reduction of NTDs , other CMs and other adverse pregnancy outcomes .


Our hope is that these trials will act as catalysers , and lead to other large RCTs studying the effects of this supplementation on CMs and other infant and maternal outcomes .


Italian trial : ClinicalTrials.gov Identifier : NCT01244347.Dutch trial : Dutch Trial Register ID : NTR3161 .


Inflammatory processes , which raise the unsteadiness of brain neuron membrane potentials , might enhance the development of epilepsy .


Inflammation is a substantial indicator of epilepsy risk .


In this study , we evaluated whether chronic osteomyelitis ( COM ) , a chronic inflammatory disease , increases epilepsy risk .


A Taiwanese national insurance claims dataset of more than 22 million enrollees was used to select 20,996 COM patients and 83,973 randomly selected age - and gender-matched controls to investigate epilepsy development over an 11-year follow-up period , starting on January 1 , 2000 and ending on December 31 , 2010 .


The epilepsy risk was analyzed using a Cox proportional hazards regression model .


Comorbidities known to elevate epilepsy risk , including diabetes , hypertension , head injury , stroke , and cancer , were commonly noted in the COM cohort , which had considerably higher risk of epilepsy than did the control group .


Comparing only those without comorbidities , COM patients still exhibited higher epilepsy risk than the control group did ( adjusted hazard ratio [ aHR ] = 3.87 , 95 % confidence interval [ CI ] : 3.01-4 .98 ) .


The younger population exhibited an even greater risk ( age 39 years : aHR = 6.10 , 95 % CI : 4.00-9 .30 ; age 65 years : aHR = 1.66 , 95 % CI : 1.28-2 .16 ) .


This is the first study linking COM to an increased risk in epilepsy development .


The results demonstrated that COM is a significant predictor of epilepsy .


Further study of COM patients , particularly young patients , is recommended to facilitate epilepsy prevention .


Hypertension is poorly controlled .


Team-based care and changes in the process of care have been proposed to address these quality problems .


However , assessing care processes is difficult because they are often confounded even in randomized behavioral studies by unmeasured confounders based on discretion of health care providers .


To evaluate the effects of process measures including number of counseling sessions about lifestyle modification and number of antihypertensive medications on blood pressure change and payer-perspective treatment costs .


Data were obtained from two prospective , cluster randomized controlled clinical trials ( Trial A and B ) implementing physician-pharmacist collaborative interventions compared with usual care over six months in community-based medical offices in the Midwest .


Multivariate linear regression models with both instrumental variable methods and as-treated methods were utilized .


Instruments were indicators for trial and study arms .


Models of blood pressure change and costs included both process measures , demographic variables , and clinical variables .


The analysis included 496 subjects .


As-treated methods showed no significant associations between process and outcomes .


The instruments used in the study were insufficient to simultaneously identify distinct process effects .


However , the post-hoc instrumental variable models including one process measure at a time while controlling for the other process demonstrated significant associations between the processes and outcomes with estimates considerably larger than as-treated estimates .


Instrumental variable methods with combined randomized behavioral studies may be useful to evaluate the effects of different care processes .


However , substantial distinct process variation across studies is needed to fully capitalize on this approach .


Instrumental variable methods focusing on individual processes provided larger and stronger outcome relationships than those found using as-treated methods which are subject to confounding .


The pharmacokinetic properties of the immediate-release ( IR ) and the recently developed controlled-release ( CR ) formulation of pregabalin are dose proportional .


Pregabalin IR can be taken with or without food .


This analysis characterizes the effect of food on pregabalin CR .


The objectives of this analysis were : ( 1 ) to evaluate the effect of administration time and fat or caloric content of an accompanying meal on the pharmacokinetic properties of a single dose of pregabalin CR ( 330mg ) relative to a single dose of pregabalin IR ( 300mg ) ; ( 2 ) to evaluate the pharmacokinetic properties of a single dose of pregabalin CR administered fasted relative to a single dose of pregabalin CR administered immediately after food ; and ( 3 ) to determine the safety and tolerability of single-dose administration of pregabalin CR and IR with and without food .


The effect of food on the pharmacokinetic properties of pregabalin CR was determined in five phase I , open-label , single-dose , crossover studies ( 24-28 participants/study ) .


Caloric and fat content of meals were varied and treatments were administered in the morning , at midday , or in the evening .


Blood samples were collected up to 48h post-dose .


Pharmacokinetic parameters were estimated from plasma concentration-time data using standard noncompartmental methods .


Adverse events were monitored throughout all studies .


One hundred and twenty-eight healthy participants ( 19-54years of age ) received pregabalin .


Peak plasma concentrations ( C max ) were lower for CR than the respective pregabalin IR doses , and time to C max occurred later .


When pregabalin CR was administered with food at midday or in the evening , total exposures [ area under the plasma concentration-time curve from time zero extrapolated to infinite time ( AUC ) ] were equivalent for pregabalin CR and IR formulations regardless of fat or caloric content .


When pregabalin CR was administered with an 800-1 ,000 calorie medium-fat breakfast , AUC was equivalent for pregabalin CR and IR .


Bioequivalence criteria for comparison of pregabalin CR after a low - or medium-calorie breakfast relative to pregabalin IR were not met ; however , bioavailability of the pregabalin CR vs. IR formulation was relatively high ( 75-86 % ) .


When pregabalin CR was administered fasted , the AUC was 70-78 % of the AUC of pregabalin CR administered with food and bioequivalence criteria were not met .


Additionally , the AUC of the pregabalin CR formulation administered fasted was 62-69 % of that of pregabalin IR administered fasted and bioequivalence criteria were not met .


Single-dose pregabalin CR and IR were well tolerated in all studies , with no serious or severe adverse events reported .


Time of day of administration and the fat and caloric content of the accompanying meal had minimal overall effect on the pharmacokinetic properties and bioavailability of the pregabalin CR formulation .


