Linear regression crossover analysis identified a breakpoint ( requirement ) at minimal F ( @ ) CO@ in response to different protein intakes .


The estimated average requirement ( EAR ) for protein in early and late gestation was determined to be @ ( R ( @ ) = @ ; @ % CI : @ , @ g kg ( -@ ) d ( -@ ) ) and @ g kg ( -@ ) d ( -@ ) ( R ( @ ) = @ ; @ % CI : @ , @ g kg ( -@ ) d ( -@ ) ) , respectively .


These estimates are considerably higher than the EAR of @ g kg ( -@ ) d ( -@ ) currently recommended by the Dietary Reference Intakes .


To our knowledge , this study is the first to directly estimate gestational stage-specific protein requirements in healthy pregnant women and suggests that current recommendations based on factorial calculations underestimate requirements .


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


To evaluate the impact of concurrent treatments for substance use disorder and nicotine-dependence for stimulant-dependent patients .


A randomized , @-week trial with follow-up at @ and @ months after smoking quit date conducted at @ substance use disorder treatment programs between February @ and July @ .


Adults meeting DSM-IV-TR criteria for cocaine and/or methamphetamine dependence and interested in quitting smoking were randomized to treatment as usual ( n = @ ) or treatment as usual with smoking-cessation treatment ( n = @ ) .


All participants received treatment as usual for substance use disorder treatment .


Participants assigned to treatment as usual with concurrent smoking-cessation treatment received weekly individual smoking cessation counseling and extended-release bupropion ( @ mg/d ) during weeks @-@ .


During post-quit treatment ( weeks @-@ ) , participants assigned to treatment as usual with smoking-cessation treatment received a nicotine inhaler and contingency management for smoking abstinence .


Weekly proportion of stimulant-abstinent participants during the treatment phase , as assessed by urine drug screens and self-report , was the primary outcome .


Secondary measures included other substance/nicotine use outcomes and treatment attendance .


There were no significant treatment effects on stimulant-use outcomes , as measured by the primary outcome and stimulant-free days , on drug-abstinence , or on attendance .


Participants assigned to treatment as usual with smoking-cessation treatment , relative to those assigned to treatment as usual , had significantly better outcomes for drug-free days at @-month follow-up ( ( @ ) ( @ ) = @ , P < @ ) , with a decrease in drug-free days from baseline of -@ % in treatment as usual with smoking-cessation treatment and of -@ % in treatment as usual .


Participants receiving treatment as usual with smoking-cessation treatment , relative to those receiving treatment as usual , had significantly better outcomes on smoking point-prevalence abstinence ( @ % vs @ % ; ( @ ) ( @ ) = @ , P < @ ; OR = @ ) .


These results suggest that providing smoking-cessation treatment to illicit stimulant-dependent patients in outpatient substance use disorder treatment will not worsen , and may enhance , abstinence from nonnicotine substance use .


High tibial osteotomy is a common procedure to treat symptomatic osteoarthritis of the medial compartment of the knee with varus alignment .


This is achieved by overcorrecting the varus alignment to @-@ of valgus .


Various high tibial osteotomy techniques are currently used to this end .


Common procedures are medial opening wedge and lateral closing wedge tibial osteotomies .


The lateral closing wedge technique is a primary stable correction with a high rate of consolidation , but has the disadvantage of bone loss and change in tibial condylar offset .


The medial opening wedge technique does not result in any bone loss but needs to be fixated with a plate and may cause tibial slope and medial collateral ligament tightening .


A relatively new technique , the combined valgus high tibial osteotomy , claims to include the advantages of both techniques without bone loss .


Aim of this prospective randomized trial is to compare the lateral closing wedge with the combined wedge osteotomy in patients with symptomatic varus osteoarthritis of the knee .


A group of @ patients with osteoarthritis of the medial compartment of the knee with @-@ varus malalignment over @ years of age are recruited to participate a randomized controlled trial .


Patients are randomized to undergo a high tibial osteotomy , with either a lateral closing wedge technique or a combined wedge osteotomy technique .


Primary outcome measure is achievement of an overcorrection of @ valgus after one year of surgery , assessed by measuring the hip-knee-ankle angle .


Secondary objectives are radiological scores and anatomical changes after high tibial osteotomy ; pain , functional scores and quality of life will also be compared .


Combined high tibial osteotomy modification avoids metaphyseal tibial bone loss , decreasing transposition of the tibial condyle and shortening of the patellar tendon after osteotomy , even in case of great correction .


The clinical results of the combined wedge osteotomy technique are very promising .


Hypothesis is that the combined wedge osteotomy technique will achieve more accurate overcorrection of varus malalignment with fewer anatomical changes of the proximal tibia after one year .


To prospectively evaluate the effect of listening to music and inhaling aroma oil on patients undergoing screening computed tomography colonography .


Two hundred and twenty four participants were randomly allocated to one of the four groups including : ( @ ) combined music and aroma , ( @ ) music alone , ( @ ) aroma alone , and ( @ ) control .


The visual analog scale for pain and a questionnaire were used for subjective outcomes .


We also used a pre-testpost-test design to compare the differences in blood pressure and heart rate as objective outcomes .


There were no statistical differences between the control group and other groups in the visual analog scale or changes in heart rate .


Changes in blood pressure were similar .


Participants reported good overall experiences .


There were no differences in terms of overall satisfaction , pain rating , willingness to repeat the computed tomography colonography procedure in the future , or preference between colonoscopy and computed tomography colonography .


More participants using music and/or aroma requested music and/or aroma during the next computed tomography colonography ( P < @ ) .


Although audio and olfactory intervention had little effect on perceived pain or discomfort and vital signs , participants who listened to music and inhaled aroma during the computed tomography colonography preferred music and aroma during the next computed tomography colonography .


To evaluate the effect of the dimensions of the uterine cavity in relation to the expulsion , or removal for displacement , of intrauterine devices ( IUDs ) MLCu@ and TCu@A .


A case-control study nested in a multicentre clinical trial .


Eighteen family planning clinics in China .


Forty-eight pairs of TCu@A users and @ pairs of MLCu@ users .


The women were classified as cases if IUD expulsion or displacement occurred during the first year of follow-up after insertion .


One control was randomly selected for each case matched by IUD model , centre , age , service provider for insertion , and date of insertion .


Axial length of the uterine cavity ( LUC ) and the largest transverse diameter of the coronal section of the uterine cavity ( LTD ) were measured using abdominal ultrasound .


We used multivariate conditional logistic regressions to estimate the adjusted odds ratios ( aORs ) of expulsions or displacements among women with different sizes of uterine cavity according to the quartile of LUC and LTD , respectively .


Among MLCu@ users , women with LTD @ mm had a higher risk of expulsion or displacement ( aOR @ ; @ % confidence interval , @ % CI , @-@ @ ) , after adjusting for the volume of menstrual flow , dysmenorrhoea , parity , uterine position , MLCu@ type , and LUC .


Among TCu@A users , the association between LTD @ mm and expulsion or displacement ( aOR @ ; @ % CI @-@ @ ) was statistically significant , after adjusting for LUC and potential confounding factors .


Our study suggests that LTD should be considered when making the decision of which IUD model to use .


Analysis of the prevalence of mouth cavity urealytic microflora and determination of the level of its enzymatic activity depending on concentration and amount of urea solution taken as a substrate .


@ randomly chosen patients at the age of @-@ took part in the study .


Each of them rinsed the mouth with @ ml of @ % urea solution .


Before and after rinsing the concentration of ammonia in the mouth cavity air was measured .


In patients with highest and lowest activity of mouth cavity urealytic microflora a series of tests was carried out including mouth rinsing with urea solution in various concentrations and amounts and measuring ammonia concentration before and after rinsing .


Obtained results were analyzed using mathematical statistics methods .


It was found that in @ % @ % of randomly chosen patients ( p < @ ) mouth cavity microflora showed apparent urease activity .


The lowest concentration ( @ % in @ ml ) and volume ( @ ml of @ % solution ) levels of urea solution were obtained that can exert negative influence on the results of helicobacteriosis diagnosis by means of mouth cavity air analysis .


Urealytic microflora in the mouth cavity is very common and may constitute a factor that decreases the specificity of helicobacteriosis diagnosis by means of the methods based on detection of indicators of gas metabolites resulting from the enzymatic reaction in air samples taken from the mouth cavity after oral administration of urea .


Robotic guidance has been shown to facilitate motor skill acquisition , through altered sensorimotor control , in neurologically impaired and healthy populations .


To determine if robot-guided practice and online visual feedback availability primarily influences movement planning or online control mechanisms .


In this two-experiment study , participants first performed a pre-test involving reaches with or without vision , to obtain baseline measures .


In both experiments , participants then underwent an acquisition phase where they either actively followed robot-guided trajectories or trained unassisted .


Only in the second experiment , robot-guided or unassisted acquisition was performed either with or without online vision .


Following acquisition , all participants completed a post-test that was the same as the pre-test .


Planning and online control mechanisms were assessed through endpoint error and kinematic analyses .


The robot-guided and unassisted groups generally exhibited comparable changes in endpoint accuracy and precision .


Kinematic analyses revealed that only participants who practiced with the robot exhibited significantly reduced the proportion of movement time spent during the limb deceleration phase ( i.e. , time after peak velocity ) .


This was true regardless of online visual feedback availability during training .


The influence of robot-assisted motor skill acquisition is best explained by improved motor planning processes .


RAD@ , a central player in the response to DNA damage , has been suspected to contribute to tumour resistance to therapy .


A single-nucleotide polymorphism , RAD@ @G > C , in the untranslated region of the RAD@ gene elevates breast cancer risk among BRCA@ carriers .


In this study , it was investigated whether this polymorphism is related to prognosis of breast cancer and RAD@ protein expression and whether it is indicative of resistance to radiotherapy or cyclophosphamide/methotrexate/@-fluorouracil ( CMF ) chemotherapy .


We genotyped @ patients with early breast cancer , who were randomised to receive post-operative radiotherapy or CMF chemotherapy , for the RAD@ @G > C polymorphism .


RAD@ protein expression was evaluated with immunohistochemistry .


@ % of the patients had at least one C-allele ( three were C homozygotes ) .


There was no correlation between genotype and protein expression .


Patients who were G homozygotes benefitted from radiotherapy with decreased risk of local recurrences ( RR = @ , @ % C.I. @-@ @ , p = @ ) .


CMF chemotherapy reduced the risk of distant recurrence for patients carrying at least one C-allele ( RR = @ , @ % C.I. @-@ @ , p = @ ) , whereas G homozygotes had no benefit from chemotherapy .


There was a significant interaction between chemotherapy and genotype ( p = @ ) .


The results suggest that the RAD@ @G > C polymorphism predicts CMF chemotherapy effect in early breast cancer .


To evaluate the effects of a @-week balance training programme on self-assessed function and disability in healthy community-dwelling older adults with self-perceived balance deficits and fear of falling .


A prospective , randomized controlled trial .


