Background

Many consumers use natural health products (NHPs) concurrently with prescription medications. As NHP-related harms are under-reported through passive surveillance, the safety of concurrent NHP-drug use remains unknown. To conduct active surveillance in participating community pharmacies to identify adverse events related to concurrent NHP-prescription drug use.

Methodology/Principal Findings

Participating pharmacists asked individuals collecting prescription medications about (i) concurrent NHP/drug use in the previous three months and (ii) experiences of adverse events. If an adverse event was identified and if the patient provided written consent, a research pharmacist conducted a guided telephone interview to gather additional information after obtaining additional verbal consent and documenting so within the interview form. Over a total of 112 pharmacy weeks, 2615 patients were screened, of which 1037 (39.7%; 95% CI: 37.8% to 41.5%) reported concurrent NHP and prescription medication use. A total of 77 patients reported a possible AE (2.94%; 95% CI: 2.4% to 3.7%), which represents 7.4% of those using NHPs and prescription medications concurrently (95%CI: 6.0% to 9.2%). Of 15 patients available for an interview, 4 (26.7%: 95% CI: 4.3% to 49.0%) reported an AE that was determined to be “probably” due to NHP use.

Conclusions/Significance

Active surveillance markedly improves identification and reporting of adverse events associated with concurrent NHP-drug use. Although not without challenges, active surveillance is feasible and can generate adverse event data of sufficient quality to allow for meaningful adjudication to assess potential harms.

Background

Integrative medicine is defined as relationship-centered care that focuses on the whole person, is informed by evidence, and makes use of all appropriate therapeutic approaches, healthcare professionals and disciplines to achieve optimal health and healing, including evidence-based complementary and alternative medicine. Pediatric integrative medicine (PIM) develops and promotes this approach within the field of pediatrics. We conducted a survey to identify and describe PIM programs within academic children’s hospitals across North America. Key barriers and opportunities were identified for the growth and development of academic PIM initiatives in the US and Canada.

Methods

Academic PIM programs were identified by email and eligible for inclusion if they had each of educational, clinical, and research activities. Program directors were interviewed by telephone regarding their clinical, research, educational, and operational aspects.

Results

Sixteen programs were included. Most (75%) programs provided both inpatient and outpatient services. Seven programs operated with less than 1 FTE clinical personnel. Credentialing of complementary and alternative medicine (CAM) providers varied substantially across the programs and between inpatient and outpatient services. Almost all (94%) programs offered educational opportunities for residents in pediatrics and/or family medicine. One fifth (20%) of the educational programs were mandatory for medical students. Research was conducted in a range of topics, but half of the programs reported lack of research funding and/or time. Thirty-one percent of the programs relied on fee-for-service income.

Conclusions

Pediatric integrative medicine is emerging as a new subspecialty to better help address 21st century patient concerns.

Objective

Complementary and alternative medicine (CAM) is commonly used by children, but estimates of that use vary widely partly due to the range of questionnaires used to assess CAM use. However, no studies have attempted to appraise measurement properties of these questionnaires. The aim of this systematic review was to critically appraise and summarize measurement properties of questionnaires of CAM use in pediatrics.

Study design

A search strategy was implemented in major electronic databases in March 2011 and conference websites, scientific journals and experts were consulted. Studies were included if they mentioned a questionnaire assessing the prevalence of CAM use in pediatrics. Members of the team independently rated the methodological quality of the studies (using the COSMIN checklist) and measurement properties of the questionnaires (using the Terwee and Cohen criteria).

Results

A total of 96 CAM questionnaires were found in 104 publications. The COSMIN checklist showed that no studies reported adequate methodological quality. The Terwee criteria showed that all included CAM questionnaires had indeterminate measurement properties. According to the Cohen score, none were considered to be a well-established assessment, two approached the level of a well-established assessment, seven were promising assessments and the remainder (n = 87) did not reach the score’s minimum standards.

Conclusion

None of the identified CAM questionnaires have been thoroughly validated. This systematic review highlights the need for proper validation of CAM questionnaires in pediatrics, which may in turn lead to improved research and knowledge translation about CAM in clinical practice.

Background

Rhodiola 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.

Methods

Six 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.

Results

Of 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).

Conclusion

Research 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.

Some cruciferous plants may serve as preventive treatments for several medical conditions; our objective was to systematically investigate their safety in humans. Four electronic databases were searched, and, of 10,831 references identified, 50 were included. Data were extracted by two independent reviewers, whereafter the association between interventions and adverse events was assessed. Adverse events in 53 subjects were identified through clinical trials; of these, altered drug metabolism was rated as certainly/likely caused by cruciferous plants. Adverse events in 1247 subjects were identified through observational studies, of which none received high causality ratings. Adverse events in 35 subjects were identified through case reports, of which allergies and warfarin resistance were rated as certainly/likely caused by cruciferous plants. We conclude that cruciferous plants are safe in humans, with the exception of allergies. Individuals treated with warfarin should consult their physician. Further investigation of uses of cruciferous plants in preventative medicine is warranted.

