Influence of lack of blinding on the estimation of medication-related harms: a retrospective cohort study of randomized controlled trials.

BACKGROUND: Empirical evidence suggests that lack of blinding may be associated with biased estimates of treatment benefit in randomized controlled trials, but the influence on medication-related harms is not well-recognized. We aimed to investigate the association between blinding and clinical trial estimates of medication-related harms. METHODS: We searched PubMed from January 1, 2015, till January 1, 2020, for systematic reviews with meta-analyses of medication-related harms. Eligible meta-analyses must have contained trials both with and without blinding. Potential covariates that may confound effect estimates were addressed by restricting trials within the comparison or by hierarchical analysis of harmonized groups of meta-analyses (therefore harmonizing drug type, control, dosage, and registration status) across eligible meta-analyses. The weighted hierarchical linear regression was then used to estimate the differences in harm estimates (odds ratio, OR) between trials that lacked blinding and those that were blinded. The results were reported as the ratio of OR (ROR) with its 95% confidence interval (CI). RESULTS: We identified 629 meta-analyses of harms with 10,069 trials. We estimated a weighted average ROR of 0.68 (95% CI: 0.53 to 0.88, P < 0.01) among 82 trials in 20 meta-analyses where blinding of participants was lacking. With regard to lack of blinding of healthcare providers or outcomes assessors, the RORs were 0.68 (95% CI: 0.53 to 0.87, P < 0.01 from 81 trials in 22 meta-analyses) and 1.00 (95% CI: 0.94 to 1.07, P = 0.94 from 858 trials among 155 meta-analyses) respectively. Sensitivity analyses indicate that these findings are applicable to both objective and subjective outcomes. CONCLUSIONS: Lack of blinding of participants and health care providers in randomized controlled trials may underestimate medication-related harms. Adequate blinding in randomized trials, when feasible, may help safeguard against potential bias in estimating the effects of harms.

Measuring the impact of zero-cases studies in evidence synthesis practice using the harms index and benefits index (Hi-Bi).

OBJECTIVES: In evidence synthesis practice, dealing with studies with no cases in both arms has been a tough problem, for which there is no consensus in the research community. In this study, we propose a method to measure the potential impact of studies with no cases for meta-analysis results which we define as harms index (Hi) and benefits index (Bi) as an alternative solution for deciding how to deal with such studies. METHODS: Hi and Bi are defined by the minimal number of cases added to the treatment arm (Hi) or control arm (Bi) of studies with no cases in a meta-analysis that lead to a change of the direction of the estimates or its statistical significance. Both exact and approximating methods are available to calculate Hi and Bi. We developed the "hibi" module in Stata so that researchers can easily implement the method. A real-world investigation of meta-analyses from Cochrane reviews was employed to evaluate the proposed method. RESULTS: Based on Hi and Bi, our results suggested that 21.53% (Hi) to 26.55% (Bi) of Cochrane meta-analyses may be potentially impacted by studies with no cases, for which studies with no cases could not be excluded from the synthesis. The approximating method shows excellent specificity (100%) for both Hi and Bi, moderate sensitivity (68.25%) for Bi, and high sensitivity (80.61%) for Hi compared to the exact method. CONCLUSIONS: The proposed method is practical and useful for systematic reviewers to measure whether studies with no cases impact the results of meta-analyses and may act as an alternative solution for review authors to decide whether to include studies with no events for the synthesis or not.

Study of natural product adverse events in adult HIV-infected patients in Canada.

INTRODUCTION: Many individuals living with HIV use natural health products (NHPs) in an effort to decrease medication side effects and to enhance overall well-being. METHODS: An active surveillance study of adult patients (≥ 18 years) with HIV was conducted between 2012 and 2014 to detect prescription drug and NHP use and associated adverse events (AEs) in the last month. RESULTS: Of the 167 participants, 85 (50.9%) took prescription medications only, three (1.8%) took NHPs only, 75 (44.9%) took NHPs and prescription medications concurrently, and four (2.4%) took neither. Patients who used both prescription drugs and NHPs concurrently were more than three times more likely to experience an AE compared with those who used prescription drugs only (OR, P = 0.003, 95% CI: 1.47-6.91). CONCLUSIONS: Increased AEs are reported in patients with HIV who combine NHPs and prescription medications, and no serious AEs were reported. Active surveillance was found to be feasible in this clinical setting.

Guidelines for Reporting Outcomes in Trial Reports: The CONSORT-Outcomes 2022 Extension.