Stockholm County , Sweden .


A total of @ community-dwelling older adults ( @ women and @ men ) aged @-@ were randomized to either an intervention group ( n = @ ) or to serve as controls ( n = @ ) after baseline testing .


The intervention was a @-week , three times per week , progressive , specific and individually adjusted group balance-training programme .


Self-perceived function and disability measured with Late Life Function and Disability Instrument .


The intervention group reported improvement in overall function ( p = @ ) , as well as in basic ( p = @ ) and advanced lower extremity function ( p = @ ) compared with the control group .


The study showed no improvement in overall disability or upper extremity function .


This group balance training programme improves self-assessed function in community-dwelling older adults with balance deficits and fear of falling .


To evaluate the impact on ovarian reserve between two different methods ofhemostasis after laparoscopic ovarian endometrioma excision .


A randomized controlled study was conducted from January to December @ in Thammasat University Hospital , Thailand .


Reproductive women , age @-@years who underwent laparoscopic ovarian cystectomy were randomized in electrocoagulation and suture groups .


Clinical baseline data and ovarian reserve outcome ( anti-Mullerian hormone ( AMH ) ) were evaluated .


Fifty participants were recruited and randomized in two groups .


Electrocoagulation and suture groups consisted of @ participants .


Baseline characteristics between @ groups ( age , weight , BMI , height , cyst diameter , duration and estimated blood loss ) were not statistically different .


There were no significant difference of AMIH between electrocoagulation and suture group atpre-operative ( @ vs. @ ng/ml ) , @ week ( @ vs. @ ng/ml ) , @ month ( @ vs. @ ng/ml ) , @ months ( @ vs. @ ng/ml ) and @ months ( @ vs @ ng/ml ) , respectively .


However mean AMH ofboth groups significantly decreased since the first week of operation .


Effect oflaparoscopic ovarian surgery had significantly declined and sustained AMH level until @ months .


Laparoscopic cystectomy of ovarian endometrioma has negative impact to ovarian reserve .


Either electroco - agulation or suture method had no different effects .


Implicit learning of intraoperative auditory stimuli during general anesthesia is very difficult to quantify but may require the presence of noxious stimulation .


We hypothesized that an anesthetic regimen with a low dose of opioid would enhance implicit memory , while a regimen with a high dose of opioid would not .


One hundred-twenty patients were randomized into @ groups .


All patients were anesthetized with a target-controlled infusion of propofol and remifentanil , targeting a Bispectral Index ( BIS ) value of @ .


The remifentanil effect-site concentration ( in ng/mL ) was always double that of propofol ( in g/mL ) in the first group and half of that in the second group .


Patients in these @ groups were played a list of @ words via headphones during surgery .


The third group served as control for memory tests and was not played any word during anesthesia .


BIS was recorded during word presentation .


No statistical difference was found among the @ groups regarding @ different memory tests although @ % -LSB- @ % ; @ % -RSB- of the patients of the high-opioid group and @ % -LSB- @ % ; @ % -RSB- of the low-opioid group had at least @ episode of BIS > @ .


We could not demonstrate the presence of implicit or explicit memorization under propofol-remifentanil anesthesia either with a low - or a high-dose opioid anesthetic regimen .


The mechanisms by which a ` Mediterranean diet ' reduces cardiovascular disease ( CVD ) burden remain poorly understood .


Lycopene is a potent antioxidant found in such diets with evidence suggesting beneficial effects .


We wished to investigate the effects of lycopene on the vasculature in CVD patients and separately , in healthy volunteers ( HV ) .


We randomised @ statin treated CVD patients and @ healthy volunteers in a @ treatment allocation ratio to either @ mg lycopene or placebo daily for @ months in a double-blind trial .


Forearm responses to intra-arterial infusions of acetylcholine ( endothelium-dependent vasodilatation ; EDV ) , sodium nitroprusside ( endothelium-independent vasodilatation ; EIDV ) , and NG-monomethyl-L-arginine ( basal nitric oxide ( NO ) synthase activity ) were measured using venous plethysmography .


A range of vascular and biochemical secondary endpoints were also explored .


EDV in CVD patients post-lycopene improved by @ % ( @ % CI : +@ % to +@ % , P = @ vs. placebo ) without changes to EIDV , or basal NO responses .


HVs did not show changes in EDV after lycopene treatment .


Blood pressure , arterial stiffness , lipids and hsCRP levels were unchanged for lycopene vs. placebo treatment groups in the CVD arm as well as the HV arm .


At baseline , CVD patients had impaired EDV compared with HV ( @ % lower ; @ % CI : -@ % to -@ % , P = @ ) , despite lower LDL cholesterol ( @ mmol/L lower , @ % CI : -@ to -@ mmol/L , P < @ ) .


Post-therapy EDV responses for lycopene-treated CVD patients were similar to HVs at baseline ( @ % lower , @ % CI : -@ % to +@ % , P = @ ) , also suggesting lycopene improved endothelial function .


Lycopene supplementation improves endothelial function in CVD patients on optimal secondary prevention , but not in HVs .


The optimal regimen to prevent chemotherapy-induced nausea and vomiting ( CINV ) for patients undergoing high-dose chemotherapy and autologous stem-cell transplantation ( ASCT ) is unclear .


To evaluate the effect of aprepitant in addition to a standard regimen , we conducted this randomized , placebo-controlled phase III trial .


Patients with multiple myeloma were randomly assigned at a one-to-one ratio to receive either aprepitant ( @ mg orally on day @ and @ mg orally on days @ to @ ) , granisetron ( @ mg orally on days @ to @ ) , and dexamethasone ( @ mg orally on day @ and @ mg orally on days @ to @ ) or matching placebo , granisetron ( @ mg orally on days @ to @ ) , and dexamethasone ( @ mg orally on day @ and @ mg orally on days @ to @ ) .


Melphalan @ mg/m ( @ ) was administered intravenously on days @ to @ .


ASCT was performed on day @ .


The primary end point ( complete response ) was defined as no emesis and no rescue therapy within @ hours of melphalan administration .


Quality of life was assessed by modified Functional Living Index-Emesis ( FLIE ) questionnaire on days -@ and @ .


Overall , @ patients were available for the efficacy analysis ( @ in each treatment arm ) .


Significantly more patients receiving aprepitant reached the primary end point ( @ % v @ % ; odds ratio -LSB- OR -RSB- , @ ; @ % CI , @ to @ ; P = @ ) .


Absence of major nausea ( @ % v @ % ; OR , @ ; @ % CI , @ to @ ; P = @ ) and emesis ( @ % v @ % ; OR , @ ; @ % CI , @ to @ ; P = @ ) within @ hours was increased by aprepitant .


Mean total FLIE score ( standard deviation ) was @ @ for aprepitant and @ @ for placebo ( P < @ ) .


The addition of aprepitant resulted in significantly less CINV and had a positive effect on quality of life .


This study compared transobturator tension-free vaginal tape ( TVT-O ) and Contasure-Needleless ( C-NDL ) at long-term follow-up .


Non-inferiority , prospective , single-centre , quasi-randomised trial started in September @ and finished in April @ to compare C-NDL with transobturator vaginal tape ( TVT-O ) mesh in the treatment of stress urinary incontinence ( SUI ) .


Epidemiological information , intraoperative and postoperative complications , subjective estimates of blood loss and pain levels were recorded .


We also analysed the postoperative stress test , the subjective impression of improvement using the Sandvik Severity Index and the quality of life during follow-up using the International Consultation on Incontinence Questionnaire-Short Form ( ICIQ-SF ) .


Two hundred and fifty-seven women with primary SUI were scheduled to receive TVT-O or C-NDL and were followed up at least @ years after the procedure .


One hundred and eleven women in the C-NDL group ( @ % ) had a negative stress test , compared with @ women ( @ % ) in the TVT-O group ( p = @ for the non-inferiority test ) .


The postoperative Sandvik Severity Index was @ or better than the preoperative score in @ % of patients in the C-NDL group and @ % of patients in the TVT-O group ( p = @ ) .


The complication rate was similar in both groups .


There were significant differences ( p = @ ) in postoperative pain within the TVT-O group .


The degree of satisfaction was not statistically significant between the two groups .


The outcomes for the C-NDL group were similar to those of the TVT-O group , adding the concept of `` single incision tape '' to the tension-free sling option .


Routine drainage of the abdominal cavity after surgery has been a robust dogma for many decades .


Nevertheless , the policy of routine abdominal drainage is increasingly questioned .


Many surgeons believe that routine drainage after surgery may prevent postoperative intra-abdominal infection .


The goal of this study was to assess the role of drains in laparoscopic cholecystectomy ( LC ) for acute cholecystitis .


From May @ to July @ , @ patients that underwent LC due to acute cholecystitis at Gangnam Severance Hospital , Yonsei University Health System , Seoul , Korea , were enrolled in this study .


After surgery , patients were randomly allocated to undergo drain placement in the subhepatic space ( Group A ) or no drainage ( Group B ) .


There was no significant difference in the intra-abdominal abscess rate , which was @ % with Group A and @ % with Group B ( P = @ ) .


The median subhepatic fluid collection was @ mL ( @ mL ) in Group A and @ mL ( @ mL ) in Group B ( P = @ ) .


However , the median hospital stay was @ days ( @ days ) in Group B and @ days ( @ days ) in group A ( P = @ ) .


The subgroup of empyema patients did not have any significant differences in intra-abdominal fluid collection or intra-abdominal abscess rate .


This study suggests that postoperative routine drainage of the abdominal cavity for acute cholecystitis does not prevent intra-abdominal infections .


Fexinidazole is a @-nitroimidazole recently included in a clinical efficacy trial as an oral drug for the treatment of human African trypanosomiasis ( HAT ) .


Preclinical studies showed it acts as a pharmacologically active pro-drug with two key active metabolites : sulfoxide and sulfone ( the most active metabolite ) .


The present studies aimed to determine the best dose regimen for the treatment of stage @ sleeping sickness patients , which could eventually also treat stage @ patients .


Fexinidazole was assessed in @ healthy adult male subjects of sub-Saharan African origin .


Three initial first-in-human studies and two additional studies assessed a single ascending dose and multiple ascending doses ( both under fasted conditions ) , tablet versus suspension formulation and food effect ( fasted vs. high-fat meal and field-adapted food ) , and multiple ascending doses with a loading dose regimen under fed conditions .


Fexinidazole was well-tolerated in a single dose from @ to @,@ mg , with quick absorption of the parent drug and rapid metabolism into sulfoxide -LSB- time to maximum concentration ( t max ) @-@ h -RSB- and sulfone ( t max @-@ h ) .


The tablet formulation was approximately @ % less bioavailable than the suspension , and food intake increased drug absorption and plasma concentrations of fexinidazole and its two metabolites by approximately @ % .


Fourteen-day multiple ascending dosing administered up to @,@ mg/day in fasted conditions showed that fexinidazole was generally well-tolerated ( mild to moderate , spontaneously reversible drug-related adverse events ) .


