Antiplatelet therapy duration following bare metal or drug-eluting coronary stents: the dual antiplatelet therapy randomized clinical trial

IMPORTANCE Despite antirestenotic efficacy of coronary drug-eluting stents (DES) compared with bare metal stents (BMS), the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Although dual antiplatelet therapy (DAPT) beyond 1 year provides ischemic event protection after DES, ischemic event risk is perceived to be less after BMS, and the appropriate duration of DAPT after BMS is unknown. OBJECTIVE To compare (1) rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE; composite of death, myocardial infarction, or stroke) after 30 vs 12 months of thienopyridine in patients treated with BMS taking aspirin and (2) treatment duration effect within the combined cohorts of randomized patients treated with DES or BMS as prespecified secondary analyses. DESIGN, SETTING, AND PARTICIPANTS International, multicenter, randomized, double-blinded, placebo-controlled trial comparing extended (30-months) thienopyridine vs placebo in patients taking aspirin who completed 12 months of DAPT without bleeding or ischemic events after receiving stents. The study was initiated in August 2009 with the last follow-up visit in May 2014. INTERVENTIONS Continued thienopyridine or placebo at months 12 through 30 after stent placement, in 11,648 randomized patients treated with aspirin, of whom 1687 received BMS and 9961 DES. MAIN OUTCOMES AND MEASURES Stent thrombosis, MACCE, and moderate or severe bleeding. RESULTS Among 1687 patients treated with BMS who were randomized to continued thienopyridine vs placebo, rates of stent thrombosis were 0.5% vs 1.11% (n = 4 vs 9; hazard ratio [HR], 0.49; 95% CI, 0.15-1.64; P = .24), rates of MACCE were 4.04% vs 4.69% (n = 33 vs 38; HR, 0.92; 95% CI, 0.57-1.47; P = .72), and rates of moderate/severe bleeding were 2.03% vs 0.90% (n = 16 vs 7; P = .07), respectively. Among all 11,648 randomized patients (both BMS and DES), stent thrombosis rates were 0.41% vs 1.32% (n = 23 vs 74; HR, 0.31; 95% CI, 0.19-0.50; P < .001), rates of MACCE were 4.29% vs 5.74% (n = 244 vs 323; HR, 0.73; 95% CI, 0.62-0.87; P < .001), and rates of moderate/severe bleeding were 2.45% vs 1.47% (n = 135 vs 80; P < .001). CONCLUSIONS AND RELEVANCE Among patients undergoing coronary stent placement with BMS and who tolerated 12 months of thienopyridine, continuing thienopyridine for an additional 18 months compared with placebo did not result in statistically significant differences in rates of stent thrombosis, MACCE, or moderate or severe bleeding. However, the BMS subset may have been underpowered to identify such differences, and further trials are suggested. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00977938.

Length of the Mitral Isthmus But Not Anatomical Location of Ablation Line Predicts Bidirectional Mitral Isthmus Block in Patients Undergoing Catheter Ablation of Persistent Atrial Fibrillation: A Randomized Controlled Trial

INTRODUCTION Mitral isthmus (MI) ablation is an effective option in patients undergoing ablation for persistent atrial fibrillation (AF). Achieving bidirectional conduction block across the MI is challenging, and predictors of MI ablation success remain incompletely understood. We sought to determine the impact of anatomical location of the ablation line on the efficacy of MI ablation. METHODS AND RESULTS A total of 40 consecutive patients (87% male; 54 ± 10 years) undergoing stepwise AF ablation were included. MI ablation was performed in sinus rhythm. MI ablation was performed from the left inferior PV to either the posterior (group 1) or the anterolateral (group 2) mitral annulus depending on randomization. The length of the MI line (measured with the 3D mapping system) and the amplitude of the EGMs at 3 positions on the MI were measured in each patient. MI block was achieved in 14/19 (74%) patients in group 1 and 15/21 (71%) patients in group 2 (P = NS). Total MI radiofrequency time (18 ± 7 min vs. 17 ± 8 min; P = NS) was similar between groups. Patients with incomplete MI block had a longer MI length (34 ± 6 mm vs. 24 ± 5 mm; P < 0.001), a higher bipolar voltage along the MI (1.75 ± 0.74 mV vs. 1.05 ± 0.69 mV; P < 0.01), and a longer history of continuous AF (19 ± 17 months vs. 10 ± 10 months; P < 0.05). In multivariate analysis, decreased length of the MI was an independent predictor of successful MI block (OR 1.5; 95% CI 1.1-2.1; P < 0.05). CONCLUSIONS Increased length but not anatomical location of the MI predicts failure to achieve bidirectional MI block during ablation of persistent AF.