There is a high medical need for an interferon-free , all-oral , short-duration therapy for hepatitis C virus ( HCV ) that is highly effective across diverse patient populations , including patients with cirrhosis or previous null response to pegylated interferon ( peginterferon ) plus ribavirin ( PR-null responders ) .


We aimed to assess the efficacy , safety , and effective treatment duration of grazoprevir ( an HCV NS3/4A protease inhibitor ) combined with elbasvir ( an HCV NS5A inhibitor ) with or without ribavirin in patients with HCV genotype 1 infection with baseline characteristics of poor response .


The C-WORTHY trial is a randomised , open-label phase 2 trial of grazoprevir plus elbasvir with or without ribavirin ; here we report findings for two cohorts of previously untreated patients with cirrhosis ( cohort 1 ) and those with previous PR-null response with or without cirrhosis ( cohort 2 ) enrolled in part B of the study .


Eligible patients were adults aged 18 years or older with chronic HCV genotype 1 infection and HCV RNA concentrations of 10000 IU/mL or higher in peripheral blood .


We randomly assigned patients to receive grazoprevir ( 100 mg daily ) and elbasvir ( 50 mg daily ) with or without ribavirin for 12 or 18 weeks .


Randomisation was done centrally with an interactive voice response system ; patients and study investigators were masked to treatment duration up to week 12 but not to treatment allocation .


The primary endpoint was the proportion of patients achieving HCV RNA less than 25 IU/mL at 12 weeks after end of treatment ( SVR12 ) , assessed by COBAS TaqMan version 2.0 .


This study is registered with ClinicalTrials.gov , number NCT01717326 .


We describe findings for 253 patients enrolled in cohort 1 ( n = 123 ) or cohort 2 ( n = 130 ) .


In cohort 1 , we randomly assigned 60 patients to the 12-week regimen ( 31 with ribavirin and 29 with no ribavirin ) and 63 to the 18-week regimen ( 32 with ribavirin and 31 with no ribavirin ) ; in cohort 2 , we randomly assigned 65 patients to the 12-week regimen ( 32 with ribavirin and 33 with no ribavirin ) and 65 to the 18-week regimen ( 33 with ribavirin and 32 with no ribavirin .


High SVR12 rates were achieved irrespective of the use of ribavirin or extension of the treatment duration from 12 to 18 weeks ; SVR12 rates ranged from 90 % ( 95 % CI 74-98 ; 28/31 ; cohort 1 , 12 weeks , ribavirin-containing ) to 100 % ( 95 % CI 89-100 ; 33/33 ; cohort 2 , 18 weeks , ribavirin-containing ) .


Among patients treated for 12 weeks with grazoprevir plus elbasvir without ribavirin , 97 % ( 95 % CI 82-100 , 28/29 ) of patients in cohort 1 and 91 % ( 76-98 , 30/33 ) of patients in cohort 2 achieved SVR12 .


Adverse events reported in more than 10 % of patients were fatigue ( 66 patients , 26 % [ 95 % CI 21-32 ] ) , headache ( 58 patients , 23 % [ 95 % CI 18-29 ] ) , and asthenia ( 35 patients , 14 % [ 95 % CI 10-19 ] ) .


Treatment with grazoprevir plus elbasvir , both with and without ribavirin and for both 12 and 18 weeks ' treatment duration , showed high rates of efficacy in previously untreated patients with cirrhosis and previous PR-null responders with and without cirrhosis .


These results support the phase 3 development of grazoprevir plus elbasvir .


Merck & Co , Inc. .


Suvorexant ( MK-4305 ) is an orexin receptor antagonist shown to be efficacious for insomnia over 3 months .


We aimed to assess its clinical profile during and after 1 year of treatment .


We did a randomised , placebo-controlled , parallel-group trial at 106 investigational centres in the Americas , Australia , Europe , and South Africa from December , 2009 , to August , 2011 .


Patients aged 18 years or older with primary insomnia by DSM-IV-TR criteria were assigned using a computer-generated randomised allocation schedule to receive nightly suvorexant ( 40 mg for patients younger than 65 years , 30 mg for patients aged 65 years or older ) or placebo at a 2:1 ratio for 1 year with a subsequent 2-month randomised discontinuation phase in which patients on suvorexant either continued suvorexant or were abruptly switched to placebo while patients on placebo remained on placebo .


Treatment assignment was masked from patients and investigators .


The primary objective was to assess the safety and tolerability of suvorexant for up to 1 year .


Secondary objectives were to assess the efficacy of suvorexant for improving patient-reported subjective total sleep time ( sTST ) and time to sleep onset ( sTSO ) over the first month of treatment .


Efficacy endpoints over the first month were assessed with a mixed model with terms for baseline value of the response variable , age , sex , region , treatment , time , and treatment by time interaction .


This trial is registered with ClinicalTrials.gov , number NCT01021813 .


322 ( 62 % ) of 522 patients randomly assigned to receive suvorexant and 162 ( 63 % ) of 259 assigned to receive placebo completed the 1-year phase .


Over 1 year , 362 ( 69 % ) of 521 patients treated with suvorexant experienced any adverse events compared with 164 ( 64 % ) of 258 treated with placebo .


Serious adverse events were recorded in 27 patients ( 5 % ) who received suvorexant and 17 ( 7 % ) who received placebo .


The most common adverse event , somnolence , was reported for 69 patients ( 13 % ) who received suvorexant and seven ( 3 % ) who received placebo .


At month 1 , suvorexant ( 517 patients in the efficacy population ) showed greater efficacy than placebo ( 254 in the efficacy population ) in improving sTST ( 387 min vs 160 min ; difference 227 , 95 % CI 164 to 290 ; p < 00001 ) and sTSO ( -180 min vs -84 min , difference -95 , -146 to -45 ; p = 00002 ) .


Our findings show that suvorexant was generally safe and well tolerated over 1 year of nightly treatment in patients with insomnia , with efficacy noted for subjective measures of sleep onset and maintenance .


Merck & Co Inc. .


Denmark has inferior cancer survival rates compared with many European countries .


The main reason for this is suggested to be late diagnosis at advanced cancer stages .