Following the high-fat food effect finding , another study was conducted to evaluate the impact of a low-fat regimen closer to that of the target population , showing that the type of meal does not influence fexinidazole absorption .


The last study showed that a loading dose of @,@ mg/day for @ days followed by a @,@ mg/day regimen for @ days with a normal meal provided the desired exposure of fexinidazole and its metabolites , particularly sulfone , with good tolerability .


Based on preclinical evidence from a chronic infection mouse model , systemic drug concentrations obtained are expected to be clinically effective in stage @ HAT .


These studies show that fexinidazole can be safely assessed in patients as a potential oral cure for both stages of HAT .


During development of an A/H@N@ pandemic influenza vaccine , this study was performed to identify the antigen and adjuvant content which would provide optimal antibody response and persistence in adults and the elderly .


Dose-sparing strategies , such as inclusion of adjuvants , are critical in ensuring the widest possible population coverage in the event of an influenza pandemic , despite a limited global capacity for vaccine manufacture .


Healthy subjects aged @-@ years ( n = @ ) and @ years ( n = @ ) were vaccinated with @ of @ investigational vaccine formulations varying in antigen quantity ( @ g to @ g of hemagglutinin ) and MF@ ( ) adjuvant ( none , half dose , or full dose ) .


All subjects received @ vaccine doses administered @ weeks apart .


Antibody response was assessed by hemagglutination inhibition assay @ and @ weeks after administration of first and second doses .


Antibody persistence was assessed after @ and @ mo. .


Vaccine safety was monitored over @ mo. .


All @ investigational A/H@N@ vaccine formulations were well tolerated , and rapidly induced high antibody titers which met all of the Center for Biologics Evaluation and Research ( CBER ) and Committee for Medicinal Products for Human Use ( CHMP ) licensure criteria @ weeks after one dose .


The highest antibody titers were observed in participants vaccinated with higher quantities of antigen and adjuvant .


A single vaccine dose containing @ g of A/California/@ / @ ( H@N@ ) antigen with MF@ adjuvant was identified as optimal for young to middle-aged ( @-@ years ) and older ( @ years ) adult populations .


We assessed the efficacy and tolerability of onabotulinumtoxinA @ U vs placebo to treat lower urinary tract symptoms/benign prostatic hyperplasia inmen previously treated with oral benign prostatic hyperplasia medication in a@-week phase @ , multicenter , double-blind , randomized , placebo controlled , parallel group trial .


Patients with I-PSS ( International Prostate Symptom Score ) @ or greater , peak urinary flow rate @ to @ ml per second and total prostate volume @ to @ ml were randomized @:@ to a single intraprostatic treatment of onabotulinumtoxinA @ U or placebo .


A single-blind sham procedure followed by a @-week run-in was included to attempt to minimize any potential placebo effect .


Patients who still met eligibility criteria after the run-in entered the double-blind active treatment period .


The primary end point was the change from baseline in total I-PSS at week @ .


Other end points assessed at weeks @ , @and @ included the change from baseline in total I-PSS , peak urinary flow rate , total prostate volume and post-void residual urine volume .


Of @ patients enrolled @ were randomized and treated .


Decreases from baseline in I-PSS were observed in the onabotulinumtoxinA and placebo groups ( -@ vs -@ points , p < @ ) with no difference between the groups overall or in subgroups .


Improvement was observed in the peak urinary flow rate , which was significant only at week @ compared to placebo .


Improvement was significant at all time points in a patient subgroup on stable concurrent - blockers or @-reductase inhibitors during the study .


Adverse events were similar in the @ treatment groups .


OnabotulinumtoxinA @ U and placebo improved I-PSS and were well tolerated but no between group difference in efficacy was observed .


General anesthesia ( GA ) for endovascular therapy ( EVT ) of acute ischemic stroke may be associated with worse outcomes .


The Interventional Management of Stroke III trial randomized patients within @ hours of acute ischemic stroke onset to intravenous tissue-type plasminogen activatorEVT .


GA use within @ hours of stroke onset was recorded per protocol .


Good outcome was defined as @-day modified Rankin Scale @ .


A multivariable analysis adjusting for dichotomized National Institutes of Health Stroke Scale ( NIHSS ; @-@ versus @ ) , age , and time from onset to groin puncture was performed .


Four hundred thirty-four patients were randomized to EVT , @ ( @ % ) were treated under local anesthesia and @ ( @ % ) under GA ; @ ( @ % ) were undetermined .


The @ groups were comparable except for median baseline NIHSS ( @ local anesthesia versus @ GA ; P < @ ) .


The GA group was less likely to achieve a good outcome ( adjusted relative risk , @ ; confidence interval , @-@ @ ; P = @ ) and had increased in-hospital mortality ( adjusted relative risk , @ ; confidence interval , @-@ @ ; P = @ ) .


Those with medically indicated GA had worse outcomes ( adjusted relative risk , @ ; confidence interval , @-@ @ ; P = @ ) and increased mortality ( relative risk , @ ; confidence interval , @-@ @ ; P < @ ) with a trend for higher mortality with routine GA. .


There was no significant difference in the adjusted risks of subarachnoid hemorrhage ( P = @ ) or symptomatic intracerebral hemorrhage ( P = @ ) .


GA was associated with worse neurological outcomes and increased mortality in the EVT arm ; this was primarily true among patients with medical indications for GA. .


Relative risk estimates , though not statistically significant , suggest reduced risk for subarachnoid hemorrhage and symptomatic intracerebral hemorrhage under local anesthesia .


Although the reasons for these associations are not clear , these data support the use of local anesthesia when possible during EVT .


To compare the clinical therapeutic effects differences between acupuncture at Suliao ( GV @ ) and Shuigou ( GV @ ) on promoting regain of consciousness from coma in severe craniocerebral injury .


Based on regular emergency treatments of neurosurgery , eighty-two cases of craniocerebral injury who were under stable condition were randomly divided into an observation group ( @ cases ) and a control group ( @ cases ) .


Suliao ( GV @ ) was selected as main aupoint , while Laogong ( PC @ ) and Yongquan ( KI @ ) , etc. were selected as adjuvant acupoints and Neiguan ( PC @ ) , Sanyinjiao ( SP @ ) , Yifeng ( TE @ ) and Wangu ( GB @ ) , etc. were selected as matching acupoints in the observation group where a strong needle manipulation was applied to improve the regain of consciousness .


The main acupoint of Shuigou ( GV @ ) along with identical adjuvant acupoints and matching acupoints in the observation group were selected in the control group with identical strong needle manipulation .


The treatment was given once a day in both groups , five times per week and ten times were considered as one session .


The immediate clinical symptoms after acupuncture at Suliao ( GV @ ) and Shuigou ( GV @ ) were observed as well as Glasgow coma scale ( GCS ) before the treatment , after @ days and @ days of treatment to assess the resuscitation time and rate .


Also the clinical efficacy was compared between both groups .


The occurrence rate of sneezing reflex was @ % ( @/@ ) in the observation group , which was higher than @ % ( @/@ ) in the control group ( P < @ ) .


The average resuscitation time was ( @ + / - @ ) days in the observation group , which was obviously shorter than ( @ + / - @ ) days in the control group ( P < @ ) .


The resuscitation rate was @ % ( @/@ ) in the observation group , which was similar to @ % ( @/@ ) in the control group ( P > @ ) .


Compared before the treatment , GCS were both improved after the treatment in two groups ( both P < @ ) .


The @-day GCS was @ + / - @ in the observation group , which was superior to @ + / -@ in the control group ( P < @ ) .


The curative and markedly effective rate was @ % ( @/@ ) in the observation group , which was superior to @ % ( @/@ ) in the control group ( P < @ ) .


The effect of acupuncture at Suliao ( GV @ ) on improving regain of consciousness from coma in severe craniocerebral injury is positive .


It could specifically improve sneezing reflex and stimulate respiratory center , which has more obvious effect than acupuncture at Shuigou ( GV @ ) .


Maternal nutritional status is a major determinant of low birth weight and fluctuates across seasons .


Seasonality may influence the outcome of prenatal nutrition interventions that aim to enhance fetal growth .


This study investigated seasonal modifications of the efficacy of a randomized controlled prenatal nutrition intervention trial in pregnant women to improve fetal growth in rural Burkina Faso .


The second Micronutriments et Sant de la Mre et de l'Enfant study compared a lipid-based nutrient supplement ( LNS ) fortified with multiple micronutrients ( MMNs ) to an MMN supplement .


Truncated Fourier series were used to characterize seasonality in birth outcomes .


Models that included the Fourier series and newborn and maternal characteristics were used to assess seasonal effect modifications of prenatal supplementation on birth outcomes .


Birth weight , birth length , small for gestational age as a proxy for intrauterine growth retardation , and preterm birth were significantly related to date of birth and showed important seasonal variations .


LNSs , which supply energy in addition to MMNs , resulted in a significant increase in birth length ( +@ mm , @ % CI : @ , @ mm ) at the transition from rain to dry season ( September to November ) compared to MMNs alone .


The climatologic and agricultural seasonal patterns in Burkina Faso affect the efficacy of prenatal LNSs on birth length .


In this context , prenatal MMN supplementation programs should be complemented by energy supplementation during the annual rain season to promote fetal growth .


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


To compare the efficacy of intracoronary administration of combined high-dose adenosine and tirofiban versus intracoronary tirofiban during primary percutaneous coronary intervention ( PCI ) in patients with acute myocardial infarction .


Consecutive @ patients with acute ST-segment elevation myocardial infarction ( STEMI ) underwent primary PCI , treated with thrombus aspiration and then intracoronary tirofiban , were randomly divided into adenosine group ( n = @ ) and control group ( n = @ ) .


Adenosine group received @ times intracoronary adenosine ( @ mg ) after thrombus aspiration and after stenting of the infarct-related artery through the aspiration catheter .


Control group received placebo .


The primary end point was myocardial blush grade ( MBG ) after PCI .


Secondary end points were thrombolysis in myocardial infarction ( TIMI ) flow grade and corrected TIMI frame count ( CTFC ) after PCI , ST-segment elevation resolution ( STR ) , and major adverse cardiac events ( MACE ) at @ days and @ months .


TIMI flow grade post PCI did not differ between the @ groups , while CTFC favored the adenosine-treated patients -LSB- ( @ @ ) frames -RSB- compared with the placebo-treated patients -LSB- ( @ @ ) frames , P = @ -RSB- .


MBG @ was more frequently observed in the adenosine compared to the control group -LSB- @ % ( @/@ ) vs. @ % ( @/@ ) , P = @ -RSB- .


Patients in the adenosine group had a trend of higher rate of compete STR after the procedure compared patients in the control group -LSB- @ % ( @/@ ) vs. @ % ( @/@ ) , P = @ -RSB- .


The incidence of MACE was comparable between patients randomized to adenosine and placebo at @ days -LSB- @ % ( @/@ ) vs. @ % ( @/@ ) , P = @ -RSB- and at @ months -LSB- @ % ( @/@ ) vs. @ % ( @/@ ) , P = @ -RSB- .


