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.

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.

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.

Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric conditions affecting children and adolescents. Amphetamines are among the most commonly prescribed medications to manage ADHD. There are three main classes of amphetamines: dexamphetamine, lisdexamphetamine and mixed amphetamine salts, which can be further broken down into short- and long-acting formulations. A systematic review assessing their efficacy and safety in this population has never been conducted. OBJECTIVES: To assess the efficacy and safety of amphetamines for ADHD in children and adolescents. SEARCH METHODS: In August 2015 we searched CENTRAL, Ovid MEDLINE, Embase, PsycINFO, ProQuest Dissertation and Theses, and the Networked Digital Library of Theses and Dissertations. We also searched ClinicalTrials.gov, and checked the reference lists of relevant studies and reviews identified by the searches. No language or date restrictions were applied. SELECTION CRITERIA: Parallel-group and cross-over randomized controlled trials (RCTs) comparing amphetamine derivatives against placebo in a pediatric population (< 18 years) with ADHD. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data on participants, settings, interventions, methodology, and outcomes for each included study. For continuous outcomes, we calculated the standardized mean difference (SMD) and for dichotomous outcomes we calculated the risk ratio (RR). Where possible, we conducted meta-analyses using a random-effects model. We also performed a meta-analysis of the most commonly reported adverse events in the primary studies. MAIN RESULTS: We included 23 trials (8 parallel-group and 15 cross-over trials), with 2675 children aged three years to 17 years. All studies compared amphetamines to placebo. Study durations ranged from 14 days to 365 days, with the majority lasting less than six months. Most studies were conducted in the United States; three studies were conducted across Europe. We judged 11 included studies to be at a high risk of bias due to insufficient blinding methods, failing to account for dropouts and exclusions from the analysis, and failing to report on all outcomes defined a priori. We judged the remaining 12 studies to be at unclear risk of bias due to inadequate reporting.Amphetamines improved total ADHD core symptom severity according to parent ratings (SMD -0.57; 95% confidence interval (CI) -0.86 to -0.27; 7 studies; 1247 children/adolescents; very low quality evidence), teacher ratings (SMD -0.55; 95% CI -0.83 to -0.27; 5 studies; 745 children/adolescents; low quality evidence), and clinician ratings (SMD -0.84; 95% CI -1.32 to -0.36; 3 studies; 813 children/adolescents; very low quality evidence). In addition, the proportion of responders as rated by the Clinical Global Impression - Improvement (CGI-I) scale was higher when children were taking amphetamines (RR 3.36; 95% CI 2.48 to 4.55; 9 studies; 2207 children/adolescents; very low quality evidence).The most commonly reported adverse events included decreased appetite, insomnia/trouble sleeping, abdominal pain, nausea/vomiting, headaches, and anxiety. Amphetamines were associated with a higher proportion of participants experiencing decreased appetite (RR 6.31; 95% CI 2.58 to 15.46; 11 studies; 2467 children/adolescents), insomnia (RR 3.80; 95% CI 2.12 to 6.83; 10 studies; 2429 children/adolescents), and abdominal pain (RR 1.44; 95% CI 1.03 to 2.00; 10 studies; 2155 children/adolescents). In addition, the proportion of children who experienced at least one adverse event was higher in the amphetamine group (RR 1.30; 95% CI 1.18 to 1.44; 6 studies; 1742 children/adolescents; low quality evidence).We performed subgroup analyses for amphetamine preparation (dexamphetamine, lisdexamphetamine, mixed amphetamine salts), amphetamine release formulation (long acting versus short acting), and funding source (industry versus non industry). Between-group differences were observed for proportion of participants experiencing decreased appetite in both the amphetamine preparation (P < 0.00001) and amphetamine release formulation (P value = 0.008) subgroups, as well as for retention in the amphetamine release formulation subgroup (P value = 0.03). AUTHORS' CONCLUSIONS: Most of the included studies were at high risk of bias and the overall quality of the evidence ranged from low to very low on most outcomes. Although amphetamines seem efficacious at reducing the core symptoms of ADHD in the short term, they were associated with a number of adverse events. This review found no evidence that supports any one amphetamine derivative over another, and does not reveal any differences between long-acting and short-acting amphetamine preparations. Future trials should be longer in duration (i.e. more than 12 months), include more psychosocial outcomes (e.g. quality of life and parent stress), and be transparently reported.