Improving Pediatric Basic Life Support Performance Through Blended Learning With Web-Based Virtual Patients: Randomized Controlled Trial

BACKGROUND E-learning and blended learning approaches gain more and more popularity in emergency medicine curricula. So far, little data is available on the impact of such approaches on procedural learning and skill acquisition and their comparison with traditional approaches. OBJECTIVE This study investigated the impact of a blended learning approach, including Web-based virtual patients (VPs) and standard pediatric basic life support (PBLS) training, on procedural knowledge, objective performance, and self-assessment. METHODS A total of 57 medical students were randomly assigned to an intervention group (n=30) and a control group (n=27). Both groups received paper handouts in preparation of simulation-based PBLS training. The intervention group additionally completed two Web-based VPs with embedded video clips. Measurements were taken at randomization (t0), after the preparation period (t1), and after hands-on training (t2). Clinical decision-making skills and procedural knowledge were assessed at t0 and t1. PBLS performance was scored regarding adherence to the correct algorithm, conformance to temporal demands, and the quality of procedural steps at t1 and t2. Participants' self-assessments were recorded in all three measurements. RESULTS Procedural knowledge of the intervention group was significantly superior to that of the control group at t1. At t2, the intervention group showed significantly better adherence to the algorithm and temporal demands, and better procedural quality of PBLS in objective measures than did the control group. These aspects differed between the groups even at t1 (after VPs, prior to practical training). Self-assessments differed significantly only at t1 in favor of the intervention group. CONCLUSIONS Training with VPs combined with hands-on training improves PBLS performance as judged by objective measures.

An Assessment of the Risk of Bias in Randomized Controlled Trial Reports Published in Prosthodontic and Implant Dentistry Journals

PURPOSE The objective of this study was to assess the risk of bias of randomized controlled trials (RCTs) published in prosthodontic and implant dentistry journals. MATERIALS AND METHODS The last 30 issues of 9 journals in the field of prosthodontic and implant dentistry (Clinical Implant Dentistry and Related Research, Clinical Oral Implants Research, Implant Dentistry, International Journal of Oral & Maxillofacial Implants, International Journal of Periodontics and Restorative Dentistry, International Journal of Prosthodontics, Journal of Dentistry, Journal of Oral Rehabilitation, and Journal of Prosthetic Dentistry) were hand-searched for RCTs. Risk of bias was assessed using the Cochrane Collaboration's risk of bias tool and analyzed descriptively. RESULTS From the 3,667 articles screened, a total of 147 RCTs were identified and included. The number of published RCTs increased with time. The overall distribution of a high risk of bias assessment varied across the domains of the Cochrane risk of bias tool: 8% for random sequence generation, 18% for allocation concealment, 41% for masking, 47% for blinding of outcome assessment, 7% for incomplete outcome data, 12% for selective reporting, and 41% for other biases. CONCLUSION The distribution of high risk of bias for RCTs published in the selected prosthodontic and implant dentistry journals varied among journals and ranged from 8% to 47%, which can be considered as substantial.

A randomized controlled trial of the efficacy of autologous platelet therapy for the treatment of osteoarthritis in dogs.

OBJECTIVE To determine efficacy of a single intra-articular injection of an autologous platelet concentrate for treatment of osteoarthritis in dogs. DESIGN Randomized, controlled, 2-center clinical trial. ANIMALS 20 client-owned dogs with osteoarthritis involving a single joint. PROCEDURES Dogs were randomly assigned to a treatment or control group. In all dogs, severity of lameness and pain was scored by owners with the Hudson visual analog scale and the University of Pennsylvania Canine Brief Pain Inventory, respectively, and peak vertical force (PVF) was determined with a force platform. Dogs in the treatment group were then sedated, and a blood sample (55 mL) was obtained. Platelets were recovered by means of a point-of-use filter and injected intra-articularly within 30 minutes. Control dogs were sedated and given an intra-articular injection of saline (0.9% NaCl) solution. Assessments were repeated 12 weeks after injection of platelets or saline solution. RESULTS Dogs weighed between 18.3 and 63.9 kg (40.3 and 140.6 lb) and ranged from 1.5 to 8 years old. For control dogs, lameness scores, pain scores, and PVF at week 12 were not significantly different from pretreatment values. In contrast, for dogs that received platelet injections, lameness scores (55% decrease in median score), pain scores (53% decrease in median score), and PVF (12% increase in mean PVF) were significantly improved after 12 weeks, compared with pretreatment values. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that a single intra-articular injection of autologous platelets resulted in significant improvements at 12 weeks in dogs with osteoarthritis involving a single joint.