Intracoronary administration of high-dose adenosine combined with tirofiban provides further improvement on myocardial perfusion after primary PCI but does not affect the clinical outcomes in patients with STEMI .


Despite high initial sensitivity to chemotherapy , TNBC is associated with a poor prognosis , highlighting the need for novel therapeutic strategies .


The aim of this multicenter , randomized , open-label phase II trial was to assess the efficacy of ixabepilone as monotherapy , and the combination of ixabepilone with cetuximab , as first-line treatment in patients with triple-negative locally advanced nonresectable and/or metastatic breast cancer .


Women were randomly assigned to receive either ixabepilone ( @ mg/m ( @ ) ) every @ days ( n = @ ) , or ixabepilone ( @ mg/m ( @ ) ) every @ days with cetuximab ( @ mg/m ( @ ) loading dose , followed by @ mg/m ( @ ) ) once weekly ( n = @ ) .


The primary end point of the trial was to estimate the response rates of ixabepilone monotherapy and ixabepilone with cetuximab combination therapy .


Of @ randomized patients , @ were treated .


Based on an intent-to-treat analysis , an objective response rate of @ % ( @ % confidence interval -LSB- CI -RSB- , @-@ @ ) was observed in the monotherapy arm , and @ % ( @ % CI , @-@ @ ) in the combination arm .


Median progression-free survival was @ months in both treatment groups .


Safety findings were consistent with the known individual toxicity profiles of ixabepilone and cetuximab .


Skin and subcutaneous tissue disorders were more common with combination therapy , as were discontinuations because of adverse events .


Ixabepilone monotherapy and the ixabepilone and cetuximab combination demonstrated similar levels of clinical activity in first-line treatment of advanced TNBC , with a predictable safety profile .


Further investigation of novel therapies for TNBC is required to improve patient outcomes .


We previously reported a positive association between serum @-hydroxyvitamin D ( @ ( OH ) D ) and colorectal cancer risk .


To further elucidate this association , we examined the molar ratio of @ ( OH ) D to vitamin D binding protein ( DBP ) , the primary @ ( OH ) D transport protein , and whether DBP modified the association between @ ( OH ) D and colorectal cancer risk .


In a nested case-control study within the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study , controls were @ matched to @ colorectal cancer cases based on age and date of blood collection .


Logistic regression was used to estimate odds ratios ( ORs ) and @ % confidence intervals ( CI ) for quartiles of @ ( OH ) D , DBP , and the molar ratio of @ ( OH ) D : DBP , a proxy for free , unbound circulating @ ( OH ) D.


Comparing highest to lowest quartiles , DBP was not associated with colorectal cancer risk ( OR = @ ; @ % CI : @ , @ , p for trend = @ ) ; however , a positive risk association was observed for the molar ratio of @ ( OH ) D : DBP ( OR = @ ; @ % CI : @ , @ , p for trend = @ ) .


In stratified analyses , the positive association between @ ( OH ) D and colorectal cancer was stronger among men with DBP levels above the median ( OR = @ ; @ % CI : @ , @ , p for trend = @ ) than below the median ( OR = @ ; @ % CI : @ , @ , p for trend = @ ) , although the interaction was not statistically significant ( p for interaction = @ ) .


Circulating DBP may influence the association between @ ( OH ) D and colorectal cancer in male smokers , with the suggestion of a stronger positive association in men with higher DBP concentrations .


This finding should be examined in other populations , especially those that include women and non-smokers .


Osteoporosis and vertebral fracture can have a considerable impact on an individual 's quality of life .


There is increasing evidence that physiotherapy including manual techniques and exercise interventions may have an important treatment role .


This pragmatic randomised controlled trial will investigate the clinical and cost-effectiveness of two different physiotherapy approaches for people with osteoporosis and vertebral fracture , in comparison to usual care .


Six hundred people with osteoporosis and a clinically diagnosed vertebral fracture will be recruited and randomly allocated to one of three management strategies , usual care ( control - A ) , an exercise-based physiotherapy intervention ( B ) or a manual therapy-based physiotherapy intervention ( C ) .


Those in the usual care arm will receive a single session of education and advice , those in the active treatment arms ( B+C ) will be offered seven individual physiotherapy sessions over @ weeks .


The trial is designed as a prospective , adaptive single-blinded randomised controlled trial .


An interim analysis will be completed and if one intervention is clearly superior the trial will be adapted at this point to continue with just one intervention and the control .


The primary outcomes are quality of life measured by the disease specific QUALLEFO @ and the Timed Loaded Standing test measured at @ year .


There are a variety of different physiotherapy packages used to treat patients with osteoporotic vertebral fracture .


At present , the indication for each different therapy is not well defined , and the effectiveness of different modalities is unknown .


The aim of the study was to measure the effects on blood pressure ( BP ) of the angiotensin receptor blocker azilsartan medoxomil , in @ and @ mg doses , combined with @ mg of the calcium channel blocker amlodipine and to compare these effects with placebo plus amlodipine @ mg .


This was a randomized , controlled , double-blind study of @ weeks ' duration in @ patients with stage @ hypertension .


The primary endpoint was @-h systolic BP by ambulatory monitoring .


The mean age of the participants was @ years ; men and women were equally represented , and baseline @-h BP ( @-@/@ mmHg ) and clinic BP ( @-@/@ -@ mmHg ) were similar across the three treatment groups .


After @ weeks , @-h BP decreased by @/@ mmHg in both the azilsartan medoxomil/amlodipine @/@ and @/@ mg groups .


These reductions were each greater than the @/@ mmHg decrease with placebo plus amlodipine @ mg ( P@ @ for both comparisons ) .


All treatments were well tolerated , and adverse events did not increase with the azilsartan medoxomil doses .


Edema or fluid retention was less common in both combination groups ( @ and @ % ) than with placebo plus amlodipine ( @ % ) .


Coadministration of azilsartan medoxomil with amlodipine was well tolerated and led to meaningful additional BP reductions compared with placebo plus amlodipine .


To determine whether increasing the viscosity of a standard hemoglobin-based oxygen-carrying solution ( HBOC ) would offset its associated vasoconstrictive effects and result in improved microvascular perfusion in healthy splenectomized dogs with experimentally induced hemorrhagic shock .


@ male American Foxhounds .


Each dog underwent anesthesia and splenectomy .


Shock was induced by controlled hemorrhage until a mean arterial blood pressure of @ mm Hg was achieved and maintained for @ minutes .


Dogs were then randomly assigned to receive either a standard or hyperviscous HBOC ( @ dogs/group ) .


Sidestream dark-field microscopy was used to assess the effects of shock and HBOC administration on the microcirculation of the buccal mucosa and the jejunal serosa .


Video recordings of the microcirculation were collected before shock was induced ( baseline ) and at intervals up to @ minutes following HBOC administration .


Vascular analysis software was used to compute microcirculatory variables .


Compared with baseline findings , hemorrhagic shock resulted in decreases in all microvascular variables in the buccal mucosa and the jejunal serosa .


At all time points following HBOC administration , microvascular variables were similar to initial values and no significant differences between treatment groups were detected .


At all time points following HBOC administration , blood and plasma viscosities in dogs treated with the hyperviscous solution were significantly higher than values in dogs receiving the standard solution .


In splenectomized dogs with experimentally induced hemorrhagic shock , administration of a hyperviscous HBOC did not significantly affect microvascular variables , compared with effects of a standard HBOC .


Microcirculatory flow returned to baseline values in both treatment groups , suggesting that marked HBOC-associated vasoconstriction did not occur .


Intraventricular fibrinolysis ( IVF ) through bilateral external ventricular drains ( EVD ) may provide better access of the thrombolytic agent to the intraventricular clot , potentially leading to faster clot clearance .


To compare the feasibility and safety between single and bilateral EVD groups .


Patients with spontaneous intraventricular haemorrhage ( IVH ) ( Graeb score@ ) were treated with IVF .


The selection for placement of one or two EVDs was randomized .


The average daily CSF drainage volume , the indwelling EVD time , the time for monitoring in intensive care unit ( ICU ) , intracranial re-haemorrhage and intracranial infection , Glasgow coma score ( GCS ) , Graeb score and the reserved IVH volume have been analysed for patients with one ( group I , n = @ ) or two EVDs ( group II , n = @ ) .


Significant difference was found in the average daily CSF drainage volume between the two groups ( @ ( SD = @ ) vs. @ ( @ ) ml ) .


No difference was found in the indwelling EVD time , the time for monitoring in the ICU .


Through repeated measurements of the variance analysis , the test for a difference in IVH volume over time was statistically significant ( F = @ , p = @ ) and the test for the interaction between treatment and time was also significant ( F = @ , p = @ ) , indicating that the IVH volume decreased over time in both groups , with a sharper decrease in Group II .


Intracranial re-haemorrhage and infection was not found in this study .


The results provide some evidence to support the use of bilateral EVDs for IVF in patients with severe IVH .


We undertook this study to determine the efficacy of oral magnesium supplementation in the improvement of the metabolic profile and blood pressure in metabolically obese , normal-weight ( MONW ) individuals .


A total of @ MONW individuals with hypomagnesemia were enrolled in clinical a randomized double-blind placebo-controlled trial .


Individuals in the intervention group received @ mL of MgCl@ @ % solution ( equivalent to @ mg of magnesium ) and individuals in the control group @ mL of placebo solution , once daily during @ months .


In the absence of obesity or overweight , the presence of fasting glucose levels @ mg/dL , HOMA-IR index @ , triglyceride levels @ mg/dL and/or systolic and diastolic blood pressure @ and @ mmHg defined the presence of the MONW phenotype .


Hypomagnesemia was defined by serum magnesium concentration @ mg/dL .


At basal conditions there were no significant differences between groups .


At the end of follow-up , changes in the mean of systolic ( -@ vs. @ % mmHg , p < @ ) and diastolic ( -@ vs. @ % mmHg , p < @ ) blood pressures , HOMA-IR index ( -@ vs. -@ % , p < @ ) , fasting glucose ( -@ vs. -@ % mg/dL , p < @ ) and triglyceride levels ( -@ % vs. @ % mg/dL , p < @ ) were significantly lower in the subjects who received MgCl@ compared with individuals in the control group .


Oral magnesium supplementation improves the metabolic profile and blood pressure of MONW individuals .


Tablets are a novel line of computers controlled by a multitouch screen .


Fine motor movements are captured on the tablet computer through electrical fields and can be qualitatively and quantitatively assessed .


Evidence is limited on tablet use for stroke rehabilitation .


iHOME is an investigator-initiated randomized controlled pilot trial with a single-blinded outcome assessment .


The intervention consists of iPad use ( investigational group ) vs. usual care ( control group ) among patients receiving conventional outpatient rehabilitation .


Eligibility includes aged @-@ years who experienced a mild ischemic or hemorrhagic stroke ( as diagnosed on neuroimaging and determined by the Chedoke-McMaster score @ .