In this study we used event-related brain potentials (ERP) as neural markers of cognitive operations to examine emotion and attentional processing in a population of high-risk adolescents with mental health problems that included attention deficit and hyperactivity disorder (ADHD), anxiety, and depression. We included a healthy control group for comparison purposes, and employed a modified version of the emotional oddball paradigm, consisting of frequent distracters (scrambled pictures), infrequent distracters (sad, fearful, and neutral pictures), and infrequent targets (circles). Participants were instructed to make a right hand button press to targets and a left hand button press to all other stimuli. EEG/ERP recordings were taken using a high-density 256-channel recording system. Behavioral data showed that for both clinical and non-clinical adolescents, reaction time (RT) was slowest in response to the fearful images. Electrophysiological data differentiated emotion and target processing between clinical and non-clinical adolescents. In the clinical group we observed a larger P100 and late positive potential (LPP) in response to fearful compared to sad or neutral pictures. There were no differences in these ERPs in the healthy sample. Emotional modulation of target processing was also identified in the clinical sample, where we observed an increase in P300 amplitude, and a larger sustained LPP in response to targets that followed emotional pictures (fear and sad) compared to targets that followed neutral pictures or other targets. There were no differences in these target ERPs for the healthy participants. Taken together, we suggest that these data provide important and novel evidence of affective and attention dysfunction in this clinical population of adolescents, and offer an example of the disruptive effects of emotional reactivity on basic cognition.

BACKGROUND

Despite many studies confirming that the use of complementary and alternative medicine (CAM) by children is common, few have assessed related adverse events.

OBJECTIVE

To conduct a national survey to identify the frequency and severity of adverse events associated with paediatric CAM use.

METHODS

Survey questions were developed based on a review of relevant literature and consultation with content experts. In January 2006, the Canadian Paediatric Surveillance Program distributed the survey to all paediatricians and paediatric subspecialists in active practice in Canada.

RESULTS

Of the 2489 paediatricians who received the survey, 583 (23%) responded. Respondents reported that they asked patients about CAM use 38% of the time and that patients disclosed this information before being questioned only 22% of the time. Forty-two paediatricians (7%) reported seeing adverse events, most commonly involving natural health products, in the previous year. One hundred five paediatricians (18%) reported witnessing cases of delayed diagnosis or treatment (n=488) that they attributed to the use of CAM.

CONCLUSION

While serious adverse events associated with paediatric CAM appear to be rare, delays in diagnosis or treatment seem more common. Given the lack of paediatrician-patient discussion regarding CAM use, our findings may under-represent adverse events. A lack of reported adverse events should not be interpreted as a confirmation of safety. Active surveillance is required to accurately assess the incidence, nature and severity of paediatric CAM-related adverse events. Patient safety demands that paediatricians routinely inquire about the use of CAM.

Background

Exogenous melatonin has been increasingly used in the management of sleep disorders.

Purpose

To conduct a systematic review of the efficacy and safety of exogenous melatonin in the management of primary sleep disorders.

Data Sources

A number of electronic databases were searched. We reviewed the bibliographies of included studies and relevant reviews and conducted hand-searching.

Study Selection

Randomized controlled trials (RCTs) were eligible for the efficacy review, and controlled trials were eligible for the safety review.

Data Extraction

One reviewer extracted data, while the other verified data extracted. The Random Effects Model was used to analyze data.

Data Synthesis

Melatonin decreased sleep onset latency (weighted mean difference [WMD]: −11.7 minutes; 95% confidence interval [CI]: −18.2, −5.2)); it was decreased to a greater extent in people with delayed sleep phase syndrome (WMD: −38.8 minutes; 95% CI: −50.3, −27.3; n=2) compared with people with insomnia (WMD: −7.2 minutes; 95% CI: −12.0, −2.4; n=12). The former result appears to be clinically important. There was no evidence of adverse effects of melatonin.

Conclusions

There is evidence to suggest that melatonin is not effective in treating most primary sleep disorders with short-term use (4 weeks or less); however, additional large-scale RCTs are needed before firm conclusions can be drawn. There is some evidence to suggest that melatonin is effective in treating delayed sleep phase syndrome with short-term use. There is evidence to suggest that melatonin is safe with short-term use (3 months or less).

Background

Antibiotic treatment is known to disturb gastrointestinal microflora, which results in a range of clinical symptoms — most notably, diarrhea. This is especially important in children, for whom antibiotics are prescribed frequently. Although meta-analyses have been conducted to evaluate the ability of probiotics to prevent antibiotic-induced diarrhea in the general population, little is known about which probiotic strains and doses might be of most benefit to children. Our objective in this study was to assess the efficacy of probiotics (of any specified strain or dose) for the prevention of antibiotic-associated diarrhea in children and to assess adverse events associated with the use of probiotics when coadministered with antibiotics to children.

