A randomized crossover clinical study showing that methylphenidate-SODAS improves attention-deficit/hyperactivity disorder symptoms in adolescents with substance use disorder

Our objective was to evaluate the effectiveness of a long-acting formulation of methylphenidate (MPH-SODAS) on attention-deficit/hyperactivity disorder (ADHD) symptoms in an outpatient sample of adolescents with ADHD and substance use disorders (SUD). Secondary goals were to evaluate the tolerability and impact on drug use of MPH-SODAS. This was a 6-week, single-blind, placebo-controlled crossover study assessing efficacy of escalated doses of MPH-SODAS on ADHD symptoms in 16 adolescents with ADHD/SUD. Participants were randomly allocated to either group A (weeks 1-3 on MPH-SODAS, weeks 4-6 on placebo) or group B (reverse order). The primary outcome measures were the Swanson, Nolan and Pelham Scale, version IV (SNAP-IV) and the Clinical Global Impression Scale (CGI). We also evaluated the adverse effects of MPH-SODAS using the Barkley Side Effect Rating Scale and subject reports of drug use during the study. The sample consisted of marijuana (N = 16; 100%) and cocaine users (N = 7; 43.8%). Subjects had a significantly greater reduction in SNAP-IV and CGI scores (P < 0.001 for all analyses) during MPH-SODAS treatment compared to placebo. No significant effects for period or sequence were found in analyses with the SNAP-IV and CGI scales. There was no significant effect on drug use. MPH-SODAS was well tolerated but was associated with more severe appetite reduction than placebo (P < 0.001). MPH-SODAS was more effective than placebo in reducing ADHD symptoms in a non-abstinent outpatient sample of adolescents with comorbid SUD. Randomized clinical trials, with larger samples and SUD intervention, are recommended.

Contact force-guided catheter ablation for the treatment of atrial fibrillation: a meta-analysis of randomized, controlled trials

Contact force (CF) sensing technology allows real-time monitoring during catheter ablation for atrial fibrillation (AF). However, the effect of CF sensing technology on procedural parameters and clinical outcomes still needs clarification. Because of the inconsistent results thus far in this area, we performed a meta-analysis to determine whether CF sensing technology can improve procedural parameters and clinical outcomes for the treatment of AF. Studies examining the benefits of CF sensing technology were identified in English-language articles by searching the MEDLINE, Web of Science, and Cochrane Library databases (inception to May 2015). Ten randomized, controlled trials involving 1834 patients (1263 males, 571 females) were included in the meta-analysis (681 in the CF group, 1153 in the control group). Overall, the ablation time was significantly decreased by 7.34 min (95%CI=-12.21 to -2.46; P=0.003, Z test) in the CF group compared with the control group. CF sensing technology was associated with significantly improved freedom from AF after 12 months (OR=1.55, 95%CI=1.20 to 1.99; P=0.0007) and complications were significantly lower in the CF group than in the control group (OR=0.50, 95%CI=0.29 to 0.87; P=0.01). However, fluoroscopy time analysis showed no significantly decreased trend associated with CF-guided catheter ablation (weighted mean difference: -2.59; 95%CI=-9.06 to 3.88; P=0.43). The present meta-analysis shows improvement in ablation time and freedom from AF after 12 months in AF patients treated with CF-guided catheter ablation. However, CF-guided catheter ablation does not decrease fluoroscopy time.

Randomized controlled trials of serotonin-norepinephrine reuptake inhibitor in treating major depressive disorder in children and adolescents: a meta-analysis of efficacy and acceptability

New generation antidepressant therapies, including serotonin-norepinephrine reuptake inhibitor (SNRIs), were introduced in the late 1980s; however, few comprehensive studies have compared the benefits and risks of various contemporary treatments for major depressive disorder (MDD) in young patients. A comprehensive literature search of PubMed, Cochrane, Embase, Web of Science, and PsycINFO databases was conducted from 1970 to January 2015. Only clinical trials that randomly assigned one SNRI or placebo to patients aged 7 to 18 years who met the diagnostic criteria for major depressive disorder were included. Treatment success, dropout rate, and suicidal ideation/attempt outcomes were measured. Primary efficacy was determined by pooling the risk ratios (RRs) of treatment response and remission. Acceptability was determined by pooling the RRs of dropouts for all reasons and for adverse effects as well as suicide-risk outcomes. Five trials with a total of 973 patients were included. SNRIs were not significantly more effective than placebo for treatment response but were for remission. The comparison of patients taking SNRIs that dropped out for all reasons and those taking placebo did not reach statistical significance. Significantly more patients taking SNRIs dropped out for adverse effects than those taking placebo. No significant difference was found in suicide-related risk outcomes. SNRI therapy does not display a superior efficacy and is not better tolerated compared to placebo in these young patients. However, duloxetine has a potential beneficial effect for depression in young populations, showing a need for further research.