The STROKE REHAB software for the iPad was specifically designed for patients with fine motor weakness and/or neglect .


Of the total @ patients , @ will be in iHOME Acute ( enrolled within three-months of stroke onset ) and @ patients in iHOME Chronic ( enrolled more than six-months from onset ) .


The primary feasibility outcome is the proportion of the scheduled iPad time used ( more than @ % ( @ mins ) of the total ` dose ' of intervention intended will be considered successful ) .


Efficacy in fine motor movements will be assessed using the nine-hole peg test ; time to magnify and pop the balloons in the iPad software application , and improvement in Wolf Motor Function Test .


iHOME is a randomized controlled trial assessing the feasibility , safety , and efficacy of tablet technology for home use in stroke rehabilitation .


The results of this study will serve as the basis for a larger multicenter trial .


Breast-conserving treatment ( BCT ) leads to a progressive and deteriorating breast deformity .


Fatgrafting is ideal for breast reconstruction after BCT .


The most frequently utilized technique for fat processing is centrifugation .


The PureGraft device ( Cytori Therapeutics , San Diego , CA , USA ) is a new method that involves washing and filtering the fat to prepare the graft .


We compared the subjective and objective outcomes of two fat-processing methods , centrifugation and PureGraft filtration .


Thirty patients underwent breast reconstruction performed by a single surgeon ( OM ) after BCT in our department between April @ and September @ .


The patients were preoperatively divided into two groups randomly : @ received fatgrafts processed by centrifugation , and @ received fatgrafts processed by washing in PureGraft bags .


The patients were followed up for @ to @ months .


To measure the subjective outcome , we distributed the BREAST-Q questionnaire to all the patients both preoperatively and @ year postoperatively .


The BCCT.core software evaluated the objective outcome of breast reconstruction by fatgrafting .


The Breast-Q results indicated a tremendous improvement in the modules `` Satisfaction with Breast '' and `` Psychosocial Well-being '' .


The `` Sexual Well-being '' scale also improved .


Only the module `` Satisfaction with Breasts '' significantly differed between groups ; patients treated with the PureGraft fat exhibited better outcomes .


The BCCT.core results did not significantly differ between the groups .


One year postoperatively , the outcomes of the use of PureGraft bags or centrifugation to process fat for breast reconstruction after BCT did not differ .


The unpredictability of the results following fatgrafting procedures is likely due to interindividual differences with yet-undisclosed causes .


Laparoscopic radical prostatectomy ( LARP ) may cause stress urinary incontinence ( SUI ) .


This study reports the effects of preoperative pelvic floor muscle therapy ( PFMT ) on SUI and quality of life ( QoL ) in men undergoing LARP .


In this single-center randomized controlled trial , @ patients undergoing LARP were assigned to an intervention group of PFMT with biofeedback once a week preoperatively , with @ weeks ' follow-up or to a control group receiving standard care .


Randomization and allocation to the trial group were carried out by a central computer system .


The primary analysis was based on @ ( n = @ ; n = @ ) , comparing SUI rates and QoL in the two groups in a @-year follow-up .


Validated questionnaires , the Pelvic Floor Inventories ( PeLFls ) , the King 's Health Questionnaire ( KHQ ) , the International Prostate Symptom Score ( IPSS ) , a bladder diary , a @-hr pad test and pelvic floor examination were used .


Continence was defined as no leakage at all .


All analyses were performed according to intention-to-treat .


One hundred twenty-two patients were randomized , @ patients were excluded from analysis because of early drop-out .


There were no significant differences between both groups in the incidence of SUI and QoL based on the KHQ , IPSS , and pad tests ( P @ ) .


In all patients continence was achieved in @ % at @ year postoperatively .


Preoperative PFMT does not appear to be effective in the prevention of SUI and QoL following LARP .


Benzodiazepines and related drugs affect physical functioning negatively and increase fall and fracture risk .


As impaired muscle strength and balance are risk factors for falls , we examined the effects of hypnotic withdrawal on handgrip strength and balance in older adult outpatients during and after long-term use of temazepam , zopiclone and zolpidem ( here collectively referred to as `` benzodiazepines '' ) .


Eighty-nine chronic users ( @ women , @ men ) of temazepam , zopiclone or zolpidem aged @ years participated in a benzodiazepine withdrawal study .


Individual physician-directed withdrawal was performed gradually over a one-month period and participants were followed up to six months .


Handgrip strength was assessed using a handheld dynamometer , and balance using the Short Berg 's Balance Scale during the period of benzodiazepine use ( baseline ) , and at @ , @ , @ weeks , and @ , @ and @ months after initiating withdrawal .


Withdrawal outcome and persistence were determined by plasma benzodiazepine-determinations at baseline and at four weeks ( `` short-term withdrawers '' , n = @ ; `` short-term non-withdrawers '' , n = @ ) , and by interviews at six months ( `` long-term withdrawers '' , n = @ ; `` long-term non-withdrawers '' , n = @ ) .


Also most of the non-withdrawers markedly reduced their benzodiazepine use .


Within three weeks after initiating withdrawal , handgrip strength improved significantly ( P@ @ ) compared to baseline values .


Among women , long-term withdrawers improved their handgrip strength both when compared to their baseline values ( P = @ ) or to non-withdrawers ( P = @ ) .


In men , improvement of handgrip strength from baseline was not significantly better in withdrawers than in non-withdrawers .


However , men did improve their handgrip strength values compared to baseline ( P = @ ) .


Compared to balance test results at baseline , withdrawers improved starting from the first week after withdrawal initiation .


There was , however , only a borderline difference ( P = @ ) in balance improvement between the long-term withdrawers and long-term non-withdrawers .


Of note , the non-withdrawers tended to improve their handgrip strength and balance compared to baseline values , in parallel with their reduced benzodiazepine use .


Withdrawal from long-term use of benzodiazepines can rapidly improve muscle strength and balance .


Our results encourage discontinuing benzodiazepine hypnotics , particularly in older women who are at a high risk of falling and sustaining fractures .


To determine the more effective dosing sequence of intermittent erlotinib and docetaxel for treating chemotherapy-naive patients with advanced Non-Small Cell Lung Cancer ( NSCLC ) .


Patients were randomized to receive daily erlotinib for @ consecutive days prior to docetaxel ( Arm A ) or after docetaxel ( Arm B ) .


Progression-free survival ( PFS ) was the primary end-point ; secondary end-points were overall survival ( OS ) and objective response rate ( ORR ) .


Fifty eligible patients received a total of @ treatment cycles ( median : @ ) .


Median PFS and OS were @ months and @ months , respectively ( differences were not statistically significant between the two arms ) .


Neutropenia grade @ and @ occurred in @ patients , while two patients developed grade @ diarrhea .


There were two treatment-related deaths ( pulmonary embolism and non-neutropenic sepsis ) .


Intermittent administration of erlotinib does not appear to improve the clinical outcome of single-agent docetaxel chemotherapy in unselected patients with NSCLC in the first-line setting .


The autonomic system is an important determinant of atrial arrhythmogenesis .


Current evidence indicates that a combined sympathovagal drive is most commonly responsible for eliciting atrial fibrillation ( AF ) episodes .


The purpose of this study was to test whether moxonidine , a centrally acting sympathoinhibitory agent , can lead to a reduction in postablation AF recurrence .


This was a prospective , double-blinded , randomized study of @ hypertensive patients with symptomatic paroxysmal AF who were scheduled to undergo pulmonary vein isolation .


Patients were randomly assigned to receive either moxonidine ( @-@ @ mg daily ) or placebo , along with standard antihypertensive treatment .


No significant differences in blood pressure levels were observed between the @ groups .


In the primary outcome analysis , mean recurrence-free survival was @ days ( @ % CI , @-@ days ) in the moxonidine group as compared with @ days ( @ % CI , @-@ days ) in control subjects ( log rank test , P = @ ) .


The calculated @-month recurrence rate estimates were @ % in the control group and @ % in the moxonidine group ( P = @ ) .


Moxonidine treatment was associated with lower recurrence risk after adjustment for age , body mass index , number of AF episodes in the previous year , and left atrial diameter ( adjusted hazard ratio , @ -LSB- @ % CI , @-@ @ -RSB- ; P < @ ) .


Treatment with moxonidine is associated with less AF recurrences after ablation treatment for drug-refractory AF in patients with hypertension .


The observed effect does not appear to depend on the antihypertensive action of this agent .


Erosive degenerative disc disease , also known as Modic type @ changes , is usually characterized by low back pain with an inflammatory pain pattern , as seen in spondyloarthropathies .


Intravenous pamidronate has proven to be effective in patients with ankylosing spondylitis who are refractory to nonsteroidal antiinflammatory drugs , and in painful bone diseases in general , such as Paget 's disease , fibrous dysplasia or vertebral fractures .


We therefore hypothesize that pamidronate would be effective in treating low back pain associated with Modic type @ changes .


This study , called PEPTIDE ( short for the French title `` Etude Prospective sur l'Efficacit et la tolrance du PamidronaTe dans les dIscopathies Degeneratives Erosives '' ) , will be a double-blind , randomized , placebo-controlled , parallel group , phase two clinical trial .


A total of @ patients will be recruited .


These patients will be randomly assigned to one of the two groups , with @ patients in each group : one group will be given pamidronate and the other a placebo .


Pamidronate will be administered at a dose of @mg per day for two days consecutively , and every patient , irrespective of treatment group , will be given paracetamol to maintain blinding by preventing drug-induced fever .


The primary outcome measure is a between-group difference of @ points on a @mm Visual Analogue Scale ( VAS ) at three months .


Secondary outcome measures are improvement in functional status and the drug 's safety .


Primary and secondary outcome measures will be assessed at each visit ( inclusion , at six weeks , three months , and six months ) .


If the primary goal is not attained , the patient will be offered a rigid or semi-rigid back brace , irrespective of the treatment group .


To date , only local treatments , for example intradiscal corticosteroid therapy , lumbar arthrodesis or back braces have been studied in randomized , controlled trials , with controversial results .


This trial is currently ongoing and , if conclusive , should provide physicians with an acceptable alternative to those treatments .


The results should be publicly available in spring @ .


To analyze hepatitis C virus ( HCV ) - specific immune responses in chronically infected patients under triple therapy with interferon - ( IFN - ) plus ribavirin and CIGB-@ .


CIGB-@ was administered in different schedules with respect to IFN - plus ribavirin therapy .


Paired serum and peripheral blood mononuclear cells ( PBMC ) samples from baseline and end of treatment were analyzed .


The HCV-specific humoral response was tested by enzyme-linked immunosorbent assay , neutralizing antibodies were evaluated by cell culture HCV neutralization assays , PBMC proliferation was assayed by carboxyfluorescein succinimidyl ester staining and IFN - secretion was assessed by enzyme-linked immunospot .


Data on virological and histological response and their association with immune variables are also provided .


From week @ to week @ , all groups of patients showed a significant reduction in mean leukocyte counts .