Methods

A comprehensive search was performed of the major electronic databases (e.g., CENTRAL, MEDLINE, EMBASE, CINAHL, AMED) from their inception to January 2005. We also contacted experts and searched registries and meeting abstracts for additional relevant articles. Randomized controlled trials that compared probiotic treatment with placebo or no treatment, involving pediatric subjects less than 19 years of age were included. Two reviewers independently applied eligibility criteria and assessed the studies for methodological quality. Data were independently extracted by 2 reviewers and analyzed via the standard Cochrane methodology.

Results

Six studies were included (total n = 707 patients). The combined results, analyzed with a per-protocol method that reported on the incidence of diarrhea during antibiotic treatment, showed significant benefit for the use of probiotics over placebo (relative risk [RR] 0.43, 95% confidence interval [CI] 0.25–0.75, Ι2 = 70.1%). In contrast, results from intention-to-treat analysis were nonsignificant overall (RR 1.01, 95% CI 0.64–1.61). Subgroup analysis on 4 studies that provided at least 5 billion single-strain colony-forming units (CFUs) daily (range 5.5–40 × 109 Lactobacillus GG, L. sporogens or Saccharomyces boulardii) showed strong evidence with narrow CIs for the preventative effects of probiotics for antibiotic-associated diarrhea (RR 0.36, 95% CI 0.25–0.53, Ι2 = 3.5%). No serious adverse events were reported.

Interpretation

The potential protective effects of probiotics to prevent antibiotic-associated diarrhea in children do not withstand intention-to-treat analysis. Before routine use is recommended, further studies (with limited losses of subjects to follow-up) are merited. Trials should involve those probiotic strains and doses with the most promising evidence (i.e., Lactobacillus GG, L. sporogens or S. boulardii at 5–40 × 109 CFUs daily).

Complementary and alternative medicine (CAM) use, including paediatric use, is common. The Hospital for Sick Children Foundation organized a priority-setting forum regarding paediatrics and the use of CAM/natural health products in November 2001. Four priority areas were identified: the creation of a national paediatric research network and/or centre of excellence in CAM; support for experiential learning, education, and training; completion of a needs/use assessment; and facilitation of knowledge transfer. These priority areas are discussed in the context of research, education, knowledge transfer and health systems. The present article represents a call for action for Canadian funding agencies to support the development of an evidence base in paediatric CAM.

Objective To conduct a systematic review of the efficacy and safety of exogenous melatonin in managing secondary sleep disorders and sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder.

Data sources 13 electronic databases and reference lists of relevant reviews and included studies; Associated Professional Sleep Society abstracts (1999 to 2003).

Study selection The efficacy review included randomised controlled trials; the safety review included randomised and non-randomised controlled trials.

Quality assessment Randomised controlled trials were assessed by using the Jadad Scale and criteria by Schulz et al, and non-randomised controlled trials by the Downs and Black checklist.

Data extraction and synthesis One reviewer extracted data and another reviewer verified the data extracted. The inverse variance method was used to weight studies and the random effects model was used to analyse data.

Main results Six randomised controlled trials with 97 participants showed no evidence that melatonin had an effect on sleep onset latency in people with secondary sleep disorders (weighted mean difference -13.2 (95% confidence interval -27.3 to 0.9) min). Nine randomised controlled trials with 427 participants showed no evidence that melatonin had an effect on sleep onset latency in people who had sleep disorders accompanying sleep restriction (-1.0 (-2.3 to 0.3) min). 17 randomised controlled trials with 651 participants showed no evidence of adverse effects of melatonin with short term use (three months or less).

Conclusions There is no evidence that melatonin is effective in treating secondary sleep disorders or sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder. There is evidence that melatonin is safe with short term use.

Background

Patients across North America are using complementary and alternative medicine (CAM) with increasing frequency as part of their management of many different health conditions. The objective of this study was to develop a guide for academic health sciences centers that may wish to consider starting an integrative medicine program.

Methods

We queried North American leaders in the field of integrative medicine to identify initial sites. Key stakeholders at each of the initial sites visited were then asked to identify additional potential study sites (snowball sampling), until no new sites were identified. We conducted structured interviews to identify critical factors associated with success and failure in each of four domains: research, education, clinical care, and administration. During the interviews, field notes were recorded independently by at least two investigators. Team meetings were held after each visit to reach consensus on the information recorded and to ensure that it was as complete as possible. Content analysis techniques were used to identify key themes that emerged from the field notes.

Results

We identified ten leading North American integrative medical centers, and visited nine during 2002–2003. The centers visited suggested that the initiation of an integrative medicine program requires a significant initial outlay of funding and a motivated "champion". The centers had important information to share regarding credentialing, medico-legal issues and billing for clinical programs; identifying researchers and research projects for a successful research program; and strategies for implementing flexible educational initiatives and establishing a functional administrative structure.

Conclusion

Important lessons can be learned from academic integrative programs already in existence. Such initiatives are timely and feasible in a variety of different ways and in a variety of settings.