To determine whether statin therapy reduces the risk of fracture and , in a secondary analysis , whether baseline levels of the inflammatory biomarker high-sensitivity C-reactive protein ( hs-CRP ) are associated with the risk of fracture .


The JUPITER ( Justification for the Use of Statins in Prevention : an Intervention Trial Evaluating Rosuvastatin ) trial was an international , randomized , double-blind , placebo-controlled study enrolling @,@ men older than @ years and women older than @ years with hs-CRP level of at least @ mg/L .


Participants were screened from @ to @ and observed prospectively for up to @ years ( median follow-up , @ years ) .


Rosuvastatin calcium , @ mg daily , or placebo .


Incident fracture was a prespecified secondary end point of JUPITER .


Fractures were confirmed by radiographs , computed tomography , bone scan , or other methods .


Cox proportional hazards models were used to calculate hazard ratios ( HRs ) and associated @ % confidence intervals for the risk of fracture according to randomized treatment assignment , as well as increasing tertiles of hs-CRP , controlling for potential confounders .


During the study , @ incident fractures were reported and confirmed .


Among participants allocated to rosuvastatin , @ fractures were confirmed , compared with @ among those allocated to placebo , such that the incidence of fracture in the rosuvastatin and placebo groups was @ and @ per @ person-years , respectively ( adjusted HR , @ -LSB- @ % CI , @-@ @ -RSB- ; P = @ ) .


Overall , increasing baseline hs-CRP level was not associated with an increased risk of fractures ( adjusted HR for each unit increase in hs-CRP tertile , @ -LSB- @ % CI , @-@ @ -RSB- ; P for trend , @ ) .


Among men and women with elevated hs-CRP level enrolled in a large trial of rosuvastatin therapy for cardiovascular disease , statin therapy did not reduce the risk of fracture .


Higher baseline hs-CRP level was not associated with an increased risk of incident fracture .


Primary data about rates of formal diagnosis of dementia in the German primary care sector are widely lacking .


Main objectives are to analyze the rate of syndrome diagnosis in primary care patients who screened positive for dementia , the distribution of differential diagnoses , and factors associated with undiagnosed dementia .


DelpHi-MV ( Dementia : life - and person-centered help in Mecklenburg-Western Pomerania ) is an ongoing general practitioner ( GP ) - based , randomized , controlled intervention trial .


A total of @,@ patients ( @ years , living at home ) recruited from @ participating GP practices were screened for dementia ( DemTect < @ ) .


Of @ eligible patients ( @ % ) , a total of @ subjects ( @ % ) provided informed consent .


Present analyses are based on the data of @ patients with complete baseline assessment on January @ , @ ( preliminary data ) .


Formal diagnoses were retrieved from the medical records of the treating GPs .


A conditional fixed effect regression analysis was performed to analyze factors associated with undiagnosed dementia .


A total of @ % of patients who screened positive for dementia had been formally diagnosed with dementia .


Unspecified dementia was diagnosed in @ % , vascular dementia in @ % , and Alzheimer 's disease in @ % of these patients .


Undiagnosed dementia was significantly associated with a higher mean score in the Mini-Mental State Examination ( odds ratio , @ ; p < @ , @ % confidence interval @-@ @ ) .


The diagnosis rate of dementia in German primary care ( @ % ) is well within the range of the international data ( @-@ % ) .


The results emphasize the need for action to enhance recognition and differential diagnosis of dementia .


The aim was to test a new protocol of luteal phase administration of clomiphene citrate ( CC ) for ovulation induction in women with polycystic ovary syndrome ( PCOS ) .


This was a prospective , randomized , controlled trial .


Two hundred and fifty-two women ( cycles ) with PCOS were utilized to create two groups .


Patients in Group @ ( @ patients ) received @mg of CC daily for @days starting on day @ of menses , and patients in Group @ ( @ patients ) received @mg of CC daily for @days starting the next day after finishing medroxyprogesterone acetate ( MPA ) ( before withdrawal bleeding ) .


The main outcome measures were the number of growing and mature follicles , serum E@ ( in pg/mL ) , serum progesterone ( in ng/mL ) levels , endometrial thickness ( in mm ) , pregnancy , and miscarriage rates .


The total number of follicles and the number of follicles @mm during stimulation were significantly greater in Group @ .


The endometrial thickness at the time of human chorionic gonadotrophin ( hCG ) administration was significantly greater in Group @ as compared to Group @ ( @ and @ , respectively ) .


Serum E@ levels were also significantly higher ( p < @ ) in Group @ as compared to Group @ ( @ vs. @ pg/mL ) .


Pregnancy occurred in @ patients ( @ % ) in Group @ and in @ patients ( @ % ) in Group @ .


The difference was not statistically significant .


Luteal phase administration of CC in patients with PCOS leads to increased follicular growth and endometrial thickness , which might result in a higher pregnancy rate .


The risks associated with gestational diabetes mellitus ( GDM ) are well recognized , and there is increasing evidence to support treatment of the condition .


However , clear guidance on the ideal approach to screening for GDM is lacking .


Professional groups continue to debate whether selective screening ( based on risk factors ) or universal screening is the most appropriate approach .


Additionally , there is ongoing debate about what levels of glucose abnormalities during pregnancy respond best to treatment and which maternal and neonatal outcomes benefit most from treatment .


Furthermore , the implications of possible screening options on health care costs are not well established .


In response to this uncertainty there have been repeated calls for well-designed , randomised trials to determine the efficacy of screening , diagnosis , and management plans for GDM .


We describe a randomised controlled trial to investigate screening uptake rates and the clinical and cost effectiveness of screening in primary versus secondary care settings .


This will be an unblinded , two-group , parallel randomised controlled trial ( RCT ) .


The target population includes @ women presenting for their first antenatal visit at @ to @ weeks gestation at two hospitals in the west of Ireland : Galway University Hospital and Mayo General Hospital .


Participants will be offered universal screening for GDM at @ to @ weeks gestation in either primary care ( n = @ ) or secondary care ( n = @ ) locations .


The primary outcome variable is the uptake rate of screening .


Secondary outcomes include indicators of clinical effectiveness of screening at each screening site ( primary and secondary ) including gestational week at time of screening , time to access antenatal diabetes services for women diagnosed with GDM , and pregnancy and neonatal outcomes for women with GDM .


In addition , parallel economic and qualitative evaluations will be conducted .


The trial will cover the period from the woman 's first hospital antenatal visit at @ to @ weeks gestation , until the completion of the pregnancy .


We report the role of relative lymphocyte count ( RLC ) as a potential biomarker with prognostic impact for catumaxomab efficacy and overall survival ( OS ) based on a post hoc analysis of the pivotal phase II/III study of intraperitoneal catumaxomab treatment of malignant ascites .


The impact of treatment and RLC on OS was evaluated using multivariate Cox models .


Kaplan-Meier and log-rank tests were used for group comparisons .


Survival analyses were performed on the safety population -LSB- patients with paracentesis plus @ dose of catumaxomab ( n = @ ) and paracentesis alone ( n = @ ) -RSB- .


Determination of the optimal cutoff value for RLC was based on five optimality criteria .


OS was significantly longer with catumaxomab versus paracentesis alone ( P = @ ) .


The @-month OS rate with catumaxomab was @ % versus @ % with paracentesis alone .


RLC had a positive impact on OS and was an independent prognostic factor ( P < @ ) .


In patients with RLC > @ % ( n = @ : catumaxomab , @ and control , @ ) , catumaxomab was associated with a favorable effect on OS versus paracentesis alone ( P = @ ) , with a median/mean OS benefit of @/@ days and an increased @-month survival rate of @ % versus @ % , respectively .


In patients with RLC @ % at screening ( n = @ : catumaxomab , @ and control , @ ) , the median ( mean ) OS difference between the catumaxomab and the control group was @ ( @ ) days , respectively ( P = @ ) .


OS was significantly improved after catumaxomab treatment in patients with malignant ascites .


An RLC > @ % at baseline was a significant prognostic biomarker .


Primary percutaneous coronary intervention ( PCI ) has considerably improved clinical outcomes in patients with ST-segment elevation myocardial infarction ( STEMI ) when compared with thrombolytic therapy .


Prognosis after primary PCI might be further improved by decreasing stent-related complications such as stent thrombosis .


The STENTYS self-apposing stent has been shown to be superior compared with balloon-expandable stents with regard to stent apposition .


The current prospective randomized trial was designed to evaluate whether the superior stent apposition of the STENTYS stent results in clinical outcomes that are at least noninferior to a conventional balloon-expandable stent .


The APPOSITION V is a prospective , multicenter , international , single-blinded , randomized controlled trial in STEMI patients .


Randomization will be performed in a @:@ ratio between the self-apposing nitinol bare-metal STENTYS stent and the balloon-expandable bare-metal MULTI-LINK .


The primary end point is defined as target vessel failure , which is a composite of cardiac death , target vessel-related recurrent myocardial infarction , or clinically driven target vessel revascularization , at @-year follow-up .


Baseline intravascular ultrasound and optical coherence tomography ( OCT ) substudies will be performed in @ and @ subjects , respectively , and a repeat angiography at @ to @ months will be performed in @ subjects , including intravascular ultrasound and OCT ( in the @ OCT patients ) .


This study is registered on ClinicalTrials.gov with number NCT@ .


APPOSITION V will be the first randomized trial powered on clinical end points that directly compares the STENTYS self-apposing stent with a conventional balloon-expandable stent in patients presenting with STEMI undergoing primary PCI .


Reliability of coronary angiography by multidetector row CT ( MDCT-CA ) for stent evaluation is still a matter for debate , and it is unknown whether contrast medium characteristics may affect diagnostic performance of MDCT-CA .


We compared iomeprol-@ with iodixanol-@ to evaluate coronary stents with MDCT-CA .


We randomly assigned @ patients undergoing coronary stent follow-up with the use of MDCT-CA to iomeprol-@ at @ mL/sec flow rate ( group @ ; n = @ ) , iodixanol-@ at @ mL/sec flow rate ( group @ ; n = @ ) , and iodixanol-@ at @ mL/sec flow rate ( group @ ; n = @ ) .


Heart rate ( HR ) immediately before and at the end of scanning , HR variation , premature heart beats , and heat sensation by visual analog scale during scanning were recorded .


Mean attenuation was measured in the aortic root and coronary arteries .


Image quality score and type of artifacts were assessed .


Mean attenuation was significantly lower in group @ than in the other groups .


In group @ , stent evaluability was significantly higher and artifact rate was significantly lower than in group @ ( @ % vs. @ % and @ % vs. @ % ) and group @ ( @ % vs. @ % and @ % vs. @ % ) , respectively , mainly because of a significant lower rate of beam-hardening artifacts ( @ cases in group @ vs. @ and @ in groups @ and @ , respectively ) .


In group @ , visual analog scale , HR at the end of imaging , and number of patients with premature heart beats during the scan were significantly lower than in the other groups .