Cancer diagnostic work-up begins in general practice in 85 % of all cancer cases .


Thus , general practitioners ( GPs ) play a key role in the diagnostic process .


The latest Danish Cancer Plan included continuing medical education ( CME ) on early cancer diagnosis in general practice to improve early diagnosis .


This dual aims of this protocol are , first , to describe the conceptualisation , operationalisation and implementation of the CME and , second , to describe the study design and outcomes chosen to evaluate the effects of the CME .


The intervention is a CME in early cancer diagnosis targeting individual GPs .


It was developed by a step-wise approach .


Barriers for early cancer diagnosis at GP level were identified systematically and analysed using the behaviour system involving capability , opportunity and motivation described by Michie et al. .


The study will be designed as a geographical cluster randomised stepped wedge study .


The study population counts 836 GPs from 417 general practices in the Central Denmark Region , geographically divided into eight clusters .


GPs from each cluster will be invited to a CME meeting at a certain date three weeks apart .


The primary outcomes will be primary care interval and GP referral rate on cancer suspicion .


Data will be obtained from national registries , GP-completed forms on patients referred to cancer fast-track pathways and GP-completed online questionnaires before and after the intervention .


To our knowledge , this will be the first study to measure the effect of a theory-based CME in early cancer diagnosis at three levels : GP knowledge and attitude , GP activity and patient outcomes .


The achieved knowledge will contribute to the understanding of whether and how general practice 's ability to perform cancer diagnosis may be improved .


Registered as NCT02069470 on ClinicalTrials.gov .


To observe the clinical effects of early use of neuromuscular blocking agents ( NMBA ) in patients with severe sepsis and acute respiratory distress syndrome ( ARDS ) .


A prospective study was conducted .


96 patients with severe sepsis and ARDS admitted from July 2012 to September 2013 to intensive care unit ( ICU ) of Liuzhou People 's Hospital in Guangxi Zhuang Autonomous Region were enrolled and divided into severe ARDS group ( n = 48 ) and moderate ARDS group ( n = 48 ) according to the Berlin definition of ARDS .


Then patients in each group were randomly divided into treatment group ( n = 24 ) and control group ( n = 24 ) .


All patients with diagnosis in accordance with the 2008 international septic shock and severe sepsis treatment guidelines were provided with comprehensive treatment and mechanical ventilation on the basis of analgesia and sedation .


The patients in treatment group were given a loading dose of vecuronium during mechanical ventilation , started with 0.1 mg/kg up to 0.05 mgkg ( -1 ) h ( -1 ) for continuous intravenous infusion for 24-48 hours .


The acute physiology and chronic health evaluation II ( APACHEII ) score , sequential organ failure assessment ( SOFA ) , arterial oxygenation index ( PaO2/FiO2 ) , central venous oxygen saturation ( ScvO2 ) , arterial blood lactate ( Lac ) , C-reactive protein ( CRP ) levels of two groups were compared before treatment and 48 hours after treatment , and 21-day mortality rate was finally compared .


In moderate or severe ARDS group , there were no statistically significant difference in APACHEII score , SOFA score , PaO2/FiO2 , ScvO2 , Lac and CRP before treatment between two groups .


APACHEII score , SOFA score , PaO2/FiO2 , ScvO2 , and Lac 48 hours after treatment were significantly improved in severe ARDS group compared with control group ( APACHEII score : 16.582.41 vs. 19.793.52 , t = 3.679 , P = 0.010 ; SOFA score : 12.042.17 vs. 14.753.26 , t = 3.385 , P = 0.010 ; PaO2/FiO2 : 159.3122.57 mmHg vs. 131.8134.93 mmHg , t = 3.239 , P = 0.020 ; ScvO2 : 0.6730.068 vs. 0.5720.142 , t = 3.137 , P = 0.030 ; Lac : 3.101.01 mmol/L vs. 4.391.72 mmol/L , t = 3.161 , P = 0.030 ) , while the value of CRP showed no significant difference ( 180.9137.14 mg/L vs. 174.6638.46 mg/L , t = 0.572 , P = 0.570 ) .


21-day mortality in treatment group was significantly lower than that in control group [ 20.8 % ( 5/24 ) vs. 50.0 % ( 12/24 ) , ( 2 ) = 4.463 , P = 0.035 ] .


In moderate ARDS group , each of the above clinical parameters were improved in both groups expect for CRP at 48 hours after treatment , but the indexes showed no statistically significant difference between two groups ( all P > 0.05 ) .


21-day mortality rate in the treatment group was slightly lower than that in the control group which showed no statistically significant difference [ 16.7 % ( 4/24 ) vs. 25.0 % ( 6/24 ) , ( 2 ) = 0.505 , P = 0.477 ] .


The early use of NMBA treatment of patients with severe sepsis and severe ARDS can not only improve the severity but also reduce 21-day mortality .


Shivering is the most common complication during the recovery period after general anesthesia , and there is no clear consensus about the best strategy for its prophylactic .


The aim of the study was to evaluate the efficacy of parecoxib in prevention of postoperative shivering .


Eighty patients with American Society of Anesthesiologists physical status I-II , who were scheduled for minor urological surgeries under general anesthesia , were randomly assigned to two groups ( n = 40 in each group ) : group P received 40 mg of parecoxib by intravenous bolus injection and group S received the same volume of normal saline in the same way just after the induction of anesthesia .


Hemodynamic parameters and body temperatures including tympanic and axillary temperature were monitored .


The occurrence of shivering and pain intensity score were recorded during the recovery period .


Parecoxib significantly reduced the incidence and severity of shivering in comparison with the placebo .


Postoperative shivering was observed in 22 patients in group S ( 55 % ) , compared with nine in group P ( 22.5 % ) ( P = 0.003 ) .


In addition , pain intensity scores were lower in group P during recovery period ; consequently , less rescue analgesics were required in group P when compared with group S ( P = 0.001 ) .


Regarding the body temperature , it was found that core temperature decreased but peripheral temperature increased significantly in both groups .