Importance: Clinicians, patients, and policy makers rely on published results from clinical trials to help make evidence-informed decisions. To critically evaluate and use trial results, readers require complete and transparent information regarding what was planned, done, and found. Specific and harmonized guidance as to what outcome-specific information should be reported in publications of clinical trials is needed to reduce deficient reporting practices that obscure issues with outcome selection, assessment, and analysis. Objective: To develop harmonized, evidence- and consensus-based standards for reporting outcomes in clinical trial reports through integration with the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement. Evidence Review: Using the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework, the CONSORT-Outcomes 2022 extension of the CONSORT 2010 statement was developed by (1) generation and evaluation of candidate outcome reporting items via consultation with experts and a scoping review of existing guidance for reporting trial outcomes (published within the 10 years prior to March 19, 2018) identified through expert solicitation, electronic database searches of MEDLINE and the Cochrane Methodology Register, gray literature searches, and reference list searches; (2) a 3-round international Delphi voting process (November 2018-February 2019) completed by 124 panelists from 22 countries to rate and identify additional items; and (3) an in-person consensus meeting (April 9-10, 2019) attended by 25 panelists to identify essential items for the reporting of outcomes in clinical trial reports. Findings: The scoping review and consultation with experts identified 128 recommendations relevant to reporting outcomes in trial reports, the majority (83%) of which were not included in the CONSORT 2010 statement. All recommendations were consolidated into 64 items for Delphi voting; after the Delphi survey process, 30 items met criteria for further evaluation at the consensus meeting and possible inclusion in the CONSORT-Outcomes 2022 extension. The discussions during and after the consensus meeting yielded 17 items that elaborate on the CONSORT 2010 statement checklist items and are related to completely defining and justifying the trial outcomes, including how and when they were assessed (CONSORT 2010 statement checklist item 6a), defining and justifying the target difference between treatment groups during sample size calculations (CONSORT 2010 statement checklist item 7a), describing the statistical methods used to compare groups for the primary and secondary outcomes (CONSORT 2010 statement checklist item 12a), and describing the prespecified analyses and any outcome analyses not prespecified (CONSORT 2010 statement checklist item 18). Conclusions and Relevance: This CONSORT-Outcomes 2022 extension of the CONSORT 2010 statement provides 17 outcome-specific items that should be addressed in all published clinical trial reports and may help increase trial utility, replicability, and transparency and may minimize the risk of selective nonreporting of trial results.

Guidelines for Reporting Outcomes in Trial Protocols: The SPIRIT-Outcomes 2022 Extension.

Importance: Complete information in a trial protocol regarding study outcomes is crucial for obtaining regulatory approvals, ensuring standardized trial conduct, reducing research waste, and providing transparency of methods to facilitate trial replication, critical appraisal, accurate reporting and interpretation of trial results, and knowledge synthesis. However, recommendations on what outcome-specific information should be included are diverse and inconsistent. To improve reporting practices promoting transparent and reproducible outcome selection, assessment, and analysis, a need for specific and harmonized guidance as to what outcome-specific information should be addressed in clinical trial protocols exists. Objective: To develop harmonized, evidence- and consensus-based standards for describing outcomes in clinical trial protocols through integration with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 statement. Evidence Review: Using the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework, the SPIRIT-Outcomes 2022 extension of the SPIRIT 2013 statement was developed by (1) generation and evaluation of candidate outcome reporting items via consultation with experts and a scoping review of existing guidance for reporting trial outcomes (published within the 10 years prior to March 19, 2018) identified through expert solicitation, electronic database searches of MEDLINE and the Cochrane Methodology Register, gray literature searches, and reference list searches; (2) a 3-round international Delphi voting process (November 2018-February 2019) completed by 124 panelists from 22 countries to rate and identify additional items; and (3) an in-person consensus meeting (April 9-10, 2019) attended by 25 panelists to identify essential items for outcome-specific reporting to be addressed in clinical trial protocols. Findings: The scoping review and consultation with experts identified 108 recommendations relevant to outcome-specific reporting to be addressed in trial protocols, the majority (72%) of which were not included in the SPIRIT 2013 statement. All recommendations were consolidated into 56 items for Delphi voting; after the Delphi survey process, 19 items met criteria for further evaluation at the consensus meeting and possible inclusion in the SPIRIT-Outcomes 2022 extension. The discussions during and after the consensus meeting yielded 9 items that elaborate on the SPIRIT 2013 statement checklist items and are related to completely defining and justifying the choice of primary, secondary, and other outcomes (SPIRIT 2013 statement checklist item 12) prospectively in the trial protocol, defining and justifying the target difference between treatment groups for the primary outcome used in the sample size calculations (SPIRIT 2013 statement checklist item 14), describing the responsiveness of the study instruments used to assess the outcome and providing details on the outcome assessors (SPIRIT 2013 statement checklist item 18a), and describing any planned methods to account for multiplicity relating to the analyses or interpretation of the results (SPIRIT 2013 statement checklist item 20a). Conclusions and Relevance: This SPIRIT-Outcomes 2022 extension of the SPIRIT 2013 statement provides 9 outcome-specific items that should be addressed in all trial protocols and may help increase trial utility, replicability, and transparency and may minimize the risk of selective nonreporting of trial results.