Statistically significant reductions in antibody titers were frequent , but only individuals immunized with CIGB-@ as early add-on treatment sustained the core-IgG response , and the neutralizing antibody response was enhanced only in patients receiving CIGB-@ .


Cell-mediated immune responses also tended to decline , but significant reductions in IFN - secretion and total absence of core-specific lymphoproliferation were exclusive of the control group .


Only CIGB-@-immunized individuals showed de novo induced lymphoproliferative responses against the structural antigens .


Importantly , it was demonstrated that the quality of the CIGB-@-induced immune response depended on the number of doses and timing of administration in relation to the antiviral therapy .


Specifically , the administration of @ doses of CIGB-@ as late add-on to therapy increased the neutralizing antibody activity and the de novo core-specific IFN - secretion , both of which were associated with the sustained virological response .


CIGB-@ , combined with IFN -- based therapy , modifies the immune response in chronic patients .


The study provides evidence for the design of more effective therapeutic vaccine interventions against HCV .


Evaluating the role of cystone , a polyherbal preparation , in protecting cancer patients against cisplatin-induced nephrotoxicity , and its impact on the cytotoxic activity of cisplatin .


A prospective open-label randomized controlled trial conducted on @ cancer patients who received six cycles of @ mg/m ( @ ) cisplatin-based regimens .


The study comprised two groups , a control group ( A ) in which @ patients received cisplatin without cystone supplement , and an experimental group ( B ) in which @ patients received cisplatin with cystone supplement .


Renal function parameters including serum creatinine , creatinine clearance , blood urea , and serum cystatin C were compared between both groups throughout chemotherapy cycles .


Patient response to treatment was evaluated in both groups after @rd and @th cycles .


At the end of the study , mean levels of serum creatinine , blood urea , and serum cystatin C were significantly lower , whereas creatinine clearance was significantly higher in group ( B ) compared with group ( A ) .


In group ( B ) , there was no significant difference between mean levels of renal markers at baseline and after completion of treatment ; while significant changes were observed in group ( A ) .


Grading of acute kidney injury according to Common Terminology Criteria for Adverse Events revealed significantly better renal status among patients in group ( B ) `` grades @ and @ in @ and @ % of the patients , respectively '' compared with group ( A ) `` grades @ , @ , and @ in @ , @ , and @ % of the patients , respectively '' .


Based on Response Evaluation Criteria in Solid Tumors , there was no significant difference between both groups .


Cystone can protect cancer patients from cisplatin nephrotoxicity without interfering with its antitumor activity .


To present the outcomes of flexible ureteroscopy ( F-URS ) , shock wave lithotripsy ( SWL ) , and observation in the management of asymptomatic lower calyceal stones .


A total of @ patients with asymptomatic lower calyceal stones were randomized into F-URS ( group @ ) , SWL ( group @ ) , and observation ( group @ ) groups .


The main criteria for patient enrollment were having asymptomatic single lower pole stones < @ cm .


In F-URS , the mean stone-free rate was @ % ( @ of @ ) .


The mean number of sessions for the SWL group was @ @ .


Stone-free rate was @ % ( @ of @ ) .


In the observation group , patients were followed up for a mean of @ @ months .


Three stones passed spontaneously without any symptoms .


Pain developed in @ patients during follow-up , and @ of them passed a stone and responded to analgesics without further treatment .


Complication rates for groups @ and @ were similar , but group @ had higher Clavien grades .


For asymptomatic small-sized lower calyceal stones , SWL and F-URS are established treatment modalities .


However , with low auxiliary treatment rates , observation may be an option for the management of nonsymptomatic small-sized lower pole kidney stones .


To determine whether the tumor necrosis factor inhibitor etanercept is well tolerated and obtain preliminary data on its safety in Alzheimer disease dementia .


In a double-blind study , patients with mild to moderate Alzheimer disease dementia were randomized ( @:@ ) to subcutaneous etanercept ( @ mg ) once weekly or identical placebo over a @-week period .


Tolerability and safety of this medication was recorded including secondary outcomes of cognition , global function , behavior , and systemic cytokine levels at baseline , @ weeks , @ weeks , and following a @-week washout period .


This trial is registered with EudraCT ( @-@-@ ) and ClinicalTrials.gov ( NCT@ ) .


Forty-one participants ( mean age @ years ; @ % men ) were randomized to etanercept ( n = @ ) or placebo ( n = @ ) .


Etanercept was well tolerated ; @ % of participants ( @/@ ) completed the study compared with @ % ( @/@ ) in the placebo group .


Although infections were more common in the etanercept group , there were no serious adverse events or new safety concerns .


While there were some interesting trends that favored etanercept , there were no statistically significant changes in cognition , behavior , or global function .


This study showed that subcutaneous etanercept ( @ mg/wk ) was well tolerated in this small group of patients with Alzheimer disease dementia , but a larger more heterogeneous group needs to be tested before recommending its use for broader groups of patients .


This study shows Class I evidence that weekly subcutaneous etanercept is well tolerated in Alzheimer disease dementia .


Internet-based Smoking Cessation Interventions ( ISCIs ) may help pregnant smokers who are unable , or unwilling , to access face-to-face stop smoking support .


Targeting ISCIs to specific groups of smokers could increase their uptake and effectiveness .


The current study explored the needs and preferences of pregnant women seeking online stop smoking support with an aim to identify features and components of ISCIs that might be most attractive to this population .


We conducted qualitative interviews with thirteen pregnant women who completed the intervention arm of a pilot randomized controlled trial of a novel ISCI for pregnant smokers ( ` MumsQuit ' ) .


The interviews explored women 's views towards MumsQuit and online support with quitting smoking in general , as well as their suggestions for how ISCIs could be best targeted to pregnancy .


Interview transcripts were analyzed using Framework Analysis .


Participants expressed preferences for an accessible , highly engaging and targeted to pregnancy smoking cessation website , tailored to individuals ' circumstances as well as use of cessation medication , offering comprehensive and novel information on smoking and quitting smoking in pregnancy , ongoing support with cravings management , as well as additional support following relapse to smoking .


Participants also viewed as important targeting of the feedback and progress reports to baby 's health and development , offering personal support from experts , and providing a discussion forum allowing for communication with other pregnant women wanting to quit .


The present study has identified a number of potential building blocks for ISCIs targeted to quitting smoking in pregnancy .


Pregnant smokers willing to try using ISCI may particularly value an engaging intervention offering a high degree of targeting of comprehensive information to them as a group and tailoring support and advice to their individual needs , as well as one providing post-relapse support , peer-to-peer communication and personal support from experts .


A prospective randomized phase II trial was conducted to evaluate the efficacy of ghrelin administration in reducing systemic inflammatory response syndrome ( SIRS ) duration after esophagectomy .


Esophagectomy for esophageal cancer is highly invasive and leads to prolonged SIRS duration and postoperative complications .


Ghrelin has multiple effects , including anti-inflammatory effects .


Forty patients undergoing esophagectomy were randomly assigned to either the ghrelin group ( n = @ ) , which received continuous infusion of ghrelin ( @ g/kg/h ) for @ days , or the placebo group ( n = @ ) , which received pure saline for @ days .


The primary endpoint was SIRS duration .


The secondary endpoints were the incidence of postoperative complications , time of a negative nitrogen balance , changes in body weight and composition , and levels of inflammatory markers , including C-reactive protein ( CRP ) and interleukin-@ ( IL-@ ) .


The ghrelin group had a shorter SIRS duration and lower CRP and IL-@ levels than did the placebo group .


The incidence of pulmonary complications was lower in the ghrelin group than in the placebo group , whereas other complications did not differ between the groups .


Although time of the negative nitrogen balance was shorter in the ghrelin group than in the placebo group , changes in total body weight and lean body weight did not differ significantly .


Postoperative ghrelin administration was effective for inhibiting inflammatory mediators and improving the postoperative clinical course of patients with esophageal cancer .


Smoking during pregnancy is common , and quitting at any point during pregnancy can yield benefits to both the fetus and mother .


Smoking cessation is typically followed by withdrawal symptoms and a strong desire to smoke , both of which are likely to contribute to relapse .


Research has shown that a bout of exercise minimizes cravings and tobacco withdrawal symptoms ( TWS ) after temporary abstinence in smokers , but these findings have not been replicated in pregnant smokers .


This study examined the effect of @min of exercise on cravings ( primary outcome ) and TWS ( secondary outcomes ) among temporary abstinent , inactive pregnant smokers .


Thirty female smokers ( Mean ( M ) age = @ years , Standard Deviation ( SD ) = @ ; M weeks pregnant = @ , SD = @ ; Fagerstrom Test for Cigarette Dependence = @ , SD = @ ; M @ cigarettes/day , SD = @ ; M hours abstained = @ , SD = @ ) were randomized to @ min of mild-to-moderate intensity exercise ( EC ; n = @ ) or passive ( PC ; n = @ ) condition .


Cravings and TWS were assessed immediately before , during ( at @ min ) , immediately post , and at @ , @ , and @ min post-condition .


A @ ( condition ) @ ( time ) repeated measures ANOVA revealed that the EC significantly ( p < @ ) reduced cravings ( ( @ ) = @ ) compared with the PC , across time .


Non-significant , but nevertheless , large effects were evident favouring the EC over time for TWS restlessness ( ( @ ) = @ ) , stress ( ( @ ) = @ ) , irritability ( ( @ ) = @ ) , tension ( ( @ ) = @ ) , and depression ( ( @ ) = @ ) .


Consistent with previous research , this study reveals that in pregnant smokers , a bout of exercise is associated with a reduction in cravings and similar patterns exist for TWS .


Therefore , exercise may have the potential to assist in the initial stages of smoking cessation attempts during pregnancy .


The clinical efficacy of autologous blood therapy ( ABT ) in patients with atopic dermatitis ( AD ) was demonstrated by a randomized double-blind placebo-controlled study .


To characterize the blood component mediating the therapeutic efficacy of ABT for AD , we evaluated the clinical efficacy of autologous plasma therapy ( APT ) and autologous high-molecular-weight plasma protein fraction therapy ( AHPT ) in patients with AD in this study .


A total of @ patients with recalcitrant AD were treated with @ weekly intramuscular injections of either autologous plasma ( n = @ ) or autologous high-molecular-weight plasma protein fraction ( n = @ ) for @ weeks .


The clinical severity score of AD ( SCORAD value ) of @ patients who completed AHPT significantly decreased from @ @ ( mean SD ) at baseline to @ @ at @ weeks and @ @ at @ weeks ( Wilcoxon signed-rank test , p < @ ) .


There were no significant differences among the SCORAD values measured at baseline ( @ @ ) , at @ weeks ( @ @ ) and at @ weeks ( @ @ ) in @ patients who completed APT ( p > @ ) .


This result suggests that the blood component mediating the therapeutic efficacy of ABT in patients with AD might be present in the high-molecular-weight plasma protein fraction .


