Cecilia Bukutu

Rhodiola rosea for physical and mental fatigue: a systematic review

BackgroundRhodiola rosea (R. rosea) is grown at high altitudes and northern latitudes. Due to its purported adaptogenic properties, it has been studied for its performance-enhancing capabilities in healthy populations and its therapeutic properties in a number of clinical populations. To systematically review evidence of efficacy and safety of R. rosea for physical and mental fatigue.MethodsSix electronic databases were searched to identify randomized controlled trials (RCTs) and controlled clinical trials (CCTs), evaluating efficacy and safety of R. rosea for physical and mental fatigue. Two reviewers independently screened the identified literature, extracted data and assessed risk of bias for included studies.ResultsOf 206 articles identified in the search, 11 met inclusion criteria for this review. Ten were described as RCTs and one as a CCT. Two of six trials examining physical fatigue in healthy populations report R. rosea to be effective as did three of five RCTs evaluating R. rosea for mental fatigue. All of the included studies exhibit either a high risk of bias or have reporting flaws that hinder assessment of their true validity (unclear risk of bias).ConclusionResearch regarding R. rosea efficacy is contradictory. While some evidence suggests that the herb may be helpful for enhancing physical performance and alleviating mental fatigue, methodological flaws limit accurate assessment of efficacy. A rigorously-designed well reported RCT that minimizes bias is needed to determine true efficacy of R. rosea for fatigue.

CONSORT extension for reporting N-of-1 trials (CENT) 2015 Statement

N-of-1 trials provide a mechanism for making evidence based treatment decisions for an individual patient. They use key methodological elements of group clinical trials to evaluate treatment effectiveness in a single patient, for situations that cannot always accommodate large scale trials: rare diseases, comorbid conditions, or in patients using concurrent therapies. Improvement in the reporting and clarity of methods and findings in N-of-1 trials is essential for reader to gauge the validity of trials and to replicate successful findings. A CONSORT extension for N-of-1 trials (CENT 2015) provides guidance on the reporting of individual and series of N-of-1 trials. CENT provides additional guidance for 14 of the 25 items of the CONSORT 2010 checklist and recommends a diagram for depicting an individual N-of-1 trial and modifies the CONSORT flow diagram to address the flow of a series of N-of-1 trials. The rationale, development process, and CENT 2015 checklist and diagrams are reported in this document.

CONSORT extension for reporting N-of-1 trials (CENT) 2015: Explanation and elaboration

N-of-1 trials are a useful tool for clinicians who want to determine the effectiveness of a treatment in a particular individual. The reporting of N-of-1 trials has been variable and incomplete, hindering their usefulness in clinical decision making and by future researchers. This document presents the CONSORT (Consolidated Standards of Reporting Trials) extension for N-of-1 trials (CENT 2015). CENT 2015 extends the CONSORT 2010 guidance to facilitate the preparation and appraisal of reports of an individual N-of-1 trial or a series of prospectively planned, multiple, crossover N-of-1 trials. CENT 2015 elaborates on 14 items of the CONSORT 2010 checklist, totalling 25 checklist items (44 sub-items), and recommends diagrams to help authors document the progress of one participant through a trial or more than one participant through a trial or series of trials, as applicable. Examples of good reporting and evidence based rationale for CENT 2015 checklist items are provided.

CONSORT extension for reporting N-of-1 trials (CENT) 2015 Statement.

N-of-1 trials provide a mechanism for making evidence-based treatment decisions for an individual patient. They use key methodological elements of group clinical trials to evaluate treatment effectiveness in a single patient, for situations that cannot always accommodate large-scale trials: rare diseases, comorbid conditions, or in patients using concurrent therapies. Improvement in the reporting and clarity of methods and findings in N-of-1 trials is essential for reader to gauge the validity of trials and to replicate successful findings. A Consolidated Standards of Reporting Trials (CONSORT) extension for N-of-1 trials (CENT 2015) provides guidance on the reporting of individual and series of N-of-1 trials. CENT provides additional guidance for 14 of the 25 items of the CONSORT 2010 checklist, recommends a diagram for depicting an individual N-of-1 trial, and modifies the CONSORT flow diagram to address the flow of a series of N-of-1 trials. The rationale, development process, and CENT 2015 checklist and diagrams are reported in this document.

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.

