The aim of this randomized clinical trial ( RCT ) was to compare the clinical performance of the tunnel technique with subepithelial connective tissue graft ( TUN ) versus a coronally advanced flap with enamel matrix derivative ( CAF ) in the treatment of gingival recession defects .


The use of innovative 3D digital measuring methods allowed to study healing dynamics at connective tissue ( CT ) - grafted sites and to evaluate the influence of the thickness of the root covering soft tissues on the outcome of surgical root coverage .


Twenty-four patients contributed a total of 47 Miller class I or II recessions for scientific evaluation .


Precise study models collected at baseline and follow-up examinations were optically scanned and virtually superimposed for digital evaluation of clinical outcome measures including mean marginal soft tissue thickness ( THK ) .


Healing dynamics were measured in a defined region of interest at CT-grafted sites where volume differences between time points were calculated .


At 12months , recession reduction as well as mean root coverage were significantly better at CT-grafted sites treated in the TUN group ( 1.94 mm and 98.4 % respectively ) compared to the non-augmented sites of the CAF group ( 1.17 mm and 71.8 % respectively ) and statistical analysis revealed a positive correlation of THK ( 1.63 mm TUN versus 0.91 mm CAF , p < 0.0001 ) to both these variables .


Soft tissue healing following surgical root coverage with CT-grafting was mainly accomplished after 6months , with around two-thirds of the augmented volume being maintained after 12months .


The TUN resulted in thicker gingiva and better clinical outcomes compared to CAF .


Increased gingival thickness was associated with better surgical outcomes in terms of recession reduction and root coverage .


Pazopanib is an oral , multikinase inhibitor of vascular endothelial growth factor receptor ( VEGFR ) -1 / -2 / -3 , platelet-derived growth factor receptor ( PDGFR ) - / - , and c-Kit .


Preclinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment .


This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy .


Nine hundred forty patients with histologically confirmed cancer of the ovary , fallopian tube , or peritoneum , International Federation Gynecology Obstetrics ( FIGO ) stages II-IV , no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were randomized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months .


The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators .


Maintenance pazopanib prolonged progression-free survival compared with placebo ( hazard ratio [ HR ] , 0.77 ; 95 % CI , 0.64 to 0.91 ; P = .0021 ; median , 17.9 v 12.3 months , respectively ) .


Interim survival analysis based on events in 35.6 % of the population did not show any significant difference .


Grade 3 or 4 adverse events of hypertension ( 30.8 % ) , neutropenia ( 9.9 % ) , liver-related toxicity ( 9.4 % ) , diarrhea ( 8.2 % ) , fatigue ( 2.7 % ) , thrombocytopenia ( 2.5 % ) , and palmar-plantar erythrodysesthesia ( 1.9 % ) were significantly higher in the pazopanib arm .


Treatment discontinuation related to adverse events was higher among patients treated with pazopanib ( 33.3 % ) compared with placebo ( 5.6 % ) .


Pazopanib maintenance therapy provided a median improvement of 5.6 months ( HR , 0.77 ) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy .


Overall survival data to this point did not suggest any benefit .


Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity ( NCT00866697 ) .


Large prospective studies in patients with type 2 diabetes mellitus have demonstrated that metformin treatment improves cardiovascular prognosis , independent of glycemic control .


Administration of metformin potently limits infarct size in murine models of myocardial infarction .


This study examined , for the first time in humans , whether metformin limits ischemia-reperfusion ( IR ) injury in vivo using a well-validated forearm model of endothelial IR-injury .


Twenty-eight healthy volunteers ( age 416 years , 10 male/16 female ) were randomized between pretreatment with metformin ( 500 mg three times a day for 3 days ) or no treatment in a Prospective Randomized Open Blinded Endpoint study .


Brachial artery flow mediated dilation ( FMD ) was measured before and after 20 minutes of forearm ischemia and 20 minutes of reperfusion .


FMD analysis was performed offline by investigators blinded for the treatment arm .


Baseline FMD did not differ between metformin pretreatment and no pretreatment ( 6.93.6 % and 6.13.5 % , respectively , p = 0.27 , n = 26 ) .


FMD was significantly lower after forearm IR in both treatment arms ( 4.43.3 % and 4.32.8 % , respectively , P < 0.001 in both conditions ) .


A linear mixed model analysis revealed that metformin treatment did not prevent the decrease in FMD by IR .


A 3 day treatment with metformin in healthy , middle-aged subjects does not protect against endothelial IR-injury , measured with brachial artery FMD after forearm ischemia .


Further studies are needed to clarify what mechanism underlies the cardiovascular benefit of metformin treatment .


ClinicalTrials.gov NCT01610401 .


Dietary fibers are associated with enhanced satiety .


However , the mechanism of different dietary fibers contributing to satiety-related gastrointestinal ( GI ) peptide release , especially in an obese population , is still poorly understood .


Polydextrose ( PDX ) , a water-soluble glucose polymer , has demonstrated its ability to reduce energy intake at a subsequent meal , but its mechanism of action requires further research .


Also , there is limited evidence on its capacity to regulate subjective feelings of appetite .


This study examines the effects of PDX on postprandial secretion of satiety-related GI peptides , short chain fatty acids ( SCFAs ) , lactic acid , and subjective appetite ratings in obese participants .


18 non-diabetic , obese participants ( 42.0 y , 33.6 kg/m2 ) consumed a high-fat meal ( 4293 kJ , 36 % from fat ) with or without PDX ( 15 g ) in an acute , multicenter , randomized , double-blind , placebo-controlled and crossover trial .


Postprandial plasma concentrations of satiety-related peptides , namely ghrelin , cholecystokinin ( CCK ) , glucagon-like peptide 1 ( GLP-1 ) , and peptide YY ( PYY ) , as well as SCFAs and lactic acid were assessed .


GI peptide , SCFA and lactate concentrations were then modeled using a linear mixed-effects model.The subjective feelings of hunger , satisfaction , and desire to eat were evaluated using visual analogue scales ( VAS ) , which were analyzed as incremental areas under the curve ( iAUC ) during the satiation and satiety periods .


We found that PDX supplementation increased plasma GLP-1 levels more than the placebo treatment ( P = 0.02 ) .


In the whole group , GLP-1 concentrations found in participants older than 40 years old were significantly lower ( P = 0.01 ) as compared to those aged 40 years or less .


There were no statistically significant differences in postprandial ghrelin , CCK , or PYY responses .


The lactic acid concentrations were significantly ( P = 0.01 ) decreased in the PDX group , while no significant changes in SCFAs were found .


PDX reduced iAUC for hunger by 40 % ( P = 0.03 ) and marginally increased satisfaction by 22.5 % ( P = 0.08 ) during the post-meal satiety period .


Polydextrose increased the postprandial secretion of the satiety hormone GLP-1 and reduced hunger after a high-fat meal .


PDX also reduced the elevated postprandial lactic acid levels in plasma .


Therefore , PDX may offer an additional means to regulate inter-meal satiety and improve postprandial metabolism in obese participants .


To evaluate the effect of sustained American College of Rheumatology ( ACR ) / European League Against Rheumatism ( EULAR ) Boolean remission on residual joint inflammation assessed by magnetic resonance imaging ( MRI ) and to secondarily evaluate other clinical definitions of remission , within an early seropositive rheumatoid arthritis ( RA ) cohort .


A subcohort of 118 RA patients was enrolled from patients who completed the 2-year , double-blind randomized Treatment of Early Aggressive Rheumatoid Arthritis ( TEAR ) trial .


Patients received a single contrast-enhanced 1.5 T MRI of their most involved wrist .


Two readers scored MRIs for synovitis , osteitis , tenosynovitis , and erosions .


Clinical assessments were performed every 3 months during the trial and at time of MRI .


The subcohort was 92 % seropositive with mean age 51 years , duration 4.1 months , and Disease Activity Score in 28 joints using the erythrocyte sedimentation rate 5.8 at TEAR entry .


Total MRI inflammatory scores ( tenosynovitis + synovitis + osteitis ) were lower among patients in clinical remission .


Lower MRI scores were correlated with longer duration of Clinical Disease Activity Index ( CDAI ) remission ( = 0.22 , P = 0.03 ) .


At the time of MRI , 89 patients had no wrist pain/tenderness/swelling ; however , all 118 patients had MRI evidence of residual joint inflammation after 2 years .


No statistically significant differences in damage or MRI inflammatory scores were observed across treatment groups .


This is the first detailed appraisal describing the relationship between clinical remission cut points and MRI inflammatory scores within an RA randomized controlled trial .


The most stringent remission criteria ( 2011 ACR/EULAR and CDAI ) best differentiate the total MRI inflammatory scores .


These results document that 2 years of triple therapy or tumor necrosis factor plus methotrexate treatment in early RA does not eliminate MRI evidence of joint inflammation .


To assess the efficacy , safety and tolerability of sodium valproate ( 800mg/die ) compared with placebo in medication-overuse headache patients with a history of migraine without aura .


This is a multicenter , randomized , double-blind , placebo-controlled study enrolled medication-overuse headache patients for a 3-month treatment period with sodium valproate ( 800mg/day ) or placebo after a 6 day outpatient detoxification regimen , followed by a 3-month follow-up .


Primary outcome was defined by the proportion of patients achieving 50 % reduction in the number of days with headache per month ( responders ) from the baseline to the last 4 weeks of the 3-month treatment .


Multivariate logistic regression models were used on the primary endpoint , adjusting for age , sex , disease duration , comorbidity and surgery .


The last-observation-carried-forward method was used to adjust for missing values .


Nine sites enrolled 130 patients and , after a 6-day detoxification phase , randomized 88 eligible patients .


The 3-month responder rate was higher in the sodium valproate ( 45.0 % ) than in the placebo arm ( 23.8 % ) with an absolute difference of about 20 % ( p = 0.0431 ) .


Sodium valproate had safety and tolerability profiles comparable to placebo .


The present study supports the efficacy and safety of sodium valproate in the treatment of medication overuse headache with history of migraine after detoxification .


Internet-based guided self-help has been successfully used in the general population , but it is unknown whether this method can be effectively used in outpatient clinics for patients waiting for face-to-face psychotherapy for phobias .


The aim was to assess the clinical effectiveness of Phobias Under Control , an Internet-based intervention based on exposure therapy with weekly guidance .


We conducted a randomized controlled trial , recruiting 212 outpatients scheduled to receive face-to-face psychotherapy for any type of phobia at an outpatient clinic .


Participants suffering from at least 1 DSM-IV or ICD-10 classified phobia ( social phobia , agoraphobia with or without panic disorder , and/or specific phobia as ascertained by a telephone interview at baseline ) were randomly allocated to either a 5-week Internet-based guided self-help program based on exposure therapy with weekly student support followed by face-to-face psychotherapy ( n = 105 ) or a wait-list control group followed by face-to-face psychotherapy ( n = 107 ) .


Primary outcome was the Fear Questionnaire ( FQ ) .


