Lack Of Randomized Control Trials Research Articles

A Review of Traumatic Brain Injury Randomized Controlled Trials

<h3>Objective(s)</h3> To describe the landscape of traumatic brain injury (TBI) randomized controlled trial (RCT) publications, in terms of number of studies, country of origin, and time post injury. <h3>Data Sources</h3> Scopus, PubMed, CINAHL, EMBASE and PsycINFO. <h3>Study Selection</h3> Articles published up to and including June 30, 2021 meeting the following criteria were included: (1) human subjects with a mean age of ≥18 years, (2) ≥50% of the sample had moderate to severe TBI, (3) the study design was a RCT, and (4) written in English. Protocols and post-hoc analyses of RCTs were not included. <h3>Data Extraction</h3> Author(s), year, journal, country (based on primary authors affiliation), sample size, time post injury, and primary study objective. <h3>Data Synthesis</h3> A total of 674 TBI RCTs met inclusion; 45 different countries were represented. The largest volume of RCTs originated in North America (n=246; 36.5%), predominately the United States (n=234). Over half of the RCTs (53.6%) were published in the last 10 years (2011-2021). The majority of RCTs studied medical outcomes (55%), followed by cognition and cognitive-communication (17.5%). Of those articles that provided data on time post injury (n=496), interventions were studied most frequently within the first 72 hours post injury (50.0%), and after 6 months post injury (34.3%). <h3>Conclusions</h3> By examining high level trends we are able to see where research efforts have been focused across the continuum of TBI rehabilitation care. While there has been an increase in the number of RCTs published in recent years, there is a lack of RCTs in the subacute rehabilitation phase between 3 days and 6 months. <h3>Author(s) Disclosures</h3> None.

P1014: OVERALL SURVIVAL IN PATIENTS WITH ADVANCED SYSTEMIC MASTOCYTOSIS RECEIVING AVAPRITINIB VERSUS MIDOSTAURIN OR CLADRIBINE

Background: Avapritinib, a selective KIT D816V inhibitor, was approved for the treatment of adults with advanced systemic mastocytosis (AdvSM) in the United States (US), based on two single-arm trials: Phase 1 EXPLORER (NCT02561988) and Phase 2 PATHFINDER (NCT03580655). No randomized controlled trial (RCT) has been conducted comparing efficacy of avapritinib versus alternative therapies for AdvSM. Aims: This study (NCT04695431) compared overall survival (OS) between AdvSM patients treated with avapritinib in the EXPLORER and PATHFINDER trials and those treated with midostaurin or cladribine in real-world clinical practice. Methods: Pooled data from the EXPLORER and PATHFINDER trials were compared with data for patients with AdvSM obtained through a multi-center, global, observational, retrospective chart review study conducted at 6 study sites (4 European, 2 US). Patients treated with midostaurin or cladribine were identified using inclusion/exclusion criteria similar to the trials and could contribute multiple lines of therapy (LOTs) to the analysis. OS, assessed using Kaplan-Meier analysis, was defined as time from initiation of avapritinib, midostaurin, or cladribine to death from any cause; patients were censored at date of last follow-up if alive. Inverse probability of treatment weighting (IPTW) was used to adjust for differences in key variables between treatment cohorts, including age, sex, AdvSM subtype, anemia, thrombocytopenia, leukocyte count, skin involvement, number and type of prior treatments, performance status, serum tryptase level, and presence of SRSF2/ASXL1/RUNX1 mutations. IPTW-weighted Cox proportional hazards models, adjusted for variables that remained unbalanced after weighting, were used to compare OS between cohorts. Results: This analysis included 176 patients treated with avapritinib, 94 treated with midostaurin (LOT, n=99), and 44 treated with cladribine (LOT, n=49). Median (range) age was 68 (31−88) for avapritinib, 69 (26−87) for midostaurin, and 66 (45−88) years for cladribine patients. 103 (59%) avapritinib patients were male, versus 64 (68%) in the midostaurin and 27 (61%) in the cladribine cohort. In the avapritinib cohort, 136 (77%) patients from both trials were dosed at ≤200mg and 40 (23%) patients, all from EXPLORER, were dosed at ≥300mg. In unweighted analysis of avapritinib versus midostaurin, mean follow-up durations were 17.9 and 27.9 months, respectively, during which 34 (19%) avapritinib patients and 56 (60%) midostaurin patients died. Median OS was not reached (NR) (95% CI: 46.9, not estimable) in the avapritinib cohort and was 28.6 months (95% CI: 18.2, 44.6) in the midostaurin cohort (Figure 1). In weighted Cox analysis, OS was significantly improved in the avapritinib versus midostaurin cohort (hazard ratio [HR] [95% CI]: 0.59 [0.36, 0.97]; P<0.001). The mean-follow-up duration for the cladribine cohort was 24.2 months, during which 29 (66%) patients died. The median OS in the cladribine cohort was 23.4 months (95% CI: 14.8, 40.6). Weighted Cox analysis showed that OS was significantly improved in the avapritinib versus cladribine cohort (HR [95% CI]: 0.32 [0.15, 0.67]; P=0.003). Image:Summary/Conclusion: The results from this study indicate that AdvSM patients treated with avapritinib in clinical trials experienced significantly improved survival compared with patients treated with midostaurin or cladribine in the real world. Given the lack of RCTs, these data offer essential insights into the improved survival of patients treated with avapritinib compared to alternative therapies for AdvSM.