Iodixanol-@ provides better image quality of coronary stents , allowing higher MDCT-CA evaluability , than iomeprol-@ .


The efficacy of pre-exposure prophylaxis ( PrEP ) in HIV will diminish with poor adherence ; pharmacologic measures of drug exposure have proven critical to PrEP trial interpretation .


We assessed drug exposure in hair against other pharmacologic and more routinely used measures to assess pill-taking .


Participants were randomized to placebo , daily PrEP , or intermittent PrEP to evaluate safety and tolerability of daily versus intermittent tenofovir/emtricitabine ( TFV/FTC ) in @ phase II PrEP clinical trials conducted in Africa .


Different measures of drug exposure , including self-report , medication event monitoring system ( MEMS ) - caps openings , and TFV/FTC levels in hair and other biomatrices were compared .


At weeks @ and @ , self-reported pill-taking , MEMS-caps openings , and TFV/FTC levels in hair , plasma , and peripheral blood mononuclear cells ( PBMCs ) were measured .


Regression models evaluated predictors of TFV/FTC concentrations in the @ biomatrices ; correlation coefficients between pharmacologic and nonpharmacologic measures were calculated .


Both trials were registered on ClinicalTrials.gov ( NCT@/NCT@ ) .


Hair collection was highly feasible and acceptable ( @ % in week @ ; @ % in week @ ) .


In multivariate analysis , strong associations were seen between pharmacologic measures and MEMS-caps openings ( all P < @ ) ; self-report was only weakly associated with pharmacologic measures .


TFV/FTC hair concentrations were significantly correlated with levels in plasma and PBMCs ( correlation coefficients , @-@ @ , all P < @ ) .


Measuring TFV/FTC exposure in small hair samples in African PrEP trials was feasible and acceptable .


Hair levels correlated strongly with PBMC , plasma concentrations , and MEMS-caps openings .


As in other PrEP trials , self-report was the weakest measure of exposure .


Further study of hair TFV/FTC levels in PrEP trials and demonstration projects to assess adherence/exposure is warranted .


Sleep apnea ( SA ) is associated with cardiovascular diseases and is highly prevalent in patients with pacemakers ( PMs ) .


To validate a transthoracic impedance sensor with an advanced algorithm ( sleep apnea monitoring ) for identifying severe SA .


Patients with indications for PM ( VVI/DDD ) were enrolled regardless of symptoms suggesting SA .


Severe SA diagnosis was acknowledged when the full polysomnography gave an apnea-hypopnea index ( PSG-AHI ) of @ events/h .


The PSG-AHI was compared with the respiratory disturbance index evaluated by the SAM algorithm ( SAM-RDI ) compiled from the device during the same diagnosis night , and the performance of the device and the SAM algorithm was calculated to identify patients with severe SA .


The agreement between methods was assessed by using Bland and Altman statistics .


Forty patients ( mean age @ @ years ; @ % men ; body mass index @ @ kg/m ( @ ) ) were included .


Severe SA was diagnosed by PSG in @ % of the patients .


We did not retrieve SAM-RDI data in @ % of the patients .


An optimal cutoff value for the SAM-RDI at @ events/h was obtained by a receiver operator characteristic curve analysis , which yielded a sensitivity of @ % ( @ % confidence interval -LSB- CI -RSB- @ % -@ % ) , a positive predictive value of @ % ( @ % CI @ % -@ % ) , and a specificity of @ % ( @ % CI @ % -@ % ) ( n = @ ) .


The Bland-Altman limits of agreement for PSG-AHI ( in events per hour ) were -LSB- -@ to @ -RSB- .


The results suggest that an advanced algorithm using PM transthoracic impedance could be used to identify SA in patients with PMs outside the clinic or at home .


Although maintenance bacillus Calmette-Gurin ( BCG ) is the recommended treatment in high-risk non-muscle-invasive bladder cancer ( NMIBC ) , its efficacy in older patients is controversial .


To determine the effect of age on prognosis and treatment outcome in patients with stage Ta T@ NMIBC treated with maintenance BCG .


A total of @ patients with intermediate - or high-risk Ta T@ ( without carcinoma in situ ) NMIBC were randomized in European Organization for Research and Treatment of Cancer ( EORTC ) trial @ comparing six weekly instillations of epirubicin , BCG , and BCG plus isoniazid followed by three weekly maintenance instillations over @ yr .


Cox multivariate proportional hazards regression models were used to assess the relative importance of age for recurrence , progression , overall survival , and NMIBC-specific survival with adjustment for EORTC risk scores .


Overall , @ eligible patients were included : @ patients in the BCG with or without INH arms and @ in the epirubicin arm .


In patients treated with BCG with or without INH , @ % were > @ yr of age and @ % were > @ yr .


With a median follow-up of @ yr , patients > @ yr had a shorter time to progression ( p = @ ) , overall survival ( p < @ ) , and NMIBC-specific survival ( p = @ ) after adjustment for EORTC risk scores in the multivariate analysis .


The time to recurrence was similar compared with the younger patients .


BCG was more effective than epirubicin for all four end points considered , and there was no evidence that BCG was any less effective compared with epirubicin in patients > @ yr .


In intermediate - and high-risk Ta T@ urothelial bladder cancer patients treated with BCG , patients > @ yr of age have a worse long-term prognosis ; however , BCG is more effective than epirubicin independent of patient age .


Intravesical bacillus Calmette-Gurin for non-muscle-invasive bladder cancer is less effective in patients > @ yr of age , but it is still more effective than epirubicin .


Patients with end stage renal disease on hemodialysis are affected by physiological and psychological stressors , which contribute to poor quality of life and negative clinical outcomes .


Depression , anxiety , and stress are highly prevalent in this population .


Effective interventional strategies are required to manage these psychological symptoms .


Acupressure has been believed to be one of the complementary therapies that could promote psychological wellbeing .


The aim of this study was to evaluate the effects of acupressure on depression , anxiety , stress , and general psychological distress in patients with hemodialysis .


Open-label randomized controlled trial .


Three hemodialysis centers .


A total of @ patients with hemodialysis were randomly recruited into the acupressure group ( n = @ ) and the control group ( n = @ ) .


The intervention was carried out from January to March @ .


The acupressure group received routine hemodialysis treatment plus @ min acupressure applied three times a week for four weeks .


The control group received only usual care with routine hemodialysis treatment .


The outcome measurements were the Depression , Anxiety Stress Scales ( DASS-@ ) , and general psychological distress using the General Health Questionnaire ( GHQ-@ ) .


Statistical analysis was performed using Wilcoxon signed-rank test to compare DASS scales and GHQ-@ scores before and after acupressure intervention .


The acupressure group had significantly lower DASS scores and GHQ scores compared to the control group , signifying improvements in depression , anxiety , stress and general psychological distress .


The sub-score of the GHQ-@ for social dysfunction , however , were similar in both groups .


Findings from this study indicates that acupressure therapy delivered three times a week for four weeks was able to significantly reduce depression , anxiety , stress , and general psychological distress in patients with hemodialysis .


This positive finding suggests that acupressure may have a role in promoting psychological wellbeing of patients .


Promoting psychological wellness will improve patients ' quality of life , and reduce negative outcomes associated with psychological illnesses and distress experienced by patients with hemodialysis .


Botulinum toxins have been widely used in cosmetic dermatology .


Neurotoxin from the CBFC@ strain ( NTC ) is a recently developed botulinum toxin type A product manufactured through refined procedures .


A double-blinded , randomized , multicentre-designed , phase III trial to investigate the non-inferiority of NTC to existing botulinum toxin A , onabotulinumtoxin A in the treatment of moderate to severe glabellar lines .


A total of @ subjects were randomized in a @ : @ ratio to receive @ U of NTC or onabotulinumtoxin A.


The primary endpoint was the response rate of physicians ' assessment ( PA ) using the Facial Wrinkle Scale at week @ .


The secondary endpoints included the response rate of PA at weeks @ , @ and @ , and photographic assessment at weeks @ , @ , @ and @ .


Subjects ' improvement assessment and subjective self-satisfaction levels were also investigated .


Response rates for maximum frown were @ % in the NTC group and @ % in the onabotulinumtoxin A group at week @ .


NTC also resulted in comparable results for both the response rates of the other evaluation points and incidence of adverse events compared to those of onabotulinumtoxin A.


In subjects ' improvement assessment and photographic evaluations , NTC even demonstrated better results compared with onabotulinumtoxin A in the early phase after treatment .


Analysis of these results strongly supports the non-inferiority of NTC to onabotulinumtoxin A in the efficacy and safety .


NTC is as effective as onabotulinumtoxin A in the treatment of glabellar lines , and both products were well tolerated .


To determine whether endometrial hCG infusion at the time of human blastocyst transfer impacts implantation rates .


Randomized double-blinded placebo-controlled trial .


Academic .


Infertile couples with the female partner less than @ years old ( n = @ ) undergoing fresh or frozen ET of one or two blastocysts .


Patients undergoing ET were randomized into either a treatment or a control group .


The treatment group received an infusion of @ IU of hCG diluted in ET media .


The control group received a sham infusion of ET media .


Infusions were done using a separate catheter less than @ minutes before actual ET .


Sustained implantation rate : ongoing viable gestation ( primary outcome ) and ongoing pregnancy rate ( secondary outcome ) .


A total of @ blastocysts were transferred into @ patients .


There were no differences between the two groups in sustained implantation rate ( @ % in the hCG group , @ % in the control group ) or ongoing pregnancy rate ( @ % in the hCG group , @ % in the control group ) .


Endometrial infusion of hCG at the time of blastocyst ET does not improve sustained implantation rates .


Daily oral antiretroviral preexposure prophylaxis ( PrEP ) is a promising strategy for prevention of HIV-@ acquisition .


Three clinical trials demonstrated PrEP efficacy ; however , two PrEP trials among women did not find protection against HIV-@ .


One hypothesis proposed for these divergent results is that PrEP efficacy may be reduced in populations with higher HIV-@ incidence .


Using data from the Partners PrEP Study , a randomized , placebo-controlled trial of daily oral tenofovir ( TDF ) and emtricitabine/tenofovir ( FTC/TDF ) PrEP among heterosexual HIV-@ serodiscordant couples from Kenya and Uganda , we assessed PrEP efficacy among subgroups at higher risk for HIV-@ acquisition , including subgroups of women with high HIV-@ incidence .


The overall placebo arm HIV-@ incidence was @ per @ person-years .


Among higher risk subgroups , placebo arm HIV-@ incidence ranged from @ to @ per @ person-years .


In all subgroups , PrEP was protective against HIV-@ acquisition , with efficacy point estimates ranging from @ to @ % .


Among subgroups of women with placebo-arm HIV-@ incidence more than @ , efficacy estimates ranged from @ to @ % .


Monthly visit attendance for PrEP refills and tenofovir detection in plasma were high .