Utilization of the evidence from studies with no events in meta-analyses of adverse events: an empirical investigation.

BACKGROUNDS: Zero-events studies frequently occur in systematic reviews of adverse events, which consist of an important source of evidence. We aimed to examine how evidence of zero-events studies was utilized in the meta-analyses of systematic reviews of adverse events. METHODS: We conducted a survey of systematic reviews published in two periods: January 1, 2015, to January 1, 2020, and January 1, 2008, to April 25, 2011. Databases were searched for systematic reviews that conducted at least one meta-analysis of any healthcare intervention and used adverse events as the exclusive outcome. An adverse event was defined as any untoward medical occurrence in a patient or subject in healthcare practice. We summarized the frequency of occurrence of zero-events studies in eligible systematic reviews and how these studies were dealt with in the meta-analyses of these systematic reviews. RESULTS: We included 640 eligible systematic reviews. There were 406 (63.45%) systematic reviews involving zero-events studies in their meta-analyses, among which 389 (95.11%) involved single-arm-zero-events studies and 223 (54.93%) involved double-arm-zero-events studies. The majority (98.71%) of these systematic reviews incorporated single-arm-zero-events studies into the meta-analyses. On the other hand, the majority (76.23%) of them excluded double-arm-zero-events studies from the meta-analyses, of which the majority (87.06%) did not discuss the potential impact of excluding such studies. Systematic reviews published at present (2015-2020) tended to incorporate zero-events studies in meta-analyses than those published in the past (2008-2011), but the difference was not significant (proportion difference=-0.09, 95% CI -0.21 to 0.03, p = 0.12). CONCLUSION: Systematic review authors routinely treated studies with zero-events in both arms as "non-informative" carriers and excluded them from their reviews. Whether studies with no events are "informative" or not largely depends on the methods and assumptions applied, thus sensitivity analyses using different methods should be considered in future meta-analyses.

Systematic Review of Mind-Body Interventions to Treat Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Background and Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic condition distinguished by disabling fatigue associated with post-exertional malaise, as well as changes to sleep, autonomic functioning, and cognition. Mind-body interventions (MBIs) utilize the ongoing interaction between the mind and body to improve health and wellbeing. Purpose: To systematically review studies using MBIs for the treatment of ME/CFS symptoms. Materials and Methods: MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane CENTRAL were searched (inception to September 2020). Interventional studies on adults diagnosed with ME/CFS, using one of the MBIs in comparison with any placebo, standard of care treatment or waitlist control, and measuring outcomes relevant to the signs and symptoms of ME/CFS and quality of life were assessed for inclusion. Characteristics and findings of the included studies were summarized using a descriptive approach. Results: 12 out of 382 retrieved references were included. Seven studies were randomized controlled trials (RCTs) with one including three reports (1 RCT, 2 single-arms); others were single-arm trials. Interventions included mindfulness-based stress reduction, mindfulness-based cognitive therapy, relaxation, Qigong, cognitive-behavioral stress management, acceptance and commitment therapy and isometric yoga. The outcomes measured most often were fatigue severity, anxiety/depression, and quality of life. Fatigue severity and symptoms of anxiety/depression were improved in nine and eight studies respectively, and three studies found that MBIs improved quality of life. Conclusions: Fatigue severity, anxiety/depression and physical and mental functioning were shown to be improved in patients receiving MBIs. However, small sample sizes, heterogeneous diagnostic criteria, and a high risk of bias may challenge this result. Further research using standardized outcomes would help advance the field.

Massage therapy for paediatric procedural pain: A rapid review.

BACKGROUND: Pain is a common paediatric problem, and procedural pain, in particular, can be difficult to manage. Complementary therapies are often sought for pain management, including massage therapy (MT). We assessed the evidence for use of MT for acute procedural pain management in children. METHODS: We searched five main databases for (i) primary studies in English, (ii) included children 0 to 18 years of age, (iii) compared MT for procedural pain management to standard care alone or placebo, and (iv) measured pain as the primary or secondary outcome. The data were extracted by one author and verified by a second author. Randomized controlled trials were evaluated using the Cochrane Risk of Bias tool. RESULTS: Eleven paediatric trials of procedural pain in neonatal, burn, and oncology populations, a total of 771 participants, were identified. Eight reported statistically significant reductions in pain after MT compared to standard care. Pain was measured using validated pain scales, or physiologic indicators. The studies were heterogeneous in population, techniques, and outcome measures used. No adverse events associated with MT were identified. CONCLUSION: MT may be an effective nonpharmacologic adjunct for management of procedural pain in children.