Secondary outcomes were the Beck Anxiety Inventory ( BAI ) and Center of Epidemiological Studies-Depression scale ( CES-D ) .


Assessments took place by telephone at baseline ( T0 ) and on the Internet at posttest ( T1 , self-assessment at 5 weeks after baseline ) .


Missing data at T1 were imputed .


At posttest , analysis of covariance on the intention-to-treat sample showed significant but small effect sizes between intervention and control groups on the FQ ( d = 0.35 , P = .02 ) , CES-D ( d = 0.34 , P = .03 ) , and a nonsignificant effect size on the BAI ( d = 0.28 .


P = .05 ) .


Although initial acceptance was good , high nonresponse was observed , with 86 of 212 participants ( 40.5 % ) lost to follow-up at T1 and only 14 of 105 ( 13.3 % ) intervention participants finishing all 5 weeks .


Phobias Under Control is modestly effective in lowering phobic and depressive symptoms in a relatively short period and may be clinically beneficial when implemented in routine outpatient practice .


Netherlands Trial Register NTR2233 ; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2233 ( Archived by WebCite at http://www.webcitation.org/6O2ioOQSs ) .


Non-invasive characterization of a tumor 's molecular features could enhance treatment management .


Quantitative computed tomography ( CT ) based texture analysis ( QTA ) has been used to derive tumor heterogeneity information , and the appearance of the tumors has been shown to relate to patient outcome in non-small cell lung cancer ( NSCLC ) and other cancers .


In this study , we examined the potential of tumoral QTA to differentiate K-ras mutant from pan-wildtype tumors and its prognostic potential using baseline pre-treatment non-contrast CT imaging in NSCLC .


Tumor DNA from patients with early-stage NSCLC was analyzed on the LungCarta Panel .


Cases with a K-ras mutation or pan-wildtype for 26 oncogenes and tumor suppressor genes were selected for QTA .


QTA was applied to regions of interest in the primary tumor .


Non-parametric Mann Whitney test assessed the ability of the QTA , clinical and patient characteristics to differentiate between K-ras mutation from pan-wildtype .


A recursive decision tree was developed to determine whether the differentiation of K-ras mutant from pan-wildtype tumors could be improved by sequential application of QTA parameters .


Kaplan-Meier survival analysis assessed the ability of these markers to predict survival .


QTA was applied to 48 cases identified , 27 had a K-ras mutation and 21 cases were pan-wildtype .


Positive skewness and lower kurtosis were significantly associated with the presence of a K-ras mutation .


A five node decision tree had sensitivity , specificity , and accuracy values ( 95 % CI ) of 96.3 % ( 78.1-100 ) , 81.0 % ( 50.5-97 .4 ) , and 89.6 % ( 72.9-97 .0 ) ; respectively .


Kurtosis was a significant predictor of OS and DFS , with a lower kurtosis value linked with poorer survival .


Lower kurtosis and positive skewness are significantly associated with K-ras mutations .


A QTA feature such as kurtosis is prognostic for OS and DFS .


Non-invasive QTA can differentiate the presence of K-ras mutation from pan-wildtype NSCLC and is associated with patient survival .


Edentulism and sleep disturbance are chronic conditions that are common in older people and have serious adverse consequences for their functioning and quality of life .


Edentulism can disturb sleep through the alteration of the craniofacial structure and surrounding soft tissue .


However , the effect of prosthetic rehabilitation of edentulism on sleep quality is still not well understood .


The objectives of this study are to test whether nocturnal denture wear affects sleep quality , daytime sleepiness , and the oral health related quality of life of edentate older people with moderate to severe sleep apnea , and to identify modifiers of effect of nocturnal denture wear .


We will carry out a single-blind randomized cross-over trial .


Seventy edentate older people with moderate to severe obstructive sleep apnea will be enrolled .


The study participants will be assigned to wear and not wear their dentures on alternate periods of 30 days .


The outcome measures will be sleep quality ( assessed by portable polysomnography ) , daytime sleepiness ( assessed by the Epworth Sleepiness Scale ) , and oral health related quality of life ( assessed by validated questionnaire ) .


A number of characteristics ( sociodemographic , oropharyngeal morphology , oral and prosthesis characteristics , and perceived general health quality of life ) will be assessed by means of clinical examination , 3D imaging of the craniofacial structure , and validated questionnaires at baseline .


Linear mixed effects regression models for repeated measures will be fitted to test the study hypotheses .


The main analyses will be based on the intention-to-treat principle .


To assess the robustness of the findings to potential incomplete adherence , sensitivity analyses will be conducted while applying the per-protocol principle .


This practice-relevant evidence could represent a preventive approach to improve sleep characteristics of the older population and improve their well-being and quality of life .


ClinicalTrials.gov NCT01868295 .


To study the efficacy and safety of certolizumab pegol ( CZP ) in patients with active rheumatoid arthritis ( RA ) who had discontinued an initially effective TNF inhibitor ( TNF-IR ) .


A randomised 12-week double-blind trial with CZP ( n = 27 ) or placebo ( n = 10 ) followed by an open-label 12 week extension period with CZP .


Baseline characteristics of the 2 groups were similar .


ACR20 response ( primary end point ) at week 12 was achieved in 61.5 % , and none of CZP and placebo-treated patients , respectively .


Weeks 12-24 showed a maximum effect for CZP at 12 weeks , and that placebo patients switched blindly to CZP attained similar results seen with CZP in weeks 0-12 .


Since this result was highly significant , study inclusion was terminated after entry of 33.6 % of the originally planned 102 patients .


Adverse events occurred in 16/27 ( 59.3 % ) CZP subjects and 4/10 ( 40 % ) placebo subjects .


There were no serious adverse events , neoplasms , opportunistic , or serious infections .


This first , prospective , blinded trial of CZP in secondary TNF-IR shows that the ACR20 response rate observed with CZP was higher than that reported in most previous studies of TNF-IR .


Additionally , CZP demonstrated good safety and tolerability .


This study supports the use of CZP in RA patients who are secondary non-responders to anti-TNF therapies .


To compare two thoracotomy closure techniques ( pericostal and transcostal suture ) in terms of postoperative pain and pulmonary function .


This was a prospective , randomized , double-blind study carried out in the Department of Thoracic Surgery of the Luzia de Pinho Melo Hospital das Clnicas and at the University of Mogi das Cruzes , both located in the city of Mogi das Cruzes , Brazil .


We included 30 patients ( 18-75 years of age ) undergoing posterolateral or anterolateral thoracotomy .


The patients were randomized into two groups by the type of thoracotomy closure : pericostal suture ( PS ; n = 16 ) and transcostal suture ( TS ; n = 14 ) .


Pain intensity during the immediate and late postoperative periods was assessed by a visual analogic scale and the McGill Pain Questionnaire .


Spirometry variables ( FEV1 , FVC , FEV1/FVC ratio , and PEF ) were determined in the preoperative period and on postoperative days 21 and 60 .


Pain intensity was significantly greater in the PS group than in the TS group .


Between the preoperative and postoperative periods , there were decreases in the spirometry variables studied .


Those decreases were significant in the PS group but not in the TS group .


The patients in the TS group experienced less immediate and late post-thoracotomy pain than did those in the PS group , as well as showing smaller reductions in the spirometry parameters .


Therefore , transcostal suture is recommended over pericostal suture as the thoracotomy closure technique of choice .


Botulinum toxin type A has been widely used to correct unwanted hyperfunctional facial lines .


Most forms of botulinum toxin type A currently used require reconstitution , which is very inconvenient for users .


The authors compared the efficacy and safety of a newly developed liquid-type botulinum toxin type A ( MT10109L ) and onabotulinumtoxinA ( Botox ) for moderate to severe glabellar lines .


A double-blind , randomized , active drug-controlled , phase III study with 168 enrolled subjects was performed .


The primary efficacy endpoint was the improvement rate at maximum frown at week 4 by the investigators ' live assessment .


The secondary efficacy endpoint included the improvement rate at maximum frown at week 16 and at rest at weeks 4 and 16 by live assessment , and the improvement rate at maximum frown and at rest based on photographic assessment at week 4 .


Self-assessment and self-satisfaction with glabellar line improvement were also evaluated .


The improvement rate at maximum frown by live assessment was not significantly different between the MT10109L and Botox groups .


In addition , the improvement rate of glabellar lines at rest based on the investigators ' live assessment and photographic assessment was similar in both treatment groups .


However , the improvement rate at maximum frown by live assessment at week 16 was significantly higher in the MT10109L group compared with the Botox group .


There were no severe adverse events .


The efficacy and safety of MT10109L were comparable to those of Botox for the management of glabellar frown lines .


MT10109L provides greater convenience because it does not require dilution and has long-lasting effects .


Therapeutic , II .


This prospective , randomized , multicenter trial evaluated the 6-month success rate of sacral neuromodulation ( SNM ) with InterStim Therapy versus standard medical therapy ( SMT ) for overactive bladder ( OAB ) .


Enrolled subjects discontinued OAB medications prior to and during baseline data collection and were randomized 1:1 to SNM or SMT .


Subjects had bothersome symptoms of overactive bladder ( OAB ) including urinary urge incontinence ( 2 leaks/72hr ) and/or urgency-frequency ( 8voids/day ) .


Subjects failed at least one anticholinergic medication , and had at least one medication not yet attempted .


The primary objective was to compare OAB therapeutic success rate at 6 months between SNM and SMT .


Overall , 147 subjects were randomized ( 70 to SNM and 77 to SMT ) ; 93 % were female and mean age was 58 .


The primary intent to treat analysis showed OAB therapeutic success was significantly greater in the SNM group ( 61 % ) than the SMT group ( 42 % ; P = 0.02 ) .


In the as treated analysis , OAB therapeutic success was 76 % for SNM and 49 % for SMT ( P = 0.002 ) .


The SNM group showed significant improvements in quality of life versus the SMT group ( all P < 0.001 ) and 86 % of SNM subjects reported improved or greatly improved urinary symptom interference score at 6 months , compared to 44 % for SMT subjects .


The device-related adverse event rate was 30.5 % and the medication-related adverse event rate was 27.3 % .


This study demonstrates superior objective and subjective success of SNM compared to SMT .


SNM is shown to be a safe and effective treatment for OAB patients with mild to moderate symptoms .


Neurourol .


Urodynam .


34:224 -230 , 2015.2014 Wiley Periodicals , Inc. .


Isolation of the pulmonary veins ( PVs ) for the treatment of atrial fibrillation ( AF ) is often supplemented with linear lesions within the left atrium ( LA ) .


However , there are conflicting data on the effects of creating a roof line ( RL ) joining the superior PVs in paroxysmal atrial fibrillation ( PAF ) .


A cohort of 120 patients with drug-refractory PAF referred for ablation were prospectively randomized into 2 strategies : ( 1 ) PV isolation in combination with RL ablation ( LA roof ablation [ LARA ] -1 : 59 patients ) or ( 2 ) PV isolation ( LARA-2 : 61 patients ) .


Follow-up was performed at 1 , 3 , and 6 months after the procedure and every 6 months thereafter .