Toward integrated pediatric medicine: Key learnings from the pediatric integrative medicine trial.

OBJECTIVE: The purpose of this study is to explore the facilitators to integrating complementary therapies in conventional pediatric hospital practice based on the experiences of parents, healthcare providers, and complementary therapy providers. DESIGN: This study is part of a larger research study that examined the introduction of a pediatric integrative medicine service in an acute care children's hospital in Canada. A qualitative descriptive study was conducted using semi-structured one-on-one telephone and in-person interviews with a sample of parents of children, as well as healthcare providers and complementary therapy providers. RESULTS: A total of 50 individuals, from key-stakeholder groups, were interviewed between May 2014 and January 2016. This study identified the following facilitators for the integration of complementary therapies within conventional care: 1) stakeholders' open-mindedness and familiarity with care practices outside of their experiences; 2) stakeholders' open communication, respect for eachothers' roles in the process of care, and appreciation for the role of complementary therapies within conventional medicine; and 3) stakeholders' receptiveness to redefining the meaning of a 'positive outcome' in the context of hospital care. CONCLUSION: The findings of this study demonstrate that some of the existing barriers to the integration of complementary therapies in conventional hospital care could be mediated by creating an environment where the fundamental value of commitment to patient wellbeing is equally shared by all stakeholders.

Use of digital technologies in the nutritional management of catabolism-prone chronic diseases: A rapid review.

BACKGROUND: Diet and nutrition applications (apps) have become more readily accessible as smartphone ownership increases. These apps have the potential to improve nutritional outcomes, but it remains unclear whether they are effective in patients with catabolism-prone conditions and specialized nutritional needs. AIMS: The primary aim of this rapid review was to determine if delivery of a nutrition intervention via an app was more effective than standard care in improving nutritional outcomes in patients with a selected set of catabolism-prone chronic diseases. Secondary aims included summarizing intervention components and reviewing adherence and acceptance. METHODS: The research question was developed using the Population, Intervention, Comparison, Outcomes (PICO) framework. Comprehensive literature searches were conducted across three databases. Screening, study selection, extraction, and risk of bias (RoB) assessment were conducted for the included randomized controlled trials (RCTs). RESULTS: 15 articles were included, including 5 RCTs; 3/5 RCTs were judged to be at high RoB. The study aims, measured outcomes, and intervention components were diverse. Adherence and acceptance to the app interventions were encouraging. CONCLUSIONS: Due to the heterogeneity of study design, nutrition interventions, outcomes, and reporting across studies, we were unable to aggregate data regarding the impact on nutritional outcomes. Reassuringly though, the available evidence suggests high adherence and acceptance, which needs to be interpreted in light of the associated personnel support provided within each study. The use of digital technology to deliver diet and nutrition interventions in catabolism-prone conditions is feasible, easy to adhere to, and well-accepted by participants.

A caregiver, an expert, a patient: How complementary therapies support the roles of parents of children with life threatening conditions in hospital settings.

OBJECTIVE: The purpose of this study was to understand emerging roles of parents of hospitalized children with life threatening conditions and to explore how complementary therapies integrated into conventional pediatric care may shift and/or support these roles. DESIGN: This study is part of a larger research study that examined the introduction of a pediatric integrative medicine service at an acute care children's hospital in Canada. A qualitative descriptive study was conducted using one-on-one telephone interviews with a sample of parents of children included in the larger study. Children had access to complementary therapies including Reiki, massage therapy, and acupuncture. RESULTS: A total of 36 interviews were conducted between May 2014 and January 2016. This study found that parents of hospitalized children assume complex roles including that of caregiver, expert and patient (due to high levels of stress and anxiety). Moreover, the study reveals that the integration of complementary therapies with conventional care supports these parental roles. CONCLUSION: This study reveals that complementary therapies, introduced as a part of integrated approach to pediatric hospital care, and aimed primarily at managing distressing symptoms in patients, had simultaneously a positive contribution in providing parents with the means to navigate the complexities of parenting in the pediatric oncology and cardiology hospital wards and addressing some of their own needs.