Among higher-risk subgroups in the Partners PrEP Study , including groups solely of higher-risk women , both TDF alone and combined FTC/TDF PrEP had consistently high efficacy for HIV-@ protection .


PrEP , when used with high adherence , is a highly effective prevention strategy for higher risk heterosexuals .


Prioritizing PrEP for persons at high risk of HIV-@ will maximize its prevention impact .


The anti-programmed-death-receptor-@ ( PD-@ ) antibody pembrolizumab has shown potent antitumour activity at different doses and schedules in patients with melanoma .


We compared the efficacy and safety of pembrolizumab at doses of @ mg/kg and @ mg/kg every @ weeks in patients with ipilimumab-refractory advanced melanoma .


In an open-label , international , multicentre expansion cohort of a phase @ trial , patients ( aged @ years ) with advanced melanoma whose disease had progressed after at least two ipilimumab doses were randomly assigned with a computer-generated allocation schedule ( @:@ final ratio ) to intravenous pembrolizumab at @ mg/kg every @ weeks or @ mg/kg every @ weeks until disease progression , intolerable toxicity , or consent withdrawal .


Primary endpoint was overall response rate ( ORR ) assessed with the Response Evaluation Criteria In Solid Tumors ( RECIST , version @ ) by independent central review .


Analysis was done on the full-analysis set ( all treated patients with measurable disease at baseline ) .


This study is registered with ClinicalTrials.gov , number NCT@ .


@ patients received pembrolizumab @ mg/kg ( n = @ ) or @ mg/kg ( n = @ ) .


Median follow-up duration was @ months .


ORR was @ % at both doses -- @ of @ patients in the @ mg/kg group and @ of @ in the @ mg/kg group ( difference @ % , @ % CI -@ to @ ; p = @ ) .


Treatment was well tolerated , with similar safety profiles in the @ mg/kg and @ mg/kg groups and no drug-related deaths .


The most common drug-related adverse events of any grade in the @ mg/kg and @ mg/kg groups were fatigue ( @ -LSB- @ % -RSB- vs @ -LSB- @ % -RSB- ) , pruritus ( @ -LSB- @ % -RSB- vs @ -LSB- @ % -RSB- ) , and rash ( @ -LSB- @ % -RSB- vs @ -LSB- @ % -RSB- ) .


Grade @ fatigue , reported in five ( @ % ) patients in the @ mg/kg pembrolizumab group , was the only drug-related grade @ to @ adverse event reported in more than one patient .


The results suggest that pembrolizumab at a dose of @ mg/kg or @ mg/kg every @ weeks might be an effective treatment in patients for whom there are few effective treatment options .


The aim of this study was to analyze diurnal profiles of physical activity for community-dwelling adults aged @ years and over , and to explore the moderating effect of sex , age , morbidity , mobility limitation , and season on physical activity throughout the day .


A sample of @ primary health care patients ( mean age @ @ years , @ % females ) was included in the analyses .


Participants ' physical activity was measured on up to six consecutive days via Omron Walking Style Pro HJ-@IT-E@ pedometer .


Step count per day and per hour , and pedometer wear time were descriptively analyzed .


A repeated measures ANOVA with physical activity per hour as dependent variable was performed to analyze the moderating effect of sex , age , morbidity , mobility limitation , and season on diurnal profiles of physical activity .


The diurnal profile for the total sample and adjusted diurnal profiles for subgroups are presented .


Participants ' daily step count averaged @ @ steps/day .


They wore the pedometer for @ @ hours per day and walked on average @ @ steps per hour .


With respect to diurnal profiles , there were two peaks at @-@ AM ( mean -LSB- @ % - confidence interval -RSB- : @ -LSB- @-@ -RSB- steps ) and at @-@ pm ( @ -LSB- @-@ -RSB- steps ) interrupted by a period of lower activity with a low point at @-@ pm ( @ -LSB- @-@ -RSB- steps ) .


A mobility limitation , defined by use of a cane or a rollator , had a significant moderating effect ( p = @ ) on diurnal physical activity .


This is the first study to explore pedometer-determined diurnal profiles of physical activity in chronically ill and mobility-limited older adults .


Prolonging periods of elevated physical activity in the afternoon while respecting individual daily routine and commitments could be one option for facilitating the integration of physical activity and for making it a habit in older adults ' daily lives .


The use of a walking aid seems to be an indicator for a quite low activity plateau during the second half of the day .


People who use walking aids should be motivated to increase their physical activity during afternoon ; this might help to increase the overall low physical activity level of this vulnerable subgroup of older adults .


We evaluated the endogenous glucose production ( EGP ) and glucose disposal rate ( GDR ) over a range of doses of basal insulin peglispro ( BIL ) and insulin glargine in healthy subjects .


This was a single-center , randomized , open-label , four-period , incomplete-block , crossover study conducted in eight healthy male subjects .


Subjects had @-h euglycemic clamps performed with primed , continuous infusions of BIL ( @ to @ mU/min ) in three dosing periods and insulin glargine ( @ or @ mU/m ( @ ) / min ) in a fourth period , targeted to achieve @-@ % suppression of EGP .


D - -LSB- @ - ( @ ) H -RSB- glucose was infused to assess rates of glucose appearance and disappearance .


Mean BIL and insulin glargine concentrations ( targeted to reflect the differences in intrinsic affinities of the two basal insulins ) ranged from @ to @,@ and @ to @ pmol/L , respectively , and increased accordingly with increases in dose .


Suppression of EGP and stimulation of GDR were observed with increasing concentrations of both insulins .


At insulin concentrations where EGP was significantly suppressed , insulin glargine resulted in increased GDR .


In contrast , at comparable suppression of EGP , BIL had minimal effect on GDR at lower doses and had substantially less effect on GDR than insulin glargine at higher doses .


The novel basal insulin analog BIL has relative hepatopreferential action and decreased peripheral action , compared with insulin glargine , in healthy subjects .


The consequences of alcohol dependence are severe and may range from physical disease to neuropsychological deficits in several cognitive domains .


Alcohol abuse has also been related to brain dysfunction specifically in the prefrontal cortex .


Conventional neuropsychological interventions ( paper-and-pencil cognitive stimulation training ) have a positive effect but are time-consuming , costly , and not motivating for patients .


Our goal was to test the cognitive effects of a novel approach to neuropsychological intervention , using mobile technology and serious games , on patients with alcohol dependence .


The trial design consisted of a two-arm study assessing the cognitive outcomes of neuropsychological intervention with mobile serious games ( mHealth ) versus control ( treatment-as-usual with no neuropsychological intervention ) in patients undergoing treatment for alcohol dependence syndrome .


Sixty-eight patients were recruited from an alcohol-rehab clinic and randomly assigned to the mHealth ( n = @ ) or control condition ( n = @ ) .


The intervention on the experimental group consisted of a therapist-assisted cognitive stimulation therapy for @ weeks on a @-@ days/week basis .


Fourteen patients dropped out of the study .


The results of the neuropsychological assessments with the remaining @ patients showed an overall increase ( P < @ ) of general cognitive abilities , mental flexibility , psychomotor processing speed , and attentional ability in both experimental ( n = @ ) and control groups ( n = @ ) .


However , there was a more pronounced improvement ( P = @ ) specifically in frontal lobe functions from baseline ( mean @ , SE @ ) to follow-up ( mean @ , SE @ ) in the experimental group but not in the control group .


The overall increase in general cognitive function for both experimental and control groups supports the beneficial role of existing alcohol treatment protocols aimed at minimizing withdrawal symptoms , but the differential improvements observed in frontal lobe functioning supports the use of mobile serious games for neuropsychological stimulation to overcome executive dysfunction in patients with alcohol dependence .


This trial was negative on two neuropsychological/cognitive tests , and positive on one .


To assess the efficacy of oral transmucosal meloxicam for pain relief in lambs at marking .


A blinded , placebo-controlled , randomised , block design field study of @ Merino lambs aged @-@ weeks allocated to placebo and meloxicam treatments and studied in two cohorts of @ .


Placebo-treated lambs received @mL/@kg of drug vehicle and meloxicam-treated lambs received @mg/kg meloxicam at @mg/mL .


Treatments were administered into the buccal cavity immediately before knife castration and hot-iron tail docking .


Lambs were then released into a grassed paddock ( @ ha ) .


Time to mother-up was recorded and behaviours were observed every @min for @h and again for @min at @h .


The sequence in which lambs exited the paddock with their mothers was then recorded .


Weight change and wound scores were recorded @ and @ days after marking .


Meloxicam did not affect mothering-up .


In the @h following marking , meloxicam led to a @-fold reduction ( P < @ ) in combined abnormal behaviours ( hunched standing , standing with a stretched posture , walking stiffly ) .


The meloxicam group spent significantly less time in standing postures and tended to spend more time grazing , suckling and in normal lying postures .


At @h , the meloxicam group spent more time lying and less time standing .


There was no effect of treatments on the sequence in which lambs moved into a fresh paddock or on weight change .


The buccal meloxicam formulation provided substantial analgesia to lambs on the day of marking .


Slight benefits were evident the following morning .


Coronary artery bypass grafting success is limited by vein graft failure ( VGF ) .


Understanding the factors associated with VGF may improve patient outcomes .


We examined @ participants in the Project of Ex Vivo Vein Graft Engineering via Transfection IV ( PREVENT IV ) trial undergoing protocol-mandated follow-up angiography @ to @ months post-coronary artery bypass grafting or earlier clinically driven angiography .


Outcomes included patient - and graft-level angiographic VGF ( @ % stenosis or occlusion ) .


Variables were selected by using Fast False Selection Rate methodology .


We examined relationships between variables and VGF in patient - and graft-level models by using logistic regression without and with generalized estimating equations .


At @ to @ months post-coronary artery bypass grafting , @ of @ ( @ % ) patients had VGF , and @ of @ ( @ % ) vein grafts had failed .


Demographic and clinical characteristics were similar between patients with and without VGF , although VGF patients had longer surgical times , worse target artery quality , longer graft length , and they more frequently underwent endoscopic vein harvesting .


After multivariable adjustment , longer surgical duration ( odds ratio per @-minute increase , @ ; @ % confidence interval , @-@ @ ) , endoscopic vein harvesting ( odds ratio , @ ; @ % confidence interval , @-@ @ ) , poor target artery quality ( odds ratio , @ ; @ % confidence interval , @-@ @ ) , and postoperative use of clopidogrel or ticlopidine ( odds ratio , @ ; @ % confidence interval , @-@ @ ) were associated with patient-level VGF .


The predicted likelihood of VGF in the graft-level model ranged from @ % to @ % .


VGF is common and associated with patient and surgical factors .


These findings may help identify patients with risk factors for VGF and inform the development of interventions to reduce VGF .


The insulin secretion/insulin resistance ( IR ) ( disposition ) index ( I/G IR , where is change from baseline , I is insulin , and G is glucose ) is commonly used as a measure of - cell function .


This relationship is curvilinear and becomes linear when log transformed .