After a 3-month blanking period , recurrence was defined as the ocurrence of any atrial tachyarrhythmia lasting 30 seconds .


PV isolation was achieved in 89 % and complete RL block in 81 % .


RF duration , fluoroscopy , and procedural times were slightly , but not significantly , longer in the LARA-1 group .


After 1510 months , there was no difference in the arrhythmia-free survival after a single AF ablation procedure ( LARA-1 : 59 % vs. LARA-2 : 56 % at 12 months ; log rank P = 0.77 ) .


The achievement of complete RL block did not influence the results .


The incidence of LA macroreentrant tachycardias was 5.1 % in the LARA-1 group ( n = 3 ) versus 8.2 % in the LARA-2 ( n = 5 ) ( P = ns ) .


Univariate analysis only identified AF duration as a covariate associated with arrhythmia recurrence ( hazard ratio , 1.01 [ 95 % confidence interval , 1.002 to 1.012 ] ; P < 0.01 ) .


The linear block at the LA roof is not associated with an improved clinical outcome compared with PV isolation alone .


ClinicalTrials.gov .


Unique identifier : NCT01203241 .


It is estimated that 1 in 5 children in the United States is affected by chronic pain .


Increasing adaptive coping strategies and decreasing stress may be important in treatment .


Research has suggested that mindfulness can help alleviate symptoms associated with medical illnesses and increase quality of life .


Little is known about the effectiveness of mindfulness-based stress reduction ( MBSR ) in youth , partly due to insufficient methodological rigor in related studies .


The primary purpose of the present study was to examine the feasibility , acceptability , and effectiveness of MBSR for a treatment-seeking sample of youth with chronic pain .


The current study was the first randomized , controlled pilot study of MBSR for pediatric chronic pain .


The research team had intended to use block randomization involving a total of five recruitment waves , with each wave consisting of one MBSR group and one psychoeducation group .


Due to difficulties with recruitment and attrition before the start of either group , however , only MBSR was conducted at each wave after the first wave .


Participants were recruited from a multidisciplinary pain clinic in a large , Midwestern children 's hospital .


The final sample included six adolescents between the ages of 12 and 17 y , four in the MBSR group and two in the psychoeducation group .


Weekly sessions for the MBSR group were 90 min in length and followed a structured protocol .


Sessions included a review of homework , an introduction to and practice of meditation , discussion of the session , and a review of the home practice assignment .


The psychoeducation group participated in six group sessions , which were based on a cognitive-behavioral model of pain , and discussion topics included the nature of chronic pain and stress management .


Health-related quality of life , pain catastrophizing , anxiety , functional disability , mindfulness , and treatment acceptability were all assessed pre - and postintervention as well as at follow-up .


Recruitment and retention difficulties were experienced .


Qualitative examination of participants ' scores suggested increased mindfulness but inconsistent patterns on other outcome measures .


The research team highlighted critical challenges faced by potential researchers aiming to investigate MBSR for pediatric chronic pain , and the study provides recommendations for research and implications for clinical practice .


The use of opioid analgesics in prehospital trauma care has been reported to have negative side effects on the airway and circulation .


Several studies of urban trauma management have recommend ketamine as a safe and efficient analgesic .


To date , however , no controlled trials of prehospital opioid analgesics versus ketamine in rural trauma management have been published .


This study aimed to compare the analgesic effects and side effects of ketamine and morphine in a prehospital , low-resource setting .


The study was conducted with a prospective , cluster-randomized design .


The Quang Tri province of Vietnam was divided into two sectors that alternated monthly between ketamine and morphine treatments .


A total of 169 trauma patients were treated outside hospital settings with ketamine , while 139 patients were treated with morphine .


The treatment effects were measured by comparing the Visual Analogue Scale ( VAS ) ratings in the field to those upon on admission .


The analgesic effects were positive and similar for the two drugs .


The rate of vomiting was significantly lower in the ketamine group ( 5 % ) than in the morphine group ( 19 % , 95 % CI for difference 8-22 % ) .


The rate of hallucinations and agitation was higher in ketamine-treated patients ( 11 % ) than in the morphine-treated patients ( 1.5 % , 95 % CI for difference 4-16 % ) .


In this study , patients with head trauma ( n = 57 ) showed no adverse effects on consciousness level after being treated with ketamine .


Ketamine had an analgesic effect similar to morphine and carried a lower risk of airway problems .


The risk of hallucinations and agitation was increased in the ketamine group .


These findings are of medical significance , particularly in rough and low-resource scenarios .


Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications , yet the benefits and risks of treatment beyond 1 year are uncertain .


Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed .


After 12 months of treatment with a thienopyridine drug ( clopidogrel or prasugrel ) and aspirin , patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months ; all patients continued receiving aspirin .


The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events ( a composite of death , myocardial infarction , or stroke ) during the period from 12 to 30 months .


The primary safety end point was moderate or severe bleeding .


A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo .


Continued treatment with thienopyridine , as compared with placebo , reduced the rates of stent thrombosis ( 0.4 % vs. 1.4 % ; hazard ratio , 0.29 [ 95 % confidence interval { CI } , 0.17 to 0.48 ] ; P < 0.001 ) and major adverse cardiovascular and cerebrovascular events ( 4.3 % vs. 5.9 % ; hazard ratio , 0.71 [ 95 % CI , 0.59 to 0.85 ] ; P < 0.001 ) .


The rate of myocardial infarction was lower with thienopyridine treatment than with placebo ( 2.1 % vs. 4.1 % ; hazard ratio , 0.47 ; P < 0.001 ) .


The rate of death from any cause was 2.0 % in the group that continued thienopyridine therapy and 1.5 % in the placebo group ( hazard ratio , 1.36 [ 95 % CI , 1.00 to 1.85 ] ; P = 0.05 ) .


The rate of moderate or severe bleeding was increased with continued thienopyridine treatment ( 2.5 % vs. 1.6 % , P = 0.001 ) .


An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment .


Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent , as compared with aspirin therapy alone , significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding .


( Funded by a consortium of eight device and drug manufacturers and others ; DAPT ClinicalTrials.gov number , NCT00977938 . )


Ivabradine is a pure heart rate-lowering agent that acts by inhibiting I ( f ) , an important ionic current involved in pacemaker activity in the cells of the sinoatrial node .


In the 2012 European Society of Cardiology Guidelines on Heart Failure , it was recommended that patients with a persistently high heart rate , despite treatment with an evidence-based dose of a - blocker , should be considered for treatment with ivabradine .


The aim of this study was to explore the pharmacokinetic/pharmacodynamic properties and safety profile of ivabradine in healthy Chinese men .


This Phase I , randomized , open-label , parallel-arm , single - and multiple-dose study was conducted at the Clinical Pharmacology Center of the Cardiovascular Institute and Fu Wai Hospital at the Chinese Academy of Medical Sciences & Peking Union Medical College in Beijing , People 's Republic of China .


Healthy , nonsmoking volunteers were randomly assigned to 1 of 3 treatment groups based on treatment with 5 , 10 or 20 mg of ivabradine .


After a single dose , the subjects assigned to the 3 dose groups received repeated oral doses of ivabradine BID for 6 days .


The plasma concentrations of ivabradine were determined by using a HPLC-MS/MS method .


Systolic and diastolic blood pressure and heart rate measurements were taken , and ECG and Holter monitoring was performed .


Tolerability was assessed throughout the study by physical and ophthalmologic examinations , vital signs measurement , laboratory analyses , and monitoring of adverse effects .


A total of 36 healthy Chinese men were enrolled in the study .


After the single dose , plasma ivabradine Cmax and AUC increased approximately linearly with dosage , no statistically significant differences were found in t or Tmax between the dose groups .


After multiple doses , there was no significant change in Tmax compared with the results after a single dose .


After repeated doses , t , Cmax , and AUC increased significantly ( P < 0.001 ) .


After a single dose , a significant reduction in heart rate at 2 hours ' postdose was observed in the highest dose group , whereas after repeated doses , a significant reduction in heart rate was observed from 2 to 4 hours ' postdose for all 3 groups .


The mean ( SD ) heart rate after repeated doses decreased 12.5 ( 4.8 ) , 12.4 ( 6.9 ) , and 20.5 ( 5.8 ) beats/min for the 5 - , 10 - , and 20-mg dose groups , respectively .


No clear trend in the changes in QTc , systolic and diastolic blood pressures , or respiration rate was observed .


Ivabradine was well tolerated in these healthy Chinese men .


The results of the study in a small population of healthy Chinese men suggest that the PK properties of ivabradine are linear with respect to dosing .


After single and repeated oral administration of ivabradine , a significant decrease in heart rate was observed .


Ivabradine appeared well tolerated in the population studied .


Trial identifier : ACTRN1261300027741 .


This study sought to compare paclitaxel-eluting balloon ( PEB ) with conventional percutaneous transluminal angioplasty ( PTA ) , followed by systematic implantation of a self-expanding nitinol bare-metal stent ( BMS ) in patients at risk for restenosis .


PTA is an effective strategy for treating atherosclerosis of the femoropopliteal axis ( FPA ) .


Whereas PEB have shown advantage over uncoated balloons in the treatment of simple lesions , it is unknown whether these results are applicable to complex degrees of FPA atheroma .


A total of 104 patients ( 110 FPA lesions in 110 limbs ) were randomly assigned to either PEB + BMS or PTA + BMS .


The primary endpoint was 12-month binary restenosis .


Secondary endpoints were freedom from target lesion revascularization and major amputation .


Post hoc subanalyses were performed for the comparison of long ( 100 mm ) versus short lesions and true lumen versus subintimal approach .


Mean lesion length was 94 60 versus 96 69 mm in the PEB + BMS and PTA + BMS groups ( p = 0.8 ) , respectively .


The primary endpoint occurred in 9 ( 17 % ) versus 26 ( 47.3 % ) of lesions in the PEB + BMS and PTA + BMS groups ( p = 0.008 ) , respectively .


A near-significant ( p = 0.07 ) 1-year freedom from target lesion revascularization advantage was observed in the PEB + BMS group .


No major amputation occurred .


No significant difference was observed according to lesion characteristics or technical approach .


Pre-dilation with PEB angioplasty prior to BMS implantation , as compared to PTA + BMS in complex FPA lesions , reduces restenosis and target lesion revascularization at 12-month follow-up .


Restenosis reduction is maintained irrespective of lesion length and recanalization technique .


( DrugEluting Balloon in Peripheral Intervention for the Superficial Femoral Artery [ DEBATE-SFA ] ; NCT01556542 ) .


Organizational and wider health system factors influence the implementation and success of interventions .


Clinical Pathways in Acute Coronary Syndromes 2 is a cluster randomized trial of a clinical pathway-based intervention to improve acute coronary syndrome care in hospitals in China .


We performed a qualitative evaluation to examine the system-level barriers to implementing clinical pathways in the dynamic healthcare environment of China .