Ximelagatran versus warfarin for prophylaxis of venous thromboembolism in major orthopedic surgery: systematic review of randomized controlled trials

INTRODUÇÃO: O ximelagatrano foi recentemente estudada para profilaxia do tromboembolismo venoso (TEV). OBJETIVO: Avaliar se o ximelagatrano comparado com a varfarina melhora a profilaxia do TEV em pacientes submetidos à cirurgia ortopédica do joelho. FONTE DE DADOS: Estudos randomizados identificados por pesquisa eletrônica na literatura médica, até 2006, cujos dados foram compilados no programa Review Manager, versão 4.2.5. RESULTADOS: Foram incluídos três estudos randomizados bem conduzidos envolvendo 4.914 participantes. Foram definidos dois sub-grupos com dosagens diferentes de ximelagatrano (24 mg and 36 mg, duas vezes ao dia). O tratamento com ximelagatrano mostrou freqüência significantemente menor de TEV que o tratamento com varfarina, mas somente na dosagem de 36-mg [risco relativo, RR 0.72 ([intervalo de confiança, IC, 95% 0.64, 0.81), p < 0.00001]. A freqüência de TEV no sub-grupo de 24-mg foi similar a da varfarina [RR 0.86 (IC 95% 0.73, 1.01), p = 0.06]. Para TEV maior, embolia pulmonar, sangramento e sangramento maior não houve diferença entre varfarina e a ximelagatrano. Ao final do tratamento, a elevação da alanino-aminotransferase (ALT) foi menos freqüente no sub-grupo de 24 mg de ximelagatrano que no grupo da varfarina [RR 0.33 (IC 95% 0.12, 0.91) p = 0.03], mas no período de acompanhamento essa elevação foi maior com 36 mg de ximelagatrano [RR 6.97 (IC 95% 1.26, 38.50) p = 0.03]. CONCLUSÃO: O ximelagatrano foi mais efetivo que a varfarina quando usado em dosagens maiores (36 mg, 2 vezes ao dia), mas às expensas de aumento de enzimas hepáticas no período de acompanhamento.

A quantitative and qualitative evaluation of reports of clinical trials published in six Brazilian dental journals indexed in the Scientific Electronic Library Online (SciELO)

Introduction: Open access publishing is becoming increasingly popular within the biomedical sciences. SciELO, the Scientific Electronic Library Online, is a digital library covering a selected collection of Brazilian scientific journals many of which provide open access to full-text articles. This library includes a number of dental journals some of which may include reports of clinical trials in English, Portuguese and/or Spanish. Thus, SciELO could play an important role as a source of evidence for dental healthcare interventions especially if it yields a sizeable number of high quality reports. Objective: The aim of this study was to identify reports of clinical trials by handsearching of dental journals that are accessible through SciELO, and to assess the overall quality of these reports. Material and methods: Electronic versions of six Brazilian dental Journals indexed in SciELO were handsearched at www.scielo.br in September 2008. Reports of clinical trials were identified and classified as controlled clinical trials (CCTs - prospective, experimental studies comparing 2 or more healthcare interventions in human beings) or randomized controlled trials (RCTs - a random allocation method is clearly reported), according to Cochrane eligibility criteria. Criteria to assess methodological quality included: method of randomization, concealment of treatment allocation, blinded outcome assessment, handling of withdrawals and losses and whether an intention-to-treat analysis had been carried out. Results: The search retrieved 33 CCTs and 43 RCTs. A majority of the reports provided no description of either the method of randomization (75.3%) or concealment of the allocation sequence (84.2%). Participants and outcome assessors were reported as blinded in only 31.2% of the reports. Withdrawals and losses were only clearly described in 6.5% of the reports and none mentioned an intention-to-treat analysis or any similar procedure. Conclusions: The results of this study indicate that a substantial number of reports of trials and systematic reviews are available in the dental journals listed in SciELO, and that these could provide valuable evidence for clinical decision making. However, it is clear that the quality of a number of these reports is of some concern and that improvement in the conduct and reporting of these trials could be achieved if authors adhered to internationally accepted guidelines, e. g. the CONSORT statement.