There was no significant difference between groups in all time intervals .


Prophylactic administration of parecoxib produces dual effects on antishivering and postoperative analgesia .


This implies that cyclooxygenase 2-prostaglandin E2 pathways may be involved in the regulation of shivering .


We previously found that inflammation in benign prostate tissue is associated with an increased odds of prostate cancer , especially higher-grade disease .


Since part of this link may be due to genetics , we evaluated the association between single nucleotide polymorphisms ( SNPs ) in immune response genes and prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial .


We genotyped 16 candidate SNPs in IL1 , IL2 , IL4 , IL6 , IL8 , IL10 , IL12 ( p40 ) , IFNG , MSR1 , RNASEL , TLR4 , and TNFA and seven tagSNPs in IL10 in 881 prostate cancer cases and 848 controls negative for cancer on an end-of-study biopsy .


Cases and controls were non-Hispanic white and frequency matched on age and family history .


We classified cases as lower ( Gleason sum < 7 ; N = 674 ) and higher ( 7-10 ; N = 172 ) grade , and used logistic regression to estimate odds ratios ( OR ) and 95 % confidence intervals ( CI ) adjusting for age and family history .


The minor allele ( C ) of rs3212227 in IL12 ( p40 ) was associated with an increased risk of total ( log additive : OR = 1.30 , 95 % CI 1.10-1 .53 ; P-trend = 0.0017 ) and lower-grade ( OR = 1.36 , 95 % CI 1.15-1 .62 ; P-trend = 0.0004 ) prostate cancer .


The minor allele ( A ) of rs4073 in IL8 was possibly associated with a decreased risk of higher-grade ( OR = 0.81 , 95 % CI 0.64-1 .02 ; P-trend = 0.07 ) , but not total disease .


None of the other candidates was associated with risk .


The minor alleles of IL10 tagSNPs rs1800890 ( A ; OR = 0.87 , 95 % CI : 0.75-0 .99 ; P-trend = 0.04 ) and rs3021094 ( C ; OR = 1.31 , 95 % CI 1.03-1 .66 , P-trend = 0.03 ) were associated with risk ; the latter also with lower - ( P-trend = 0.04 ) and possibly higher - ( P-trend = 0.06 ) grade disease .


These patterns were similar among men with PSA < 2ng/ml at biopsy .


Variation in some immune response genes may be associated with prostate cancer risk .


These associations were not fully explained by PSA-associated detection bias .


Our findings generally support the role of inflammation in the etiology of prostate cancer .


The objective of this study is to assess the index of decayed , missing and filled teeth ( DMF-T ) , habit of brushing teeth , and the microbiological agents accumulating on the children 's toothbrushes for 4 weeks and response of these agents to disinfection via a chlorhexidine solution , then compare those results with the education and income levels of the children 's parents .


Included in the study were 187 children ( 96 in the control group and 91 in the experiment group - chlorhexidine ) chosen randomly from 600 kindergarten children whose ages ranged from 24 months to 72 months .


The children selected had not taken any antibiotics , antimicotics for three months and dental treatments during this trial .


The distribution of these children to the groups was also done randomly .


After performing a survey for the education , occupation , and income status of the parents , the children were examined and the number of decayed teeth was recorded .


The children were given toothbrushes , toothpaste ( with fluroide ) , and the solutions ( including distilled water and chlorhexidine ) for four weeks under the condition that toothbrushes were returned at the end of each week .


The 14 different microbiological agents observed as a result of the assessment of the samples taken in the first week were also included in the assessments of the samples taken over the four-week period .


The decrease in the DMF-T index was found to be meaningful according to the differences in education , income , and occupation status of the parents .


Of all the samples taken from the toothbrushes , the bacteria with the greatest rate of reproduction included Streptococcus mutans , Escherichia Coli , Pseudomonas aeuroginosa , Enterococcus spp , Staphylococcus epidermidis and Candida albicans .


Except for Candida albicans , the other microorganisms taken as samples from the toothbrushes reproduced less overall .


In the group using the solution with chlorhexidine , a meaningful decrease in bacterial reproduction was discovered compared to the control group .


The findings of this study show that the education , occupation , and socioeconomic situations of the parents should be considered when discussing children 's oral and dental health .


Moreover , the study shows that disinfection of toothbrushes in order to prevent reinfection and contamination oral flora with the bacteria again is important in terms of preventive medicine and family-children health .


Although the evidence is mixed , female smokers appear to have more difficulty quitting smoking than male smokers .


Craving , stress , and negative affect have been hypothesized as potential factors underlying gender differences in quit rates .


In the current study , the cue-reactivity paradigm was used to assess craving , stress , and negative affect in response to cues presented in the natural environment of cigarette smokers using ecological momentary assessment .


Seventy-six daily smokers ( 42 % female ) responded to photographs ( smoking , stress , and neutral ) presented 4 times per day on an iPhone over the course of 2 weeks .


Both smoking and stress cues elicited stronger cigarette craving and stress responses compared to neutral cues .


Compared with males , females reported higher levels of post-stress cue craving , stress , and negative affect , but response to smoking cues did not differ by gender .


Findings from this project were largely consistent with results from laboratory-based research and extend previous work by measuring response to cues in the natural environment of cigarette smokers .


This study extends previous cue reactivity ecological momentary assessment research by using a new platform and by measuring response to stress cues outside of the laboratory .


Findings from this project highlight the importance of addressing coping in response to stress cues in clinical settings , especially when working with female smokers .


Fundamentals of Laparoscopic Surgery ( FLS ) certification is required for general surgery .


The recommended practice for learning FLS is to practice tasks one at a time until proficient ( blocked practice ) .


Learning theory suggests that interleaved practice , a method in which tasks are rotated rather than learned one at a time , may result in superior learning .


Residents were randomized into 1 of 2 groups : blocked practice or interleaved practice .


We compared the performance of residents across groups over 20 trials of each of 4 FLS tasks ( peg transfer , pattern cut , extracorporeal suture , and intracorporeal suture ) .