A qualitative descriptive analysis of 40 in-depth interviews with health professionals conducted in a sample of 10 hospitals purposively selected to explore barriers to implementation of the intervention .


Qualitative data were analyzed using the Framework method .


In-depth interviews identified 5 key system-level barriers to effective implementation : ( 1 ) leadership support for implementing quality improvement , ( 2 ) variation in the capacity of clinical services and quality improvement resources , ( 3 ) fears of patient disputes and litigation , ( 4 ) healthcare funding constraints and high out-of-pocket expenses , and ( 5 ) patient-related factors .


System-level barriers affect the ability of acute coronary syndrome clinical pathways to change practice .


Addressing these barriers in the context of current and planned national health system reform will be critical for future improvements in the management of acute coronary syndromes , and potentially other hospitalized conditions , in China .


Clinical Trial Registration - URL : http://www.anzctr.org.au/default.aspx .


Register .


Unique identifier : ACTRN12609000491268 .


Fractional flow reserve ( FFR ) - guided percutaneous coronary intervention ( PCI ) improved outcomes compared with an angiography-guided strategy in patients with multivessel coronary artery disease ( CAD ) .


However , the effect of age on FFR has not been well-studied .


We aimed to evaluate the impact of age on the favorable results of routine FFR-guided PCI for multivessel CAD .


We compared 1 year outcomes between FFR-guided PCI and angiography-guided PCI in the 512 patients enrolled in the FAME study < 65 years old compared to the 493 patients 65 years old .


We also evaluated the effect of age on the FFR result of varying degrees of visually estimated coronary stenosis .


The 1-year rate of death , myocardial infarction or repeat revascularization in the angiography-guided group tended to be higher than in the FFR-guided group for both those patients < 65 ( 17.2 % vs. 12.0 % , P = 0.098 ) and those 65 years old ( 19.7 % vs. 14.3 % , P = 0.111 ) with no significant interaction based on age ( P = 0.920 ) .


Older patients had higher FFR in vessels with 50 % to 70 % stenosis ( 0.83 0.11 vs. 0.80 0.13 , P = 0.028 ) and in vessels with 71 % to 90 % stenosis ( 0.69 0.15 vs. 0.65 0.16 , P = 0.002 ) .


The proportion of functionally significant lesions ( FFR 0.80 ) in vessels with 71 % to 90 % stenosis was significantly lower in elderly compared to younger patients ( 75.3 % vs. 84.1 % , P = 0.013 ) .


FFR-guided PCI is beneficial regardless of age , however , older patients have fewer functionally significant lesions , despite a similar angiographic appearance .


To evaluate the efficacy and safety of ribavirin aerosol in children with hand-foot-mouth disease ( HFMD ) .


A randomized , double-blind , placebo-controlled trial was performed .


A total of 119 children with mild HFMD were randomly divided into an observed group ( n = 59 ) and a control group ( n = 60 ) .


In the observed group , ribavirin aerosol was given four times within the first hour , followed by once every other hour for the remaining time of the day and day 2 ; from days 3 to 7 , it was given 4 times per day , with 2-3 sprays every time , for 7 days .


In the control group , placebo was given in the same way as in the observed group .


Additionally , both groups used oral antiviral liquid .


The scores of clinical symptoms including oral ulcer , skin rash , nasal congestion , runny nose , sneezing , cough , and fever before and after treatment were recorded to evaluate treatment outcomes .


Throat swabs were taken before treatment and 5-7 days after treatment to measure viral load by RT-PCR and to compare the negative conversion rate between the two groups .


Fifty-seven patients in the observed group and 56 patients in the control group were tested according to the original research design .


After 5-7 days of treatment , the observed group had a significantly higher overall negative conversion rate of enterovirus than the control group ( P < 0.01 ) .


The overall marked response rate and overall response rate of the observed group were 89 % and 89 % , respectively , significantly higher than those of the control group ( 29 % and 43 % ) .


During treatment , there were no adverse reactions such as dizziness , vomiting , and notable decreases in hemoglobin , white blood cells , and platelets in the two groups .


Ribavirin aerosol can be effectively and safely used for treating mild HFMD .


With low dosage and few adverse reactions , it holds promise for clinical application .


Lowering blood pressure ( BP ) and reducing diurnal variation are important for the prevention of stroke in patients with hypertension .


This study was conducted to compare the BP-lowering and diurnal BP variation effects of amlodipine and losartan on acute stroke patients .


Seventy-seven hypertensive patients with acute stroke were enrolled in this randomized , double-blind , single-center clinical trial .


They were randomly assigned to receive either amlodipine or losartan daily .


To evaluate whether amlodipine was noninferior to losartan , ambulatory BP monitoring was performed before the drugs were first administered and at the end of week 8 .


BP variables analyzed included the mean awake , sleep , morning , evening , and prewake BP values ; the nocturnal dipping status ; and the morning surge .


Thirty-nine patients in the amlodipine group and 38 patients in the losartan group completed the follow-up .


In the baseline characteristics , mean age was 63.6 years , and 68.8 % were male .


In the intention-to-treat analysis , the mean ( SD ) systolic BP decreased 14.82 ( 11.71 ) mm Hg in the amlodipine group and 13.11 ( 12.69 ) mm Hg in the losartan group , and amlodipine proved noninferior to losartan ( mean difference , 1.71 mm Hg [ 95 % CI , -3.83 to 7.26 ] ) .


However , in the per-protocol analysis , noninferiority was not proven ( BP reduction , 16.06 [ 11.33 ] vs 17.17 [ 11.85 ] mm Hg ; mean difference , -1.11 mm Hg [ 95 % CI , -6.88 to 4.65 ] ) .


Amlodipine had a greater tendency than losartan to produce a blunt morning surge .


The noninferiority of amlodipine was not confirmed by the per-protocol analysis .


However , amlodipine showed a favorable effect on the morning surge .


ClinicalTrials.gov identifier : NCT01830517 .


The objective of this study was to evaluate short term and long term efficacy of a transurethral injection ( TUI ) using bulking agent Bulkamid for female stress ( SUI ) and mixed urinary incontinence by women with ISD or where anti-incontinence surgery has failed .


Retrospective clinical study .


Gynecological and Obstetric Dpt .


1st Medical Faculty UK and VFN , Prague .


A retrospective study was performed on 52 women with urinary incontinence ( stress , 43 ; mixed 9 ) .


One patient died during study .


Forty patients had previously undergone anti-incontinence surgery .


The efficacy of TUI was evaluated 3 months ( 1 week ) and an average of 22 months after surgery .


Subjective assessment of the leakage of urine was based on the International Consultation on Incontinence Questionnaire - Short form ( ICIQ-UI SF ) filled in before , three and - on average - 22 months after the surgery ( minimum time after surgery was 6 months ) .


Improvement in urinary incontinence was defined as a drop in the score of more than 50 % .


Objective assessment of leakage of urine was assessed by cough test .


The cure effect was evaluated by VAS ( Visual Analogue Scale ) score and by using the five-point Likert score .


Ethical committee approval was obtained , and all subjects gave written informed consent to participate in the study .


Mean age of patients was 70 years , mean body mass index ( BMI ) 28.65 , and mean parity was 1.76 .


The cough test showed that 19/51 ( 37.3 % ) of patients had negative results for this test 3 months and 10/51 ( 19.6 % ) 22 months after the operation .


The ICIQ-UI SF questionnaire showed that 16/51 ( 31.4 % ) of our patients were completely dry 3 months after the operation and 8/51 ( 15.7 % ) 22 months after the operation .


41/51 ( 80.4 % ) of patients were dry or improved 3 months after the operation and 23/51 ( 45.13 % ) 22 months after the operation .


The mean cure effect evaluated by VAS score 3 months after the operation was 72 and 22 months after the operation it was 51.3 .


The Likert score was 4 or 5 ( cured or improved ) three and 22 months after operation by 78.4 % / 54.9 % patients .


The cure effect of Bulkamid operation decreases in correlation with the time that elapses after the operation , although this procedure is minimally invasive and is an option in cases where anti-incontinence surgery has failed .


The purpose of this single blind , prospective , parallel randomized trial study was to compare the effects of face mask and fixed tongue appliance in treatment of Class III malocclusion with maxillary deficiency in growing patients .


88 patients with maxillary deficiency were selected .


60 fulfilled the study requirements .


The patients were randomly assigned to 2 groups by computer generated tables .


One group was treated with removable face mask and the other group was treated by fixed tongue appliance .


4 of the patients dropped out of study leaving a final number of 56 patients .


Thus , the face mask group included 30 patients ( 13 males , 17 females ) with the mean age of 8.5 ( SD 1.4 ) years and the fixed tongue appliance group included 26 patients ( 13 males , 13 females ) with the mean age of 8.9 ( SD 1.7 ) years .


The patients Lateral cephalograms obtained at the beginning and end of the study were analyzed .


Paired t-tests showed that SNA increased by 1.3 ( SD 1.1 ) in face mask group ( P < 0.001 ) and it increased by 1.8 ( SD 0.9 ) in fixed tongue appliance group ( P < 0.001 ) .


T-test showed that there were no statistically significant differences between the two groups except for SNB .


IMPA decreased significantly in both groups .


Both treatment modalities were successful in moving the maxilla forward and improving the profile of the patients ; however , the bulky size of face masks might reduce patients ' compliance and make them less favorite choice of treatment .


Although combination pharmacotherapy is common in child and adolescent psychiatry , there has been little research evaluating it .


The value of adding risperidone to concurrent psychostimulant and parent training ( PT ) in behavior management for children with severe aggression was tested .


One hundred sixty-eight children 6 to 12 years old ( mean age 8.89 2.01 years ) with severe physical aggression were randomized to a 9-week trial of PT , stimulant ( STIM ) , and placebo ( Basic treatment ; n = 84 ) or PT , STIM , and risperidone ( Augmented treatment ; n = 84 ) .


All had diagnoses of attention-deficit/hyperactivity disorder and oppositional-defiant disorder ( n = 124 ) or conduct disorder ( n = 44 ) .


Children received psychostimulant ( usually Osmotic Release Oral System methylphenidate ) for 3 weeks , titrated for optimal effect , while parents received PT .


If there was room for improvement at the end of week 3 , placebo or risperidone was added .


Assessments included parent ratings on the Nisonger Child Behavior Rating Form ( Disruptive-Total subscale was the primary outcome ) and Antisocial Behavior Scale ; blinded clinicians rated change on the Clinical Global Impressions scale .


Compared with Basic treatment ( PT + STIM [ 44.8 14.6 mg/day ] + placebo [ 1.88 mg/day 0.72 ] ) , Augmented treatment ( PT + STIM [ 46.1 16.8 mg/day ] + risperidone [ 1.65 mg/day 0.75 ] ) showed statistically significant improvement onthe Nisonger Child Behavior Rating Form Disruptive-Total subscale ( treatment-by-time interaction , p = .0016 ) , the Nisonger Child Behavior Rating Form Social Competence subscale ( p = .0049 ) , and Antisocial Behavior Scale Reactive Aggression subscale ( p = .01 ) .