Effects of motor intervention in elderly patients with dementia: An analysis of randomized controlled trials

The objective of this study was to analyze randomized controlled trials published in the last decades involving motor intervention as a treatment for dementia, based on Physiotherapy Evidence Database (PEDro) criteria. A database search was performed using the following keywords: randomized controlled trial, dementia, physiotherapy, physical therapy, occupational therapy, physical education, motor approach, exercise, and physical activity. Ten trials were found: 4 related to physiotherapy, 3 to occupational therapy, 1 to physical education, and 2 to interdisciplinary motor intervention. The efficacy of motor intervention was confirmed in the following variables: psychosocial function, physical health and function, affective status, and caregiver's distress (P < .05). Results related to mobility were not significant (P > .05). Behavior, cognitive performance, activities of daily living, and risk of falls were not similar among the articles. From a total score of 10 points, with excellence characterized as the highest punctuation, the articles were classified between 3 and 7 by PEDro. Motor intervention was shown to be an alternative for minimizing physical and mental decline. PEDro has been confirmed as a very reliable tool to analyze studies and as an evaluation criteria, both qualitative and quantitative, allowing the establishment of motor intervention strategies for the treatment of patients with dementia. © 2007 Lippincott Williams & Wilkins, Inc.

Systematic review of randomized controlled trials of new anticoagulants for venous thromboembolism prophylaxis in major orthopedic surgeries, compared with enoxaparin

Background: In the past 10 years, new anticoagulants (NACs) have been studied for venous thromboembolism (VTE) prophylaxis. Objective: To evaluate the risk/benefit profile of NACs versus enoxaparin for VTE prophylaxis in major orthopedic surgery. Methods: A systematic review of double-blind randomized phase III studies was performed. The search strategy was run from 2000 to 2011 in the main medical electronic databases in any language. Independent extraction of articles was performed by 2 authors using predefined data fields, including study quality indicators. Results: Fifteen published clinical trials evaluating fondaparinux, rivaroxaban, dabigatran, and apixaban were included. Primary efficacy (any deep vein thrombosis [DVT], nonfatal pulmonary embolism, or all-cause mortality) favored fondaparinux (relative risk [RR] 0.50; 95% CI, 0.39, 0.63) and rivaroxaban (RR, 0.50; 95% CI, 0.34, 0.73) over enoxaparin, although significant heterogeneity was observed in both series. The primary efficacy of dabigatran at 220 mg, apixaban, and bemiparin were similar, with RRs of 1.02 (95% CI, 0.86, 1.20), 0.63 (95% CI, 0.39, 1.01), and 0.87 (95% CI, 0.65, 1.17), respectively. The primary efficacy of dabigatran at 150 mg (RR, 1.20; 95% CI, 1.03, 1.41), was inferior to enoxaparin. The incidence of proximal DVT favored apixaban (RR, 0.45; 95% CI, 0.27, 0.75) only. Rivaroxaban (RR, 0.45; 95% CI, 0.27, 0,77) and apixaban (RR, 0.38; 95% CI, 0.16, 0.90) produced significantly lower frequencies of symptomatic DVT. The incidence of major VTE favored rivaroxaban (RR, 0.44; 95% CI, 0.25, 0.81), only. Bleeding risk was similar for all NACs, except fondaparinux (RR, 1.27; 95% CI, 1.04, 1.55), which exhibited a significantly higher any-bleeding risk compared with enoxaparin, and apixaban (RR, 0.88; 95% CI, 0.79, 0.99), which was associated with a reduced risk of any bleeding. Alanine amino transferase was significantly lower with 220 mg of dabigatran, (RR, 0.67; 95% CI, 0.79, 0.99) than with enoxaparin. Conclusions: NACs can be considered alternatives to conventional thromboprophylaxis regimens in patients undergoing elective major orthopedic surgery, depending on clinical characteristics and cost-effectiveness. The knowledge of some differences concerning efficacy or safety profile, pointed out in this systematic review, along with the respective limitations, may be useful in clinical practice. © 2013 Elsevier Inc. All rights reserved.

An alternative approach to deal with the absence of clinical trials: a proportional meta-analysis of case series studies

PURPOSE: Systematic reviews are criticized for frequently offering inconsistent evidences and absence of straightforward recommendations. Their value seems to be depreciated when the conclusions are uncertain. To describe an alternative approach of evaluating case series studies in health care when there is absence of clinical trials. METHODS: We provide illustrations from recent experiences. Proportional meta-analysis was performed on surgical outcomes: (a) case series studies, (b) use of cryoablation or radiofrequency ablation, and (c) patients with small renal cell carcinoma. The statistically significant difference between both interventions studied was defined if their combined 95% confidential interval (CI) did not overlap. RESULTS: As demonstrated by the example, this analysis is an alternative approach to provide some evidence of the intervention´s effects under evaluation and plotting all available case series in the absence of clinical trials for the health field. CONCLUSIONS: Although we are leading to a low level of evidence to determine efficacy, effectiveness and safety of interventions this alternative approach can help surgeons, physicians and health professionals for a provisionally decision in health care along with their clinical expertise and the patient´s wishes and circumstances in the absence of high-quality primary studies. It´s not a replacement for the gold standard randomized clinical trial, but an alternative analysis for clinical research.