I is determined by @ variables : insulin secretion rate ( ISR ) and metabolic clearance of insulin .


We postulated that the characteristic curvilinear relationship would be lost if plasma C-peptide ( CP ) ( instead of plasma insulin ) was plotted against insulin sensitivity .


A total of @ individuals with impaired glucose tolerance ( IGT ) from ACT NOW received an oral glucose tolerance test and were randomized to pioglitazone or placebo for @ years .


Pioglitazone reduced IGT conversion to diabetes by @ % ( P < @ ) .


I/G vs the Matsuda index of insulin sensitivity showed the characteristic curvilinear relationship .


However , when CP/G or ISR/G was plotted against the Matsuda index , the curvilinear relationship was completely lost .


This discordance was explained by @ distinct physiologic effects that altered plasma insulin response in opposite directions : @ ) increased ISR and @ ) augmented metabolic clearance of insulin .


The net result was a decline in the plasma insulin response to hyperglycemia during the oral glucose tolerance test .


These findings demonstrate a physiologic control mechanism wherein the increase in ISR ensures adequate insulin delivery into the portal circulation to suppress hepatic glucose production while delivering a reduced but sufficient amount of insulin to peripheral tissues to maintain the pioglitazone-mediated improvement in insulin sensitivity without excessive hyperinsulinemia .


These results demonstrate the validity of the disposition index when relating the plasma insulin response to insulin sensitivity but underscore the pitfall of this index when drawing conclusions about - cell function , because insulin secretion declined despite an increase in the plasma insulin response .


The aim of this study is to ascertain the subsequent radiobiological impact of using a consensus guideline target volume delineation atlas .


Using a representative case and target volume delineation instructions derived from a proposed IMRT rectal cancer clinical trial , gross tumor volume ( GTV ) and clinical/planning target volumes ( CTV/PTV ) were contoured by @ physician observers ( Phase @ ) .


The observers were then randomly assigned to follow ( atlas ) or not-follow ( control ) a consensus guideline/atlas for anorectal cancers , and instructed to re-contour the same case ( Phase @ ) .


The atlas group was found to have increased tumor control probability ( TCP ) after the atlas intervention for both the CTV ( p < @ ) and PTV@ ( p = @ ) with decreasing normal tissue complication probability ( NTCP ) for small intestine , while the control group did not .


Additionally , the atlas group had reduced variance in TCP for all target volumes and reduced variance in NTCP for the bowel .


In Phase @ , the atlas group had increased TCP relative to the control for CTV ( p = @ ) .


Visual atlas and consensus treatment guideline usage in the development of rectal cancer IMRT treatment plans reduced the inter-observer radiobiological variation , with clinically relevant TCP alteration for CTV and PTV volumes .


This study aims to compare the clinical outcomes and costs between endoscopic biliary stenting ( EBS ) and percutaneous transhepatic biliary stenting ( PTBS ) .


We randomly assigned @ patients with unresectable malignant biliary obstruction @ and @ to receive EBS or PTBS with self-expandable metal stent ( SEMS ) as palliative treatment .


PTBS was successfully performed in @ patients who formed the PTBS group ( failed in @ patients ) .


EBS was successfully performed in @ patients who formed the EBS group ( failed in @ patients ) .


The effectiveness of biliary drainage , hospital stay , complications , cost , survival time and mortality were compared .


Patients in PTBS group had shorter hospital stay and lower initial and overall expense than the BBS group ( P < @ ) .


There was no significant difference in effectiveness of biliary drainage ( P = @ ) or survival time between two groups ( P = @ ) .


Early complications occurred in PTBS group was significantly lower than in EBS group ( @/@ vs @/@ , P = @ ) .


Late complications in the EBS group did not differ significantly from PTBS group ( @/@ vs @/@ , P = @ ) .


The survival curves in the two groups showed no significant difference ( P = @ ) .


Conclusions : @ .


Rheumatoid arthritis ( RA ) is an inflammatory autoimmune disease in which the gut microbiota is altered .


Probiotics are microorganisms that can normalize gut microbiota ; thus , they may help to alleviate RA symptoms .


The objective of the present clinical trial was to assess the effects of probiotic supplementation on disease activity and inflammatory cytokines in patients with RA .


Forty-six patients with RA were assigned into two groups in this randomized , double-blind , placebo-controlled clinical trial .


The patients in the probiotic group received a daily capsule that contained a minimum of @ ( @ ) colony-forming units of Lactobacillus casei @ for @ wk .


The placebo group took capsules filled with maltodextrin for the same time period .


Questionnaires , anthropometric measurements , and fasting blood samples were collected , and the participants were assessed by a rheumatologist at baseline and at the end of the trial .


Disease activity score was significantly decreased by the intervention , and there was a significant difference between the two groups at the end of the study ( P < @ ) .


Three of the assessed serum proinflammatory cytokines ( tumor necrosis factor - , interleukin-@ , and interleukin-@ ) significantly decreased in the probiotic group ( P < @ ) ; however , serum levels of interleukin-@ were not significantly affected by the probiotic ( P = @ ) .


The serum level of regulatory cytokine ( interleukin-@ ) was increased by the supplementation ( P < @ ) .


The proportion of interleukin-@ to interleukin-@ was significantly increased in the probiotic group as well .


L. casei @ supplementation improved the disease activity and inflammatory status of patients with RA .


Further studies are warranted to confirm these results , and such confirmation may lead to the introduction of probiotics as adjunctive therapy for this population .


Small birth size , often associated with insufficient maternal nutrition , contributes to a large share of global child undernutrition , morbidity , and mortality .


We developed a small-quantity lipid-based nutrient supplement ( SQ-LNS ) to enrich the diets of pregnant women .


The objective was to test a hypothesis that home fortification of pregnant women 's diets with SQ-LNS would increase birth size in an African community .


We enrolled @ women with uncomplicated pregnancies ( < @ gestational weeks ) in a randomized controlled trial in Malawi .


The women were provided with one daily iron-folic acid ( IFA ) capsule , one capsule containing multiple micronutrients ( MMNs ) , or one @-g sachet of SQ-LNS ( LNS , containing @ kcal , protein , carbohydrates , essential fatty acids , and @ micronutrients ) .


Primary outcomes were birth weight and newborn length .


Secondary outcomes included newborn weight , head and arm circumference , and pregnancy duration .


Analysis was by intention to treat .


The mean SD birth weight and newborn length were @ @ , @ @ , and @ @ g ( P = @ ) and @ @ , @ @ , and @ @ cm ( P = @ ) in the IFA , MMN , and LNS groups , respectively .


For newborn weight-for-age , head circumference , and arm circumference , the point estimate for the mean was also highest in the LNS group , intermediate in the MMN group , and lowest in the IFA group , but except for midupper arm circumference ( P = @ ) , the differences were not statistically significant .


The prevalence of low birth weight ( < @ g ) was @ % , @ % , and @ % ( P = @ ) , respectively ; newborn stunting ( length-for-age z score < -@ ) was @ % , @ % , and @ % ( P = @ ) , respectively ; and newborn small head circumference ( head circumference-for-age z score < -@ ) was @ % , @ % , and @ % ( P = @ ) , respectively .


The associations between the intervention and the outcomes were not modified by maternal parity , age , or nutritional status ( P > @ ) .


The study findings do not support a hypothesis that provision of SQ-LNS to all pregnant women would increase the mean birth size in rural Malawi .


The trial was registered at clinicaltrials.gov as NCT@ .


Obesity impairs cognition and health-related quality of life ( HRQOL ) in older adults ; however , the appropriate treatment of obese older adults remains controversial .


The objective was to determine the independent and combined effects of weight loss and exercise on cognition , mood , and HRQOL in obese older adults .


One hundred seven frail , obese older adults were randomly assigned to a control , weight-management ( diet ) , exercise , or weight-management-plus-exercise ( diet-exercise ) group for @ y.


In this secondary analysis , main outcomes were Modified Mini-Mental State Examination ( @MS ) and total Impact of Weight on Quality of Life-Lite ( IWQOL ) scores .


Other outcomes included Word Fluency Test , Trail Making Test Parts A and B , and Geriatric Depression Scale ( GDS ) scores .


Scores on the @MS improved more in the diet ( mean SE : @ @ ) , exercise ( @ @ ) , and diet-exercise ( @ @ ) groups than in the control group ( @ @ ) ( between-group P = @-@ @ ) ; scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group .


Scores on the Word Fluency Test improved more in the exercise ( @ @ ) and diet-exercise ( @ @ ) groups than in the control group ( -@ @ ; both P = @ ) .


For the Trail Making Test Part A , scores in the diet-exercise group ( -@ @ ) improved more than in the control group ( -@ @ ) ( P = @ ) ; a similar finding was observed for the Trail Making Test Part B. Scores on the IWQOL improved more in the diet ( @ @ ) , exercise ( @ @ ) , and diet-exercise ( @ @ ) groups than in the control group ( @ @ ) ( P = @-@ @ ) ; scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group .


In the diet-exercise group , peak oxygen consumption and strength changes were independent predictors of @MS changes ; weight and strength changes were independent predictors of IWQOL changes .


GDS scores did not change .


Weight loss and exercise each improve cognition and HRQOL , but their combination may provide benefits similar to exercise alone .


These findings could inform practice guidelines with regard to optimal treatment strategies for obese older adults .


This trial was registered atclinicaltrials.govas NCT@ .


The purpose of this study was to determine whether contrast-enhanced sonography can improve the ability to differentiate branch duct intraductal mucinous neoplasms from serous cystadenomas of the pancreas compared to conventional ( unenhanced ) sonography alone .


Between March @ and May @ , there were @ patients with branch duct intraductal mucinous neoplasms and @ with serous cystadenomas in our institute , for whom preoperative conventional and contrast-enhanced sonographic results were available .


The final diagnosis was obtained by histopathology .


Various conventional and contrast-enhanced sonographic characteristics were retrospectively evaluated by @ radiologists in consensus .


A receiver operating characteristic curve analysis was used to evaluate the diagnostic value of conventional and contrast-enhanced sonography for discriminating between the two entities .


Three conventional sonographic characteristics ( microcysts , cysts with internal echoes , and main pancreatic duct dilatation ) and @ contrast-enhanced sonographic characteristics ( communication between the lesion and main pancreatic duct and enhancement of mural nodules ) significantly improved the ability to differentiate branch duct intraductal mucinous neoplasms from serous cystadenomas .


The area under the receiver operating characteristic curve increased from @ with conventional sonography to @ with combined contrast-enhanced and conventional ultrasonography ( P = @ ) .


In this series of patients , the addition of contrast-enhanced sonography to conventional sonography improved the ability to differentiate branch duct intraductal mucinous neoplasms from serous cystadenomas .


To test the hypothesis that an initial fraction of inspired oxygen ( FiO@ ) of @ % during resuscitation of preterm infants results in less oxidative stress and is associated with improved clinical outcomes compared with an FiO@ of @ % .