Four weeks later , participants returned to the laboratory and completed 2 additional trials of each of the 4 tasks .


Performance on each of the tasks improved with increased practice .


The interleaved group showed significantly better performance on the peg transfer task ; trends favoring the interleaved group resulted for the other tasks .


Standardized mean differences in favor of the interleaved group were substantial both at the end of practice and at follow-up ( with the exception of the pattern cut ) .


Interleaved practice appears to have advantages over blocked practice in developing and retaining FLS skills .


We encourage others to experiment with the method to confirm our findings .


Bipolar disorder places a significant burden on individuals , caregivers and family , and the broader community .


Current treatments are believed to be more effective against manic symptoms , leaving a shortfall in recovery during the depressive phase of the illness .


The current study draws on recent evidence suggesting that , in addition to increased oxidative load , alterations in mitochondrial function occur in bipolar disorder .


This 16-week study aims to explore the potential benefits of N-acetylcysteine ( NAC ) alone or in combination ( CT ) with selected nutraceuticals believed to enhance mitochondrial function .


The study includes adults diagnosed with bipolar disorder currently experiencing an episode of depression .


Participants are asked to take NAC , CT , or placebo in addition to any usual treatments .


A post-discontinuation visit is conducted 4 weeks following the treatment phase .


The primary outcome of the study will be mean change on the Montgomery-Asberg Depression Rating Scale .


Secondary outcomes include functioning , substance use , mania ratings , and quality of life .


Blood samples will be collected at baseline and week 16 to explore biochemical alterations following treatment .


This study may provide a novel adjunctive treatment for bipolar depression .


Analysis of biological samples may assist in understanding the therapeutic benefits and the underlying etiology of bipolar depression .


Australian and New Zealand Clinical Trial Registry ACTRN12612000830897 .


Compare auto-adjusting positive airway pressure ( APAP ) treatment with positive airway pressure ( PAP ) titration by polysomnography ( PSG ) followed by CPAP treatment in patients diagnosed with obstructive sleep apnea ( OSA ) by home sleep apnea testing ( HSAT ) .


Prospective randomized treatment study .


Tertiary Veterans Administration Medical Center .


156 patients diagnosed with OSA by HSAT ( apneahypopnea index [ AHI ] 10/h ) suitable for APAP treatment .


APAP arm : Treatment with an APAP device , CPAP arm : PSG PAP titration followed by CPAP treatment .


Mean PAP adherence , Epworth sleepiness scale ( ESS ) , Functional Outcomes of Sleep Questionnaire ( FOSQ ) .


The mean ( SD ) age , BMI , and diagnostic AHI ( APAP : 28.6 18.5 , CPAP : 28.3 16.0 / h , p = NS ) did not differ between the study arms .


After 6 weeks of treatment , 84.6 % of 78 patients started on APAP and 84.3 % of 70 patients started on CPAP ( 8 declined treatment after the titration ) were using PAP , p = NS .


The 90 % APAP and level of CPAP were similar ( 10.8 3.1 , 11.7 2.5 cm H2O , p = 0.07 ) .


The average nightly PAP use did not differ ( APAP : 4.45 2.3 , CPAP : 4.0 2.3 h , p = NS ) .


The improvements in the ESS ( APAP : -4.2 4.7 , CPAP : -3.7 4.8 , p = NS ) and in the FOSQ ( APAP : 2.6 3.5 , CPAP : 2.2 3.7 , p = NS ) were not different .


Following diagnosis of OSA by HSAT , treatment with APAP results in equivalent PAP adherence and improvement in sleepiness compared to a PSG titration and CPAP treatment .


A commentary on this article appears in this issue on page 1277 .


Repeated courses of intravenous ( IV ) aminoglycosides in cystic fibrosis ( CF ) patients are associated with cumulative nephrotoxicity .


Targeting their delivery through the inhaled route during acute pulmonary exacerbations may also be effective , but without systemic side effects .


Using a randomized crossover trial design , in a pilot study we compared 14 days of IV tobramycin with nebulized tobramycin 300mg twice a day ( TNS ) in acute respiratory exacerbations in 20 CF adults chronically infected with Pseudomonas aeruginosa ( Psa ) .


Patients also received IV colistin in both arms .


Improvement in spirometry was similar between the two groups [ mean change in FEV1 % predicted : IV group 16.4 ( standard deviation 8.5 ) versus TNS group 19.9 ( 11.3 ) , p = 0.26 ] , but there was more suppression of sputum Psa in the TNS group [ mean difference between treatments 0.85 log10 colony-forming units/mL ( CI 0.03 to 1.67 ) , p = 0.05 ] .


IV tobramycin was associated with a greater urinary protein leak [ mean difference between treatments 0.59 mg/24hr ( 0.30 to 0.87 ) , p = 0.0005 ] and higher urinary levels of markers of acute renal tubular injury : N-acetylglucosaminidase [ 0.72 IU/mmol ( 0.37 to 1.07 ) , p = 0.0004 ] , alanine aminopeptidase [ 1.19 IU/mmol ( 0.70 to 1.68 ) , p = 0.0001 ] , and 2-microglobulin [ 0.44 g/mmol ( 0.16 to 0.72 ) , p = 0.0046 ] than TNS .


Compared with IV tobramycin , TNS treatment prolonged the time to next exacerbation requiring hospitalization ( p < 0.001 ) .


Patient satisfaction was similar with both treatments , and no serious adverse effects were recorded .


TNS is effective in treating acute exacerbations of Psa in CF patients , but with a renal sparing potential compared with the IV preparation .


Laser beam diameter affects the depth of laser penetration .


Q-switched lasers tend to have smaller maximum spot sizes than other dermatologic lasers , making beam diameter a potentially more significant factor in treatment outcomes .


To compare the clinical effect of using the maximum-size treatment beam available for each delivered fluence during laser tattoo removal to a standard 4-mm-diameter treatment beam .