Sonothrombolysis for acute ischemic stroke: a systematic review of randomized controlled trials

Object. Sonothrombolysis has recently been considered an emerging modality for the treatment of stroke. The purpose of the present paper was to review randomized clinical studies concerning the effects of sonothrombolysis associated with tissue plasminogen activator (tPA) on acute ischemic stroke. Methods. Systematic searches for literature published between January 1996 and July 2011 were performed for studies regarding sonothrombolysis combined with tPA for acute ischemic stroke. Only randomized controlled trials were included. Data extraction was based on ultrasound variables, patient characteristics, and outcome variables (rate of intracranial hemorrhages and arterial recanalization). Results. Four trials were included in this study; 2 trials evaluated the effect of transcranial Doppler (TCD) ultrasonography on sonothrombolysis, and 2 addressed transcranial color-coded duplex (TCCD) ultrasonography. The frequency of ultrasound waves varied from 1.8 to 2 MHz. The duration of thrombus exposure to ultrasound energy ranged from 60 to 120 minutes. Sample sizes were small, recanalization was evaluated at different time points (60 and 120 minutes), and inclusion criteria were heterogeneous. Sonothrombolysis combined with tPA did not lead to an increase in symptomatic intracranial hemorrhagic complications. Two studies demonstrated that patients treated with ultrasound combined with tPA had statistically significant higher rates of recanalization than patients treated with tPA alone. Conclusions. Despite the heterogeneity and the limitations of the reviewed studies, there is evidence that sonothrombolysis associated with tPA is a safe procedure and results in an increased rate of recanalization in the setting of acute ischemic stroke when wave frequencies and energy intensities of diagnostic ultrasound systems are used. (http://thejns.org/doi/abs/10.3171/2011.10.FOCUS11251)

Radiation therapy for Graves' ophthalmopathy: a systematic review and meta-analysis of randomized controlled trials

PURPOSE: To evaluate the efficacy of radiotherapy (RT) with total dose of 20 Gy (RT 20 Gy) in the treatment of Graves' ophthalmopathy. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed comparing RT 20 Gy with or without glucocorticoid to clinical treatments for Graves' ophthalmopathy. The MEDLINE, EMBASE, Cochrane Library databases and recent relevant journals were searched. Relevant reports were reviewed by two reviewers. Response to radiotherapy was defined as clinical success according to each trial. We also evaluated the quality of life and whether RT to produce fewer side effects than other treatments. RESULTS: A total of 8 randomized controlled trials (439 patients) were identified. In the subgroup analysis, the overall response to treatment rates was better for: RT 20 Gy plus glucocorticoid vs glucocorticoids alone, OR=17.5 (CI95% 1.85-250, p=0.04), RT 20 Gy vs sham RT, OR= 3.15 (CI95%1.59-6.23, p=0.003) and RT 20Gy plus intravenous glucocorticoid vs RT 20Gy plus oral glucocorticoid, OR=4.15(CI95% 1.34-12.87, p=0.01). There were no differences between RT 20 Gy versus other fractionations and RT 20 Gy versus glucocorticoid alone. RT 20 Gy with or without glucocorticoids showed an improvement in diplopia grade, visual acuity, optic neuropathy, lid width, proptosis and ocular motility. No difference was seen for costs, intraocular pressure and quality of life. CONCLUSION: Our data have shown that RT 20 Gy should be offered as a valid therapeutic option to patients with moderate to severe ophthalmopathy. The effectiveness of orbital radiotherapy can be increased by the synergistic interaction with glucocorticoids. Moreover, RT 20 Gy is useful to improve a lot of ocular symptoms, excluding intraocular pressure, without any difference in quality of life and costs.