Experiences of shared decision-making in community rehabilitation: a focused ethnography.

BACKGROUND: Shared decision-making (SDM) can advance patient satisfaction, understanding, goal fulfilment, and patient-reported outcomes. We lack clarity on whether this physician-focused literature applies to community rehabilitation, and on the integration of SDM policies in healthcare settings. We aimed to understand patient and provider perceptions of shared decision-making (SDM) in community rehabilitation, particularly the barriers and facilitators to SDM. METHODS: We used a focused ethnography involving 14 community rehabilitation sites across Alberta, including rural, regional-urban and metropolitan-urban sites. We conducted semi-structured interviews that asked participants about their positive and negative communication experiences (n = 23 patients; n = 26 providers). RESULTS: We found SDM experiences fluctuated between extremes: Getting Patient Buy-In and Aligning Expectations. The former is provider-driven, prescriptive and less flexible; the latter is collaborative, inquisitive and empowering. In Aligning Expectations, patients and providers express humility and openness, communicate in the language of ask and listen, and view education as empowering. Patients and providers described barriers and facilitators to SDM in community rehabilitation. Facilitators included geography influencing context and connections; consistent, patient-specific messaging; patient lifestyle, capacity and perceived outlook; provider confidence, experience and perceived independence; provider training; and perceptions of more time (and control over time) for appointments. SDM barriers included lack of privacy; waitlists and financial barriers to access; provider approach; how choices are framed; and, patient's perceived assertiveness, lack of capacity, and level of deference. CONCLUSIONS: We have found both excellent experiences and areas for improvement for applying SDM in community rehabilitation. We proffer recommendations to advance high-quality SDM in community rehabilitation based on promoting facilitators and overcoming barriers. This research will support the spread, scale and evaluation of a new Model of Care in rehabilitation by the provincial health system, which aimed to promote patient-centred care.

Use of Complementary Health Approaches for Acute Complaints Presenting to the Emergency Department.

OBJECTIVE: This study aimed to determine the prevalence of complementary health approaches (CHAs) specifically for acute complaints in patients assessed in a pediatric emergency department (ED) and factors associated with use. METHODS: A cross-sectional survey was offered to patients between the age of 28 days and 18 years assessed at a tertiary pediatric ED between December 2014 and July 2015. Univariate and multivariate logistic regressions were used to identify variables associated with CHA use. RESULTS: Of 475 potential participants, 412 (86.7%) participated, of which 369 (89.5%) completed the survey. Overall, 28.7% (95% confidence interval [CI], 24.3-33.5) reported using any CHA for their child to treat the presenting complaint in the prior 72 hours to the ED visit. Gastrointestinal complaints had the highest use of CHA (46.3% of presentations endorsed use). The most common complementary health products used were vitamins and minerals (40.9%; 95% CI, 31.2-51.4); the most common complementary health practice used was massage (37.2%; 95% CI, 24.4-52.1). Multivariate analysis showed lower odds of using CHA for rash/skin complaint (odds ratio, 0.23; 95% CI, 0.09-0.59; P < 0.01) or musculoskeletal/extremity complaints (odds ratio, 0.23; 95% CI, 0.07-0.75; P = 0.01) compared with use for fever. No statistically significant association was found between CHAs use and child's sex, child's age, private insurance, or caregiver education. CONCLUSIONS: Caregivers commonly use CHA for acute pediatric complaints requiring an ED visit, with greatest use for gastrointestinal complaints. Clinicians should consider the use and safety of CHA when evaluating children presenting to the ED with acute conditions.

A systematic review of the effectiveness of sleep hygiene in children with ADHD.

Attention deficit/hyperactivity disorder (ADHD) is often accompanied by sleep problems in children. Sleep hygiene is defined as a set of behavioural, environmental, or cognitive modifications to improve sleep, and is routinely clinically utilised as first-line treatment for insomnia in ADHD. The objective of this systematic review of the literature is to evaluate the effectiveness of sleep hygiene interventions for sleep difficulties in children with ADHD. Sixteen relevant articles met the inclusion criteria, involving 1,469 participants, with a mean age of 9.6 years, across 6 countries. Fifteen studies found that sleep hygiene interventions were effective in improving sleep, while one did not show any significant improvement. Definite conclusions on the effectiveness of the interventions are difficult to draw due to the limited number of studies and a high risk of bias. There is growing evidence to support the use of sleep hygiene interventions to improve sleep quality in children with ADHD and sleep disturbance. However, well-conducted clinical trials are required to strengthen the evidence.

Effectiveness of probiotics in infantile colic: A rapid review.