Meta-Analysis: Relapse Prevention Strategies for Depression and Anxiety in Remitted Adolescents and Young Adults

Depression and anxiety cause a high burden of disease and have high relapse rates (39%-72%). This meta-analysis systematically examined effectiveness of relapse prevention strategies on risk of and time to relapse in youth who remitted. PubMed, PsycInfo, Embase, Cochrane, and ERIC databases were searched up to June 15, 2021. Eligible studies compared relapse prevention strategies to control conditions among youth (mean age 13-25 years) who were previously depressed or anxious or with≥30% improvement in symptoms. Two reviewers independently assessed titles, abstracts, and full texts; extracted study data; and assessed risk of bias and overall strength of evidence. Random-effects models were used to pool results, and mixed-effects models were used for subgroup analyses. Main outcome was relapse rate at last follow-up (PROSPERO ID: CRD42020149326). Of 10 randomized controlled trials (RCTs) that examined depression, 9 were eligible for analysis: 4 included psychological interventions (n= 370), 3 included antidepressants (n= 80), and 2 included combinations (n= 132). No RCTs for anxiety were identified. Over 6 to 75 months, relapse was half as likely following psychological treatment compared with care as usual conditions (k= 6; odds ratio 0.56, 95% CI 0.31 to 1.00). Sensitivity analyses including only studies with≥50 participants (k= 3), showed similar results. Over 6 to 12 months, relapse was less likely in youth receiving antidepressants compared with youth receiving pill placebo (k= 3; OR 0.29, 95% CI 0.10 to 0.82). Quality of studies was suboptimal. Relapse prevention strategies for youth depression reduce risk of relapse, although adequately powered, high-quality RCTs are needed. This finding, together with the lack of RCTs on anxiety, underscores the need to examine relapse prevention in youth facing these common mental health conditions.

The modulatory role of internet-supported mindfulness-based cognitive therapy on extracellular vesicles and psychological distress in people who have had cancer: a protocol for a two-armed randomized controlled study

BackgroundMindfulness-based interventions (MBIs) have been used in oncology contexts as a promising tool with numerous benefits for various health-related and psychosocial outcomes. Despite the increasing popularity of MBIs, few randomized controlled trials (RCTs) have examined their effects upon biological parameters. Specifically, no previous study has examined the effects of MBIs on extracellular vesicles (EVs), which are potentially important markers of health, disease, and stress. Moreover, the lack of RCTs is even more limited within the context of technology-mediated MBIs and long-term effects.MethodsThe current study protocol presents a two-arm, parallel, randomized controlled study investigating the effects of internet-supported mindfulness-based cognitive therapy (MBCT) compared with treatment as usual (TAU). Primary outcomes are psychological distress and EV cargo of distressed participants with previous breast, colorectal, or prostate cancer diagnoses. Secondary outcomes are self-reported psychosocial and health-related measures, and additional biological markers. Outcomes will be assessed at baseline, 4 weeks after baseline (mid-point of the intervention), 8 weeks after baseline (immediately post-intervention), 24 weeks after baseline (after booster sessions), and 52 weeks after baseline. Our goal is to recruit at least 111 participants who have been diagnosed with breast, prostate, or colorectal cancer (cancer stage I to III), are between 18 and 65 years old, and have had primary cancer treatments completed between 3 months and 5 years ago. Half of the participants will be randomized to the TAU group, and the other half will participate in an 8-week online MBCT intervention with weekly group sessions via videoconference. The intervention also includes asynchronous homework, an online retreat after the fifth week, and 4 monthly booster sessions after completion of the 8-week programme.DiscussionThis study will allow characterizing the effects of internet-based MBCT on psychosocial and biological indicators in the context of cancer. The effects on circulating EVs will also be investigated, as a possible neurobiological pathway underlying mind-body intervention effects.Trial registrationClinicalTrials.govNCT04727593 (date of registration: 27 January 2021; date of record verification: 6 October 2021).