Efficacy of experimental treatments compared with standard treatments in non-inferiority trials: a meta-analysis of randomized controlled trials

Background There is concern that non-inferiority trials might be deliberately designed to conceal that a new treatment is less effective than a standard treatment. In order to test this hypothesis we performed a meta-analysis of non-inferiority trials to assess the average effect of experimental treatments compared with standard treatments. Methods One hundred and seventy non-inferiority treatment trials published in 121 core clinical journals were included. The trials were identified through a search of PubMed (1991 to 20 February 2009). Combined relative risk (RR) from meta-analysis comparing experimental with standard treatments was the main outcome measure. Results The 170 trials contributed a total of 175 independent comparisons of experimental with standard treatments. The combined RR for all 175 comparisons was 0.994 [95% confidence interval (CI) 0.978–1.010] using a random-effects model and 1.002 (95% CI 0.996–1.008) using a fixed-effects model. Of the 175 comparisons, experimental treatment was considered to be non-inferior in 130 (74%). The combined RR for these 130 comparisons was 0.995 (95% CI 0.983–1.006) and the point estimate favoured the experimental treatment in 58% (n = 76) and standard treatment in 42% (n = 54). The median non-inferiority margin (RR) pre-specified by trialists was 1.31 [inter-quartile range (IQR) 1.18–1.59]. Conclusion In this meta-analysis of non-inferiority trials the average RR comparing experimental with standard treatments was close to 1. The experimental treatments that gain a verdict of non-inferiority in published trials do not appear to be systematically less effective than the standard treatments. Importantly, publication bias and bias in the design and reporting of the studies cannot be ruled out and may have skewed the study results in favour of the experimental treatments. Further studies are required to examine the importance of such bias.

Does land-based exercise reduce pain and disability associated with hip osteoarthritis? A meta-analysis of randomized controlled trials

Objective To determine if clinical guidelines recommending therapeutic exercise for people with hip osteoarthritis (OA) are supported by rigorous scientific evidence. Methods A meta-analysis of randomized controlled trials (RCTs) recruiting people with hip OA and comparing some form of land-based exercise program (as opposed to exercises conducted in the water) with a non-exercise group in terms of hip pain and/or self-reported physical function. Results Thirty-two RCTs were identified, but only five met the inclusion criteria. Only one of the five included RCTs restricted recruitment to people with hip OA, the other four RCTs also recruiting participants with knee OA. The five included studies provided data on 204 and 187 hip OA participants for pain and physical function, respectively. Combining the results of the five included RCTs using a fixed-effects model demonstrated a small treatment effect for pain (standardized mean difference (SMD) −0.38; 95% confidence interval (CI) −0.67 to −0.09). No significant benefit in terms of improved self-reported physical function was detected (SMD −0.02; 95% CI −0.31 to 0.28). Conclusion Currently there is only silver level evidence (one small RCT) supporting the benefit of land-based therapeutic exercise for people with symptomatic hip OA in terms of reduced pain and improved physical function. The limited number and small sample size of the included RCTs restricts the confidence that can be attributed to these results.

Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial): rationale and design

Background Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events. Methods The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism. Discussion patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011).

Reporting of consistency of blood pressure control in randomized controlled trials of antihypertensive drugs: a systematic review of 1372 trial reports

Hypertension is a powerful treatable risk factor for stroke. Reports of randomized controlled trials (RCTs) of antihypertensive drugs rightly concentrate on clinical outcomes, but control of blood pressure (BP) during follow-up is also important, particularly given that inconsistent control is associated with a high risk of stroke and that antihypertensive drug classes differ in this regard.

Reporting of randomized controlled trials in Hodgkin lymphoma in biomedical journals

BACKGROUND: Randomized controlled trials (RCTs) are the best tool to evaluate the effectiveness of clinical interventions. The Consolidated Standards for Reporting Trials (CONSORT) statement was introduced in 1996 to improve reporting of RCTs. We aimed to determine the extent of ambiguity and reporting quality as assessed by adherence to the CONSORT statement in published reports of RCTs involving patients with Hodgkin lymphoma from 1966 through 2002. METHODS: We analyzed 242 published full-text reports of RCTs in patients with Hodgkin lymphoma. Quality of reporting was assessed using a 14-item questionnaire based on the CONSORT checklist. Reporting was studied in two pre-CONSORT periods (1966-1988 and 1989-1995) and one post-CONSORT period (1996-2002). RESULTS: Only six of the 14 items were addressed in 75% or more of the studies in all three time periods. Most items that are necessary to assess the methodologic quality of a study were reported by fewer than 20% of the studies. Improvements over time were seen for some items, including the description of statistics methods used, reporting of primary research outcomes, performance of power calculations, method of randomization and concealment allocation, and having performed intention-to-treat analysis. CONCLUSIONS: Despite recent improvements, reporting levels of CONSORT items in RCTs involving patients with Hodgkin lymphoma remain unsatisfactory. Further concerted action by journal editors, learned societies, and medical schools is necessary to make authors even more aware of the need to improve the reporting RCTs in medical journals to allow assessment of validity of published clinical research.