Thirteen tattoos were treated in 12 subjects using a Q-switched Nd : YAG laser equipped with a treatment beam diameter that was adjustable in 1mm increments and a setting that would enable the maximally achievable diameter ( `` MAX-ON '' setting ) with any fluence .


Tattoos were randomly bisected and treated on one side with the MAX-ON setting and on the contralateral side with a standard 4-mm-diameter spot ( `` MAX-OFF '' setting ) .


Photographs were taken 8 weeks following each treatment and each half-tattoo was evaluated for clearance on a 10-point scale by physicians blinded to the treatment conditions .


Tattoo clearance was greater on the side treated with the MAX-ON setting in a statistically significant manner following the 1st through 4th treatments , with the MAX-OFF treatment site approaching the clearance of the MAX-ON treatment site after the 5th and 6th treatments .


This high-energy , Q-switched Nd : YAG laser with a continuously variable spot-size safely and effectively removes tattoos , with greater removal when using a larger spot-size .


To investigate the feasibility of delivering titrated oxygen therapy to adults with return of spontaneous circulation ( ROSC ) following out-of-hospital cardiac arrest ( OHCA ) caused by ventricular fibrillation ( VF ) or ventricular tachycardia ( VT ) .


We used a multicentre , randomised , single blind , parallel groups design to compare titrated and standard oxygen therapy in adults resuscitated from VF/VT OHCA .


The intervention commenced in the community following ROSC and was maintained in the emergency department and the Intensive Care Unit .


The primary end point was the median oxygen saturation by pulse oximetry ( SpO2 ) in the pre-hospital period .


159 OHCA patients were screened and 18 were randomised .


17 participants were analysed : nine in the standard care group and eight in the titrated oxygen group .


In the pre-hospital period , SpO2 measurements were lower in the titrated oxygen therapy group than the standard care group ( difference in medians 11.3 % ; 95 % CI 1.0-20 .5 % ) .


Low measured oxygen saturation ( SpO2 < 88 % ) occurred in 7/8 of patients in the titrated oxygen group and 3/9 of patients in the standard care group ( P = 0.05 ) .


Following hospital admission , good separation of oxygen exposure between the groups was achieved without a significant increase in hypoxia events .


The trial was terminated because accumulated data led the Data Safety Monitoring Board and Management Committee to conclude that safe delivery of titrated oxygen therapy in the pre-hospital period was not feasible .


Titration of oxygen in the pre-hospital period following OHCA was not feasible ; it may be feasible to titrate oxygen safely after arrival in hospital .


Recent warnings from Health Canada regarding codeine for children have led to increased use of nonsteroidal anti-inflammatory drugs and morphine for common injuries such as fractures .


Our objective was to determine whether morphine administered orally has superior efficacy to ibuprofen in fracture-related pain .


We used a parallel group , randomized , blinded superiority design .


Children who presented to the emergency department with an uncomplicated extremity fracture were randomly assigned to receive either morphine ( 0.5 mg/kg orally ) or ibuprofen ( 10 mg/kg ) for 24 hours after discharge .


Our primary outcome was the change in pain score using the Faces Pain Scale - Revised ( FPS-R ) .


Participants were asked to record pain scores immediately before and 30 minutes after receiving each dose .


We analyzed data from 66 participants in the morphine group and 68 participants in the ibuprofen group .


For both morphine and ibuprofen , we found a reduction in pain scores ( mean pre-post difference standard deviation for dose 1 : morphine 1.5 1.2 , ibuprofen 1.3 1.0 , between-group difference [ ] 0.2 [ 95 % confidence interval ( CI ) -0.2 to 0.6 ] ; dose 2 : morphine 1.3 1.3 , ibuprofen 1.3 0.9 , 0 [ 95 % CI -0.4 to 0.4 ] ; dose 3 : morphine 1.3 1.4 , ibuprofen 1.4 1.1 , -0.1 [ 95 % CI -0.7 to 0.4 ] ; and dose 4 : morphine 1.5 1.4 , ibuprofen 1.1 1.2 , 0.4 [ 95 % CI -0.2 to 1.1 ] ) .


We found no significant differences in the change in pain scores between morphine and ibuprofen between groups at any of the 4 time points ( p = 0.6 ) .


Participants in the morphine group had significantly more adverse effects than those in the ibuprofen group ( 56.1 % v. 30.9 % , p < 0.01 ) .


We found no significant difference in analgesic efficacy between orally administered morphine and ibuprofen .


However , morphine was associated with a significantly greater number of adverse effects .


Our results suggest that ibuprofen remains safe and effective for outpatient pain management in children with uncomplicated fractures .


ClinicalTrials.gov , no .


NCT01690780 .


In patients with acute pulmonary embolism , systemic thrombolysis improves right ventricular ( RV ) dilatation , is associated with major bleeding , and is withheld in many patients at risk .


This multicenter randomized , controlled trial investigated whether ultrasound-assisted catheter-directed thrombolysis ( USAT ) is superior to anticoagulation alone in the reversal of RV dilatation in intermediate-risk patients .


Fifty-nine patients ( 6314 years ) with acute main or lower lobe pulmonary embolism and echocardiographic RV to left ventricular dimension ( RV/LV ) ratio 1.0 were randomized to receive unfractionated heparin and an USAT regimen of 10 to 20 mg recombinant tissue plasminogen activator over 15 hours ( n = 30 ; USAT group ) or unfractionated heparin alone ( n = 29 ; heparin group ) .


Primary outcome was the difference in the RV/LV ratio from baseline to 24 hours .


Safety outcomes included death , major and minor bleeding , and recurrent venous thromboembolism at 90 days .


In the USAT group , the mean RV/LV ratio was reduced from 1.280.19 at baseline to 0.990.17 at 24 hours ( P < 0.001 ) ; in the heparin group , mean RV/LV ratios were 1.200.14 and 1.170.20 , respectively ( P = 0.31 ) .


The mean decrease in RV/LV ratio from baseline to 24 hours was 0.300.20 versus 0.030.16 ( P < 0.001 ) , respectively .