Data from a randomized , controlled study of adenotonsillectomy for obstructive sleep apnea syndrome ( OSAS ) were used to test the hypothesis that children undergoing surgery had greater quality of life ( QoL ) and symptom improvement than control subjects .


The objectives were to compare changes in validated QoL and symptom measurements among children randomized to undergo adenotonsillectomy or watchful waiting ; to determine whether race , weight , or baseline OSAS severity influenced changes in QoL and symptoms ; and to evaluate associations between changes in QoL or symptoms and OSAS severity .


Children aged @ to @ years with OSAS ( N = @ ) were randomly assigned to undergo adenotonsillectomy or watchful waiting with supportive care .


Polysomnography , the Pediatric Quality of Life inventory , the Sleep-Related Breathing Scale of the Pediatric Sleep Questionnaire , the @-item Obstructive Sleep Apnea QoL instrument , and the modified Epworth Sleepiness Scale were completed at baseline and @ months .


Changes in the QoL and symptom surveys were compared between arms .


Effect modification according to race and obesity and associations between changes in polysomnographic measures and QoL or symptoms were examined .


Greater improvements in most QoL and symptom severity measurements were observed in children randomized to undergo adenotonsillectomy , including the parent-completed Pediatric Quality of Life inventory ( effect size -LSB- ES -RSB- : @ ) , the @-item Obstructive Sleep Apnea QoL instrument ( ES : -@ ) , the modified Epworth Sleepiness Scale score ( ES : -@ ) , and the Sleep-Related Breathing Scale of the Pediatric Sleep Questionnaire ( ES : -@ ) .


Effect modification was not observed by obesity or baseline severity but was noted for race in some symptom measures .


Improvements in OSAS severity explained only a small portion of the observed changes .


Adenotonsillectomy compared with watchful waiting resulted in significantly more improvements in parent-rated generic and OSAS-specific QoL measures and OSAS symptoms .


High doses of intravenous methylprednisolone are recommended to treat relapses in patients with multiple sclerosis , but can be inconvenient and expensive .


We aimed to assess whether oral administration of high-dose methylprednisolone was non-inferior to intravenous administration .


We did this multicentre , double-blind , randomised , controlled , non-inferiority trial at @ centres for multiple sclerosis in France .


We enrolled patients aged @-@ years with relapsing-remitting multiple sclerosis who reported a relapse within the previous @ days that caused an increase of at least one point in one or more scores on the Kurtzke Functional System Scale .


With use of a computer-generated randomisation list and in blocks of four , we randomly assigned ( @:@ ) patients to either oral or intravenous methylprednisolone , @ mg , once a day for @ days .


Patients , treating physicians and nurses , and data and outcome assessors were all masked to treatment allocation , which was achieved with the use of saline solution and placebo capsules .


The primary endpoint was the proportion of patients who had improved by day @ ( decrease of at least one point in most affected score on Kurtzke Functional System Scale ) , without need for retreatment with corticosteroids , in the per-protocol population .


The trial was powered to assess non-inferiority of oral compared with intravenous methylprednisolone with a predetermined non-inferiority margin of @ % .


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


Between Jan @ , @ , and June @ , @ , we screened @ patients and enrolled @ .


We randomly assigned @ patients to oral methylprednisolone and @ patients to intravenous methylprednisolone with a mean time from relapse onset to treatment of @ days ( SD @ ) and @ days ( @ ) , respectively .


In the per-protocol population , @ ( @ % ) of @ patients in the oral group and @ ( @ % ) of @ patients in the intravenous group achieved the primary endpoint ( absolute treatment difference @ % , @ % CI -@ to @ ) .


Rates of adverse events were similar , but insomnia was more frequently reported in the oral group ( @ -LSB- @ % -RSB- ) than in the intravenous group ( @ -LSB- @ % -RSB- ) .


Oral administration of high-dose methylprednisolone for @ days was not inferior to intravenous administration for improvement of disability scores @ month after treatment and had a similar safety profile .


This finding could have implications for access to treatment , patient comfort , and cost , but indication should always be properly considered by clinicians .


Electronic health record ( EHR ) - linked patient portals are a promising approach to facilitate shared decision-making between families of children with chronic conditions and pediatricians .


This study evaluated the feasibility , acceptability , and impact of MyAsthma , an EHR-linked patient portal supporting shared decision-making for pediatric asthma .


We conducted a @-month randomized controlled trial of MyAsthma at @ primary care practices .


Families were randomized to MyAsthma , which tracks families ' asthma treatment concerns and goals , children 's asthma symptoms , medication side effects and adherence , and provides decision support , or to standard care .


Outcomes included the feasibility and acceptability of MyAsthma for families , child health care utilization and asthma control , and the number of days of missed school ( child ) and work ( parent ) .


Descriptive statistics and longitudinal regression models assessed differences in outcomes between study arms .


We enrolled @ families , @ in each study arm ( mean age @ years ) ; @ % of parents in the intervention group used MyAsthma during at least @ of the @ study months .


Parents of children with moderate to severe persistent asthma used the portal more than others ; @ % were satisfied with MyAsthma .


Parents reported that use improved their communication with the office , ability to manage asthma , and awareness of the importance of ongoing attention to treatment .


Parents in the intervention group reported that children had a lower frequency of asthma flares and intervention parents missed fewer days of work due to asthma .


Use of an EHR-linked asthma portal was feasible and acceptable to families and improved clinically meaningful outcomes .


The efficacy and safety of the RTS , S/AS@ candidate malaria vaccine during @ months of follow-up have been published previously .


Herein , we report the final results from the same trial , including the efficacy of a booster dose .


From March @ , @ , until Jan @ , @ , children ( age @-@ months ) and young infants ( age @-@ weeks ) were enrolled at @ centres in seven countries in sub-Saharan Africa .


Participants were randomly assigned ( @:@:@ ) at first vaccination by block randomisation with minimisation by centre to receive three doses of RTS , S/AS@ at months @ , @ , and @ and a booster dose at month @ ( R@R group ) ; three doses of RTS , S/AS@ and a dose of comparator vaccine at month @ ( R@C group ) ; or a comparator vaccine at months @ , @ , @ , and @ ( C@C -LSB- control group -RSB- ) .


Participants were followed up until Jan @ , @ .


Cases of clinical and severe malaria were captured through passive case detection .


Serious adverse events ( SAEs ) were recorded .


Analyses were by modified intention to treat and per protocol .


The coprimary endpoints were the occurrence of malaria over @ months after dose @ in each age category .


In this final analysis , we present data for the efficacy of the booster on the occurrence of malaria .


Vaccine efficacy ( VE ) against clinical malaria was analysed by negative binomial regression and against severe malaria by relative risk reduction .


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


@ children and @ young infants were included in the modified intention-to-treat analyses .


Children were followed up for a median of @ months ( IQR @-@ ) and young infants for @ months ( @-@ ) after dose @ .


From month @ until study end , compared with @ episodes of clinical malaria that met the primary case definition in children in the C@C group , @ episodes occurred in the R@R group ( VE @ % , @ % CI @-@ ) and @ occurred in the R@C group ( @ % , @-@ ) ; compared with @ children who experienced at least one episode of severe malaria in the C@C group , @ children experienced at least one episode of severe malaria in the R@R group ( @ % , @ to @ ) and @ in the R@C group ( @ % , -@ to @ ) .


In young infants , compared with @ episodes of clinical malaria that met the primary case definition in the C@C group , @ episodes occurred in the R@R group ( VE @ % , @ % CI @-@ ) and @ occurred in the R@C group ( @ % , @-@ ) ; and compared with @ infants who experienced at least one episode of severe malaria in the C@C group , @ infants experienced at least one episode of severe malaria in the R@R group ( @ % , @ % CI -@ to @ ) and @ in the R@C group ( @ % , -@ to @ ) .


In children , @ cases of clinical malaria were averted per @ children ( @ % CI @-@ ) in the R@R group and @ per @ children ( @-@ ) in the R@C group .


The numbers of cases averted per @ young infants were @ ( @ % CI @-@ ) in the R@R group and @ ( @-@ ) in the R@C group .


The frequency of SAEs overall was balanced between groups .


However , meningitis was reported as a SAE in @ children : @ in the R@R group , ten in the R@C group , and one in the C@C group .


The incidence of generalised convulsive seizures within @ days of RTS , S/AS@ booster was @ per @ doses in young infants and @ per @ doses in children .


RTS , S/AS@ prevented a substantial number of cases of clinical malaria over a @-@ year period in young infants and children when administered with or without a booster dose .


Efficacy was enhanced by the administration of a booster dose in both age categories .


Thus , the vaccine has the potential to make a substantial contribution to malaria control when used in combination with other effective control measures , especially in areas of high transmission .


To evaluate the initial safety and effectiveness of the intrauterine ball ( IUB ) , a copper intrauterine device that , upon insertion in the uterus , takes a three-dimensional spherical form .


Fifteen women were followed for @ year , with follow-up visits at @ , @ , @ , @ and @ months .


The physician reported that all devices were very easy to insert .


One subject discontinued before the @-month visit ( at @ days after insertion ) for a reason not related to the device .


There were no perforations , expulsions , malpositions or complications , or pregnancies .


No safety or efficacy concerns were raised .


Due to its form and deployment process the IUB is expected to ease insertion and reduce perforation , malposition and expulsion rates and may also reduce dysmenorrhea and menorrhagia .


Biopharmaceutical studies for anti-cancer drugs are typically conducted in cancer patients due to unacceptable toxicities to healthy volunteers .


Navitoclax is a first-in-class , orally bioavailable , targeted Bcl-@ family protein inhibitor that has been studied in cancer patients .


A strategy that integrated the evaluation of non-clinical toxicology data and clinical data in cancer patients was employed to assess the feasibility , determine doses and establish risk management plans for studying navitoclax in healthy volunteers .


Two relative bioavailability/food effect studies with either a @ mg dose or @ and @ mg doses of navitoclax were conducted sequentially in healthy female volunteers of non-childbearing potential .


Navitoclax was well-tolerated in both studies in healthy volunteers , and did not impose risks beyond the minimal levels expected in healthy volunteer studies .


Compared to a similar study in cancer patients , the studies in healthy volunteers generated higher quality data in a short period of time to support formulation selection .


The aim of this study was to compare short - and long-term root coverage and aesthetic outcomes of the coronally advanced flap ( CAF ) alone or in combination with a connective tissue graft ( CTG ) for the treatment of multiple gingival recessions .


Fifty patients with multiple ( @ ) adjacent gingival recessions ( @ mm ) in the upper jaw were enrolled .


Twenty-five patients were randomly assigned to the control group ( CAF ) , and the other @ patients to the test group ( CAF + CTG ) .


Clinical outcomes were evaluated at @ months , @ and @ years .


The aesthetic evaluations were made @ and @ years after the surgery .


No statistically significant difference was demonstrated between the two groups in terms of Rec Red and complete root coverage ( CRC ) at @ months and @ year .