BACKGROUND: Infantile colic (IC) is a troubling condition with limited treatment options for young infants. This rapid review aims to synthesize the evidence for probiotics in the treatment and prevention of IC in healthy term infants. METHODS: We searched in MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews for systematic reviews (SRs), and randomized control trials (RCTs) published between January 1, 2000 and July 11, 2018. Trials were included if they recruited healthy full-term infants who received probiotics for treatment or prevention of colic. The quality of evidence was assessed using GRADE criteria. As supplementary information, the safety of probiotics in infants was searched within the reviewed studies and other recent publications. RESULTS: We identified four SRs and meta-analyses that included six RCTs, and found an additional three RCTs evaluating probiotics for the treatment of IC. One SR and six RCTs were identified for prevention of IC; four of the RCTs were included in the SR and two were published later. The probiotic Lactobacillus reuteri was used in the majority (five of eight) of treatment trials, and was found to significantly reduce crying in colicky breast-fed infants compared to placebo. Only two of the six prevention trials showed a significant decrease in crying time compared to placebo, although another two trials showed other benefits of probiotics, including reduced use of medications (simethicone and cimetropium bromide) and physician visits. No adverse events were identified in the included studies; other research suggests probiotics are generally safe in healthy children. CONCLUSION: This rapid review identified limited but favourable evidence of benefit of using probiotics for the treatment of IC in full-term breast-fed infants. While routine use of probiotics for treating or preventing IC cannot yet be recommended, it can be an option to manage IC.

Individualized health-related quality of life instrument Measure Yourself Medical Outcome Profile (MYMOP) and its adaptations: a critical appraisal.

BACKGROUND: Health-related quality of life (HRQL) is increasingly recognized for its importance in health research. As there is increasing recognition of the inter-individual difference in response to therapeutic interventions, it may be helpful to apply individualized measures of HRQL. The MYMOP is a commonly used example of such measures, although several adaptations have been developed. OBJECTIVE: This review was conducted to identify adaptations of MYMOP, and evaluate the measurement properties of MYMOP and its adaptations. METHODS: Adaptations were identified using MYMOP website and personal communication, supplemented by a SCOPUS search in April 2017. Bibliographies of included studies were hand-searched. COSMIN criteria were used to evaluate the measurement properties. RESULTS: Sixteen studies were included in this review. Adaptations were developed to evaluate individualized therapies in cancer, psychiatry, and acupuncture. The included measures were MYMOP, measure yourself concern and wellbeing, psychological outcome profiles (PSYCHLOPS), and MYMOP-pictorial (MYMOP-P). The quality of the measurement properties varied; none of the included measures met all currently recommended quality criteria for measurement properties. CONCLUSION: Current literature provides evidence that MYMOP and its adaptations offer individualized assessment of patient-centered outcomes, and thereby provide a means to understand heterogeneity of treatment effects. However, current recommendations for psychometric testing suggest further validation of these measures would be beneficial.

On-Demand Sildenafil as a Treatment for Raynaud Phenomenon: A Series of n-of-1 Trials.

Background: Treatment of Raynaud phenomenon (RP) with phosphodiesterase-5 inhibitors has shown moderate efficacy. Adverse effects decrease the risk-benefit profile of these drugs, and patients may not be willing to receive long-term treatment. On-demand single doses before or during exposure to cold may be a good alternative. Objective: To assess the efficacy and safety of on-demand sildenafil in RP. Design: Series of randomized, double-blind, n-of-1 trials. (ClinicalTrials.gov: NCT02050360). Setting: Outpatients at a French university hospital. Participants: Patients with primary or secondary RP. Intervention: Each trial consisted of a multiple crossover study in a single patient. Repeated blocks of 3 periods of on-demand treatment were evaluated: 1 week of placebo, 1 week of sildenafil at 40 mg per dose, and 1 week of sildenafil at 80 mg per dose, with a maximum of 2 doses daily. Measurements: Raynaud Condition Score (RCS) and frequency and daily duration of attacks. Skin blood flow in response to cooling also was assessed with laser speckle contrast imaging. Mixed-effects models were used and parameters were estimated in a Bayesian framework to determine individual and aggregated efficacy. Results: 38 patients completed 2 to 5 treatment blocks. On the basis of aggregated data, the probability that sildenafil at 40 mg or 80 mg was more effective than placebo was greater than 90% for all outcomes (except for RCS with sildenafil, 80 mg). However, the aggregated effect size was not clinically relevant. Yet, substantial heterogeneity in sildenafil's efficacy was observed among participants, with clinically relevant efficacy in some patients. Limitation: The response to sildenafil was substantially heterogeneous among patients. Conclusion: Despite a high probability that sildenafil is superior to placebo, substantial heterogeneity was observed in patient response and aggregated results did not show that on-demand sildenafil has clinically relevant efficacy. In this context, the use of n-of-1 trials may be an original and relevant approach in RP. Primary Funding Source: GIRCI (Groupement Interrégional de Recherche Clinique et d'Innovation) Auvergne Rhône-Alpes (academic funding) and Pfizer.