Preterm infants of gestational age < @ weeks ( n = @ ) were randomized to start resuscitation with either @ % oxygen ( low-oxygen group ) or @ % oxygen ( high-oxygen group ) , after which the FiO@ was adjusted based on oxygen saturation values .


The primary outcome was bronchopulmonary dysplasia ( BPD ) assessed at @ weeks postmenstrual age .


Secondary outcomes included major neonatal illnesses and markers of oxidative stress .


The median gestational age of included infants was @ ( @ ) / @ weeks ( IQR , @ ( @ ) / @-@ ( @ ) / @ weeks ) .


The incidence of BPD was not significantly different between the low-oxygen and high-oxygen groups ( @ % vs. @ % ; P = @ ) .


The FiO@ in both groups was adjusted to a mean of @ % by @ minutes in the low-oxygen group and by @ minutes in the high-oxygen group .


No differences in markers of oxidative stress were noted between groups .


Initial supplementation of preterm infants with @ % oxygen during the fetal-to-neonatal transition is as safe as @ % oxygen , with no differences in oxidative stress markers or BPD .


To compare immediate surgery to scaling and root planing ( SRP ) in the treatment of advanced periodontal disease focusing on the prevalence of residual sites and cost-effectiveness ( @ ) ; to evaluate the adjunctive effects of azithromycin in a second treatment phase ( @ ) .


Thirty-nine patients ( @ males , @ females ; mean age : @ ) received oral hygiene instructions and were randomly allocated to surgery ( n = @ ) or SRP ( n = @ ) .


Patients with residual pockets ( @mm ) at @months received re-debridement of these sites and systemic azithromycin .


Treatment groups were followed up to @months and evaluated in terms of clinical response parameters and cost-effectiveness .


Chair-time was used to assess the financial impact of treatment .


Both treatment arms were equally effective in terms of clinical outcome demonstrating less than @ % residual pockets at @months .


Surgery imposed an extra @ Euro on the patient up to @months when compared to SRP .


At @months , @ Euro of this amount could be offset as a result of a reduced need for supportive care .


Only @ patients in the surgery group needed systemic antibiotics , whereas @ patients in the SRP needed such additional treatment .


Although @ Euro could be saved on average by performing SRP instead of surgery , the latter significantly reduced the need for supportive care and systemic antibiotics .


Elective interval appendectomy ( IA ) is traditionally advocated for the management of appendiceal mass ( AM ) in children .


Surgeons have debated the evidence and ` risks ' vs. ` benefits ' to support IA .


There are currently no randomised controlled trials and guiding best practice and financial costings for IA are lacking .


We herein report clinical outcomes , patient benefits and tariff charges linked with the provision of IA at a regional UK paediatric surgical centre .


Hospital case records of patients with AM were identified using pathology records and hospital admission codes during a @-year period ( @-@ ) .


Tariff costs ( Sterling ) were calculated for all admissions during the era @-@ .


@ children were admitted with AM ( @ % female , median age @ years , range @-@ years ) .


Median initial hospital stay with resolution of symptoms was @ days ( range @-@ days ) .


@ children ( @ % ) had elective IA ( median interval @ days , range @-@ days ) .


Eight ( @ % ) patients required emergency readmission for early appendectomy ( median interval @ days , range @-@ days ) .


Hospital stay for emergency readmission appendectomy in these children was significantly longer than IA ( median @ vs. @ days , p < @ ) .


Laparoscopic appendectomy vs. ` open ' appendectomy was associated with shorter length of stay in the IA cohort ( median @ vs. @ days p < @ ) .


No intra-operative morbidity was recorded in the study with only a single case developing a post-operative wound infection .


Median cost for IA was @,@ .


Costings were higher in the emergency appendectomy group-@ ,@ vs. @,@ ; p = @ , NS .


Only @ % of children at this centre develop recurrent appendicitis after primary admission with AM .


Interval and emergency appendectomy were associated with low morbidity .


Parents should be informed that IA may be ` non essential ' surgery .


Paediatric surgeons not routinely advocating IA can potentially save the NHS @,@ per patient .


Future randomised studies are warranted to confirm or refute these findings .


This in situ study assessed the effects of adhesive systems containing or not fluoride and/or the antibacterial monomer @-methacryloyloxydodecylpyridinium bromide ( MDPB ) on the microbiological composition of dental biofilm and enamel demineralization .


During two phases of @ days , ten volunteers wore intraoral palatal appliances containing two slabs of human enamel according to a double-blind , crossover design .


The slabs were randomly restored using a composite resin and one of the following adhesive systems : All-Bond SE ( TM ) ( self-etch , fluoride/MDPB free adhesive , AB ) and Clearfl Protect Bond ( self-etch containing fluoride and MDPB adhesive , CB ) .


The biofilm formed on the slabs was analyzed with regard to total and mutans streptococci and lactobacilli counts .


Demineralization represented by integrated area of hardness lesion depth Delta S ( S ) was determined on enamel by analysis of cross-sectional microhardness , at @ and @ m from the restoration margin .


Data were analyzed by ANOVA .


No statistically significant difference was found either in enamel demineralization or in the microbiological composition of dental biofilm .


All adhesive systems containing or not fluoride and/or MDPB tested were unable to inhibit secondary caries in the in situ model used in the present research .


This pilot study compared the effects of lexical-semantic stimulation through telecommunication technology ( LSS-tele ) with in-person LSS ( LSS-direct ) and unstructured cognitive treatment ( UCS ) in patients with early Alzheimer 's disease .


Twenty-seven patients with Alzheimer 's disease in the very early stage ( Mini-Mental State Examination -LSB- MMSE -RSB- > @/@ ) were divided into three groups : seven patients received LSS-tele treatment , ten received standard LSS-direct intervention , and ten participants underwent UCS as control condition .


Intervention treatments consisted of two weekly sessions of LSS ( through teleconference or face to face depending on group assignment ) or UCS exercises administered to small groups throughout a @-month period .


The main outcome measures were changes of global cognitive performance , language abilities , and memory function .


Secondary outcome measures were changes in attention , working memory , executive functions , and visual-spatial abilities tests .


The mean MMSE score improved significantly in LSS-tele and LSS-direct treatments ; LSS-tele improved language abilities , both phonemic and semantic , and stabilized delayed verbal episodic memory with respect to an improved performance after the LSS-direct intervention and to a memory decline observed in the control group .


Improvement was not achieved in any neuropsychological test score after UCS .


Clinical application of telecommunication technology to cognitive rehabilitation of elderly patients with neurodegenerative cognitive impairment is feasible and may improve global cognitive performance .


Technical aspects to ameliorate efficacy of delivery may further improve its impact on domain-specific cognitive abilities .


Activation of TRPM@ and TRPA@ receptors generates cold and cold pain sensations , respectively , and is presumably important in clinical pain manifestations , such as cold hyperalgesia .


This study investigated the interaction between TRPM@ and TRPA@ receptors through stimulation of glabrous human skin ( volar forearm ) by topical administration of @ % L-menthol and @ % trans-cinnamaldehyde ( CA ) , individually and in combination .


Sensory manifestations were assessed in @ healthy volunteers via a platform of @ quantitative sensory ( thermal and mechanical stimuli ) and vasomotor tests ( skin temperature , perfusion and axon-reflex-flare ) in a double-blinded randomized crossover design .


Cold pain threshold was increased ( p < @ , cold allodynia ) by L-menthol alone and L-menthol + CA in combination but unaffected by CA .


Mechanical pain threshold was significantly decreased ( mechanical hyperalgesia ) by all three substances ( p < @ ) , with a significant intergroup difference found between CA alone and the less decreased L-menthol + CA ( p < @ ) .


Application of CA alone and L-menthol + CA in combination showed an increase in skin temperature and perfusion significantly larger than that induced by L-menthol alone ( p < @ ) .


An axon-reflex-flare was present after CA administration , but was significantly reduced upon addition of L-menthol ( p < @ ) .


This study elucidates the potential of L-menthol as a counter-irritant to secondary neurogenic inflammation and provides evidence of an intricate interplay between cold receptors TRPA@ and TRPM@ , warranting further investigation of the neural coding of cold pain perception .


The Placement of Aortic Transcatheter Valves ( PARTNER ) trial reported a reduced rate of mortality in patients with previous coronary bypass grafting ( CABG ) operation who received surgical aortic valve replacement ( SAVR ) in comparison with transcatheter aortic valve replacement ( TAVR ) .


We sought to further evaluate these groups .


We reviewed the database of the @ patients enrolled in the PARTNER trial .


The cohort for this study consisted of @ patients ( @ % ) who had a history of CABG operation before enrollment in the PARTNER trial .


All patients were followed up for @ years .


The mean age was @ years , and @ patients ( @ % ) were men .


The preoperative characteristics were similar in @ patients ( @ % ) who received SAVR and @ ( @ % ) who received TAVR .


There were no differences between the two groups with respect to the operative outcomes of death , stroke , and myocardial infarction , but the TAVR patients experienced more paravalvular regurgitation ( p < @ ) .


At @ years , there was a trend toward greater all-cause mortality in the TAVR patients ( hazard ratio -LSB- HR -RSB- @ ; @ % confidence interval -LSB- CI -RSB- : @ , @ ; p = @ ) .


Furthermore , the TAVR patients had more repeated hospitalization ( HR @ ; @ % CI : @ , @ ; p = @ ) , death of any cause or repeated hospitalization ( HR @ ; @ % CI : @ , @ ; p = @ ) , and death of any cause or stroke ( HR @ ; @ % CI : @ , @ ; p = @ ) .


The @-year follow-up of patients with a history of previous CABG operation in the PARTNER trial demonstrated improved outcomes with SAVR in comparison with TAVR .


Further longitudinal assessment is necessary to corroborate these findings and to understand the possible causes .


To determine influenza ( flu ) vaccination status among the mentally ill population and identify factors associated with vaccination status .


A non-interventional , cross-sectional study was conducted .


A self-administered survey to investigate the vaccination status and perceptions related to flu vaccine was administered between October @-January @ in an outpatient psychiatry clinic that served the indigent , severely mentally ill population of Alabama .


All statistical analyses were based upon a significance level of @ .


Of the @ patients invited , @ participated ( @ % ) .


Only @ % were vaccinated in @-@ and @ % had been vaccinated at the time of the survey for @-@ .


Respondents who had private health insurance , received a recommendation from healthcare providers , and who perceived a greater degree of vaccine effectiveness were more likely to obtain flu vaccination while respondents who had education beyond high school and were more in agreement that they can get the flu from the vaccine were less likely to obtain flu vaccination .


All of the above factors accounted for @ % of vaccination decisions .


The flu vaccination rate among this study 's population was lower than the general population .


Interventions targeting the above factors should help increase vaccination rates among the mentally ill population .


To compare two embryo grouping strategies .


Retrospective time-course analysis in two different centres .


Two culture protocols were used at the zygote stage : `` Random Group '' in which zygotes were randomly grouped and `` Definite Group '' in which zygotes were grouped based on pronuclear pattern .