Hopes and Hypes for Artificial Intelligence in Colorectal Cancer Screening

Hopes and Hypes for Artificial Intelligence in Colorectal Cancer Screening

Clinical Outcomes of Immediate Implant Loading with Fixed Prostheses in Edentulous Maxillae: A Systematic Review.

To review the evidence from the clinical outcomes of immediately loaded implants with fixed prostheses in edentulous maxillae. An electronic search was performed in PubMed/MEDLINE, Embase, and Cochrane to identify studies investigating the outcome of implants subjected to immediate loading with fixed dental prostheses in edentulous maxillae. Only clinical studies with more than 10 patients and a mean follow-up time of more than 12 months were included. Meta-analysis was utilized to compare the clinical outcomes between immediately loaded implants and conventionally loaded implants. For immediately loaded implants, a cumulative implant survival rate (ISR) was weighted by the duration of follow-up and number of implants. The weighted marginal bone loss (MBL) was also assessed. A total of 33 studies (16 retrospective studies and 17 prospective studies) were included, which involved 2,635 patients and 12,480 implants. Meta-analysis did not reveal a significant difference of ISR or MBL between the two loading groups. For immediately loaded implants, the weighted cumulative ISR was 95.53% (median: 97.50%) with a mean follow-up of 46.07 months (SD: 30.92). Fourteen studies reported on the MBL of implants, and the mean MBL was 1.19 mm (SD: 0.88) with a mean period of 57.70 months (SD: 32.56). The results should be interpreted with caution due to the lack of randomized controlled trials (RCTs) and the heterogeneity of the data. Despite the lack of RCTs, immediate implant loading with a fixed prosthesis in the edentulous maxilla seems to be a reliable treatment alternative with a high ISR, when appropriate inclusion/exclusion criteria are followed.

Psychological Interventions in Chronic Low Back Pain: A Systematic Review

Background and Aim: Chronic low Back Pain (CLBP) is one of the most common musculoskeletal disorders with possible psychological consequences for the patients. This study aimed to review all evidence on the effectiveness of psychological interventions in improving the mental status of people with CLBP and providing recommendations for future therapeutic interventions. Methods and Materials/Patients: This systematic review was conducted on the articles published from January 2010 to December 2020. The keywords included “psychology”, “intervention”, “low back pain”, “chronic disease”, “quality of life”, “empowerment”, “psychotherapy”, “psychological interventions”, “clinical trials”, and “randomized clinical trials” in the indexing databases of Magiran, PubMed, Scopus, and Google Scholar. Of the total 1740 articles found, 14 articles were selected for review. Results: The results showed that Cognitive-Behavioral Therapy (CBT) and its combination therapies with mindfulness techniques played an influential role in improving psychological status and quality of life, and reducing pain perception in CLBP patients. The lack of RCT (randomized controlled trial) research and follow-up to assess long-term outcomes are the main limitations of the studies conducted in Iran. Conclusion: It is recommended that psychological interventions be considered alongside medical therapies to improve CLBP patients’ adjustment to chronic condition and their quality of life. Researchers and therapists should consider treatment programs based on RCT plans and long-term follow-up.

Selection and Insertion of Vascular Access Devices in Pediatrics: A Systematic Review.