Involuntary reflexive pelvic floor muscle training in addition to standard training versus standard training alone for women with stress urinary incontinence: study protocol for a randomized controlled trial

BACKGROUND Pelvic floor muscle training is effective and recommended as first-line therapy for female patients with stress urinary incontinence. However, standard pelvic floor physiotherapy concentrates on voluntary contractions even though the situations provoking stress urinary incontinence (for example, sneezing, coughing, running) require involuntary fast reflexive pelvic floor muscle contractions. Training procedures for involuntary reflexive muscle contractions are widely implemented in rehabilitation and sports but not yet in pelvic floor rehabilitation. Therefore, the research group developed a training protocol including standard physiotherapy and in addition focused on involuntary reflexive pelvic floor muscle contractions. METHODS/DESIGN The aim of the planned study is to compare this newly developed physiotherapy program (experimental group) and the standard physiotherapy program (control group) regarding their effect on stress urinary incontinence. The working hypothesis is that the experimental group focusing on involuntary reflexive muscle contractions will have a higher improvement of continence measured by the International Consultation on Incontinence Modular Questionnaire Urinary Incontinence (short form), and - regarding secondary and tertiary outcomes - higher pelvic floor muscle activity during stress urinary incontinence provoking activities, better pad-test results, higher quality of life scores (International Consultation on Incontinence Modular Questionnaire) and higher intravaginal muscle strength (digitally tested) from before to after the intervention phase. This study is designed as a prospective, triple-blinded (participant, investigator, outcome assessor), randomized controlled trial with two physiotherapy intervention groups with a 6-month follow-up including 48 stress urinary incontinent women per group. For both groups the intervention will last 16 weeks and will include 9 personal physiotherapy consultations and 78 short home training sessions (weeks 1-5 3x/week, 3x/day; weeks 6-16 3x/week, 1x/day). Thereafter both groups will continue with home training sessions (3x/week, 1x/day) until the 6-month follow-up. To compare the primary outcome, International Consultation on Incontinence Modular Questionnaire (short form) between and within the two groups at ten time points (before intervention, physiotherapy sessions 2-9, after intervention) ANOVA models for longitudinal data will be applied. DISCUSSION This study closes a gap, as involuntary reflexive pelvic floor muscle training has not yet been included in stress urinary incontinence physiotherapy, and if shown successful could be implemented in clinical practice immediately. TRIAL REGISTRATION NCT02318251 ; 4 December 2014 First patient randomized: 11 March 2015.

The ROAM/EORTC-1308 trial: Radiation versus Observation following surgical resection of Atypical Meningioma: study protocol for a randomised controlled trial.

BACKGROUND Atypical meningiomas are an intermediate grade brain tumour with a recurrence rate of 39-58 %. It is not known whether early adjuvant radiotherapy reduces the risk of tumour recurrence and whether the potential side-effects are justified. An alternative management strategy is to perform active monitoring with magnetic resonance imaging (MRI) and to treat at recurrence. There are no randomised controlled trials comparing these two approaches. METHODS/DESIGN A total of 190 patients will be recruited from neurosurgical/neuro-oncology centres across the United Kingdom, Ireland and mainland Europe. Adult patients undergoing gross total resection of intracranial atypical meningioma are eligible. Patients with multiple meningioma, optic nerve sheath meningioma, previous intracranial tumour, previous cranial radiotherapy and neurofibromatosis will be excluded. Informed consent will be obtained from patients. This is a two-stage trial (both stages will run in parallel): Stage 1 (qualitative study) is designed to maximise patient and clinician acceptability, thereby optimising recruitment and retention. Patients wishing to continue will proceed to randomisation. Stage 2 (randomisation) patients will be randomised to receive either early adjuvant radiotherapy for 6 weeks (60 Gy in 30 fractions) or active monitoring. The primary outcome measure is time to MRI evidence of tumour recurrence (progression-free survival (PFS)). Secondary outcome measures include assessing the toxicity of the radiotherapy, the quality of life, neurocognitive function, time to second line treatment, time to death (overall survival (OS)) and incremental cost per quality-adjusted life year (QALY) gained. DISCUSSION ROAM/EORTC-1308 is the first multi-centre randomised controlled trial designed to determine whether early adjuvant radiotherapy reduces the risk of tumour recurrence following complete surgical resection of atypical meningioma. The results of this study will be used to inform current neurosurgery and neuro-oncology practice worldwide. TRIAL REGISTRATION ISRCTN71502099 on 19 May 2014.