Clinical Global Impressions scores weresubstantially improved for the 2 groups but did not discriminate between treatments ( Clinical Global Impressions-Improvement score2 , 70 % forBasic treatment versus 79 % for Augmented treatment ) .


Prolactin elevations and gastrointestinal upset occurred more with Augmented treatment ; other adverse events differed modestly from Basic treatment ; weight gain in the Augmented treatment group was minor .


Risperidone provided moderate butvariable improvement in aggressive and other seriously disruptive child behaviorswhenadded to PT and optimized stimulant treatment .


Clinical trial registration information-Treatment of Severe Childhood Aggression ( The TOSCA Study ) , URL : http://clinicaltrials.gov , unique identifier : NCT00796302 .


To test the hypothesis that early enteral supplementing fat and fish oil decreases the duration of parenteral nutrition ( PN ) and increases enteral nutrition ( EN ) before bowel reanastomosis in premature infants with an enterostomy .


Premature infants ( < 2 months old ) who had an enterostomy and tolerated enteral feeding at 20 mL/kg/day were randomized to usual care ( control = 18 ) or early supplementing enteral fat supplement and fish oil ( treatment = 18 ) .


Intravenous lipid was decreased as enteral fat intake was increased .


Daily weight , clinical and nutrition data , and weekly length and head circumference were recorded .


The primary outcomes were the duration of PN and volume of EN intake , and the secondary outcomes were weight gain ( g/day ) , ostomy output ( mL/kg/d ) , and serum conjugated bilirubin level ( mg/dL ) from initiating feeding to reanastomosis .


Data were analyzed by Student t test or Wilcoxon rank sum test .


There were no differences in the duration of PN , ostomy output , and weight gain between the 2 groups before reanastomosis .


However , supplemented infants received less intravenous lipid , had greater EN intake , and lower conjugated bilirubin before reanastomosis , and they also received greater total calorie , had fewer sepsis evaluations and less exposure to antibiotics and central venous catheters before reanastomosis , and had greater weight and length gain after reanastomosis ( all P < .05 ) .


Early enteral feeding of a fat supplement and fish oil was associated with decreased exposure to intravenous lipid , increased EN intake , and reduced conjugated bilirubin before reanastomosis and improved weight and length gain after reanastomosis in premature infants with an enterostomy .


Noise-induced hearing loss ( NIHL ) is one of the most common occupational diseases and the second most common cause of workers ' claims for occupational injuries .


Due to high prevalence of NIHL and several reports of improper use of hearing protective devices ( HPDs ) , we conducted this study to compare the effect of face-to-face training in effective use of earplugs with appropriate NRR to overprotection of workers by using earplugs with higher than necessary noise reduction rating ( NRR ) .


In a randomized clinical trial , 150 workers referred to occupational medicine clinic were randomly allocated to three arms -- a group wearing earplugs with an NRR of 25 with no training in appropriate use of the device ; a group wearing earplugs with an NRR of 25 with training ; another group wearing earplugs with an NRR of 30 , with no training .


Hearing threshold was measured in the study groups by real ear attenuation at threshold ( REAT ) method .


This trial is registered with Australian New Zealand clinical trials Registry , number ACTRN00363175 .


The mean SD age of the participants was 28 5 ( range : 19-39 ) years .


42 % of participants were female .


The mean noise attenuation in the group with training was 13.88 dB , significantly higher than those observed in other groups .


The highest attenuation was observed in high frequencies ( 4 , 6 , and 8 kHz ) in the group with training .


Training in appropriate use of earplugs significantly affects the efficacy of earplugs -- even more than using an earplug with higher NRR .


The PARAMOUNT phase III trial demonstrated that pemetrexed continuation maintenance significantly reduced the risk of disease progression ( hazard ratio = 0.62 ) and death ( hazard ratio = 0.78 ) versus placebo in patients with advanced nonsquamous non-small-cell lung cancer .


To further understand the survival data , descriptive subgroup analyses were undertaken .


Nine hundred thirty-nine patients received induction therapy ( four 21-day cycles pemetrexed 500 mg/m and cisplatin 75 mg/m ) , after which 539 nonprogressing patients with an Eastern Cooperative Oncology Group performance status ( PS ) of 0/1 were randomized ( 2:1 ) to maintenance pemetrexed ( 500 mg/m ) cycles or placebo until disease progression .


Baseline characteristics of patients surviving for longer periods were comparable to patients surviving shorter periods , suggesting overall survival ( OS ) benefit for all subgroups of patients on maintenance therapy .


An examination of type and severity of induction adverse events also found no association with survival duration .


Response to induction ( tumor response versus stable disease ) was not determinate of pemetrexed maintenance OS outcome as assessed by waterfall plot and scattergrams and by the distribution of patients among various OS intervals .


The length of the interval before beginning maintenance therapy ( < 7 days versus 7/30 days ) also did not impact the survival results .


PS , a known prognostic factor , was the only baseline characteristic associated with improved OS ; however , both PS 0 and PS 1 patients exhibited a survival benefit from pemetrexed maintenance .


In PARAMOUNT , the OS benefit was seen across all subgroups .


Other than PS , no baseline or clinical parameter clearly identified a subgroup more likely to benefit .


Maintenance treatment decisions should be made on an individual basis .


To compare the clinical effects and safety of transepithelial corneal cross-linking ( CXL ) to epithelium-off ( epi-off ) CXL in progressive keratoconus .


Randomized clinical trial ( noninferiority ) .


Patients received either transepithelial CXL with Ricrolin TE ( n = 35 ) or epi-off CXL with isotonic riboflavin ( n = 26 ) in 1 academic treatment center , using a simple unrestricted randomization procedure .


The main outcome measure was clinical stabilization of keratoconus after 1 year , defined as a maximal keratometry ( Kmax ) increase < 1 diopter ( D ) .


Average Kmax was stable at all visits in the transepithelial group , while after epi-off CXL a significant flattening of 1.2-1 .5 D was demonstrated from the 3-month follow-up onwards .


The trend over time in Kmax flattening was significantly different between the groups ( P = .022 ) .


Eight eyes ( 23 % ) in the transepithelial group showed a Kmax increase of > 1 D after 1 year ( range 1.3-5 .4 D ) vs none in the epi-off group ( P = .017 ) .


There was significant different trend in corrected distance visual acuity ( CDVA ) , with a more favorable outcome in the transepithelial group ( P = .023 ) .


In the transepithelial group , no complications occurred and in the epi-off group , 4 eyes ( 15 % ) developed complications owing to healing problems ( sterile infiltrate , herpes keratitis , central haze , and stromal scar ) .


This study showed that although transepithelial CXL was a safe procedure without epithelial healing problems , 23 % of cases showed a continued keratoconus progression after 1 year .


Therefore , at this time , we do not recommend replacing epi-off CXL by transepithelial CXL for treatment of progressive keratoconus .


Cognitive behavioral therapy for insomnia ( CBT-I ) is well-validated in the western countries .


However , it has not been widely adopted or disseminated in China .


One possibility is that therapeutic approaches drawn from traditional Chinese medicine ( TCM ) will be more widely accepted .


This study aimed to evaluate the efficacy of medication in combination with a therapeutic approach drawn from TCM , Low Resistance Thought Induction Sleep-regulating Technique ( TIP3-2 ) , for acute treatment of insomnia .


A randomized controlled trial was conducted .


Ninety primary insomnia patients were randomly assigned to receive TIP3-2 combined with medication ( n = 45 ) or medication only ( n = 45 ) for 4 weeks .


Medication consisted of 1-2 mg Estazolam nightly .


On the basis of taking Estazolam , TIP3-2 combined with medication group was given Low Resistance Thought Induction Sleep-regulating Technique ( TIP3-2 ) treatment twice a week .


Outcomes were assessed with the Pittsburgh sleep quality index ( PSQI ) and polysomnography ( PSG ) before and after treatment .


Both groups demonstrated significant improvements in the PSQI and polysomnography indices .


The TIP3-2 + medication group demonstrated a significant difference between the two groups in PSQI total score , sleep medication use , daytime dysfunction , subjective sleep quality , as well as polysomnography indices of sleep efficiency and awakening times ( P < 0.05 ) .


Among patients with primary insomnia , the addition of TIP3-2 provided benefits above and beyond the role of medication alone .


Excessive alcohol consumption on single occasions among undergraduate students is a major health issue as research has shown this pattern of drinking to be related to maladaptive health and psychosocial outcomes .


Brief , theory-based interventions targeting motivation and self-control as behavior-change techniques have been identified as effective means to reduce alcohol consumption , but few studies have examined the interactive effects of these components .


The aim of the present study is to develop a brief theory-based intervention using motivational and self-control intervention techniques to reduce alcohol consumption in undergraduate students .


The intervention will adopt a factorial design to test the main and interactive effects of the techniques on alcohol consumption .


Using mental simulations and the strength model of self-control as the theoretical bases of the intervention , the study will adopt a fully randomized 2 ( mental simulation : mental simulation vs. control irrelevant visualization exercise ) 2 ( self-control training : challenging Stroop task vs. easy Stroop task ) between-participants design .


Non-abstinent undergraduate students aged 18years or older will be eligible to participate in the study .


Participants will complete an initial survey including self-reported alcohol consumption measures , measures of motivation and self - measures .


Participants will be randomly allocated to receive either a mental simulation exercise presented in print format or a control irrelevant visualization exercise .


Thereafter , participants will be randomly assigned to receive a challenging online self-control training exercise or an easy training exercise that has little self-control demand over the course of the next four weeks .


Four weeks later participants will complete a follow-up alcohol consumption , motivation and self-control measures .


This study will provide the first evidence for the individual and interactive effects of motivational and self-control training techniques in an intervention to reduce alcohol consumption .


It will also demonstrate the importance of adopting multiple theoretical perspectives and a factorial design to identify the unique and interactive impact of behavior-change techniques on health behavior .


The trial is registered with the Australian and New Zealand Clinical Trials Registry , ACTRN12613000573752 .


Safetac-based soft silicone dressings used in a management setting decrease the severity of radiation-induced acute skin reactions but do not affect moist desquamation rates .


Here we investigate the prophylactic use of another Safetac product , Mepitel Film , on moist desquamation rates .


A total of 80 breast cancer patients receiving radiation therapy were recruited between October 2012 and April 2013 ; 78 participants contributed data for analysis .


Lateral and medial halves of the skin areas to be irradiated were randomised to Mepitel Film or aqueous cream ; skin dose was measured using thermoluminescent dosimeters ; skin reaction severity was assessed using RISRAS and RTOG scales .


Overall skin reaction severity was reduced by 92 % ( p < 0.0001 ) in favour of Mepitel Film ( RISRAS ) .


All patients developed some form of reaction in cream-treated skin which progressed to moist desquamation in 26 % of patients ( RTOG grades I : 28 % ; IIA : 46 % ; IIB : 18 % ; III : 8 % ) .