Mindfulness-based stress reduction for mental health in youth: a cluster randomized controlled trial.

BACKGROUND: Mental illness is among the most common causes of morbidity, mortality, and disability in childhood. Mindfulness-based stress reduction (MBSR) has shown significant benefit in mental health; however, evidence of its effectiveness in youth is limited. The objective of this study was to compare the efficacy of MBSR plus usual care versus usual care alone for reducing mental health symptoms in youth. METHODS: A two-arm, mixed methods, randomized cluster-controlled trial of 12-18 year olds who were residents of CASA House, a voluntary residential treatment program for adolescents, between January 2011 and March 2013 (clinicaltrials.gov, NCT01307943). INTERVENTIONS: Treatment terms were randomized to usual care, or MBSR plus usual care, which included eight MBSR sessions of 2 hr/week. OUTCOMES: The primary outcome was impact on emotions and behavior at the end of the program, using the Behavior Assessment System for Children, Second Edition (BASC-2). Secondary outcomes included perceived stress levels, mindfulness, and emotional regulation. RESULTS: A total of 85 participants were randomized to either the MBSR arm (n = 45) or control arm (n = 40). Significant differences in favor of MBSR were found on Teacher ratings of the Internalizing Problems (p = .038) and Adaptive Skills subscales (p = .022) on the BASC-2. No significant differences were found on other outcomes. A post hoc analysis found that the MBSR arm had a significantly shorter time to discharge (p = .02). CONCLUSION: The results of this study indicate that MBSR is effective for improved coping with internalizing problems and adaptive emotional skills in our sample. Future studies should focus on larger, longer-term studies in youth.

Relaxation training for management of paediatric headache: A rapid review.

The objective of this review was to assess the evidence on relaxation training for management of paediatric headaches. Our methodology was a rapid review of English-language peer reviewed published literature focused on studies evaluating relaxation training as a primary or adjunct management option for headache in a paediatric population (0 to 18 years of age). Seven studies involving 571 children were included in the review. The quality of evidence was very low using GRADE criteria. Headache frequency, duration, and intensity were the primary outcomes in the included studies. Results for the effects of relaxation training for paediatric headache are inconsistent. Four of the seven studies reported decreased headache frequency, two of the five studies reported decreased headache duration, and two of the six studies reported decreased headache intensity following relaxation training. No adverse events were reported. The current state of the evidence for relaxation training for management of paediatric headache is both inconsistent and of very low quality. High-quality research evaluating the effects of relaxation training for paediatric headaches is required to advance the field.

Probiotics for paediatric functional abdominal pain disorders: A rapid review.

BACKGROUND: Functional abdominal pain disorders (FAPD) are prevalent in the paediatric population, however, there is currently no consensus regarding best practices for treatment. The use of probiotics is becoming popular to treat FAPD. The goal of this rapid review is to synthesize the best evidence on the use of probiotics in children with FAPD. METHODS: Searches were conducted on five main databases. Randomized controlled trials (RCTs) of probiotic use in children (0 to 18 years) with FAPD were searched. Populations of interest were patients with functional abdominal pain (FAP), irritable bowel syndrome (IBS), and functional dyspepsia (FD), recruited based on Rome criteria. Outcomes of interest were changes in abdominal pain severity, frequency, and duration. FINDINGS: Eleven RCTs with 829 participants with the diagnosis of FAP (n=400), IBS (n=329), FD (n=45), and mixed population (n=55) were included. Of six studies of children with FAP, two (n=103) used Lactobacillus rhamnosus GG (LGG) and reported no significant effects on pain, and four (n=281) used Lactobacillus (L) reuteri DSM 17938, of which three (n=229) reported significant positive effects on either severity or frequency of pain. Of six trials of children with IBS, four (n=219) used LGG, of which three (n=168) reported a positive effect. One (n=48) used bifidobacteria and one used VSL #3 (n=59), both demonstrating positive effects with probiotics. Two studies of FD reported no benefit. No adverse events were attributed to probiotics. CONCLUSIONS: There is preliminary evidence for use of probiotics, particularly LGG, in reducing abdominal pain in children with IBS. There are inconsistent positive effects of other probiotics, including L. reuteri DSM 17938, in reducing pain in patients with FAP, IBS, or FD. More RCTs with rigorous methodology using single or combination probiotics are warranted.

WITHDRAWN: Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome.