Sugar- and artificially sweetened beverages and intrahepatic fat: A randomized controlled trial.

OBJECTIVE To test the hypothesis that substituting artificially sweetened beverages (ASB) for sugar-sweetened beverages (SSB) decreases intrahepatocellular lipid concentrations (IHCL) in overweight subjects with high SSB consumption. METHODS About 31 healthy subjects with BMI greater than 25 kg/m(2) and a daily consumption of at least 660 ml SSB were randomized to a 12-week intervention in which they replaced SSBs with ASBs. Their IHCL (magnetic resonance spectroscopy), visceral adipose tissue volume (VAT; magnetic resonance imaging), food intake (2-day food records), and fasting blood concentrations of metabolic markers were measured after a 4-week run-in period and after a 12-week period with ASB or control (CTRL). RESULTS About 27 subjects completed the study. IHCL was reduced to 74% of the initial values with ASB (N = 14; P < 0.05) but did not change with CTRL. The decrease in IHCL attained with ASB was more important in subjects with IHCL greater than 60 mmol/l than in subjects with low IHCL. ALT decreased significantly with SSB only in subjects with IHCL greater than 60 mmol/l. There was otherwise no significant effect of ASB on body weight, VAT, or metabolic markers. CONCLUSIONS In subjects with overweight or obesity and a high SSB intake, replacing SSB with ASB decreased intrahepatic fat over a 12-week period.

Cognitively engaging chronic physical activity, but not aerobic exercise, affects executive functions in primary school children: A group-randomized controlled trial

Although the positive effects of different kinds of physical activity (PA) on cognitive functioning have already been demonstrated in a variety of studies, the role of cognitive engagement in promoting children’s executive functions is still unclear. The aim of the present study was therefore to investigate the effects of two qualitatively different chronic PA interventions on executive functions in primary school children. 181 children aged between 10 and 12 years were assigned to either a 6-week physical education program with a high level of physical exertion and high cognitive engagement (team games), a physical education program with high physical exertion but low cognitive engagement (aerobic exercise), or to a physical education program with both low physical exertion and low cognitive engagement (control condition). Executive functions (updating, inhibition, shifting) and aerobic fitness (multistage 20-meter shuttle run test) were measured before and after the respective condition. Results revealed that both interventions (team games and aerobic exercise) have a positive impact on children’s aerobic fitness (4-5 % increase in estimated VO2max). Importantly, an improvement in shifting performance was found only in the team games and not in the aerobic exercise or control condition. Thus, the inclusion of cognitive engagement in PA seems to be the most promising type of chronic intervention to enhance executive functions in children, providing further evidence for the importance of the qualitative aspects of PA.

The Process-Outcome Mindfulness Effects in Trainees (PrOMET) study: protocol of a pragmatic randomized controlled trial

Background Mindfulness has its origins in an Eastern Buddhist tradition that is over 2500 years old and can be defined as a specific form of attention that is non-judgmental, purposeful, and focused on the present moment. It has been well established in cognitive-behavior therapy in the last decades, while it has been investigated in manualized group settings such as mindfulness-based stress reduction and mindfulness-based cognitive therapy. However, there is scarce research evidence on the effects of mindfulness as a treatment element in individual therapy. Consequently, the demand to investigate mindfulness under effectiveness conditions in trainee therapists has been highlighted. Methods/Design To fill in this research gap, we designed the PrOMET Study. In our study, we will investigate the effects of brief, audiotape-presented, session-introducing interventions with mindfulness elements conducted by trainee therapists and their patients at the beginning of individual therapy sessions in a prospective, randomized, controlled design under naturalistic conditions with a total of 30 trainee therapists and 150 patients with depression and anxiety disorders in a large outpatient training center. We hypothesize that the primary outcomes of the session-introducing intervention with mindfulness elements will be positive effects on therapeutic alliance (Working Alliance Inventory) and general clinical symptomatology (Brief Symptom Checklist) in contrast to the session-introducing progressive muscle relaxation and treatment-as-usual control conditions. Treatment duration is 25 therapy sessions. Therapeutic alliance will be assessed on a session-to-session basis. Clinical symptomatology will be assessed at baseline, session 5, 15 and 25. We will conduct multilevel modeling to address the nested data structure. The secondary outcome measures include depression, anxiety, interpersonal functioning, mindful awareness, and mindfulness during the sessions. Discussion The study results could provide important practical implications because they could inform ideas on how to improve the clinical training of psychotherapists that could be implemented very easily; this is because there is no need for complex infrastructures or additional time concerning these brief session-introducing interventions with mindfulness elements that are directly implemented in the treatment sessions.