Only 44 % of patients had a skin reaction under the Film , which did not progress to moist desquamation in any of the patients ( RTOG grades I : 36 % ; IIA : 8 % ) .


Mepitel Film completely prevented moist desquamation and reduced skin reaction severity by 92 % when used prophylactically in our cohort .


To determine whether the 10-year success rate of penetrating keratoplasty for corneal endothelial disorders is associated with donor age .


Multicenter , prospective , double-masked clinical trial .


A total of 1090 participants undergoing penetrating keratoplasty at 80 sites for Fuchs ' dystrophy ( 62 % ) , pseudophakic/aphakic corneal edema ( 34 % ) , or another corneal endothelial disorder ( 4 % ) and followed for up to 12 years .


Forty-three eye banks provided corneas from donors aged 12 to 75 years , using a randomized approach to assign donor corneas to study participants without respect to recipient factors .


Surgery and postoperative care were performed according to the surgeons ' usual routines .


Graft failure defined as a regraft or , in the absence of a regraft , a cloudy cornea that was sufficiently opaque to compromise vision for 3 consecutive months .


In the primary analysis , the 10-year success rate was 77 % for 707 corneas from donors aged 12 to 65 years compared with 71 % for 383 donors aged 66 to 75 years ( difference , +6 % ; 95 % confidence interval , -1 to +12 ; P = 0.11 ) .


When analyzed as a continuous variable , higher donor age was associated with lower graft success beyond the first 5 years ( P < 0.001 ) .


Exploring this association further , we observed that the 10-year success rate was relatively constant for donors aged 34 to 71 years ( 75 % ) .


The success rate was higher for 80 donors aged 12 to 33 years ( 96 % ) and lower for 130 donors aged 72 to 75 years ( 62 % ) .


The relative decrease in the success rate with donor ages 72 to 75 years was not observed until after year 6 .


Although the primary analysis did not show a significant difference in 10-year success rates comparing donor ages 12 to 65 years and 66 to 75 years , there was evidence of a donor age effect at the extremes of the age range .


Because we observed a fairly constant 10-year success rate for donors aged 34 to 71 years , which account for approximately 75 % of corneas in the United States available for transplant , the Cornea Donor Study results indicate that donor age is not an important factor in most penetrating keratoplasties for endothelial disease .


Perimenopause is accompanied by an increased risk of new and recurrent depression .


The coincidence of declining ovarian function with the onset of depression led to the inference that `` withdrawal '' from physiologic estradiol levels underpinned depression in perimenopause .


To our knowledge , this is the first controlled systematic study to directly test the estrogen withdrawal theory of perimenopausal depression ( PMD ) .


To examine the role of estradiol withdrawal in PMD .


Initial open-label treatment with estradiol followed by randomized , double-blind , placebo-controlled , parallel-design evaluation of continued estradiol treatment was evaluated at an outpatient research facility at the National Institutes of Health Clinical Center .


An intent-to-treat analysis was performed between October 2003 and July 2012 .


Participants included asymptomatic postmenopausal women with past PMD responsive to hormone therapy ( n = 26 ) and asymptomatic postmenopausal women with no history of depression ( n = 30 ) matched for age , body mass index , and reproductive status who served as controls .


Data were analyzed between November 2012 and October 2013 by repeated-measures analysis of variance .


After 3 weeks of open-label administration of transdermal estradiol ( 100 g/d ) , participants were randomized to a parallel design to receive either estradiol ( 100 g/d ; 27 participants ) or matched placebo skin patches ( 29 participants ) for 3 additional weeks under double-blind conditions .


Center for Epidemiologic Studies-Depression Scale and 17-item Hamilton Depression Rating Scale ( completed by raters blind to diagnosis and randomization status ) , self-administered visual analog symptom ratings , and blood hormone levels obtained at weekly clinic visits .


None of the women reported depressive symptoms during open-label use of estradiol .


Women with past PMD who were crossed over from estradiol to placebo experienced a significant increase in depression symptom severity demonstrated using the Center for Epidemiologic Studies-Depression Scale and 17-item Hamilton Depression Rating Scale , with mean ( SD ) scores increasing from estradiol ( ie , 2.4 [ 2.0 ] and 3.0 [ 2.5 ] ) to placebo ( 8.8 [ 4.9 ] and 6.6 [ 4.5 ] , respectively [ P = .0004 for both ] ) .


Women with past PMD who continued estradiol therapy and all women in the control group remained asymptomatic .


Women in both groups had similar hot-flush severity and plasma estradiol levels during use of placebo .


In women with past PMD that was previously responsive to hormone therapy , the recurrence of depressive symptoms during blinded hormone withdrawal suggests that normal changes in ovarian estradiol secretion can trigger an abnormal behavioral state in these susceptible women .


Women with a history of PMD should be alert to the risk of recurrent depression when discontinuing hormone therapy .


clinicaltrials.gov Identifier : NCT00060736 .


Most persons with dementia live at home and are treated in the primary care .


However , the ambulatory health care system in Germany contains a lot of `` interface problems '' and is not optimized for the future challenges .


Innovative concepts like regional networks in dementia care exist on a project level and need to be tested for efficacy to encourage implementation .


The goal of the study is the scientific evaluation of an already existing regional dementia network .


Prospective randomized controlled trial of 235 community-living elderly with dementia and their family caregivers of network treatment ( n = 117 ) compared to usual care ( n = 118 ) in a predominantly rural region .


The allocation to intervention or control group was based on network membership of their General Practitioner .


Intervention patients received diagnostic evaluation and subsequent treatment according to network guidelines .


Main outcome measures were the early contact with a neurologic or psychiatric specialist and dementia-specific medication as well as quality of life of the patients , and as secondary outcomes caregiver burden and caregiver health-related quality of life .


Network patients were more likely to receive antidementive drugs ( 50.5 % vs. 35.8 % ; p = 0.035 ) and had more often contact to a neurologist ( 18.6 % vs. 2.8 % ; p < 0.001 ) .


No group differences were found on patient 's quality of life nor overall effects or treatment by time effects .


Intervention caregivers reported no significant improvements in health related quality of life measured by SF-36 and EQ-5D .


The management of dementia patients in an interdisciplinary regional network solelyprovides measurable advantages with respect to the provision of dementia-specific medication and utilization of medical treatment i.e. referral rates to specialists .


Further evaluation research is needed to identify relevant mechanismsof collaborative processes with respect to their impact on patient and caregiver related outcomes .


To evaluate the efficacy and safety of enteral recombinant human granulocyte colony-stimulating factor ( rhG-CSF ) and recombinant human erythropoietin ( rhEPO ) in preventing feeding intolerance .


An interventional randomized control trial was conducted in 90 preterm infants born at 33 weeks gestational age .


The neonates were assigned to 4 groups ; 20 received rhG-CSF , 20 received rhEPO , 20 received both , and 30 received distilled water ( placebo control ) .


The test solution was given at the beginning of enteral feeding and was discontinued when enteral intake reached 100 mL/kg/day or after a maximum of 7 days , whichever came first .


Feeding tolerance and adverse effects of treatment were assessed .


Serum granulocyte colony-stimulating factor and erythropoietin levels were measured on days 0 and 7 of treatment .


All neonates tolerated the treatment without side effects .


Neonates who received rhG-CSF and/or rhEPO had better feeding tolerance , as reflected by earlier achievement of 75 mL/kg/day , 100 mL/kg/day , and full enteral feeding of 150 mL/kg/day with earlier weight gain and a shorter hospital stay ( P < .05 ) .


The risk of necrotizing enterocolitis was reduced from 10 % to 0 % in all treatment groups ( P < .05 ) .


There was a shorter duration of withholding of feeding secondary to feeding intolerance among neonates receiving both rhG-CSF and rhEPO compared with those receiving placebo ( P < .05 ) .


Serum levels of granulocyte colony-stimulating factor and erythropoietin at 0 and 7 days did not differ across the treatment groups .


Enteral administration of rhG-CSF and/or rhEPO improves feeding outcome and decreases the risk of necrotizing enterocolitis in preterm neonates .


The mechanism may involve the prevention of villous atrophy .


To evaluate the effects of whole-body resistance training on exercise capacity , health-related quality of life ( HRQOL ) , and muscle strength in patients hospitalized for exacerbation of chronic obstructive pulmonary disease .


Randomized controlled trial .


University hospital .


Patients ( N = 46 ) were randomized to either a control group ( CG ) or training group ( TG ) , and 29 patients completed the study .


Training consisted of weight-lifting exercises for 6 muscle groups in the upper and lower limbs ( 2 sets of 8 repetitions each ) , and the initial load was set at 80 % of the 1-repetition maximum load .


Patients were evaluated on the second day of hospitalization , at hospital discharge , and 30 days postdischarge .


Patients were evaluated on the basis of the 6-minute walking distance ( 6MWD ) , HRQOL , muscle strength , systemic inflammatory markers , and level of physical activity in daily life ( PADL ) .


The CG showed a reduction in the strength of lower-limb muscles ( P < .05 ) but not in the 6MWD ( P > .05 ) .


In contrast , patients from the TG improved strength in the lower-limb muscles and 6MWD during and 30 days after hospitalization ( P < .05 ) .


The TG also improved the impact domain in HRQOL after hospitalization .


No improvement in PADL was observed in the TG .


Finally , a reduction in the blood levels of inflammatory markers was observed only in the TG after hospitalization .


Our results suggest that resistance training during hospitalization improves the 6MWD , HRQOL , and lower-limb muscle strength , without altering the levels of systemic inflammation .


However , future research should explore this intervention in larger randomized trials .


Neoadjuvant hormonal therapy ( NHT ) is playing an increasing role in the clinical management of breast cancer ( BC ) and may improve surgical outcomes for postmenopausal , oestrogen receptor ( ER ) - positive BC patients .


However , there is currently no consensus on the optimal duration of NHT before surgery .


Here , we present the outcomes of the TEAM IIA trial , a multicentre , phase II trial investigating the efficacy of six months of neoadjuvant exemestane in postmenopausal , strong ER-positive ( ER + , 50 % ) BC patients .


102 patients ( stage T2-T4ac ) were included in the study after exclusion of ineligible patients .


Primary end-point was clinical response at 3 and 6 months as measured by palpation .


Secondary end-point was radiological response as measured by magnetic resonance imaging ( MRI ) , mammography and/or ultrasound .


Linear mixed models ( 95 % confidence interval ( CI ) ) were used to compare changes in mean tumour size ( in mm ) between baseline , 3 and 6 months after the start of endocrine therapy .


Conversion rates from mastectomy to breast conserving surgery ( BCS ) were evaluated .


Median age of all patients was 72 years ( range 53-88 ) .


Overall response rate by clinical palpation was 64.5 % in all patients with a final palpation measurement .


Four patients had clinically progressive disease .


63 patients had both 3-month and > 3-month palpation measurements .


Overall response was 58.7 % at 3 months and 68.3 % at final palpation ( > 3 months ) .