CONSORT extension for reporting N-of-1 trials (CENT) 2015: explanation and elaboration

N-of-1 trials are a useful tool for clinicians who want to determine the effectiveness of a treatment in a particular individual. The reporting of N-of-1 trials has been variable and incomplete, hindering their usefulness in clinical decision making and by future researchers. This document presents the CONSORT (Consolidated Standards of Reporting Trials) extension for N-of-1 trials (CENT 2015). CENT 2015 extends the CONSORT 2010 guidance to facilitate the preparation and appraisal of reports of an individual N-of-1 trial or a series of prospectively planned, multiple, crossover N-of-1 trials. CENT 2015 elaborates on 14 items of the CONSORT 2010 checklist, totalling 25 checklist items (44 sub-items), and recommends diagrams to help authors document the progress of one participant through a trial or more than one participant through a trial or series of trials, as applicable. Examples of good reporting and evidence based rationale for CENT 2015 checklist items are provided.

Asthma: A Review of Complementary and Alternative Therapies

1. Cecilia Bukutu, PhD* 2. Christopher Le* 3. Sunita Vohra, MD, FRCPC, MSc* 1. *Complementary and Alternative Research and Education (CARE) Program, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. On behalf of the American Academy of Pediatrics Section on Complementary and Integrative Medicine Although effective medications for managing asthma exist within conventional Western medicine (eg, inhaled corticosteroids and bronchodilators), some parents turn to complementary and alternative medical (CAM) therapies to treat their childrens asthma. (1) Some reasons cited for using CAM therapies include concern about the long-term effects of steroid use; frustration that asthma does not resolve with conventional therapies; dissatisfaction with physician-patient interactions; belief that CAM is natural and, therefore, safe; and desire to have autonomy in making health choices. (1)(2) This review of published scientific literature assesses the efficacy and safety of some common CAM therapies in preventing and treating pediatric asthma. Natural health products (NHPs), including vitamins, minerals, herbal remedies, and other dietary supplements such as fish oil and probiotics, are used widely to prevent and treat asthma. (3) Like conventional therapies, NHPs used to treat asthma can be categorized as having anti-inflammatory, bronchodilator, and other effects. Few of these NHPs have been evaluated in pediatric trials. ### Vitamin C Vitamin C is an important antioxidant found in abundance in the extracellular fluid lining of the lung. Low intake of vitamin C is associated with pulmonary dysfunction. (4) Several observational studies in children have reported a beneficial relationship between a high fruit intake and improved lung function. (5)(6) However, a 2004 Cochrane systematic review of eight randomized, controlled trials (RCTs) concluded that evidence was insufficient to recommend a specific role for vitamin C in treating asthma. (4) Of the eight included studies, three small studies (fewer than 41 participants each) concluded that vitamin C supplementation was beneficial; five studies, including the largest trial (n=210), showed little or no beneficial effect. Larger, long-term RCTs are needed to clarify the possible role of vitamin C in the treatment of asthma. Most researchers have used daily doses of 500 to 1,000 mg. …

Complementary, holistic, and integrative medicine: therapies for acute otitis media.

1. Cecilia Bukutu, PhD* 2. Janjeevan Deol* 3. Sunita Vohra, MD, FRCPC, MSc* 1. *Complementary and Alternative Research and Education (CARE) Program, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada Acute otitis media (AOM) is diagnosed frequently in early childhood; its peak incidence is between 6 and 15 months of age. (1) Streptococcus pneumoniae, Haemophilus influenzae , and Moraxella catarrhalis are the leading bacterial causes. Eighty percent of AOM cases resolve without treatment within 3 days. (2)(3) This high rate of spontaneous resolution along with variations in diagnostic criteria complicate studies of otitis media. Most cases of AOM are treated with antibiotics and pain relievers, but antibiotics may contribute to antimicrobial resistance or produce adverse effects (AEs) such as diarrhea. (4) These concerns, in part, have led some parents to turn to the use of complementary and alternative medicine (CAM) to treat childhood AOM. This review of published scientific literature examines some commonly used CAM therapies in the prevention and treatment of childhood AOM. ### Naturopathic Herbal Ear Drops (NHEDs) A Cochrane systematic review conducted in 2004 (4) assessed the effectiveness of NHEDs in the management of ear pain associated with AOM in two randomized, controlled trials (RCTs) (Table 1). The first study compared an NHED comprised of Calendula flores (marigold), garlic ( Allium sativum ), mullein ( Verbascum thapsus ), and St. Johns wort ( Hypericum perfoliatum ) in olive oil with anesthetic eardrops. (5) The second study compared NHED (garlic, mullein, marigold, St Johns wort, lavender, and vitamin E in olive oil) to anesthetic eardrops with and without antibiotics. (6) Findings from these trials point to NHEDs being modestly therapeutic for pain associated with AOM compared with anesthetic eardrops. However, the trials have some methodologic problems: lack of allocation concealment, power calculation, and intention-to-treat analysis. Two children dropped out of the first study because of the odor of NHED; no other AEs were documented. (5) The evidence regarding safety and efficacy of NHEDs seems promising. | Citation | Study Type | Population | Intervention | Outcomes | Results | Comments | |:-------------------------:| ---------------- | ---------------------------------------------------------------------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | Sarrell et al. (2001) (5) | Double-blind RCT | 103 children ages 6 to 18 y who had otalgia associated with AOM (Israel) | Group A: Naturopathic drops ( Allium sativum, Verbascum thapsus, Calendula flores, Hypericum perforatum in olive oil) Group B: Anesthetic ear drops (amethocaine, phenazone, glycerine) In both groups, drops instilled 3 times daily for 3 days At start, all children given a single dose of acetaminophen (15 mg/kg) | Severity and duration of pain Two visual (linear and color) analog scales used Ear pain assessed prior to treatment and at 15 and 30 min after treatment | NHED reduced pain as effectively as anesthetic ear drops Pain score improved throughout the course of the study period ( P =0.007) | Children older than the age group in which peak AOM incidence occurs (6 to 15 mo) 7 dropouts (2 did not like odor of the NHED, 5 for noncompliance) Randomization method not described | | Sarrell et al. (2003) (6) | Double-blind RCT | Ambulatory clinic, 171 children (5 to 18 y) who had otalgia associated with AOM (Israel) | Children randomized into 1 of 4 treatments and received eardrops 3 times daily for 3 days Group A: NHED alone ( Allium sativum, Verbascum thapsus, Calendula flores, Hypericum perfoliatum , lavender, and vitamin E in olive oil) Group B: NHED with oral amoxicillin (antibiotic) Group C: Anesthetic eardrops alone Group D: Anesthetic eardrops with oral amoxicillin (antibiotic) | As in Sarrell, 2001 | After 3 days, rate of pain reduction: Group A=95.9%, Group B=90.9%, Group C=84.0%, Group D=77.8% Pain was mostly (80%) self-limited and explained by the passage of time | Children older than the age group in which peak AOM incidence occurs (6 to 15 mo); thus, likely greater chance of spontaneous recovery | * AOM=acute otitis media, NHED= naturopathic herbal ear drops. RCT=randomized, controlled trial. Table 1. Clinical Trials of Naturopathic …