Embryo culture was extended to blastocyst stage .


Primary and secondary outcomes were respectively the blastulation rate and the cumulative clinical pregnancy and implantation rates .


A similar blastulation rate -LSB- @ and @ % day ( @ +@ ) blastocysts -RSB- was obtained in the two groups .


Conversely , after adjusting for baseline and cycle variables , cumulative pregnancy -LSB- adjusted Odds Ratio = @ ( @ % CI : @-@ @ ) -RSB- and implantation -LSB- adjusted Odds Ratio = @ ( @ % CI : @-@ @ ) -RSB- rates were significantly higher in the `` Random Group '' compared to the `` Definite Group '' .


Two strategies of group culture gave similar results in terms of blastulation rate but the random grouping of zygotes improves pregnancy and implantation rates in IVF-cycles .


Endogenous pain modulation has been studied with the conditioned pain modulation ( CPM ) paradigm with large differences in the magnitude of the CPM effect .


We hypothesized that differences in CPM effects might be associated with differences in blood pressure responses to the conditioning stimulus when comparing the CPM effects using two different conditioning stimuli .


A single-blind repeated-measures design with block-randomization was applied on @ healthy male subjects .


The test stimulus ( TS ; tonic heat pain for @s ) was first presented alone , thereafter in parallel with a conditioning stimulus ( CS ) .


Conditioning stimuli were either a cold pressor test ( CPT ) or equally painful ischaemic muscle pain ( ISC ) , both lasting @s .


Finger blood pressure and heart rate were recorded continuously .


Data were analysed in a linear mixed model framework with CS type ( CPT or ISC ) and conditioning ( TS or TS+CS ) as independent factors .


An inhibitory CPM effect was found for both types of conditioning ( p < @ ) .


The CPM effect was larger during CPT conditioning compared with ISC conditioning ( p = @ ) .


No association with the concomitant cardiovascular response ( blood pressure and heart rate ) was found ( p > @ ) .


Cold pressor pain CS induces larger CPM effects than ischaemic pain CS .


The larger CPM effect is , however , not associated with a larger blood pressure response .


Other factors related to the CS should be investigated to understand why different CS modalities give different CPM effects .


A principal justification for the use of high-fidelity ( HF ) simulation is that , because it is closer to reality , students will be more motivated to learn and , consequently , will be better able to transfer their learning to real patients .


However , the increased authenticity is accompanied by greater complexity , which may reduce learning , and variability in the presentation of a condition on an HF simulator is typically restricted .


This study was conducted to explore the effectiveness of HF and low-fidelity ( LF ) simulation for learning within the clinical education and practice domains of cardiac and respiratory auscultation and physical assessment skills .


Senior-level nursing students were randomised to HF and LF instruction groups or to a control group .


Primary outcome measures included LF ( digital sounds on a computer ) and HF ( human patient simulator ) auscultation tests of cardiac and respiratory sounds , as well as observer-rated performances in simulated clinical scenarios .


On the LF auscultation test , the LF group consistently demonstrated performance comparable or superior to that of the HF group , and both were superior to the performance of the control group .


For both HF outcome measures , there was no significant difference in performance between the HF and LF instruction groups .


The results from this study suggest that highly contextualised learning environments may not be uniformly advantageous for instruction and may lead to ineffective learning by increasing extraneous cognitive load in novice learners .


Research in acute illness often requires an exception from informed consent .


Few studies have assessed the views of patients enrolled in exception from informed consent trials .


This study was designed to assess the views of patients and their surrogates of exception from informed consent enrollment within the context of a randomized , placebo-controlled trial of an investigational agent for traumatic brain injury .


Interactive interview study .


Nested within the Progesterone for the Treatment of Traumatic Brain Injury trial , a Phase III randomized controlled trial in acute traumatic brain injury .


Patients and surrogates ( for patients incapable of being interviewed ) enrolled in Progesterone for the Treatment of Traumatic Brain Injury under exception from informed consent at @ sites .


None .


Interviews focused on respondents ' acceptance of exception from informed consent enrollment in Progesterone for the Treatment of Traumatic Brain Injury , use of placebo and randomization , understanding of major study elements , and views regarding regulatory protections .


Descriptive statistical analysis was performed ; textual data were analyzed thematically .


Eighty-five individuals were interviewed .


Eighty-four percent had positive attitudes toward Progesterone for the Treatment of Traumatic Brain Injury inclusion .


Seventy-eight percent found their inclusion under exception from informed consent acceptable , and @ % found use of exception from informed consent in Progesterone for the Treatment of Traumatic Brain Injury acceptable in general .


Only two respondents clearly disagreed with both personal and general exception from informed consent enrollment .


The most common concerns ( @ % ) related to absence of consent .


Eighty percent and @ % were accepting of placebo use and randomization , respectively .


Although there were few black respondents ( n = @ ) , they were less accepting of personal exception from informed consent enrollment than white respondents ( @ % vs @ % ; p = @ ) .


Acceptance of exception from informed consent in this placebo-controlled trial of an investigational agent was high and exceeded acceptance among community consultation participants .


Exception from informed consent enrollment appears generally consistent with patients ' preferences .


Fluoroscopy is the routine method for localizing left ventricular ( LV ) and right ventricular ( RV ) lead positions in cardiac resynchronization therapy ( CRT ) .


However , the ability of fluoroscopy to determine lead positions in a standard ventricular segmentation is unknown .


We aimed to evaluate the accuracy and reproducibility of fluoroscopy to determine LV and RV lead positions in CRT when compared with cardiac computed tomography ( CT ) .


Fifty-nine patients undergoing CRT were included .


Bi-plane fluoroscopy and cardiac CT were evaluated in all patients .


Pacing lead positions were assessed in a standard LV @-segment model and in a simplistic RV @-segment model .


Four patients with LV lead displacement were excluded from the agreement analysis of LV lead position .


Agreement of LV lead position between fluoroscopy and cardiac CT was observed in @ ( @ % ) patients with fluoroscopy demonstrating a @-segment and @-segment error in @ ( @ % ) and @ ( @ % ) patients , respectively .


Agreement of RV lead position was found in @ ( @ % ) patients with fluoroscopy showing a @-segment and @-segment error in @ ( @ % ) and @ ( @ % ) patients , respectively .


The interobserver agreement on LV and RV lead positions was poor for fluoroscopy ( kappa @ and @ , respectively ) and excellent for cardiac CT ( kappa @ and @ , respectively ) .


Fluoroscopy is inaccurate and modestly reproducible when assessing LV and RV lead positions in a standard ventricular segmentation when compared with cardiac CT. .


Cardiac CT should be applied to determine the exact pacing site in future research evaluating the optimal pacing lead position in CRT .


To observe the safety and efficacy of early oral enteral nutrition after colorectal cancer operation .


A total of @ colorectal cancer patients in our department from March @ to December @ were prospectively enrolled in the study and randomly divided into early enteral nutrition group ( @ cases , receiving early water and enteral nutrition after operation ) and early fasting group ( @ cases , receiving conventional postoperative care protocol ) based on the random number table .


The postoperative recovery , complication morbidity , nutritional status and stress were compared between the two groups .


Compared to early fasting group , patients in early enteral nutrition group had a significantly shorter duration of postoperative fever -LSB- ( @ ) h vs. ( @ ) h , P < @ -RSB- , a shorter interval to flatus -LSB- ( @ ) h vs. ( @ ) h , P < @ -RSB- , a shorter hospital stay -LSB- ( @ ) d vs. ( @ ) d , P < @ -RSB- and lower medical cost -LSB- ( @@ ) Yuan vs. ( @@ ) Yuan , P < @ -RSB- .


There was no significant difference in complication morbidity between the two groups -LSB- @ % ( @/@ ) vs. @ % ( @/@ ) , P > @ -RSB- .


The albumin , prealbumin , and retinol binding protein on the third and seventh postoperative days were significantly higher in early oral enteral nutrition group ( P < @ ) , while the rest energy expense ( REE ) and lnHOMA-IR were significantly lower as compared to early fasting group ( all P < @ ) .


Early oral enteral nutrition after colorectal cancer operation is safe and effective , which is a natural route of nutrition and can reduce the stress response related to surgery , improve postoperative patients ' nutritional status and accelerate rehabilitation .


Enhanced reduction of multinodular goiter ( MNG ) can be achieved by stimulation with recombinant human thyrotropin ( rhTSH ) before radioiodine ( ( @ ) I ) therapy .


The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH ( MRrhTSH ) in combination with ( @ ) I therapy .


In this phase II , single-blinded , placebo-controlled study , @ patients ( @ @ years old , @ % women , @ % Caucasians ) with MNG ( median size @ mL ; range @-@ @ mL ) were randomized to receive placebo ( n = @ ) , @ mg MRrhTSH ( n = @ ) , or @ mg MRrhTSH ( n = @ ) @ hours before a calculated ( @ ) I activity .


Thyroid volume ( TV ) and smallest cross-sectional area of trachea ( SCAT ) were measured ( by computed tomography scan ) at baseline , six months , and @ months .


Thyroid function and quality of life ( QoL ) was evaluated at three-month and yearly intervals respectively .


At six months , TV reduction was enhanced in the @ mg MRrhTSH group ( @ % vs. @ % in the placebo group ; p = @ ) but not in the @ mg MRrhTSH group .


At @ months , the mean percent TV reduction from baseline was @ @ % ( SD ) in the placebo group , @ @ % in the @ mg MRrhTSH group , and @ @ % in the @ mg MRrhTSH group , with no statistically significant differences among the groups , p = @ .


In the @ mg MRrhTSH group , the subset of patients with basal ( @ ) I uptake < @ % had a @ % greater TV reduction at @ months than the corresponding subset of patients in the placebo group ( p = @ ) .


At @ months , the largest relative increase in SCAT was observed in the @ mg MRrhTSH group ( @ @ % ) , but this was not statistically different from the increases observed in the placebo or the @ mg MRrhTSH group ( p = @ ) .


Goiter-related symptoms were reduced and QoL improved , without any enhanced benefit from using MRrhTSH .


At three years , the prevalence of permanent hypothyroidism was @ % , @ % , and @ % in the placebo , @ mg , and @ mg MRrhTSH groups respectively .


The overall safety profile of the study was favorable .


When used as adjuvant to ( @ ) I , enhanced MNG reduction could not be demonstrated with MRrhTSH doses @ mg , indicating that the lower threshold for efficacy is around this level .


Intervention of medical clowns ( MC ) during various medical procedures performed in children has been used to relieve anxiety and pain .


Their role in allergy skin testing has never been evaluated .


To evaluate whether MC can diminish pain and anxiety perceived by children undergoing allergy skin prick tests ( SPT ) .


In a prospective , randomized , controlled , and blinded study , children undergoing SPT were or were not accompanied by MC .


All parents and children @years completed the State-Trait Anxiety Inventory ( STAI ) before and after SPT .