Comparative Effectiveness of Pediatric Integrative Medicine: A Pragmatic Cluster-Controlled Trial.

Symptoms of pain, nausea/vomiting, and anxiety (PNVA) are highly prevalent in pediatric inpatients. Poorly managed symptoms can lead to decreased compliance with care, and prolonged recovery times. Pharmacotherapy used to manage PNVA symptoms is of variable effectiveness and carries safety risks. Complementary therapies to manage these symptoms are gaining popularity due to their perceived benefits and low risk of harm. Pediatric integrative medicine (PIM) is the combination of complementary therapies with conventional medicine in pediatric populations. A two-arm, cluster-controlled, pragmatic clinical trial was carried out to compare the effectiveness of a PIM service in conjunction with usual care, versus usual care only to treat PNVA symptoms in hospitalized pediatric patients. The primary outcome was the improvement of PNVA symptom severity using a 10-point numerical rating scale. Participant enrollment occurred between January 2013 and January 2016. A total of 872 participants (usual care n = 497; PIM n = 375) were enrolled. The PIM therapies significantly reduced PNVA symptom severity (p < 0.001). This study found that a hospital-based PIM service is both safe and effective for alleviating PNVA symptoms. Future research should carry out this work in other pediatric inpatient divisions, and in other sites to determine the reproducibility of findings.

Parents' experiences of an inpatient pediatric integrative medicine service for symptom management.

BACKGROUND: Pediatric integrative medicine (PIM) refers to the combination of treatments from conventional medicine and complementary therapies for which there is evidence of safety and effectiveness. As pediatric use of complementary therapies increases, it is important to determine parental views on the use of these therapies by their children. OBJECTIVE: To describe parental experiences with a PIM service for management of pain, nausea/vomiting and anxiety in the context of an inpatient pediatric cardiology unit. DESIGN: Telephone interviews were carried out with the parents of pediatric cardiology inpatients. The interviews focused on their and their child's experiences with the PIM service while in the hospital. Interviews were transcribed, and analyzed using qualitative content analysis. RESULTS: Data saturation was reached after nine interviews conducted during the period between June 2015 and January 2016. Parents self-reported that the PIM service was particularly helpful at alleviating symptoms of anxiety in their children. Moreover, because their children were more at ease, parents also felt less anxiety. CONCLUSION: Pediatric integrative medicine as an adjunct to conventional care is seen as beneficial by parents of children admitted to a pediatric cardiology unit.

Observational Study of Pediatric Inpatient Pain, Nausea/Vomiting and Anxiety.

Background: The prevalence and severity of pain, nausea/vomiting, and anxiety (PNVA) among hospitalized children is not well established. We describe the prevalence and severity of PNVA among hospitalized patients from oncology, general pediatrics, and cardiology services in a tertiary care center. Methods: Patients were recruited on admission and enrolled if their caregiver consented, spoke English, and were anticipated to stay 2-30 days. Symptoms were measured weekdays using age-validated tools. PNVA symptoms were described and compared. Results: We enrolled 496 (49.4%) patients of 1005 admitted. Patients were predominantly Caucasian (57.9%) on their first admission (53.6%). The average (SD) age was 8.6 years (5.9) in oncology, 4.2 (5.3) in general pediatrics and 2.6 (4.0) in cardiology. 325 (65.6%) patients reported anxiety, 275 (55.4%) reported nausea and 256 (52.0%) reported pain. Mean (SD) severity out of 10 was 3.7 (2.5) for anxiety, 3.2 (2.1) for nausea and 3.0 (1.5) for pain. Prevalence of PNVA was no different between clinical programs, but pain (p = 0.008) and nausea (p = 0.006) severity were. PNVA symptom co-occurrence was positively correlated (p < 0.001). Conclusions: Anxiety was the most common and severe symptom for hospitalized children. Patients in oncology demonstrated the least severe pain and nausea with no difference in anxiety between services.

Protocol for a systematic review of N-of-1 trial protocol guidelines and protocol reporting guidelines.