To critically review the evidence for the selection and insertion of pediatric vascular access devices (VADs). Data were sourced from the US National Library of Medicine, Cumulative Index to Nursing and Allied Health, the Cochrane Library databases, Embase, and international clinical trial databases. Clinical practice guidelines, systematic reviews, cohort designs, randomized control trials (RCTs), quasi RCTs, before-after trials, or case-control studies that reported on complications and/or risk as well as reliability of VADs in patients aged 0 to 18 years were included. Articles were independently reviewed to extract and summarize details on the number of patients and catheters, population, age of participants, VAD type, study method, indication, comparators, and the frequency of VAD failure or complications. VAD selection and insertion decision-making in general hospitalized and some specialized patient populations were well evidenced. The use of single-lumen devices and ultrasound-guided techniques was also broadly supported. There was a lack of RCTs, and for neonates, cardiac patients, patients with difficult venous access, midline catheters, catheter-to-vein ratio, and near-infrared devices, the lack of evidence necessitated broadening the review scope. Limitations include the lack of formal assessment of the quality of evidence and the lack of RCTs and systematic reviews. Consequently, clinical decision-making in certain pediatric populations is not guided by strong, evidence-based recommendations. This is the first synthesis of available evidence for the selection and insertion of VADs in pediatric patients and is important for determining the appropriateness of VADs in pediatric patients.

The effect of tai chi and Qigong exercise on depression and anxiety of individuals with substance use disorders: a systematic review and meta-analysis

BackgroundPrevious studies have acknowledged Tai Chi and Qigong exercise could be potential effective treatments for reducing depression and anxiety in both healthy and clinical populations. However, there is a scarcity of systematic reviews summarizing the clinical evidence conducted among individuals with substance use disorders. This study tries to fill up this gap.MethodsA systematic search using Medline, EMbase, PsychINFO, Eric, SPORTDiscus, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), the Chinese National Knowledge Infrastructure (CNKI), Wanfang, and the Chinese Scientific Journal (VIP) databases was initiated to identify randomized controlled trials (RCTs) and non-randomized comparison studies (NRS) assessing the effect of Tai Chi and Qigong versus various comparison groups on depression and anxiety related outcomes. Study quality was evaluated using a Checklist to Evaluate a Report of a Nonpharmacological Trial (CLEAR-NPT) designed for nonpharmacological trial.ResultsOne RCT and six NRS with a total of 772 participants were identified. Some of them were meta-analyzed to examine the pooled effects based on different types of intervention and controls. The results of meta-analyses suggested the effect of Tai Chi was comparable to treatment as usual (TAU) on depression (standardized mean difference (SMD) = − 0.17[− 0.52, 0.17]). Qigong exercise appears to result in improvement on anxiety compared to that of medication (SMD = -1.12[− 1.47, − 0.78]), and no treatment control (SMD = -0.52[− 0.77, − 0.27]).ConclusionThe findings suggest potentially beneficial effect of Qigong exercise on symptoms of anxiety among individuals with drug abuse. Considering the small number and overall methodological weakness of included studies and lack of RCTs, results should be interpreted with caution and future rigorously designed RCTs are warranted to provide more reliable evidence.

The environmental effects of poverty programs and the poverty effects of environmental programs: The missing RCTs

Abstract For decades, government agencies and nongovernmental organizations have invested in programs aimed at alleviating poverty and those aimed at protecting the environment. Whether these investments mutually reinforce each other or act in opposition has been widely debated by scholars. Studies that have tried to resolve this debate suffer from a variety of shortcomings, including the challenge of inferring causal relationships from non-experimental data. To help address some of these shortcomings, randomized controlled trials (RCTs) can play an important role. When done well, RCTs permit credible causal inferences and can be designed to directly test competing assumptions about how the world works. Yet few RCTs of poverty programs examine their effects on the environment. Worse, we know of no RCTs reporting the poverty effects of environmental interventions, which may be unsurprising given that environmental scholars rarely use RCTs. The lack of RCTs that can shed light on the relationships between actions to alleviate poverty and actions to reverse global environmental change is an obstacle to advancing the science and practice of sustainability. If scholars of poverty include environmental outcomes in their RCTs, and if environmental scholars use RCTs to study the poverty effects of environmental programs, the long-running debates about the dual challenges of alleviating poverty and protecting the environment could be resolved. Moreover, by forcing people to pay greater attention to the mechanisms and pathways that link the solutions to these two challenges, RCTs can make it more likely that environmental and poverty programs will be designed in ways that ensure progress on one challenge will also imply progress on the other.