Videotapes recorded during the procedure were scored for anxiety ( m-YPAS ) for all children and for pain ( FLACC ) for children @-@years old by a psychologist who was unaware of the MC 's presence .


After SPT , children @years completed a visual analog score ( VAS ) for pain .


Ninety-one children ( mean age @ years , M/F = @/@ ) were recruited of whom @ were accompanied by clowns .


A significant reduction in state-STAI was found in the clowns group , in both parents and children , when compared with the regular group ( @ and @ ; P = @ , and @ and @ ; P = @ , respectively ) .


Both m-YPAS and FLACC were reduced in the clowns group compared with the regular one .


In the clowns group , m-YPAS positively correlated with both VAS and FLACC ( P = @ and @ , respectively ) .


m-YPAS was positively correlated with FLACC in the regular group ( P = @ ) .


Medical clowns significantly decrease the level of anxiety perceived by both children undergoing allergy SPT and their parents , as well as the pain perceived by young children .


An immune-enhancing diet has been used to alter eicosanoid synthesis , cytokine production , and immune function in an attempt to limit the undesired immune reactions after injury from surgery .


This prospective randomized study was designed to investigate the effect of preoperative immunonutrition on operative complications , and the participation of prostaglandin E@ ( PGE@ ) on T-cell differentiation in patients undergoing a severely stressful surgery .


The enrolled patients who were scheduled to undergo pancreatoduodenectomy were randomized into two groups .


Patients in the immunonutrition group ( n = @ ) received oral supplementation containing arginine , -@ fatty acids , and RNA for @ days before the procedure in addition to a @ % reduction in the amount of regular food .


Patients in the control group ( n = @ ) received no artificial nutrition and were allowed to consume regular food before surgery .


All patients received early postoperative enteral infusion of a standard formula intended to provide @ kcal/kg/day .


The primary endpoint was the rate of infectious complications ; the secondary endpoint was immune responses .


This study is registered with ClinicalTrials.gov ( NCT@ ) .


Infectious complication rate and severity of complications ( Clavien-Dindo classification ) were lesser in the immunonutrition group than in the control group .


mRNA expression levels of T-bet were greater in the immunonutrition group than in the control group ( P < @ ) .


Serum eicosapentaenoic acid and eicosapentaenoic acid/arachidonic acid ratios were greater in the immunonutrition group than in the control group ( P < @ ) .


The levels of plasma PGE@ were lesser in the immunonutrition group than in the control group ( P < @ ) .


Preoperative immunonutrition modulates PGE@ production and T-cell differentiation and may protect against the aggravation of operative complications in patients undergoing pancreatoduodenectomy .


To determine if sleep talkers with REM sleep behavior disorder ( RBD ) would utter during REM sleep sentences learned before sleep , and to evaluate their verbal memory consolidation during sleep .


Eighteen patients with RBD and @ controls performed two verbal memory tasks ( @ words from the Free and Cued Selective Reminding Test and a @-@ word long modified Story Recall Test ) in the evening , followed by nocturnal video-polysomnography and morning recall ( night-time consolidation ) .


In @ patients with RBD , daytime consolidation ( morning learning/recall , evening recall ) was also evaluated with the modified Story Recall Test in a cross-over order .


Two RBD patients with dementia were studied separately .


Sleep talking was recorded using video-polysomnography , and the utterances were compared to the studied texts by two external judges .


Sleep-related verbal memory consolidation was maintained in patients with RBD ( +@ % words ) as in controls ( +@ % , p = @ ) .


The two demented patients with RBD also exhibited excellent nighttime consolidation .


The post-sleep performance was unrelated to the sleep measures ( including continuity , stages , fragmentation and apnea-hypopnea index ) .


Daytime consolidation ( -@ % ) was worse than night-time consolidation ( +@ % , p = @ ) in the subgroup of @ patients with RBD .


Eleven patients with RBD spoke during REM sleep and pronounced a median of @ words , which represented @ % of sleep with spoken language .


A single patient uttered a sentence that was judged to be semantically ( but not literally ) related to the text learned before sleep .


Verbal declarative memory normally consolidates during sleep in patients with RBD .


The incorporation of learned material within REM sleep-associated sleep talking in one patient ( unbeknownst to himself ) at the semantic level suggests a replay at a highly cognitive creative level .


This is a randomized comparative study of the efficacy of celecoxib and loxoprofen in patients with frozen shoulder ( scapulohumeral periarthritis ) .


Patients with frozen shoulder who presented with pain as the symptom were divided at random into a celecoxib treatment group ( @ mg/dose , twice daily ; n = @ ) and a loxoprofen treatment group ( @ mg/dose , @ times daily ; n = @ ) .


Medication was continued for @-@ weeks in each group .


Each patient was asked to rate the pain on a visual analog scale ( score @-@ ) .


This score significantly improved ( indicating marked alleviation of pain ) in both the celecoxib group ( from @ @ before treatment to @ @ after treatment ) and the loxoprofen group ( from @ @ before treatment to @ @ after treatment ) .


In the analysis of disappearance of pain , the percentage of patients showing disappearance of nocturnal pain was significantly higher in the celecoxib group ( @ % ) than in the loxoprofen group ( @ % ) .


The results confirm that celecoxib is comparable to loxoprofen in terms of analgesic efficacy in patients with frozen shoulder .


Among other findings , we report that celecoxib was more effective for nocturnal pain than loxoprofen .


Prescription opioid dependence is increasing and creates a significant public health burden , but primary care physicians lack evidence-based guidelines to decide between tapering doses followed by discontinuation of buprenorphine hydrochloride and naloxone hydrochloride therapy ( hereinafter referred to as buprenorphine therapy ) or ongoing maintenance therapy .


To determine the efficacy of buprenorphine taper vs ongoing maintenance therapy in primary care-based treatment for prescription opioid dependence .


We conducted a @-week randomized clinical trial that enrolled @ patients with prescription opioid dependence from February @ , @ , through February @ , @ , in a single primary care site .


Patients were randomized to buprenorphine taper ( taper condition ) or ongoing buprenorphine maintenance therapy ( maintenance condition ) .


The buprenorphine taper was initiated after @ weeks of stabilization , lasted for @ weeks , and included medications for opioid withdrawal , after which patients were offered naltrexone treatment .


The maintenance group received ongoing buprenorphine therapy .


All patients received physician and nurse support and drug counseling .


Illicit opioid use via results of urinanalysis and patient report , treatment retention , and reinitiation of buprenorphine therapy ( taper group only ) .


During the trial , the mean percentage of urine samples negative for opioids was lower for patients in the taper group ( @ % -LSB- @ % CI , @ % -@ % -RSB- ) compared with those in the maintenance group ( @ % -LSB- @ % CI , @ % -@ % -RSB- ) .


Patients in the taper group reported more days per week of illicit opioid use than those in the maintenance group once they were no longer receiving buprenorphine ( mean use , @ -LSB- @ % CI , @-@ @ -RSB- vs @ -LSB- @ % CI , @-@ @ -RSB- days ) .


Patients in the taper group had fewer maximum consecutive weeks of opioid abstinence compared with those in the maintenance group ( mean abstinence , @ -LSB- @ % CI , @-@ @ -RSB- vs @ -LSB- @ % CI , @-@ @ -RSB- weeks ) .


Patients in the taper group were less likely to complete the trial ( @ of @ -LSB- @ % -RSB- vs @ of @ -LSB- @ % -RSB- ; P < @ ) .


Sixteen patients in the taper group reinitiated buprenorphine treatment after the taper owing to relapse .


Tapering is less efficacious than ongoing maintenance treatment in patients with prescription opioid dependence who receive buprenorphine therapy in primary care .


The OX@/OX@L interaction contributes to an optimal T cell response following allergic stimuli and plays an important role in the maintenance and reactivation of memory T effector cells .


We tested whether treatment with an anti-OX@L monoclonal antibody ( MAb ) would inhibit allergen-induced responses in subjects with asthma .


Twenty-eight mild , atopic asthmatic subjects were recruited for a double-blind , randomized , placebo-controlled , parallel-group trial ( ClinicalTrials.gov identifier NCT@ ) to compare blockade of OX@L using a humanized anti-OX@L MAb to placebo-administered intravenously in @ doses over @ months .


Allergen inhalation challenges were carried out @ and @ days after the first dose of study drug .


The primary outcome variable was the late-phase asthmatic response .


Other outcomes included the early-phase asthmatic response , airway hyperresponsiveness , serum IgE levels , blood and sputum eosinophils , safety and tolerability .


Treatment with anti-OX@L MAb did not attenuate the early - or late-phase asthmatic responses at days @ or @ compared with placebo .


In the anti-OX@L MAb treatment group , total IgE was reduced @ % from pre-dosing levels , and sputum eosinophils decreased @ % by day @ ( both P = @ ) .


There was no effect of anti-OX@L MAb on airway hyperresponsiveness or blood eosinophils .


The frequency of AEs was similar in both groups .


Pharmacological activity of anti-OX@L MAb was observed by decreases in serum total IgE and airway eosinophils at @ weeks post-dosing , but there was no effect on allergen-induced airway responses .


It is possible that the treatment duration or dose of antibody was insufficient to impact the airway responses .


The aim of this study was to determine the efficacy and tolerability of hydromorphone extended release ( ER ) in patients with chronic low back pain ( LBP ) with or without a neuropathic component .


This was a post hoc analysis of data from a multicenter , double-blind , placebo-controlled clinical trial using a randomized withdrawal design , performed in patients with moderate to severe chronic LBP .


Patients achieving stable doses of hydromorphone ER during a @ - to @-week conversion and titration phase were randomized to continue treatment with hydromorphone ER or taper-down to placebo during a @-week double-blind phase .


The primary efficacy outcome was the mean change in @-point Numeric Rating Scale ( NRS ) pain intensity score from randomization to the final visit of the double-blind phase .


Tolerability was assessed by recording adverse events ( AEs ) .


Data were analyzed separately for patients with non-neuropathic and neuropathic LBP .


A total of @ patients with non-neuropathic/nociceptive LBP and @ with neuropathic LBP were randomized into the double-blind phase .


During the conversion and titration phase , mean ( SD ) NRS scores decreased significantly from @ ( @ ) and @ ( @ ) at screening to @ ( @ ) and @ ( @ ) , respectively .


For both LBP subgroups , patients randomized to hydromorphone ER maintained this improvement over the double-blind treatment period , whereas those randomized to placebo reported significant increase in NRS scores .


Across subgroups , the incidence of @ or more AE was @ percent to @ percent in the conversion and titration phase and @ percent to @ percent in the double-blind phase .


The results of this study indicate that hydromorphone ER is efficacious and generally well tolerated in the management of patients with non-neuropathic and neuropathic chronic LBP .


Low-dose CT screening is recommended for individuals at high risk of developing lung cancer .


However , CT screening does not detect all lung cancers : some might be missed at screening , and others can develop in the interval between screens .