BACKGROUND: N-of-1 trials are multiple cross-over trials done in individual participants, generating individual treatment effect information. While reporting guidelines for the CONSORT Extension for N-of-1 trials (CENT) and the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) already exist, there is no standardized recommendation for the reporting of N-of-1 trial protocols. OBJECTIVE: The objective of this study is to evaluate current literature on N-of-1 design and reporting to identify key elements of rigorous N-of-1 protocol design. METHODS: We will conduct a systematic search for all N-of-1 trial guidelines and protocol-reporting guidelines published in peer-reviewed literature. We will search Medline, Embase, PsycINFO, CINAHL, the Cochrane Methodology Register, CENTRAL, and the NHS Economic Evaluation Database. Eligible articles will contain explicit guidance on N-of-1 protocol construction or reporting. Two reviewers will independently screen all titles and abstracts and then undertake full-text reviews of potential articles to determine eligibility. One reviewer will perform data extraction of selected articles, checked by the second reviewer. Data analysis will ascertain common features of N-of-1 trial protocols and compare them to the SPIRIT and CENT items. DISCUSSION: This systematic review assesses recommendations on the design and reporting of N-of-1 trial protocols. These findings will inform an international Delphi development process for an N-of-1 trial protocol reporting guideline. The development of this guideline is critical for improving the quality of N-of-1 protocols, leading to improvements in the quality of published N-of-1 trial research.

To meta-analyze or not to meta-analyze? A combined meta-analysis of N-of-1 trial data with RCT data on amphetamines and methylphenidate for pediatric ADHD.

OBJECTIVES: To assess how the inclusion of N-of-1 trial data into randomized controlled trial (RCT) meta-analyses impacts the magnitude and precision of yielded treatment effects, using amphetamines and methylphenidate for pediatric attention deficit hyperactivity disorder as a model. STUDY DESIGN AND SETTING: We combined the N-of-1 and RCT data generated from previously conducted systematic reviews using parent and teacher ratings of hyperactivity and/or impulsivity as the outcome. Data were combined using standardized mean differences assuming a random effects model. The amphetamine and methylphenidate evidence were synthesized separately. RESULTS: We found that the inclusion of N-of-1 trial data in the meta-analysis impacted both magnitude and precision. The addition of the N-of-1 trial data narrowed the confidence intervals in three of the four comparisons as compared to the treatment effect yielded by RCT-only data. Furthermore, the addition of N-of-1 trials changed the overall treatment effects yielded by the RCT-only meta-analyses from statistically nonsignificant to statistically significant in one of the four outcomes. CONCLUSIONS: If the overall goal of a meta-analysis is to synthesize all available evidence on a given topic, then N-of-1 trials should be included. This study shows it is possible to combine N-of-1 trial data with RCT data and the potential merits of this approach.

N-of-1 trials are a tapestry of heterogeneity.

OBJECTIVES: To summarize the methods of design, analysis, and meta-analysis used in N-of-1 trials. STUDY DESIGN AND SETTING: Electronic search for English language articles published from 1950 to 2013. N-of-1 trials were selected if they followed an ABAB design and if they assessed a health intervention for a medical condition. Elements of design, analysis, and meta-analysis were extracted. RESULTS: We included 100 reports representing 1,995 participants. N-of-1 trials have been conducted in over 50 health conditions. Most reports incorporated the use of elements that maintain methodological rigor, including randomization, blinding, and formal outcome assessment; however, many failed to address trial registration, funding source, and adverse events. Most reports statistically analyzed individual N-of-1 trials; however, only a small proportion of included series meta-analyzed their results. CONCLUSIONS: N-of-1 trials have the ability to assess treatment response in individual participants and can be used for a variety of health interventions for a wide range of medical conditions in both clinical and research settings. Considerable heterogeneity exists in the methods used in N-of-1 trials.

N-of-1 trials can be aggregated to generate group mean treatment effects: a systematic review and meta-analysis.