BACKGROUND: Chronic fatigue is increasingly common. Conventional medical care is limited in treating chronic fatigue, leading some patients to use traditional Chinese medicine therapies, including herbal medicine. OBJECTIVES: To assess the effectiveness of traditional Chinese medicine herbal products in treating idiopathic chronic fatigue and chronic fatigue syndrome. SEARCH METHODS: The following databases were searched for terms related to traditional Chinese medicine, chronic fatigue, and clinical trials: CCDAN Controlled Trials Register (July 2009), MEDLINE (1966-2008), EMBASE (1980-2008), AMED (1985-2008), CINAHL (1982-2008), PSYCHINFO (1985-2008), CENTRAL (Issue 2 2008), the Chalmers Research Group PedCAM Database (2004), VIP Information (1989-2008), CNKI (1976-2008), OCLC Proceedings First (1992-2008), Conference Papers Index (1982-2008), and Dissertation Abstracts (1980-2008). Reference lists of included studies and review articles were examined and experts in the field were contacted for knowledge of additional studies. SELECTION CRITERIA: Selection criteria included published or unpublished randomized controlled trials (RCTs) of participants diagnosed with idiopathic chronic fatigue or chronic fatigue syndrome comparing traditional Chinese medicinal herbs with placebo, conventional standard of care (SOC), or no treatment/wait lists. The outcome of interest was fatigue. DATA COLLECTION AND ANALYSIS: 13 databases were searched for RCTs investigating TCM herbal products for the treatment of chronic fatigue. Over 2400 references were located. Studies were screened and assessed for inclusion criteria by two authors. MAIN RESULTS: No studies that met all inclusion criteria were identified. AUTHORS' CONCLUSIONS: Although studies examining the use of TCM herbal products for chronic fatigue were located, methodologic limitations resulted in the exclusion of all studies. Of note, many of the studies labelled as RCTs and conducted in China did not utilize rigorous randomization procedures. Improvements in methodology in future studies is required for meaningful synthesis of data.

Interventions to prevent hypothermia at birth in preterm and/or low birth weight infants.

BACKGROUND: Newborn admission temperature is a strong predictor of outcomes across all gestations. Hypothermia immediately after birth remains a worldwide issue and, if prolonged, is associated with harm. Keeping preterm infants warm is difficult even when recommended routine thermal care guidelines are followed in the delivery room. OBJECTIVES: To assess the efficacy and safety of interventions designed for prevention of hypothermia in preterm and/or low birth weight infants applied within 10 minutes after birth in the delivery room, compared with routine thermal care or any other single/combination of intervention(s) also designed for prevention of hypothermia in preterm and/or low birth weight infants applied within 10 minutes after birth in the delivery room. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 5), MEDLINE via PubMed (1966 to 30 June 2016), Embase (1980 to 30 June 2016), and CINAHL (1982 to 30 June 2016). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Trials using randomised or quasi-randomised allocations to test interventions designed to prevent hypothermia (apart from 'routine' thermal care) applied within 10 minutes after birth in the delivery room for infants at < 37 weeks' gestation and/or birth weight ≤ 2500 grams. DATA COLLECTION AND ANALYSIS: We used Cochrane Neonatal methods when performing data collection and analysis. MAIN RESULTS: Twenty-five studies across 15 comparison groups met the inclusion criteria, categorised as: barriers to heat loss (18 studies); external heat sources (three studies); and combinations of interventions (four studies).Barriers to heat loss Plastic wrap or bag versus routine carePlastic wraps improved core body temperature on admission to the neonatal intensive care unit (NICU) or up to two hours after birth (mean difference (MD) 0.58°C, 95% confidence interval (CI) 0.50 to 0.66; 13 studies; 1633 infants), and fewer infants had hypothermia on admission to the NICU or up to two hours after birth (typical risk ratio (RR) 0.67, 95% CI 0.62 to 0.72; typical risk reduction (RD) -0.25, 95% CI -0.29 to -0.20; number needed to treat for an additional beneficial outcome (NNTB) 4, 95% CI 4 to 5; 10 studies; 1417 infants). Risk of hyperthermia on admission to the NICU or up to two hours after birth was increased in infants in the wrapped group (typical RR 3.91, 95% CI 2.05 to 7.44; typical RD 0.04, 95% CI 0.02 to 0.06; number needed to treat for an additional harmful outcome (NNTH) 25, 95% CI 17 to 50; 12 studies; 1523 infants), but overall, fewer infants receiving plastic wrap were outside the normothermic range (typical RR 0.75, 95% CI 0.69 to 0.81; typical RD -0.20, 95% CI -0.26 to -0.15; NNTH 5, 95% CI 4 to 7; five studies; 1048 infants).Evidence was insufficient to suggest that plastic wraps or bags significantly reduce risk of death during hospital stay or other major morbidities, with the exception of reducing risk of pulmonary haemorrhage.Evidence of practices regarding permutations on this general approach is still emerging and has been based on the findings of only one or two small studies.External heat sourcesEvidence is emerging on the efficacy of external heat sources, including skin-to-skin care (SSC) versus routine care (one study; 31 infants) and thermal mattress versus routine care (two studies; 126 infants).SSC was shown to be effective in reducing risk of hypothermia when compared with conventional incubator care for infants with birth weight ≥ 1200 and ≤ 2199 grams (RR 0.09, 95% CI 0.01 to 0.64; RD -0.56, 95% CI -0.84 to -0.27; NNTB 2, 95% CI 1 to 4). Thermal (transwarmer) mattress significantly kept infants ≤ 1500 grams warmer (MD 0.65°C, 95% CI 0.36 to 0.94) and reduced the incidence of hypothermia on admission to the NICU, with no significant difference in hyperthermia risk.Combinations of interventionsTwo studies (77 infants) compared thermal mattresses versus plastic wraps or bags for infants at ≤ 28 weeks' gestation. Investigators reported no significant differences in core body temperature nor in the incidence of hypothermia, hyperthermia, or core body temperature outside the normothermic range on admission to the NICU.Two additional studies (119 infants) compared plastic bags and thermal mattresses versus plastic bags alone for infants at < 31 weeks' gestation. Meta-analysis of these two studies showed improvement in core body temperature on admission to the NICU or up to two hours after birth, but an increase in hyperthermia. Data show no significant difference in the risk of having a core body temperature outside the normothermic range on admission to the NICU nor in the risk of other reported morbidities. AUTHORS' CONCLUSIONS: Evidence of moderate quality shows that use of plastic wraps or bags compared with routine care led to higher temperatures on admission to NICUs with less hypothermia, particularly for extremely preterm infants. Thermal mattresses and SSC also reduced hypothermia risk when compared with routine care, but findings are based on two or fewer small studies. Caution must be taken to avoid iatrogenic hyperthermia, particularly when multiple interventions are used simultaneously. Limited evidence suggests benefit and no evidence of harm for most short-term morbidity outcomes known to be associated with hypothermia, including major brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotising enterocolitis, and nosocomial infection. Many observational studies have shown increased mortality among preterm hypothermic infants compared with those who maintain normothermia, yet evidence is insufficient to suggest that these interventions reduce risk of in-hospital mortality across all comparison groups. Hypothermia may be a marker for illness and poorer outcomes by association rather than by causality. Limitations of this review include small numbers of identified studies; small sample sizes; and variations in methods and definitions used for hypothermia, hyperthermia, normothermia, routine care, and morbidity, along with lack of power to detect effects on morbidity and mortality across most comparison groups. Future studies should: be adequately powered to detect rarer outcomes; apply standardised morbidity definitions; focus on longer-term outcomes, particularly neurodevelopmental outcomes.