Effect of Virtual Reality Therapy on Balance and Walking in Children with Cerebral Palsy: A Systematic Review

ABSTRACT Aim: To investigate the effect of Virtual Reality Therapy (VRT) on balance and walking in children with cerebral palsy (CP). Method: A systematic search in Pubmed and Embase was performed until the 9th of July 2019. Articles were included if the population consisted of children with CP and data on balance and/or walking were reported. Results were pooled in two meta-analyses. Results: 26 articles were included. For ‘balance’ 5 and for ‘walking’ 4 were used for the meta-analyses. The meta-analyses showed a significant result in favor of VRT for balance, SMD 0.89 [95% CI, SD 0.14, 1.63] and for walking, SMD 3.10 [95% Cl, SD 0.78, 5.35]. Interpretation: VRT seems a promising intervention for rehabilitation in children with CP. The meta-analysis confirmed this positive effect. These results must be interpreted with caution due to differences in the interventions used, the lack of randomized-controlled trials, and the relatively small groups.

Synthesizing the Strength of the Evidence of Complementary and Integrative Health Therapies for Pain.

Pain and opioid use are highly prevalent, leading for calls to include nonpharmacological options in pain management, including complementary and integrative health (CIH) therapies. More than 2,000 randomized controlled trials (RCTs) and many systematic reviews have been conducted on CIH therapies, making it difficult to easily understand what type of CIH therapy might be effective for what type of pain. Here we synthesize the strength of the evidence for four types of CIH therapies on pain: acupuncture, therapeutic massage, mindfulness techniques, and tai chi. We conducted searches of English-language systematic reviews and RCTs in 11 electronic databases and previously published reviews for each type of CIH. To synthesize that large body of literature, we then created an "evidence map," or a visual display, of the literature size and broad estimates of effectiveness for pain. Many systematic reviews met our inclusion criteria: acupuncture (86), massage (38), mindfulness techniques (11), and tai chi (21). The evidence for acupuncture was strongest, and largest for headache and chronic pain. Mindfulness, massage, and tai chi have statistically significant positive effects on some types of pain. However, firm conclusions cannot be drawn for many types of pain due to methodological limitations or lack of RCTs. There is sufficient strength of evidence for acupuncture for various types of pain. Individual studies indicate that tai chi, mindfulness, and massage may be promising for multiple types of chronic pain. Additional sufficiently powered RCTs are warranted to indicate tai chi, mindfulness, and massage for other types of pain.

A systematic review and meta-analysis of second-line immunosuppressants for autoimmune hepatitis treatment.

The gold-standard treatment for autoimmune hepatitis (AIH) is a prednisone/azathioprine combination. However, subgroups of patients may be unresponsive to this treatment. The aim of this study is to evaluate the efficacy of second-line immunosuppressive therapies for AIH through a systematic review and meta-analysis in adult patients. The systematic review was registered at the PROSPERO platform under number 42015019831. Databases MEDLINE (PubMed), Lilacs, Cochrane, and Scielo were searched. The keywords used were 'Hepatitis, Autoimmune' and descriptors terms (MeSH and DeCS). These terms were linked with each immunosuppressant of interest. A total of 1532 studies were identified. Of these, 1492 were excluded on the basis of title and abstract reading. Among the 40 studies retrieved for detailed full-text analysis, a total of 15 fulfilled the inclusion criteria for the analysis. The most studied second-line immunosuppressive was mycophenolate mofetil (MM). The mean reduction of aminotransferases was observed in 94.3% with tacrolimus/prednisone, 91.3% for cyclosporine/prednisone, 85.5% for budesonide, and 78.7% MM/prednisone. For MM/prednisone, the mean rate of histological remission was 88.6%, liver transplantation was indicated in 11.4%, and the mortality rate was 7.2%. Limitations were also present, such as the lack of randomized-controlled trials and prospective studies, the small number of patients, and the heterogeneity between remission criteria. This is the first systematic review and meta-analysis to compare the second-line imunossupressant therapy for AIH. The most studied second-line immunosuppressive is the MM, with a reasonable histological remission. The use of combined tacrolimus/prednisone was the most effective for the normalization of aminotransferases.