OBJECTIVES: To evaluate how data from n-of-1 trials may be used in systematic reviews and meta-analyses by examining the effects of amphetamine and methylphenidate for attention-deficit hyperactivity disorder (ADHD). STUDY DESIGN AND SETTING: Electronic search of MEDLINE, EMBASE, and PsychINFO for English language articles published from 1950 to 2013. N-of-1 trials of pediatric participants with ADHD that assessed either amphetamine or methylphenidate vs. placebo were included. The primary outcome was improvement of core symptoms of ADHD, which was assessed by multiple rating scales. Studies with obtainable individual participant data were included in the meta-analysis. Weighted mean differences were computed using a random-effects model. RESULTS: Nine studies were included in the amphetamine-placebo comparison and 10 in the methylphenidate-placebo comparison. Meta-analyses were consistently in favor of amphetamine in 10 of 11 ADHD symptom domains and methylphenidate in 7 of 12 symptom domains. A high degree of heterogeneity across participant treatment response was observed. CONCLUSIONS: Meta-analysis of n-of-1 trials suggests that amphetamine and methylphenidate are effective treatments for pediatric ADHD. Synthesizing n-of-1 trials enables assessment of individual responses to treatment as well as aggregate summaries across individuals and studies. It offers a promising general approach with applications across diverse treatments and disorders.

Reporting quality of N-of-1 trials published between 1985 and 2013: a systematic review.

OBJECTIVES: To evaluate the quality of reporting of single-patient (N-of-1) trials published in the medical literature based on the CONSORT Extension for N-of-1 Trials (CENT) statement and to examine factors that influence reporting quality in these trials. STUDY DESIGN AND SETTING: Through a search of 10 electronic databases, we identified N-of-1 trials in clinical medicine published between January 1, 1985, and December 31, 2013. Two reviewers screened articles for eligibility and independently extracted data. Quality assessment was performed using the CENT statement. Discrepancies were resolved by consensus. RESULTS: We identified 112 eligible N-of-1 trials published in 87 journals and involving a total of 2,278 patients. Overall, kappa agreement between the two evaluators for compliance with CENT criteria was 0.80 (95% confidence interval: 0.79, 0.82). Trials assessed pharmacology and therapeutics (87%), behavior (11%), or diagnosis (2%). Although 87% of articles described the trial design (including the planned number of subjects and length of treatment period), the median percentage of specific CENT elements reported in the Methods was 41% (range, 16-87%), and the median percentage in the Results was 38% (range, 32-93%). First authors were predominantly from North America (46%), Europe (29%), and Australia (17%). Quality of reporting was higher in articles published in journals with relatively high-impact factors (P = 0.004). CONCLUSION: The quality of reporting of published N-of-1 trials is variable and in need of improvement. Because the CENT guidelines were not published until near the end of the period of this review, these results represent a baseline from which improvement may be expected in the future.

Melatonin in Youth: N-of-1 trials in a stimulant-treated ADHD Population (MYNAP): study protocol for a randomized controlled trial.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurological disorder affecting 5 % of children worldwide. A prevalent problem for children with ADHD is initial insomnia. The gold standard treatment to manage ADHD symptoms is stimulant medications, which may exacerbate the severity of existing initial insomnia. Currently, no gold standard treatment option exists for initial insomnia for these children. Melatonin, a hormone and a popular natural health product, is commonly provided to children by parents and recommended by healthcare providers, but high quality pediatric evidence is lacking. METHODS/DESIGN: This trial is a multicenter randomized triple-blind, placebo-controlled, parallel-group, randomized, controlled trial (RCT), in which each participant is offered an N-of-1 trial. An N-of-1 trial is a multiple-crossover, randomized, controlled trial conducted in a single individual. For the N-of-1 trial, each participant will undergo three pairs of treatment/placebo periods; each period is 1 week in length. Half the participants will have melatonin in the first period, the other half will start with placebo, and this will make up the parallel-group RCT. The primary outcome will be mean difference in sleep onset latency as measured by sleep diaries. A comparison of treatment effects yielded by the RCT data versus the aggregated N-of-1 trial data will also be assessed. DISCUSSION: This trial will provide rigorous evidence for the effectiveness of melatonin in children with ADHD on stimulants who experience initial insomnia. Further, this study will provide the first prospectively planned head-to-head comparison of RCT data with pooled data from a series of N-of-1 trials. Aggregated N-of-1 trials may be a powerful tool to produce high quality clinical trial evidence. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov, NCT02333149 . Registered on 16 December 2014. Australian New Zealand Clinical Trials Registry, ACTRN12614000542695 . Registered on 21 May 2014.