Turning a blind eye and a deaf ear to traditional and complementary medicine practice does not make it go away: a qualitative study exploring perceptions and attitudes of stakeholders towards the integration of traditional and complementary medicine into medical school curriculum in Uganda.

BACKGROUND: A substantial proportion of healthcare professionals have inadequate understanding of traditional and complementary medicine and often consider their use inappropriate. METHODS: We conducted a qualitative study to understand the perceptions and attitudes of medical students, medical school faculty and traditional and complementary medicine practitioners. In-depth interviews and focus group discussions were used to collect data. Thematic approach was used in data analysis to identify emerging themes and sub themes. Data analysis was supported with use of Atlas.ti v6.1.1. RESULTS: The majority of participants commended the inclusion of traditional and complementary medicine principles into medical school curricula. The main reasons advanced were that: patients are already using these medicines and doctors need to understand them; doctors would be more accommodating to use and not rebuke patients, thereby minimizing delays in care due to pursuit of alternative therapies; promote patient safety; foster therapeutic alliance and adherence to therapy; uphold patients' right to self-determination; lead to discovery of new drugs from traditional medicines; and set ground for regulation of practices and quality control. However, participants anticipated operational and ethical challenges that include inadequate number of faculty to teach the subject, congested curricula, increased costs in research and development to produce evidence-base data, obstruction by pharmaceutical companies, inaccessibility to and depletion of medicinal plants, and potential conflicts due to diversity in culture and values. A substantial minority of participants thought traditional medicine need not be taught in medical schools because there is lack of scientific evidence on efficacy, safety, and side effects profiles. These shortfalls could make the determination of benefits (beneficence) and harm (maleficence) difficult, as well as compromise the ability of physicians to adequately disclose benefits and harms to patients and family, thereby undermining the process of informed consent and patient autonomy. CONCLUSIONS: Training medical students in principles of traditional and complementary medicine is considered reasonable, feasible, and acceptable; and could lead to improvement in health outcomes. There are anticipated challenges to implementing a hybrid medical school curricula, but these are surmountable and need not delay introducing traditional and complementary medicine principles into medical school curricula in Uganda.