At 90 days , there was 1 death ( in the heparin group ) , no major bleeding , 4 minor bleeding episodes ( 3 in the USAT group and 1 in the heparin group ; P = 0.61 ) , and no recurrent venous thromboembolism .


In patients with pulmonary embolism at intermediate risk , a standardized USAT regimen was superior to anticoagulation with heparin alone in reversing RV dilatation at 24 hours , without an increase in bleeding complications .


http://www.clinicaltrials.gov .


Unique identifier : NCT01166997 .


To observe the impacts on the recovery of swallowing function in patients of dysphagia after acute stroke treated with acupuncture and functional electric stimulation .


Seventy-four patients were randomized into an acupuncture plus electric stimulation group ( 38 cases ) and an electric stimulation group ( 36 cases ) .


The functional electric stimulator was used in the two groups .


The electric pads were placed on the hyoid bone , the upper part of thyroid cartilage , the masseter muscle and the mandibular joint .


The treatment lasted for 30 mm each time .


In the acupuncture plus electric stimulation group , acupuncture was supplemented at motor area of Jiao 's scalp acupuncture , lower 2/5 of sensory area , Baihui ( CV 20 ) , Lianquan ( CV 23 ) , Jinjin ( EX-HN 12 ) and Yuye ( EX-HN 13 ) , 30 mm each time .


The treatment was given once a day , 6 treatments for one session and there was 1 day at interval between the sessions , 4 sessions were required totally in the two groups .


The dysphagia scale was adopted for efficacy evaluation before treatment and after 4 sessions of treatment in the two groups .


The removal rate of nasal feeding tube was observed after treatment .


The dysphagia score was increased apparently after treatment compared with that before treatment in the two groups ( both P < 0.05 ) .


After treatment , in the acupuncture plus electric stimulation group , the dysphagia score was increased much more apparently than that in the electric stimulation group ( 8.01 + / - 1.25 vs 6.73 + / - 1.36 , P < 0.05 ) .


The remarkably effective rate was 84.2 % ( 32/38 ) in the acupuncture plus electric stimulation group , better than 58.3 % ( 21/36 ) in the electric stimulation group ( P < 0.05 ) .


The removal rate of nasal feeding tube was 89.5 % ( 34/38 ) in the acupuncture plus electric stimulation group , which was higher than 50.0 % ( 18/36 ) in the electric stimulation group ( P < 0.05 ) .


Acupuncture combined with electric stimulation achieves the much better efficacy on dysphagia after acute stroke and promotes the early removal of nasal feeding tube .


The efficacy is better than that of the simple electric stimulation therapy .


Experimental studies demonstrate that higher intake of omega-3 fatty acids ( n-3 FA ) improves insulin sensitivity , however , we reported that n-3 FA 2g therapy , most commonly used dosage did not significantly improve insulin sensitivity despite reducing triglycerides by 21 % in patients .


Therefore , we investigated the effects of different dosages of n-3 FA in patients with hypertriglyceridemia .


This was a randomized , single-blind , placebo-controlled , parallel study .


Age , sex , and body mass index were matched among groups .


All patients were recommended to maintain a low fat diet .


Forty-four patients ( about 18 had metabolic syndrome/type 2 diabetes mellitus ) in each group were given placebo , n-3 FA 1 ( O1 ) , 2 ( O2 ) , or 4 g ( O4 ) , respectively daily for 2 months .


n-3 FA therapy dose-dependently and significantly decreased triglycerides and triglycerides/HDL cholesterol and improved flow-mediated dilation , compared with placebo ( by ANOVA ) .


However , each n-3 FA therapy did not significantly decrease high-sensitivity C-reactive protein and fibrinogen , compared with placebo .


O1 significantly increased insulin levels and decreased insulin sensitivity ( determined by QUICKI ) and O2 significantly decreased plasma adiponectin levels relative to baseline measurements .


Of note , when compared with placebo , each n-3 FA therapy did not significantly change insulin , glucose , adiponectin , glycated hemoglobin levels and insulin sensitivity ( by ANOVA ) .


We observed similar results in a subgroup of patients with the metabolic syndrome .


n-3 FA therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation .


Nonetheless , n-3 FA therapy did not significantly improve acute-phase reactants and insulin sensitivity in patients with hypertriglyceridemia , regardless of dosages .


Benign prostatic hyperplasia ( BPH ) is a prevalent entity in elderly men and transurethral resection of the prostate ( TURP ) still represents the gold standard of surgical treatment despite its considerable perioperative morbidity .


Recently , prostatic artery embolization ( PAE ) was described as a novel effective and less invasive treatment alternative .


Despite promising first results , PAE still has to be considered experimental due to a lack of good quality studies .


Prospective randomized controlled trials comparing PAE with TUR-P are highly warranted .


This is a single-centre , prospective , randomized , non-inferiority trial comparing treatment effects and adverse events of PAE and TURP in a tertiary referral centre .


One hundred patients who are electable for both treatment options are randomized to either PAE or TURP .


Changes of the International Prostate Symptom Score ( IPSS ) after 3 months are defined as primary endpoint .


Changes in bladder diaries , laboratory analyses , urodynamic investigations and standardised questionnaires are assessed as secondary outcome measures .


In addition contrast-enhanced magnetic resonance imaging of the pelvis before and after the interventions will provide crucial information regarding morphological changes and vascularisation of the prostate .


Adverse events will be assessed on every follow-up visit in both treatment arms according to the National Cancer Institute Common Terminology Criteria for Adverse events and the Clavien classification .


The aim of this study is to assess whether PAE represents a valid treatment alternative to TURP in patients suffering from BPH in terms of efficacy and safety .


ClinicalTrials.gov NCT02054013 .


The current study examined 11 male veterans with military sexual trauma ( MST ) - related posttraumatic stress disorder ( PTSD ) who participated in a larger randomized control trial comparing cognitive processing therapy ( CPT ) to a well-established control treatment ( Present Centered Therapy ; PCT ) among men and women with MST-related PTSD .


All participants ( n = 11 ) completed a 12 session protocol of CPT .