Mean tumour size by clinical palpation at T = 0 was 39.1 mm ( 95 % CI 34.8-43 .4 mm ) , and decreased to 23.0 mm ( 95 % CI 18.7-27 .2 mm ) and 16.7 mm ( 95 % CI 12.6-20 .8 ) at T = 3 and T > 3 months , respectively ( p = 0.001 ) .


Final radiological response rates at the end of treatment for MRI ( n = 37 ) , ultrasound ( n = 77 ) and mammography ( n = 56 ) were 70.3 % , 41.6 % and 48.2 % , respectively .


Feasibility of BCS improved from 61.8 % to 70.6 % ( McNemar p = 0.012 ) .


6 months of neoadjuvant exemestane therapy helps reduce mean tumour size further in strongly ER-positive BC patients without significant side-effects compared to 3 months .


Nevertheless , some patients still experience disease progression under exemestane .


Feasibility of breast conservation rates improved by almost 10 % .


Hypoparathyroidism results in impaired mineral homoeostasis , including hypocalcaemia and hyperphosphataemia .


Treatment with high-dose oral calcium and active vitamin D does not provide adequate or consistent control of biochemical indices and can lead to serious long-term complications .


We aimed to test the efficacy , safety , and tolerability of once-daily recombinant human parathyroid hormone 1-84 ( rhPTH [ 1-84 ] ) in adults with hypoparathyroidism .


In this double-blind , placebo-controlled , randomised phase 3 study ( REPLACE ) , we recruited patients with hypoparathyroidism ( 18 months duration ) aged 18-85 years from 33 sites in eight countries .


After an optimisation period , during which calcium and active vitamin D doses were adjusted to achieve consistent albumin-corrected serum calcium , patients were randomly assigned ( 2:1 ) via an interactive voice response system to 50 g per day of rhPTH ( 1-84 ) or placebo for 24 weeks .


Active vitamin D and calcium were progressively reduced , while rhPTH ( 1-84 ) could be titrated up from 50 g to 75 g and then 100 g ( weeks 0-5 ) .


The primary endpoint was the proportion of patients at week 24 who achieved a 50 % or greater reduction from baseline in their daily dose of oral calcium and active vitamin D while maintaining a serum calcium concentration greater than or the same as baseline concentrations and less than or equal to the upper limit of normal , analysed by intention to treat .


This trial is registered with ClinicalTrials.gov , number NCT00732615 .


Between June 23 , 2009 , and Feb 28 , 2011 , 134 eligible patients were recruited and randomly assigned to rhPTH ( 1-84 ) ( n = 90 ) or placebo ( n = 44 ) .


Six patients in the rhPTH ( 1-84 ) group and seven in the placebo group discontinued before study end .


48 ( 53 % ) patients in the rhPTH ( 1-84 ) group achieved the primary endpoint compared with one ( 2 % ) patient in the placebo group ( percentage difference 51.1 % , 95 % CI 39.9-62 .3 ; p < 0.0001 ) .


The proportions of patients who had at least one adverse event were similar between groups ( 84 [ 93 % ] patients in the rhPTH [ 1-84 ] group vs 44 [ 100 % ] patients in the placebo group ) , with hypocalcaemia , muscle spasm , paraesthesias , headache , and nausea being the most common adverse events .


The proportions of patients with serious adverse events were also similar between the rhPTH ( 1-84 ) group ( ten [ 11 % ] patients ) and the placebo group ( four [ 9 % ] patients ) .


50 g , 75 g , or 100 g per day of rhPTH ( 1-84 ) , administered subcutaneously in the outpatient setting , is efficacious and well tolerated as a PTH replacement therapy for patients with hypoparathyroidism .


Second line endocrine therapy has limited antitumour activity .


Fulvestrant inhibits and downregulates the oestrogen receptor .


The mitogen-activated protein kinase ( MAPK ) pathway is one of the major cascades involved in resistance to endocrine therapy .


We assessed the efficacy and safety of fulvestrant with selumetinib , a MEK 1/2 inhibitor , in advanced stage breast cancer progressing after aromatase inhibitor ( AI ) .


This randomised phase II trial included postmenopausal patients with endocrine-sensitive breast cancer .


They were ramdomised to fulvestrant combined with selumetinib or placebo .


The primary endpoint was disease control rate ( DCR ) in the experimental arm .


ClinicalTrials.gov Indentifier : NCT01160718 .


Following the planned interim efficacy analysis , recruitment was interrupted after the inclusion of 46 patients ( 23 in each arm ) , because the selumetinib-fulvestrant arm did not reach the pre-specified DCR .


DCR was 23 % ( 95 % confidence interval ( CI ) 8-45 % ) in the selumetinib arm and 50 % ( 95 % CI 27-75 % ) in the placebo arm .


Median progression-free survival was 3.7 months ( 95 % CI 1.9-5 .8 ) in the selumetinib arm and 5.6 months ( 95 % CI 3.4-13 .6 ) in the placebo arm .


Median time to treatment failure was 5.1 ( 95 % CI 2.3-6 .7 ) and 5.6 ( 95 % CI 3.4-10 .2 ) months , respectively .


The most frequent treatment-related adverse events observed in the selumetinib-fulvestrant arm were skin disorders , fatigue , nausea/vomiting , oedema , diarrhoea , mouth disorders and muscle disorders .


The addition of selumetinib to fulvestrant did not show improving patients ' outcome and was poorly tolerated at the recommended monotherapy dose .


Selumetinib may have deteriorated the efficacy of the endocrine therapy in some patients .


Biochemical markers of myocardial injury are frequently altered after cardiac surgery .


So far there is no evidence whether oral beta-blockers may reduce myocardial injury after coronary artery bypass grafting .


To determine if oral administration of prophylactic metoprolol reduces the release of cardiac troponin I in isolated coronary artery bypass grafting , not complicated by new Q waves .


A prospective randomized study , including 68 patients , divided in 2 groups : Group A ( n = 33 , control ) and B ( n = 35 , beta-blockers ) .


In group B , metoprolol tartrate was administered 200 mg/day .


The myocardial injury was assessed by troponin I with 1 hour and 12 hours after coronary artery bypass grafting .


No significant difference between groups regarding pre-surgical , surgical , complication in intensive care ( 15 % versus 14 % , P = 0.92 ) and the total number of hospital events ( 21 % versus 14 % , P = 0.45 ) was observed .


The median value of troponin I with 12 hours in the study population was 3.3 ng/ml and was lower in group B than in group A ( 2.5 ng/ml versus 3.7 ng/ml , P < 0,05 ) .


In the multivariate analysis , the variables that have shown to be independent predictors of troponin I release after 12 hours were : no beta-blockers administration and number of vessels treated .


The results of this study in uncomplicated coronary artery bypass grafting , comparing the postoperative release of troponin I at 12 hours between the control group and who used oral prophylactic metoprolol for at least 72 hours , allow to conclude that there was less myocardial injury in the betablocker group , giving some degree of myocardial protection .


The purpose of this study was to compare the efficacy of radiofrequency catheter ablation ( RFCA ) versus antiarrhythmic drugs ( AADs ) for treatment of patients with frequent ventricular premature beats ( VPBs ) originating from the right ventricular outflow tract ( RVOT ) .


A total of 330 eligible patients were included in the study and were randomly assigned to RFCA or AADs group .


The absolute number and the burden of VPBs on 12-lead Holter monitors were measured at baseline and at 1st , 3rd , 6th , and 12th months after randomization .


Left ventricular eject fraction was evaluated by transthoracic echocardiogram at baseline and at 3 and 6 months after randomization .


During the 1-year follow-up period , VPB recurrence was significantly lower in patients randomized to RFCA group ( 32 patients , 19.4 % ) versus AADs group ( 146 patients , 88.6 % ; P < 0.001 , log-rank test ) .


In a Poisson generalized estimating equations ( GEE ) regression model , RFCA was associated with a greater decrease in the burden of VPBs ( incidence rate ratio 0.105 ; 95 % confidence intervals [ 0.104-0 .105 ] ; P < 0.001 ) compared with AADs .


In a liner GEE model , the left ventricular eject fraction had a tendency to increase after the treatment in both groups ( coefficient , 0.584 ; 95 % confidence intervals [ 0.467-0 .702 ] ; P < 0.001 ) .


In a Cox proportional model , the QS morphology in lead I was the only predictor of VPB recurrence free for catheter ablation ( hazards ratio , 0.154 ; 95 % confidence intervals [ 0.044-0 .543 ] ; P = 0.004 ) .


Catheter ablation is more efficacious than AADs for preventing VPB recurrence in patients with frequent VPBs originating from the RVOT .


QS morphology in lead I was associated with better outcome after ablation .


Although there is no direct evidence , it is generally believed that bed rest shifts the haemostatic system towards hypercoagulability ; thus , immobilized patients are commonly treated with anticoagulants .


We therefore aimed to investigate whether long-term bed rest actually leads to an elevated risk for thromboembolic events .


Eleven healthy men were enrolled in our study ( bed rest campaign in MEDES Clinique d'Investigation , Toulouse , France ) .


Besides various standard laboratory methods , we used calibrated automated thrombography ( CAT ) and thrombelastometry ( TEM ) .


Activation of samples with minute amounts of relipidated tissue factor allowed sensitive detection of hyper - or hypocoagulable states .


CAT and TEM values were not indicative of bed rest-induced hypercoagulability .


On the contrary , several parameters were indicative of a tendency towards a hypocoagulable state .


Peak and thrombin formation velocity ( VELINDEX ) were significantly decreased during bed rest compared to baseline .


Coagulation times were significantly increased and alpha angles were significantly decreased , indicating attenuated clot formation .


Moreover , F1 +2 and thrombin/antithrombin complex ( TAT ) values were significantly decreased during bed rest , indicating suppressed coagulation activation .


FVII plasma levels were also significantly decreased during the first week of bed rest .


Our data indicate that the re-ambulation period is associated with a tendency towards hypercoagulability : ttPeak and StartTail were significantly shorter , Peak and VELINDEX were significantly higher compared to baseline .


Moreover , plasma levels of F1 +2 , TAT , FVII and FVIII were significantly higher compared to baseline .


The results from our study suggest that bed rest by itself is not associated with hypercoagulable states in healthy subjects .


Specific immunotherapy ( SIT ) with an ultrarush administration schedule with Purethal for tree pollen allergens has been evaluated to assess its efficacy and safety .


The study group consisted of 22 patients with symptoms of allergic rhinitis and confirmed allergy to tree pollens .


Patients were randomized and given an administration schedule of either ultrarush therapy or conventional preseasonal SIT .


Treatment was performed during three consecutive years .


After three years of treatment , a similar reduction in nasal symptoms was observed ; according to the visual analog scale , there was a decrease from 3.991 0.804 points to 1.634 0.540 in the ultrarush group and from 3.845 0.265 to 1.501 0.418 in the group desensitized using the conventional method ( P > 0.05 ) .


There was also a comparable reduction in the use of relief drugs during pollen season and an increase in the serum concentration of IgG4 to tree pollens .


No significant differences in the safety profile were observed .