Effects of a Transdiagnostic Internet Intervention («velibra») for Anxiety Disorders in Primary Care: Results of a Randomized Controlled Trial

Internet-based cognitive behavioral self-help treatment (ICBT) for anxiety disorders has shown promising results in several trials, but there is yet a lack of studies of ICBT in „real world” primary care settings. In this randomized controlled trial we recruited participants through general practitioners. The aim of the study was to examine whether treatment-as-usual (TAU) in primary care settings plus ICBT is superior to TAU alone in reducing anxiety symptoms and other outcome measures among individuals meeting diagnostic criteria of a least one of three anxiety disorders (social anxiety disorder, panic disorder with or without agoraphobia, generalized anxiety disorder). 150 adults fulfilling diagnostic criteria for a least one of the anxiety disorders according to a diagnostic interview are randomly assigned to one of the two conditions: TAU plus ICBT versus TAU. Randomization is stratified by primary disorder, medication (yes/no) and concurrent psychotherapy. ICBT consists of a transdiagnostic and tailored Internet-based self-help program for several anxiety disorders which also includes cognitive bias modification for interpretation (CBM-I). Primary outcomes are symptoms of disorder-specific anxiety measures and diagnostic status after the intervention (9 weeks). Secondary outcomes include primary outcomes at 3-month follow-up and secondary measures such as general symptomatology, depression, quality of life, adherence to ICBT and satisfaction with ICBT. The study is currently being completed. Primary results along with results for specific subgroups (e.g. primary diagnosis, concurrent medication and/or psychotherapy) will be presented and discussed.

A sorrow shared is a sorrow halved? Internet-based group therapy versus individual therapy for social anxiety disorder: A randomized controlled trial

Purpose: Social anxiety disorder is one of the most researched conditions in the field of Internet-based self-help. Various studies have shown that cognitive-behavioral treatments can be efficacious to reduce social phobic symptoms. Most of the interventions tested include some form of support, whereas the efficacy of a web-based group format has yet to be investigated. The present study aims at investigating the possible added value of therapist-guided group support in an Internet-based guided self-help treatment for SAD. Methods: A total of 150 adults with a diagnosis of SAD are randomly assigned to either a wait-list control group or one of two active treatment conditions. Participants in the two active conditions use the same Internet-based self-help program, either with individual guidance by a therapist or with the support of a therapist-guided group of 6 individuals. In the group condition, participants communicate with each other via an integrated, protected discussion forum. The primary outcome variables are symptoms of SAD and diagnostic status immediately after the intervention (12 weeks) and at 6-month follow-up. Secondary endpoints are general symptomatology, depression, quality of life and adherence to treatment. Furthermore, process variables such as group processes and the working alliance are studied. Results: Results are currently being analyzed. Results at post-treatment will be presented and discussed. Potential moderating and mediating variables of treatment success will be addressed. Conclusion: The results of this study should indicate whether therapist-guided group support could enhance the efficacy of an internet based self-help treatment for SAD. This novel treatment format, if shown efficacious, could represent a cost-effective option and could be further modified to treat other conditions.

Feasibility study of a single-blind randomised controlled trial of an occupational therapy intervention.

BACKGROUND Several factors facilitate or hinder efficacy research in occupational therapy. Strategies are needed, therefore, to support the successful implementation of trials. AIM To assess the feasibility of conducting a randomised controlled trial (RCT). The main feasibility objectives of this study were to assess the process, resources, management, and scientific basis of a trial RCT. MATERIAL AND METHODS A total of 10 occupational therapists, between the ages of 30 and 55 (M 43.4; SD 8.3) with seven to 26 years' (M 14.3; SD 6.1) experience, participated in this study. Qualitative data collected included minutes of meetings, reports, and field notes. The data were analysed based on the principles of content analysis, using feasibility objectives as the main categories. RESULTS Data analysis revealed strengths in relation to retention and inclusion criteria of participants, the study protocol, study organisation, and the competence of researchers. Weaknesses were found related to recruitment, randomisation, data collection, time for training and communication, commitment, and design. CONCLUSION The findings indicated that there are several factors which had a considerable impact on the implementation of an RCT in practice. However, it was useful to assess methods and procedures of the trial RCT as a basis to refine research plans.