The Clinician Administered PTSD Scale ( CAPS ) , PTSD Checklist ( PCL ) , and Quick Inventory of Depressive Symptomatology ( QIDS ) were administered at baseline and post-treatment sessions 2 , 4 , and 6 months after CPT completion .


Additionally , the PCL and QIDS were administered every two sessions during CPT treatment .


Piecewise growth curve analyses revealed that significant change over time in both PTSD and depressive symptoms was associated with the active treatment phase and that participants maintained treatment gains over the 6-month follow-up period .


CPT effectively reduced self-reported symptoms of PTSD as well as depressive symptoms for men with MST-related PTSD .


Additionally , participants maintained the gains they made during treatment over a 6-month follow-up period .


It is recommended that future studies examine patient characteristics that might impact outcome in order to improve understanding of who benefits the most from treatment .


To determine if phosphodiesterase 5 ( PDE5 ) inhibitors can augment immune function in patients with head and neck cancer through inhibition of myeloid-derived suppressor cells ( MDSC ) .


We performed a randomized , prospective , double blinded , placebo controlled , phase II clinical trial to determine the in vivo effects of systemic PDE5 inhibition on immune function in patients with head and neck squamous cell carcinoma ( HNSCC ) .


Tadalafil augmented immune response , increasing ex vivo T-cell expansion to a mean 2.4-fold increase compared with 1.1-fold in control patients ( P = 0.01 ) , reducing peripheral MDSC numbers to mean 0.81-fold change compared with a 1.26-fold change in control patients ( P = 0.001 ) , and increasing general immunity as measured by delayed type hypersensitivity response ( P = 0.002 ) .


Tumor-specific immunity in response to HNSCC tumor lysate was augmented in tadalafil-treated patients ( P = 0.04 ) .


These findings demonstrate that tadalafil augments general and tumor-specific immunity in patients with HNSCC and has therapeutic potential in HNSCC .


Evasion of immune surveillance and suppression of systemic and tumor-specific immunity is a significant feature of head and neck cancer development .


This study demonstrates that a PDE5 inhibitor , tadalafil , can reverse tumor-specific immune suppression in patients with head and neck cancer , with potential for therapeutic application .


The interferon-free regimen of ABT-450 with ritonavir ( ABT-450 / r ) , ombitasvir , and dasabuvir with or without ribavirin has shown efficacy in inducing a sustained virologic response in a phase 2 study involving patients with hepatitis C virus ( HCV ) genotype 1 infection .


We conducted two phase 3 trials to examine the efficacy and safety of this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis .


We randomly assigned 419 patients with HCV genotype 1b infection ( PEARL-III study ) and 305 patients with genotype 1a infection ( PEARL-IV study ) to 12 weeks of ABT-450 / r-ombitasvir ( at a once-daily dose of 150 mg of ABT-450 , 100 mg of ritonavir , and 25 mg of ombitasvir ) , dasabuvir ( 250 mg twice daily ) , and ribavirin administered according to body weight or to matching placebo for ribavirin .


The primary efficacy end point was a sustained virologic response ( an HCV RNA level of < 25 IU per milliliter ) 12 weeks after the end of treatment .


The study regimen resulted in high rates of sustained virologic response among patients with HCV genotype 1b infection ( 99.5 % with ribavirin and 99.0 % without ribavirin ) and among those with genotype 1a infection ( 97.0 % and 90.2 % , respectively ) .


Of patients with genotype 1b infection , 1 had virologic failure , and 2 did not have data available at post-treatment week 12 .


Among patients with genotype 1a infection , the rate of virologic failure was higher in the ribavirin-free group than in the ribavirin group ( 7.8 % vs. 2.0 % ) .


In both studies , decreases in the hemoglobin level were significantly more common in patients receiving ribavirin .


Two patients ( 0.3 % ) discontinued the study drugs owing to adverse events .


The most common adverse events were fatigue , headache , and nausea .


Twelve weeks of treatment with ABT-450 / r-ombitasvir and dasabuvir without ribavirin was associated with high rates of sustained virologic response among previously untreated patients with HCV genotype 1 infection .


Rates of virologic failure were higher without ribavirin than with ribavirin among patients with genotype 1a infection but not among those with genotype 1b infection .


( Funded by AbbVie ; PEARL-III and PEARL-IV ClinicalTrials.gov numbers , NCT01767116 and NCT01833533 . )


To examine costs associated with obesity in an employee population and factors associated with increased costs .


We used data from the Physical Activity and Life Style ( PALS ) study , a randomized prospective design evaluating three interventions to increase physical activity among physically inactive nonfaculty university employees ( n = 454 ) .


The primary exposure variable , obesity ( measured by body mass index ) , was obtained from the in-person baseline survey .


Covariates were obtained from the baseline survey and included demographic characteristics and health status .


Data from the baseline survey was linked with administrative data to determine pharmaceutical , inpatient , outpatient , and total health care costs for three years .


Average monthly expenditures for obese and nonobese individuals were compared using t-tests and a two-part multivariate regression model adjusted for demographic and socioeconomic characteristics and health behaviors .


Although in-patient and outpatient expenses were not associated with obesity , pharmaceutical expenditures were $ 408 or 87.2 % higher per year ( $ 468 versus $ 876 ) for obese individuals than for nonobese individuals , which reflected poorer health behaviors and health status of obese adults .


Awareness of the costs associated with obesity among employees can stimulate employers to make the investment in providing employer-sponsored wellness and health improvement programs to address obesity .


Improved understanding of presurgical risk factors for transfusions will lead to reduction in their number and related complications .


The goal of this study is to identify these factors in coronary artery bypass graft ( CABG ) surgery .


Presented herein are results of analyses of data from an ongoing study of transfusion in CABG surgery .


Of 122 patients , 81 received transfusion ( Tx ) and 41 did not ( NoTx ) .


In addition to routine tests , presurgical levels of microparticles from platelets ( PMPs ) , red cells ( RMPs ) , and other lineages were assayed .