Are Biologics Efficacious in Atopic Dermatitis? A Systematic Review and Meta-Analysis.

Current systemic treatments for atopic dermatitis (AD) offer limited efficacy and are often restricted by safety concerns. Biologics may address the unmet need for improved AD therapeutics. The aim of this study was to evaluate the efficacy and safety of biologic agents in AD. A systematic review and meta-analysis of studies evaluating AD patients treated with biologics was performed. The primary outcome was the Eczema Area and Severity Index (EASI)-75 response, while secondary outcomes were SCOring Atopic Dermatitis (SCORAD)-75, EASI-50, SCORAD-50, Investigator Global Assessment 0/1 responses, change in responses from baseline, and adverse events. We included 13 randomized controlled trials (RCTs) and 10 observational studies evaluating nine biologics. High-quality evidence was available for dupilumab, nemolizumab and ustekinumab. Pooling five studies, at weeks 12-16 dupilumab 300mg every week to every 2weeks achieved EASI-75 responses of 55%, superior to placebo [relative risk (RR) 3.3, 95% confidence interval (CI) 2.9-3.6]. Nemolizumab had similar EASI-75 responses as placebo, but significantly improved pruritus. In online reports, lebrikizumab demonstrated superior EASI-50 responses versus placebo (RR 1.3, 95% CI 1.04-1.7), while tralokinumab had superior SCORAD-50 responses versus placebo, with borderline significance (RR 1.7, 95% CI 0.97-3.1). In two RCTs each, omalizumab and ustekinumab were comparable with placebo, while antithymic stromal lymphopoietin receptor, infliximab, and rituximab lacked adequate evidence of efficacy. All medications had a comparable safety profile to placebo. Lack of RCTs and the use of variable outcome measures limited conclusions. Dupilumab is currently the only biologic with robust evidence of efficacy in AD. Nemolizumab, lebrikizumab, and tralokinumab show promise but further data are needed. Longer follow-up and larger studies will establish their safety profile.

Smartphone-Based Monitoring of Objective and Subjective Data in Affective Disorders: Where Are We and Where Are We Going? Systematic Review.

BackgroundElectronic mental health interventions for mood disorders have increased rapidly over the past decade, most recently in the form of various systems and apps that are delivered via smartphones.ObjectiveWe aim to provide an overview of studies on smartphone-based systems that combine subjective ratings with objectively measured data for longitudinal monitoring of patients with affective disorders. Specifically, we aim to examine current knowledge on: (1) the feasibility of, and adherence to, such systems; (2) the association of monitored data with mood status; and (3) the effects of monitoring on clinical outcomes.MethodsWe systematically searched PubMed, Web of Science, PsycINFO, and the Cochrane Central Register of Controlled Trials for relevant articles published in the last ten years (2007-2017) by applying Boolean search operators with an iterative combination of search terms, which was conducted in February 2017. Additional articles were identified via pearling, author correspondence, selected reference lists, and trial protocols.ResultsA total of 3463 unique records were identified. Twenty-nine studies met the inclusion criteria and were included in the review. The majority of articles represented feasibility studies (n=27); two articles reported results from one randomized controlled trial (RCT). In total, six different self-monitoring systems for affective disorders that used subjective mood ratings and objective measurements were included. These objective parameters included physiological data (heart rate variability), behavioral data (phone usage, physical activity, voice features), and context/environmental information (light exposure and location). The included articles contained results regarding feasibility of such systems in affective disorders, showed reasonable accuracy in predicting mood status and mood fluctuations based on the objectively monitored data, and reported observations about the impact of monitoring on clinical state and adherence of patients to the system usage.ConclusionsThe included observational studies and RCT substantiate the value of smartphone-based approaches for gathering long-term objective data (aside from self-ratings to monitor clinical symptoms) to predict changes in clinical states, and to investigate causal inferences about state changes in patients with affective disorders. Although promising, a much larger evidence-base is necessary to fully assess the potential and the risks of these approaches. Methodological limitations of the available studies (eg, small sample sizes, variations in the number of observations or monitoring duration, lack of RCT, and heterogeneity of methods) restrict the interpretability of the results. However, a number of study protocols stated ambitions to expand and intensify research in this emerging and promising field.