At @ years , statistically greater recession reduction and probability of CRC , greater increase in buccal KTH and better contour evaluation made by an independent periodontist were observed in the CAF + CTG group .


Better post-operative course and better colour match were demonstrated in CAF-treated patients both at @ and @ years .


CAF + CTG provided better CRC at @ years ; keloid formation due to graft exposure was responsible for the worse colour match evaluation .


The root of Scutellaria baicalensis Georgi has been used extensively in traditional Chinese medicine for the treatment of inflammation , fever , cough , dysentery , and hypertension .


Baicalein is a flavonoid isolated from the root of Scutellaria baicalensis Georgi and is a novel neuroprotective agent under development for the treatment of Parkinsons disease .


We aimed to investigate the pharmacokinetic ( PK ) properties of baicalein and its main metabolite , bacalin , after single-dose administration in healthy Chinese subjects .


The safety and tolerability of baicalein were also assessed .


This was a Phase I , randomized , double-blind , single-dose trial of baicalein ( @-@ mg ) in @ healthy adults .


Samples of blood , urine and feces were collected at regular intervals up to @ h after administration of the study drug .


Baicalein and baicalin were then analyzed using liquid chromatography-tandem mass spectrometry ( LC/MS/MS ) .


The maximum concentration that the drug achieved after dosing ( Cmax ) , time to Cmax ( Tmax ) , terminal half-life ( t / ) , area under the curve from time zero to time of last quantifiable concentration ( AUC ( @ , t ) ) , area under the curve from time zero to infinity ( AUC ( @ , ) ) , apparent total plasma clearance ( CL/F ) , and apparent total volume of distribution ( V/F ) were determined using non-compartmental models .


Dose proportion was tested using a method combining the equivalence criterion and power model .


Physical examinations , vital signs , ECG findings , hematology , and urinalysis were monitored before and at regular intervals after administration of the study drug .


The PK profile of baicelein and baicelin was characterized by a median Tmax of @-@ @ h and @-@ h , respectively , followed by a multiphasic profile with a t / of @-@ @ h and @-@ @ h , respectively .


The estimates of the proportionality coefficient ( @ % CI ) for Cmax , AUC-t and AUC - were @ ( @-@ @ ) , @ ( @-@ @ ) and @ ( @-@ @ ) , respectively .


All values overlapped within the pre-specified range of ( @-@ @ ) , ( @-@ @ ) , and ( @-@ @ ) , respectively .


Dose proportionality was inconclusive for a baicalein dose range of @-@ mg .


The total urinary clearance of baicalein and baicalin was < @ % .


Approximately @ % of baicalein was eliminated as unchanged drug in feces .


Baicalein was well tolerated .


Eleven treatment-related adverse events were observed , and all were rated as `` mild '' and resolved without further treatment .


No serious adverse events occurred .


Single oral doses of @-@ mg of baicalein were safe and well tolerated by healthy subjects .


Clinical laboratory assessments showed no signs of toxicity in the liver or kidney .


The favorable safety profile and PK properties warrant further clinical studies for baicalein .


To assess the efficacy of continuous therapy ( cont ) and on-demand therapy ( on-demand ) as maintenance therapy for gastroesophageal reflux disease ( GERD ) .


Patients with upper GI endoscopy ( EGD ) - proven GERD who completed @ weeks of initial therapy were randomized to cont ( omeprazole @ mg od ) or on-demand ( omeprazole @ mg on-demand ) group .


Assessments by the Global Overall Symptom ( GOS ) scale at baseline ( at the start of maintenance therapy ) and at @-week , @-week , and @-week visits were made and EGD was performed at @ weeks .


Symptom relief was defined as percentages of patients whose GOS score of @ or @ .


Of the @ enrolled patients , cont/on-demand was @/@ and nonerosive reflux disease ( NERD ) / reflux esophagitis ( RE ) before the initial therapy was @/@ .


Symptom relief in cont/on-demand were @ % / @ % at baseline ( n.s. ) , @ % / @ % at @ week ( n.s. ) , @ % / @ % at @ weeks ( n.s. ) , and @ % / @ % at @ weeks ( n.s. ) .


When subjects were divided into NERD and RE , symptom relief in cont/on-demand were @ % / @ % at baseline ( n.s. ) , @ % / @ % at @ weeks ( n.s. ) , @ % / @ % at @ weeks ( n.s. ) , and @ % / @ % at @ weeks ( n.s. ) in NERD , while those were @ % / @ % at baseline ( n.s. ) , @ % / @ % at @ weeks ( p < @ ) , @ % / @ % at @ weeks ( n.s. ) , and @ % / @ % at @ weeks ( n.s. ) in RE , respectively .


At @-week EGD , all patients in NERD remained as NERD but number of healed patients was significantly higher in cont ( @ % ) than in on-demand ( @ % ) ( p < @ ) in RE .


Since NERD is defined by symptoms , as a result of the limited efficacy of continuous therapy , on-demand therapy would be sufficient as maintenance therapy in NERD patients .


Regarding RE , continuous therapy would be recommended in terms of reduced symptoms and maintaining mucosal healing .


This was the second study in a Phase @ program treating crow 's feet lines ( CFL ) with onabotulinumtoxinA .


To evaluate the efficacy and safety of onabotulinumtoxinA treatment of CFL alone or with glabellar lines ( GL ) .


This multicenter , double-blind , placebo-controlled , repeat treatment , @-month study randomized subjects with moderate-to-severe CFL and GL ( maximum contraction ) to onabotulinumtoxinA @ U ( CFL : @ U , GL : @ U ; n = @ ) , onabotulinumtoxinA @ U ( CFL : @ U , GL : placebo ; n = @ ) , or placebo ( n = @ ) .


Coprimary end points were investigator-assessed and subject-assessed proportion of subjects achieving a CFL Facial Wrinkle Scale Grade of @ or @ ( maximum smile ; Day @ , Cycle @ ) .


Additional efficacy end points and safety/adverse events ( AEs ) were evaluated .


All primary and secondary end points were achieved ; statistically significant differences favored onabotulinumtoxinA ( p < @ , all comparisons vs placebo ) .


Investigator and subject responder rates were : CFL , @ % and @ % ; CFL + GL , @ % and @ % ; and placebo , @ % ( both ) , respectively .


Responder rates on other end points also significantly favored onabotulinumtoxinA treatments .


Most AEs were mild or moderate .


Two subjects discontinued : @ serious AE unrelated to treatment ( myocardial infarction ) and @ treatment-related AE ( injection site pain ) .


OnabotulinumtoxinA was effective and well tolerated for treating moderate-to-severe CFL alone or in combination with GL .


The decision to treat subclinical hypothyroidism ( SCH ) with or without autoimmune thyroiditis ( AIT ) in children , presents a clinical dilemma .


This study was undertaken to evaluate the efficacy of individualized homeopathy in these cases .


The study is an exploratory , randomized , placebo controlled , single blind trial .


Out of @ school children ( @-@ years ) screened for thyroid disorders , @ children had SCH/AIT and @ consented to participate .


Based on primary outcome measures ( TSH and/or antiTPOab ) three major groups were formed : Group A - SCH + AIT ( n = @ ; high TSH with antiTPOab + ) , Group B - AIT ( n = @ ; normal TSH with antiTPOab + ) and Group C - SCH ( n = @ ; only high TSH ) and were further randomized to two subgroups-verum and control .


Individualized homeopathy or identical placebo was given to respective subgroup .


@ patients completed @ months of study .


Baseline characteristics were similar in all the subgroups .


The post treatment serum TSH ( Group A and C ) returned to normal limits in @ % of verum and @ % of controls ( p < @ ) , while serum AntiTPOab titers ( Group A and B ) returned within normal limits in @ % of verum and @ % controls ( p < @ ) .


Eight children ( @ % ) progressed to overt hypothyroidism ( OH ) from control group .


A statistically significant decline in serum TSH values and antiTPOab titers indicates that the homeopathic intervention has not only the potential to treat SCH with or without antiTPOab but may also prevent progression to OH .


There is little data to guide radiation oncologists on appropriate margin selection in the post-prostatectomy setting .


The aim of this study was to quantify interfraction variation in motion of the prostate bed to determine these margins .


The superior and inferior surgical clips in the prostate bed were tracked on pretreatment cone beam CT images ( n = @ ) for @ patients who had received post-prostatectomy radiotherapy .


Prostate bed motion was calculated for the upper and lower segments by measuring the position of surgical clips located close to midline relative to bony anatomy in the axial ( translational ) and sagittal ( tilt ) planes .


The frequency of potential geographic misses was calculated for either @cm or @ cm posterior planning target volume margins .


The mean magnitude of movement of the prostate bed in the anterior-posterior , superior-inferior and left-right planes , respectively , were as follows : upper portion , @ cm , @ cm , @ cm ; lower portion , @ cm , @ cm , @ cm .


The random and systematic errors , respectively , of the prostate bed motion in the anterior-posterior , superior-inferior and left-right planes , respectively , were as follows : upper portion , @ cm and @ cm , @ cm and @ cm , @ cm and @ cm ; lower portion , @ cm and @ cm , @ cm and @ cm , @ cm and @ cm .


Most geographic misses occurred in the upper prostate bed in the anterior-posterior plane .


The median prostate bed tilt was @ ( range -@ to @ ) .


Variability was seen in all planes for the movement of both surgical clips .


The greatest movement occurred in the anterior-posterior plane in the upper prostate bed , which could cause geographic miss of treatment delivery .


The variability in the movement of the superior and inferior clips indicates a prostate bed tilt that would be difficult to correct with standard online matching techniques .


This creates a strong argument for using anisotropic planning target volume margins in post-prostatectomy radiotherapy .


Male and female pattern hair loss are common , chronic dermatologic disorders with limited therapeutic options .


In recent years , a number of commercial devices using low-level laser therapy have been promoted , but there have been little peer-reviewed data on their efficacy .


To determine whether treatment with a low-level laser device , the US FDA-cleared HairMax Lasercomb , increases terminal hair density in both men and women with pattern hair loss .


Randomized , sham device-controlled , double-blind clinical trials were conducted at multiple institutional and private practices .


A total of @ male and @ female subjects with pattern hair loss were screened .


A total of @ male and @ female subjects were randomized to receive either a lasercomb ( one of three models ) or a sham device in concealed sealed packets , and were treated on the whole scalp three times a week for @ weeks .


Terminal hair density of the target area was evaluated at baseline and at @ - and @-week follow-ups , and analyzed to determine whether the hypothesis formulated prior to data collection , that lasercomb treatment would increase terminal hair density , was correct .


The site investigators and the subjects remained blinded to the type of device they dispensed/received throughout the study .


The evaluator of masked digital photographs was blinded to which trial arm the subject belonged .


Seventy-eight , @ , @ , and @ subjects were randomized in four trials of @-beam lasercomb treatment in female subjects , @-beam lasercomb treatment in female subjects , @-beam lasercomb treatment in male subjects , and @ - and @-beam lasercomb treatment in male subjects , compared with the sham device , respectively .