Rhodiola rosea for mental and physical fatigue in nursing students: a randomized controlled trial.

BACKGROUND: Fatigue is one of many unintended consequences of shift work in the nursing profession. Natural health products (NHPs) for fatigue are becoming an increasingly popular topic of clinical study; one such NHP is Rhodiola rosea. A well-designed, rigorously conducted randomized controlled trial is required before therapeutic claims for this product can be made. OBJECTIVE: To compare the efficacy of R. rosea with placebo for reducing fatigue in nursing students on shift work. DESIGN: A parallel-group randomized, double-blinded, placebo-controlled trial of 18-55 year old students from the Faculty of Nursing from the University of Alberta, participating in clinical rotations between January 2011 and September 2011. INTERVENTIONS: Participants were randomized to take 364 mg of either R. rosea or identical placebo at the start of their wakeful period and up to one additional capsule within the following four hours on a daily basis over a 42-day period. OUTCOMES: The primary outcome was reduction in fatigue over the 42-day trial period measured using the Vitality-subscale of the RAND-36, cross-validated by the visual analogue scale for fatigue (VAS-F). Secondary outcomes included health-related quality of life, individualized outcomes assessment, and adverse events. RESULTS: A total of 48 participants were randomized to R. rosea (n = 24) or placebo (n = 24). The mean change in scores on the Vitality-subscale was significantly different between the study groups at day 42 in favor of placebo (-17.3 (95% CI -30.6, -3.9), p = 0.011), The mean change in scores on the VAS-F was also significantly difference between study groups at day 42 in favour of placebo (1.9 (95% CI 0.4, 3.5), p = 0.015). Total number of adverse events did not differ between R. rosea and placebo groups. CONCLUSION: This study indicates that among nursing students on shift work, a 42-day course of R. Rosea compared with placebo worsened fatigue; however, the results should be interpreted with caution. TRIAL REGISTRATION: Clinicaltrials.gov NCT01278992.

Long-acting versus short-acting methylphenidate for paediatric ADHD: a systematic review and meta-analysis of comparative efficacy.

OBJECTIVE: To synthesise existing knowledge of the efficacy and safety of long-acting versus short-acting methylphenidate for paediatric attention deficit hyperactivity disorder (ADHD). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Electronic literature search of CENTRAL, MEDLINE, PreMEDLINE, CINAHL, EMBASE, PsychINFO, Scopus and Web of Science for articles published in the English language between 1950 and 2012. Reference lists of included studies were checked for additional studies. STUDY SELECTION: Randomised controlled trials of paediatric ADHD patients (<18 years), comparing a long-acting methylphenidate form to a short-acting methylphenidate form. DATA EXTRACTION: Two authors independently selected trials, extracted data and assessed risk of bias. Continuous outcomes were compared using standardised mean differences (SMDs) between treatment groups. Adverse events were compared using risk differences between treatment groups. Heterogeneity was explored by subgroup analysis based on the type of long-acting formulation used. RESULTS: Thirteen RCTs were included; data from 882 participants contributed to the analysis. Meta-analysis of three studies which used parent ratings to report on hyperactivity/impulsivity had an SMD of -0.30 (95% CI -0.51 to -0.08) favouring the long-acting forms. In contrast, three studies used teacher ratings to report on hyperactivity and had an SMD of 0.29 (95% CI 0.05 to 0.52) favouring the short-acting methylphenidate. In addition, subgroup analysis of three studies which used parent ratings to report on inattention/overactivity indicate that the osmotic release oral system generation long-acting formulation was favoured with an SMD of -0.35 (95% CI -0.52 to -0.17), while the second generation showed less efficacy than the short-acting formulation with an SMD of 0.42 (95% CI 0.17 to 0.68). The long-acting formulations presented with slightly more total reported adverse events (n=578) as compared with the short-acting formulation (n=566). CONCLUSIONS: The findings from this systematic review indicate that the long-acting forms have a modest effect on the severity of inattention/overactivity and hyperactivity/impulsivity according to parent reports, whereas the short-acting methylphenidate was preferred according to teacher reports for hyperactivity.