The NELSON trial is a randomised trial to assess the effect of screening with increasing screening intervals on lung cancer mortality .


In this prespecified analysis , we aimed to assess screening test performance , and the epidemiological , radiological , and clinical characteristics of interval cancers in NELSON trial participants assigned to the screening group .


Eligible participants in the NELSON trial were those aged @-@ years , who had smoked @ or more cigarettes per day for more than @ years or ten or more cigarettes for more than @ years , and were still smoking or had quit less than @ years ago .


We included all participants assigned to the screening group who had attended at least one round of screening .


Screening test results were based on volumetry using a two-step approach .


Initially , screening test results were classified as negative , indeterminate , or positive based on nodule presence and volume .


Subsequently , participants with an initial indeterminate result underwent follow-up screening to classify their final screening test result as negative or positive , based on nodule volume doubling time .


We obtained information about all lung cancer diagnoses made during the first three rounds of screening , plus an additional @ years of follow-up from the national cancer registry .


We determined epidemiological , radiological , participant , and tumour characteristics by reassessing medical files , screening CTs , and clinical CTs .


The NELSON trial is registered at www.trialregister.nl , number ISRCTN@ .


@,@ participants were enrolled in the NELSON trial , of whom @ were assigned to low-dose CT screening with increasing interval between screens , and @ to no screening .


We included @ participants in our study , with median follow-up of @ years ( IQR @-@ ) .


@ ( @ % ) of @ screened participants were diagnosed with @ screen-detected lung cancers , and another @ ( < @ % ; @ -LSB- @ % -RSB- in the first year after screening , and @ -LSB- @ % -RSB- in the second year after screening ) were diagnosed with @ interval cancers .


For the three screening rounds combined , with a @-year follow-up , sensitivity was @ % ( @ % CI @-@ ) , specificity was @ % ( @ % CI @-@ ) , positive predictive value was @ % ( @ % CI @-@ ) , and negative predictive value was @ % ( @ % CI @-@ ) .


Retrospective assessment of the last screening CT and clinical CT in @ patients with interval cancer showed that interval cancers were not visible in @ ( @ % ) cases .


In the remaining cases , cancers were visible when retrospectively assessed , but were not diagnosed because of radiological detection and interpretation errors ( @ -LSB- @ % -RSB- ) , misclassification by the protocol ( two -LSB- @ % -RSB- ) , participant non-compliance ( two -LSB- @ % -RSB- ) , and non-adherence to protocol ( one -LSB- @ % -RSB- ) .


Compared with screen-detected cancers , interval cancers were diagnosed at more advanced stages ( @ -LSB- @ % -RSB- of @ interval cancers vs @ -LSB- @ % -RSB- of @ screen-detected cancers diagnosed in stage III or IV ; p < @ ) , were more often small-cell carcinomas ( seven -LSB- @ % -RSB- vs eight -LSB- @ % -RSB- ; p = @ ) and less often adenocarcinomas ( nine -LSB- @ % -RSB- vs @ -LSB- @ % -RSB- ; p = @ ) .


Lung cancer screening in the NELSON trial yielded high specificity and sensitivity , with only a small number of interval cancers .


The results of this study could be used to improve screening algorithms , and reduce the number of missed cancers .


Despite the beneficial effect of cardiac rehabilitation after myocardial infarction , a rehabilitation program to improve cardiorespiratory fitness and influence secondary prevention has not been implemented for ischemic stroke and transient ischemic attack ( TIA ) .


To investigate the safety and feasibility of a post-stroke care including an exercise program after minor ischemic stroke or TIA .


In a randomised controlled trial , @ patients with a recent minor stroke or TIA without cardiac contraindications were randomly assigned to one of the two interventions ; post-stroke care without exercise or post-stroke care with exercise .


Patients were evaluated at baseline , @ and @ months .


Eighteen patients completed the intervention .


In none of the patients cardiopulmonary contraindications for the maximal exercise test and exercise program were found .


No cardiovascular events occurred during the maximal exercise tests and exercise program .


After one year , significantly more patients in the post-stroke care with exercise group achieved the composite endpoint of optimal medical therapy .


Post-stroke care including an exercise program is safe and feasible in the acute phase after minor stroke or TIA and might be a way to increase effectiveness of secondary stroke prevention .


We are currently conducting a larger trial to validate these results .


@ subjects with type @ diabetes and moderate to severe CP were randomly distributed to groups receiving either NSPT or OHI .


Periodontal parameters , glycosylated haemoglobin ( HbA@c ) and high-sensitivity C-reactive protein ( hs-CRP ) were evaluated at baseline , @ - and @-months intervals .


@ subjects from NSPT group and @ from OHI group completed the study .


The difference in plaque index ( PI ) between NSPT and OHI groups were significant at @ months recall ( p = @ ) .


There was no significant difference between NSPT and OHI group for all other clinical periodontal parameters , HbA@c and CRP levels .


At @ months post-therapy , periodontal parameters improved significantly in both groups with sites with probing pocket depth ( PPD ) < @ mm reported as @ @ % in NSPT group and @ @ % in OHI group .


Mean PPD and mean probing attachment loss ( PAL ) within the NSPT group reduced significantly from baseline ( @ @ mm , @ @ mm ) to final visit ( @ @ mm , @ @ mm ) ( p = @ , p < @ ) .


For OHI group , improvements in mean PPD and mean PAL were also seen from baseline ( @ @ mm , @ @ mm ) to final visit ( @ @ mm , @ @ mm ) ( p < @ for both ) .


Similarly , HbA@c levels decreased in both groups with NSPT group recording statistically significant reduction ( p = @ ) .


Participants who demonstrated @ % reduction in PPD showed significant reductions of HbA@c and hs-CRP levels ( p = @ and p = @ ) .


NSPT significantly reduced PI at @ months post-therapy as compared to OHI .


Both NSPT and OHI demonstrated improvements in other clinical parameters as well as HbA@c and CRP levels .


The early management of orthopaedic outpatients by physiotherapists may be useful in reducing public hospital waiting lists .


Physiotherapists in Australia are prevented by legislation and funding models from investigating , prescribing , injecting and referring autonomously .


This gap in service is particularly noticeable in the management of shoulder pain in early-access physiotherapy services , as patients needing corticosteroid injection face delays or transfer to other services for this procedure .


This trial will investigate the clinical ( decision making and outcomes ) and economic feasibility of a physiotherapist prescribing and delivering corticosteroid and local anaesthetic injections for shoulder pain in an Australian public hospital setting .


A double-blinded ( patient and assessor ) non-inferiority randomised controlled trial will compare an orthopaedic surgeon and a physiotherapist prescribing and delivering corticosteroid injections to the shoulder .


Agreement in decision making between the two clinicians will be investigated , and economic information will be obtained for estimating disease burden and an economic evaluation .


The surgeon and the physiotherapist will independently assess patients , and @ eligible participants will be randomised to receive subacromial injection of corticosteroid and local anaesthetic from either the surgeon or the physiotherapist .


Post-injection , all participants will receive physiotherapy .


The primary outcome measure will be the Shoulder Pain and Disability Index measured at baseline , and at @ and @weeks post-injection .


Analysis will be conducted on an intention-to-treat basis and compared to a per-protocol analysis .


A cost-utility analysis will be undertaken from the perspective of the health funder .


Findings will assist policy makers and services in improving access for orthopaedic patients .


Intestinal inflammation is a hallmark of cystic fibrosis ( CF ) .


Administration of probiotics can reduce intestinal inflammation and the incidence of pulmonary exacerbations .


We investigated the composition of intestinal microbiota in children with CF and analyzed its relationship with intestinal inflammation .


We also investigated the microflora structure before and after Lactobacillus GG ( LGG ) administration in children with CF with and without antibiotic treatment .


The intestinal microbiota were analyzed by denaturing gradient gel electrophoresis ( DGGE ) , real-time polymerase chain reaction ( RT-PCR ) , and fluorescence in situ hybridization ( FISH ) .


Intestinal inflammation was assessed by measuring fecal calprotectin ( CLP ) and rectal nitric oxide ( rNO ) production in children with CF as compared with healthy controls .


We then carried out a small double-blind randomized clinical trial with LGG .


Twenty-two children with CF children were enrolled in the study ( median age , @ years ; range , @-@ years ) .


Fecal CLP and rNO levels were higher in children with CF than in healthy controls ( @ g/g vs. @ g/g ; @ vs. @ mol/L NO@ ( - ) , respectively ; P < @ ) .


Compared with healthy controls , children with CF had significantly different intestinal microbial core structures .


The levels of Eubacterium rectale , Bacteroides uniformis , Bacteroides vulgatus , Bifidobacterium adolescentis , Bifidobacterium catenulatum , and Faecalibacterium prausnitzii were reduced in children with CF. A similar but more extreme pattern was observed in children with CF who were taking antibiotics .


LGG administration reduced fecal CLP and partially restored intestinal microbiota .


There was a significant correlation between reduced microbial richness and intestinal inflammation .


CF causes qualitative and quantitative changes in intestinal microbiota , which may represent a novel therapeutic target in the treatment of CF. Administration of probiotics restored gut microbiota , supporting the efficacy of probiotics in reducing intestinal inflammation and pulmonary exacerbations .


To investigate the therapeutic effects of a manual therapy protocol for improving pain , function , pressure pain thresholds ( PPT ) , quality of sleep , and depressive symptoms in women and men with fibromyalgia syndrome ( FMS ) .


Eighty-nine patients were randomly assigned to experimental or control group .


The experimental group ( @ female , @ male ) received @ sessions of manual therapy and the control group ( @ female , @ male ) did not receive any intervention .


PPT , pain , impact of FMS symptoms , quality of sleep , and depressive symptoms were assessed in both groups at baseline and after @ hours of the last intervention in the experimental group .


The analysis of covariance found significant GroupTimeSex interactions for McGill PPI and Center for Epidemiologic Studies Depressive Symptoms Scale ( P < @ ) was also found : men exhibited a larger effect size for depressive symptoms than women , whereas women exhibited a greater effect size than men in the McGill PPI .


A significant GroupTimeSex interaction for PPT over suboccipital , upper trapezius , supraspinatus , second rib , gluteal region , and tibialis anterior muscle was also found : men included in the experimental group experienced significant greater improvements in PPT as compared with women with FMS in the experimental group .


Manual therapy protocol was effective for improving pain intensity , widespread pressure pain sensitivity , impact of FMS symptoms , sleep quality , and depressive symptoms .


In addition , sex differences were observed in response to treatment : women and men get similar improvements in quality of sleep and tender point count , whereas women showed a greater reduction in pain and impact of FMS symptoms than men , but men reported higher decreases in depressive symptoms and pressure hypersensitivity than women .


This study tested the effects of two fundamental forms of distraction , including visual-manual and cognitive-audio distraction , with comparison under both operational and tactical driving .


Strategic control remains for future study .


Driving is a complex control task involving operational , tactical , and strategic control .