&lt;b&gt;New drugs for the treatment of agitation in schizophrenia: a systematic review and meta-analysis of inhaled loxapine and infused sodium nitroprusside

The use of novel drugs such as inhaled loxapine (LOXi) for schizophrenia and the off-label use of substances such as sodium nitroprusside (NIT) for the management of mental disorders require further investigation. We aimed to evaluate the efficacy and safety of LOXi and NIT for the treatment of agitation associated with schizophrenia. A systematic review of randomized controlled trials (RCTs) comparing the use of LOXi or NIT versus placebo or other antipsychotic agents was conducted, and we evaluated the efficacy (CGI-scale) and safety (adverse events) of the therapies. Altogether, 71 studies were identified, of which 2 (LOXi) were included in the meta-analysis, and 1 (NIT) was included in the systematic review only. The efficacy data showed superiority of LOXi against placebo, regardless of the dose (5 and 10 mg). No significant differences were observed concerning the safety results. Treatment with NIT showed favorable results, with significant reduction of the symptoms. The efficacy of these medications is difficult to assess because of the lack of RCTs. However, there is some information regarding the efficacy and safety of LOXi in the treatment of agitation in schizophrenic patients.

Electronic self-monitoring of mood using IT platforms in adult patients with bipolar disorder: A systematic review of the validity and evidence.

BackgroundVarious paper-based mood charting instruments are used in the monitoring of symptoms in bipolar disorder. During recent years an increasing number of electronic self-monitoring tools have been developed. The objectives of this systematic review were 1) to evaluate the validity of electronic self-monitoring tools as a method of evaluating mood compared to clinical rating scales for depression and mania and 2) to investigate the effect of electronic self-monitoring tools on clinically relevant outcomes in bipolar disorder.MethodsA systematic review of the scientific literature, reported according to the Preferred Reporting items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was conducted. MEDLINE, Embase, PsycINFO and The Cochrane Library were searched and supplemented by hand search of reference lists. Databases were searched for 1) studies on electronic self-monitoring tools in patients with bipolar disorder reporting on validity of electronically self-reported mood ratings compared to clinical rating scales for depression and mania and 2) randomized controlled trials (RCT) evaluating electronic mood self-monitoring tools in patients with bipolar disorder.ResultsA total of 13 published articles were included. Seven articles were RCTs and six were longitudinal studies. Electronic self-monitoring of mood was considered valid compared to clinical rating scales for depression in six out of six studies, and in two out of seven studies compared to clinical rating scales for mania.The included RCTs primarily investigated the effect of heterogeneous electronically delivered interventions; none of the RCTs investigated the sole effect of electronic mood self-monitoring tools. Methodological issues with risk of bias at different levels limited the evidence in the majority of studies.ConclusionsElectronic self-monitoring of mood in depression appears to be a valid measure of mood in contrast to self-monitoring of mood in mania. There are yet few studies on the effect of electronic self-monitoring of mood in bipolar disorder. The evidence of electronic self-monitoring is limited by methodological issues and by a lack of RCTs. Although the idea of electronic self-monitoring of mood seems appealing, studies using rigorous methodology investigating the beneficial as well as possible harmful effects of electronic self-monitoring are needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-016-0713-0) contains supplementary material, which is available to authorized users.

Wound Healing Society 2014 update on guidelines for arterial ulcers.

Wound Healing Society 2014 update on guidelines for arterial ulcers.

Alternative approaches for studying humanitarian interventions: propensity score methods to evaluate reintegration packages impact on depression, PTSD, and function impairment among child soldiers in Nepal.