P05.50. CONSORT extension for N-of-1 trials (CENT) guidelines

Purpose N-of-1 trials have been used in medicine to generate treatment information when evidence from randomized controlled trials (RCTs) is not available or applicable. Nof-1 study design maintains the methodological safeguards provided by RCTs (blinding, randomization and controls) yet avoids the disadvantages associated with large trials. A standardized method of reporting of N-of1 trials, such as the Consolidated Standards of Reporting Trials (CONSORT), would greatly improve the quality and consistency of trial reports in this area. The objective of this study was to develop a CONSORT Extension for N-of-1 Trials (CENT).

Complementary, Holistic, and Integrative Medicine: Fish Oils and Neurodevelopmental Disorders

1. Jayna Brulotte* 2. Cecilia Bukutu, PhD* 3. Sunita Vohra, MD, FRCPC, MSc* 1. *Complementary and Alternative Research and Education (CARE) Program, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. On behalf of the American Academy of Pediatrics Section on Complementary and Integrative Medicine Omega-3 and omega-6 fatty acids are essential to human health and development. During the last century, intake of omega-6-rich foods (eg, plant-based oils) increased, while that of omega-3-rich foods (eg, fish and fish oils) decreased. (1)(2) The recommended ratio for dietary intake of omega-6:omega-3 ranges from 4:1 to 7.5:1. (3) The modern western diet is deficient in omega-3 fatty acids; (4) recent data suggest a 17:1 to 25:1 ratio in North America. (5)(6)(7) Evidence suggests that omega-3 deficiencies may play a role in neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), dyslexia, dyspraxia, developmental coordination disorder (DCD), and the autism spectrum disorders (ASDs). These conditions are increasingly prevalent in western societies, with estimated prevalence rates of more than 10% in children. (8) Such conditions share a number of features: 1) affected children often experience problems in motor or oculomotor function, language development and proficiency, social skills, and visual and auditory processing; 2) the disorders are disproportionally more prevalent among males; 3) there is substantial comorbidity among the disorders; and 4) the disorders often cluster in families. (7)(8)(9)(10) This review describes the effects of omega-3 fatty acid on the course and outcome of neurodevelopmental disorders. The most important omega-3 fatty acids for cognitive development are the polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). (7) These essential fatty acids (EFAs) are synthesized in the body from alpha-linolenic acid, but because the conversion process is inefficient, (11)(12) EPA and DHA must be provided by the diet. Known to have anti-inflammatory effects, the omega-3 fatty acids inhibit platelet aggregation (13) and are critical for brain development and function. (7) ### ADHD The role of PUFAs in ADHD, a disorder characterized by inattention, hyperactivity, and impulsivity, was hypothesized initially by …