An administration schedule of ultrarush SIT with Purethal Trees is a safe treatment in preliminary observations .


This therapy is comparable with conventional administration of SIT in the field of efficacy and safety .


To evaluate the feasibility and safety of utilizing a commercially available virtual reality gaming system as a treatment intervention for balance training .


A randomized controlled trial in which assessment and analysis were blinded .


An inpatient rehabilitation facility .


Interventions included balance-based physical therapy using a Nintendo Wii , as monitored by a physical therapist , and receipt of one-on-one balance-based physical therapy using standard physical therapy modalities available for use in the therapy gym .


Participants in the standard physical therapy group were found to have slightly higher enjoyment at mid-intervention , while those receiving the virtual reality-based balance intervention were found to have higher enjoyment at study completion .


Both groups demonstrated improved static and dynamic balance over the course of the study , with no significant differences between groups .


Correlational analyses suggest a relationship exists between Wii balance board game scores and BBS scores for measures taken beyond the baseline assessment .


This study provides a modest level of evidence to support using commercially available VR gaming systems for the treatment of balance deficits in patients with a primary diagnosis of TBI receiving inpatient rehabilitation .


Additional research of these types of interventions for the treatment of balance deficits is warranted .


Monitoring of fruit and vegetable ( F&V ) intake is fraught with difficulties .


Available dietary assessment methods are associated with considerable error , and the use of biomarkers offers an attractive alternative .


Few studies to date have examined the use of plasma biomarkers to monitor or predict the F&V intake of volunteers consuming a wide range of intakes from both habitual F&V and manipulated diets .


This study tested the hypothesis that an integrated biomarker calculated from a combination of plasma vitamin C , cholesterol-adjusted carotenoid concentration and Ferric Reducing Antioxidant Power ( FRAP ) had more power to predict F&V intake than each individual biomarker .


Data from a randomized controlled dietary intervention study [ FLAVURS ( Flavonoids University of Reading Study ) ; n = 154 ] in which the test groups observed sequential increases of 2.3 , 3.2 , and 4.2 portions of F&V s every 6 wk across an 18-wk period were used in this study .


An integrated plasma biomarker was devised that included plasma vitamin C , total cholesterol-adjusted carotenoids , and FRAP values , which better correlated with F&V intake ( r = 0.47 , P < 0.001 ) than the individual biomarkers ( r = 0.33 , P < 0.01 ; r = 0.37 , P < 0.001 ; and r = 0.14 , respectively ; P = 0.099 ) .


Inclusion of urinary potassium concentration did not significantly improve the correlation .


The integrated plasma biomarker predicted F&V intake more accurately than did plasma total cholesterol-adjusted carotenoid concentration , with the difference being significant at visit 2 ( P < 0.001 ) and with a tendency to be significant at visit 1 ( P = 0.07 ) .


Either plasma total cholesterol-adjusted carotenoid concentration or the integrated biomarker could be used to distinguish between high - and moderate-F & V consumers .


This trial was registered at www.controlled-trials.com as ISRCTN47748735 .


Nearly 2 % of youths suffer from chronic migraine or chronic tension-type headache ( CTTH ) .


A contributing factor in approximately 20 % -50 % of these youths is medication overuse , which involves taking analgesics three or more times per week for three months .


The objective of this study was to test motivational interviewing ( MI ) as an approach to promote adherence to recommendations regarding not only analgesic overuse but also other aspects of treatment plans .


A randomized controlled trial was conducted comparing the experimental condition ( standard of care clinic-based treatment with supplemental MI phone calls ; N = 24 ) to a control condition ( standard of care clinic-based treatment without these supplemental MI phone calls ; N = 23 ) .


Four months after enrollment , a research assistant who was blinded to study condition telephoned adolescents inquiring about headache frequency , headache severity , and disability .


Headache frequency was lower in the experimental condition versus control condition for those with relatively lower initial levels of headache frequency .


In contrast , we did not find greater improvement in headache severity and disability for the experimental condition relative to the control condition .


Our findings provided some preliminary , albeit limited , support for MI as an approach to improve outcomes for adolescent medication-overuse headache ( MOH ) .


Single-injection transversus abdominis plane ( TAP ) block provides postoperative analgesia and decreases supplemental analgesic requirements .


However , there is currently no evidence from randomized , controlled studies investigating the possible benefits of continuous TAP blocks .


Therefore , the aim of this randomized , triple-masked , placebo-controlled study was to determine if benefits are afforded by adding a multiple-day , ambulatory , continuous ropivacaine TAP block to a single-injection block following hernia surgery .


Preoperatively , subjects undergoing unilateral inguinal ( N = 19 ) or peri-umbilical ( N = 1 ) hernia surgery received unilateral or bilateral TAP perineural catheter ( s ) , respectively .


All received a ropivacaine 0.5 % ( 20 mL ) bolus via the catheter ( s ) .


Subjects were randomized to either postoperative perineural ropivacaine 0.2 % or normal saline using portable infusion pump ( s ) .


Subjects were discharged home where the catheter ( s ) were removed the evening of postoperative day ( POD ) 2 .


Subjects were contacted on POD 0-3 .


The primary endpoint was average pain with movement ( scale : 0-10 ) queried on POD 1 .


Twenty subjects of a target 30 were enrolled due to the primary surgeon 's unanticipated departure from the institution .


Average pain queried on POD 1 for subjects receiving ropivacaine ( N = 10 ) was a mean ( standard deviation ) of 3.0 ( 2.6 ) vs 2.8 ( 2.7 ) for subjects receiving saline ( N = 10 ; 95 % confidence interval difference in means -2.9 to 3.4 ; P = 0.86 ) .


There were no statistically significant differences detected between treatment groups in any secondary endpoint .


The results of this study do not support adding an ambulatory , continuous ropivacaine infusion to a single-injection ropivacaine TAP block for hernia surgery .


However , the present investigation was underpowered , and further study is warranted .


To determine whether prescription opioid use is associated with higher dementia risk or greater cognitive decline .


Prospective cohort study .


Group Health , an integrated healthcare delivery system .


Community-dwelling individuals aged 65 and older without dementia with at least 10 years of Group Health enrollment at baseline ( N = 3,434 ; median age 74 ) .


The Cognitive Abilities Screening Instrument ( CASI ) was administered every 2 years .


Low scores triggered detailed evaluation , and a multidisciplinary committee assigned dementia diagnoses .


From computerized pharmacy data , cumulative opioid exposure was defined as total standardized doses ( TSDs ) dispensed over 10 years ( excluding the most recent year because of possible prodromal symptoms ) .


For comparison , use of nonsteroidal anti-inflammatory drugs ( NSAIDs ) , characterized similarly , was examined .


Dementia risk was analyzed using Cox proportional hazards models and CASI trajectory using linear regression models and generalized estimating equations .


Seven hundred ninety-seven participants ( 23 % ) developed dementia over a mean follow-up of 7.3 years ; 637 ( 19 % ) had possible or probable Alzheimer 's disease .


For cumulative opioid use , the hazard ratios ( HRs ) for dementia were 1.06 ( 95 % confidence interval ( CI ) = 0.88-1 .26 ) for 11 to 30 TSDs , 0.88 ( 95 % CI = 0.70-1 .09 ) for 31 to 90 TSDs , and 1.29 ( 95 % CI = 1.02-1 .62 ) for 91 or more TSDs , versus 0 to 10 TSDs .


A similar pattern was seen for NSAID use .


Heavier opioid use was not associated with more-rapid cognitive decline .


People with the heaviest opioid or NSAID use had slightly higher dementia risk than people with little or no use .


These results may reflect an effect of chronic pain on cognition or residual confounding .


Although opioids have other risks , little evidence of long-term cognitive harm specific to opioids was found .


Repetitive transcranial magnetic stimulation ( rTMS ) of the dorsolateral-prefrontal cortex ( DLPFC ) with conventional figure-of-8 ( = butterfly ) coils has been used as an antidepressant therapeutic tool for almost twenty years .


Very recently , an innovative rTMS coil , the so-called double cone coil ( DC ) , was introduced allowing the modulation of the anterior cingulate cortex ( AC ) .


We investigated safety and therapeutic effectiveness of this stimulation in a naturalistic clinical setting .


Forty-five patients suffering a moderate to severe depressive episode were randomized to receive 15 sessions of either conventional rTMS of the left DLPFC ( `` butterfly-rTMS '' ; 10Hz ; 2000 stimuli/day , RMT 110 % ) , mediofrontal double cone coil stimulation of the anterior cingulate cortex ( `` ACDC-rTMS '' with equal parameters ) , or sham-stimulation .


The primary outcome was the change in the 21-items Hamilton Rating Scale for Depression ( HAMD ) from baseline to the end of treatment .


Secondary outcome measures were changes over the course of the trial regarding the HAMD , the Beck Depression Inventory ( BDI ) , the Clinical Global Impression ( CGI ) and the Global Assessment of Functioning ( GAF ) scales .


There was a significant grouptime interaction effect regarding the primary outcome ( F = 3.269 ; df = 2,37 ; P = 0.049 ) .


Post-hoc t-testing revealed a significant effect for the comparison ACDC vs. butterfly at week 3/end of treatment ( T = 2.646 ; df = 26 ; P = 0.014 ) .


No severe adverse events occurred during the study .


ACDC-stimulation was well tolerated by the majority of patients similar like butterfly-rTMS and sham-stimulation .


This pilot study demonstrated the feasibility of ACDC-rTMS-stimulation as an add-on-treatment for depression .


Its clinical effects warrant further investigation in the future .


The duration of the spinal block is a concern for anesthetists .


Low dose intrathecal lidocaine has vasodilatory effects and increases the local anesthetic clearance from the intrathecal space .


The aim was to investigate whether this effect of lidocaine can be used to increase the resolution of levobupivacaine spinal anesthesia .


After obtaining ethical approval and informed patient consent , 40 patients underwent transurethral prostate resection were studied .


Patients were randomized into two groups and patients received either levobupivacaine 6.75 mg + 0.3 mL 2 % lidocaine ( Group L ) or levobupivacaine 6.75 mg + saline ( Group C ) .


The main outcome measures were the difference between groups regarding the duration of the spinal block and PACU stay .


Secondary outcome measures were the difference between groups in onset and resolution of the spinal block , adverse events and treatments were also investigated .


Spinal block resolved faster in Group L than Group C ; 162.4339.4 min vs 219.73 37.3 min ( p = 0.000 ) .


PACU time was shorter in Group L ( 109 49.9 min in Group L vs 148 56.8 min in Group C ) ( p = 0.036 ) .


There was no difference between groups with respect to the incidence of adverse events and treatments .


Groups were also similar regarding complications .


PDPH and TNS were not observed in any group .


Addition of low dose lidocaine to hyperbaric levobupivacaine reduces the duration of the intrathecal block provided by hyperbaric levobupivacaine .


This technique can be used to reduce the spinal block duration for relatively short procedures like TUR-P .


Brain injury affects neurologic function and quality of life in survivors after cardiac arrest .