Ethical, logistical, and funding approaches preclude conducting randomized control trials (RCTs) in some humanitarian crises. A lack of RCTs and other intervention research has contributed to a limited evidence-base for mental health and psychosocial support (MHPS) programs after disasters, war, and disease outbreaks. Propensity score methods (PSMs) are an alternative analysis technique with potential application for evaluating MHPS programs in humanitarian emergencies. PSMs were used to evaluate impacts of education reintegration packages (ERPs) and other (vocational or economic) reintegration packages (ORPs) v. no reintegration programs on mental health of child soldiers. Propensity scores were used to determine weighting of child soldiers in each of the three treatment arms. Multiple linear regression was used to estimate adjusted changes in symptom score severity on culturally validated measures of depression, post-traumatic stress disorder (PTSD), and functional impairment from baseline to 1-year follow-up. Among 258 Nepali child soldiers participating in reintegration programs, 54.7% completed ERP and 22.9% completed ORP. There was a non-significant reduction in depression by 0.59 (95% CI -1.97 to 0.70) for ERP and by 0.60 (95% CI -2.16 to 0.96) for ORP compared with no treatment. There were non-significant increases in PTSD (1.15, 95% CI -1.55 to 3.86) and functional impairment (0.91, 95% CI -0.31 to 2.14) associated with ERP and similar findings for ORP (PTSD: 0.66, 95% CI -2.24 to 3.57; functional impairment (1.05, 95% CI -0.71 to 2.80). In a humanitarian crisis in which a non-randomized intervention assignment protocol was employed, the statistical technique of PSMs addressed differences in covariate distribution between child soldiers who received different integration packages. Our analysis did not demonstrate significant changes in psychosocial outcomes for ERPs and ORPs. We suggest the use of PSMs in evaluating non-randomized interventions in humanitarian crises when non-randomized conditions are not utilized.

Treatment for cryoglobulinemic and non-cryoglobulinemic peripheral neuropathy associated with hepatitis C virus infection.

Peripheral neuropathy is the most common neurologic complication of hepatitis C virus (HCV) infection.The pathophysiology of the neuropathy associated with HCV is not definitively known; however, proposed mechanisms include cryoglobulin deposition in the vasa nervorum and HCV-mediated vasculitis. The optimal treatment for HCV-related peripheral neuropathy has not been established. To assess the effects of interventions (including interferon alfa, interferon alfa plus ribavirin, corticosteroids, cyclophosphamide, plasma exchange, and rituximab) for cryoglobulinemic or non-cryoglobulinemic peripheral neuropathy associated with HCV infection. On 26 August 2014, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, and EMBASE. We also searched two trials registers, the Networked Digital Library of Theses and Dissertations (NDLTD) (October 2014), and three other databases. We checked references in identified trials and requested information from trial authors to identify any additional published or unpublished data. We included all randomized controlled trials (RCTs) and quasi-RCTs involving participants with cryoglobulinemic or non-cryoglobulinemic peripheral neuropathy associated with HCV infection.We considered any intervention (including interferon alfa, interferon alfa plus ribavirin, corticosteroids, cyclophosphamide, plasma exchange, and rituximab) alone or in combination versus placebo or another intervention ('head-to-head' comparison study design) evaluated after a minimum interval to follow-up of at least six months. We used standard methodological procedures expected by The Cochrane Collaboration. The planned primary outcome was change in sensory impairment (using any validated sensory neuropathy scale or quantitative sensory testing) at the end of the follow-up period. Other planned outcomes were: change in impairment (any validated combined sensory and motor neuropathy scale), change in disability (any validated disability scale), electrodiagnostic measures, number of participants with improved symptoms of neuropathy (global impression of change), and severe adverse events. Four trials of HCV-related cryoglobulinemia fulfiled selection criteria and the review authors included three in quantitative synthesis. All studies were at high risk of bias. No trial addressed the primary outcome of change in sensory impairment. No trial addressed secondary outcomes of change in combined sensory and motor impairment, disability, or electrodiagnostic measures. A single trial of HCV-related mixed cryoglobulinemia treated with pegylated interferon alfa (peginterferon alfa), ribavirin, and rituximab versus peginterferon alfa and ribavirin did not show a significant difference in the number of participants with improvement in neuropathy at 36 months post treatment (risk ratio (RR) 4.00, 95% confidence interval (CI) 0.27 to 59.31, n = 9). One study of interferon alfa (n = 22) and two studies of rituximab (n = 61) provided adverse event data. Severe adverse events were no more common with interferon alfa (RR 7.00, 95% CI 0.38 to 128.02) or rituximab (RR 3.00, 95% CI 0.13 to 67.06) compared to the control group. There is a lack of RCTs and quasi-RCTs addressing the effects of interventions for peripheral neuropathy associated with HCV infection. At present, there is insufficient evidence from RCTs and quasi-RCTs to make evidence-based decisions about treatment.