Commentary on Mathie RT et al. Method for appraising model validity of randomised controlled trials of homeopathic treatment: multi-rater concordance study.

Although many researchers agree that applying conventional drug-trial quality criteria to CAM studies lacks plausibility, few take on the burden of devising alternative criteria in a specific area of CAM. This commentary points out strengths and weaknesses in the approach taken in the work of Mathie and colleagues to do this for homeopathy.

Effectiveness Guidance Document (EGD) for acupuncture research - a consensus document for conducting trials.

BACKGROUND: There is a need for more Comparative Effectiveness Research (CER) to strengthen the evidence base for clinical and policy decision-making. Effectiveness Guidance Documents (EGD) are targeted to clinical researchers. The aim of this EGD is to provide specific recommendations for the design of prospective acupuncture studies to support optimal use of resources for generating evidence that will inform stakeholder decision-making. METHODS: Document development based on multiple systematic consensus procedures (written Delphi rounds, interactive consensus workshop, international expert review). To balance aspects of internal and external validity, multiple stakeholders including patients, clinicians and payers were involved. RESULTS: Recommendations focused mainly on randomized studies and were developed for the following areas: overall research strategy, treatment protocol, expertise and setting, outcomes, study design and statistical analyses, economic evaluation, and publication. CONCLUSION: The present EGD, based on an international consensus developed with multiple stakeholder involvement, provides the first systematic methodological guidance for future CER on acupuncture.

Nonlinear dynamical systems effects of homeopathic remedies on multiscale entropy and correlation dimension of slow wave sleep EEG in young adults with histories of coffee-induced insomnia.

BACKGROUND: Investigators of homeopathy have proposed that nonlinear dynamical systems (NDS) and complex systems science offer conceptual and analytic tools for evaluating homeopathic remedy effects. Previous animal studies demonstrate that homeopathic medicines alter delta electroencephalographic (EEG) slow wave sleep. The present study extended findings of remedy-related sleep stage alterations in human subjects by testing the feasibility of using two different NDS analytic approaches to assess remedy effects on human slow wave sleep EEG. METHODS: Subjects (N=54) were young adult male and female college students with a history of coffee-related insomnia who participated in a larger 4-week study of the polysomnographic effects of homeopathic medicines on home-based all-night sleep recordings. Subjects took one bedtime dose of a homeopathic remedy (Coffea cruda or Nux vomica 30c). We computed multiscale entropy (MSE) and the correlation dimension (Mekler-D2) for stages 3 and 4 slow wave sleep EEG sampled in artifact-free 2-min segments during the first two rapid-eye-movement (REM) cycles for remedy and post-remedy nights, controlling for placebo and post-placebo night effects. RESULTS: MSE results indicate significant, remedy-specific directional effects, especially later in the night (REM cycle 2) (CC: remedy night increases and post-remedy night decreases in MSE at multiple sites for both stages 3 and 4 in both REM cycles; NV: remedy night decreases and post-remedy night increases, mainly in stage 3 REM cycle 2 MSE). D2 analyses yielded more sporadic and inconsistent findings. CONCLUSIONS: Homeopathic medicines Coffea cruda and Nux vomica in 30c potencies alter short-term nonlinear dynamic parameters of slow wave sleep EEG in healthy young adults. MSE may provide a more sensitive NDS analytic method than D2 for evaluating homeopathic remedy effects on human sleep EEG patterns.

A community-based intervention to prevent obesity beginning at birth among American Indian children: study design and rationale for the PTOTS study.

Eating and physical activity behaviors associated with adult obesity have early antecedents, yet few studies have focused on obesity prevention interventions targeting very young children. Efforts to prevent obesity beginning at birth seem particularly important in populations at risk for early-onset obesity. National estimates indicate that American Indian (AI) children have higher rates of overweight and obesity than children of other races/ethnicities. The Prevention of Toddler Obesity and Teeth Health Study (PTOTS) is a community-partnered randomized controlled trial designed to prevent obesity beginning at birth in AI children. PTOTS was developed to test the effectiveness of a multi-component intervention designed to: promote breastfeeding, reduce sugar-sweetened beverage consumption, appropriately time the introduction of healthy solid foods, and counsel parents to reduce sedentary lifestyles in their children. A birth cohort of 577 children from five AI tribes is randomized by tribe to either the intervention (three tribes) or the comparison condition (two tribes). The strengths and weaknesses of PTOTS include a focus on a critical growth phase, placement in the community, and intervention at many levels, using a variety of approaches.

Randomized Controlled Trials of Acupuncture (1997-2007): An Assessment of Reporting Quality with a CONSORT- and STRICTA-Based Instrument.

The present study describes the development of a comprehensive quality of reporting assessment tool and its application to acupuncture RCTs from 1997-2007. This Oregon CONSORT STRICTA Instrument (OCSI) is based on the revised CONSORT guidelines as modified by the STRICTA recommendations for acupuncture trials. Each of the resulting 27 OCSI items were applied to English language prospective RCTs that compared acupuncture, using manual and/or electro-stimulation, to no treatment, a sham procedure, or usual biomedical care. The 333 RCTs that met inclusion criteria were dispersed among 27 countries and 141 journals. Mean quality of reporting score for all articles was 63.0% (SD 16.5). Mean OCSI scores revealed a 30.9% improvement over the ten-year period (P < .001). Our findings suggest that to enhance quality of reporting, authors should better attend to seven specific OCSI items in three categories: practitioner training, adverse events, and aspects of randomization and blinding (n = 5). The broad diversity in geographical origin, publication site and quality of reporting, viewed in light of the considerable room for improvement in mean OCSI scores, emphasizes the importance of making STRICTA as well as CONSORT more widely known to journals and to the acupuncture research community.

Acupuncture and chiropractic care for chronic pain in an integrated health plan: a mixed methods study.

BACKGROUND: Substantial recent research examines the efficacy of many types of complementary and alternative (CAM) therapies. However, outcomes associated with the "real-world" use of CAM has been largely overlooked, despite calls for CAM therapies to be studied in the manner in which they are practiced. Americans seek CAM treatments far more often for chronic musculoskeletal pain (CMP) than for any other condition. Among CAM treatments for CMP, acupuncture and chiropractic (A/C) care are among those with the highest acceptance by physician groups and the best evidence to support their use. Further, recent alarming increases in delivery of opioid treatment and surgical interventions for chronic pain--despite their high costs, potential adverse effects, and modest efficacy--suggests the need to evaluate real world outcomes associated with promising non-pharmacological/non-surgical CAM treatments for CMP, which are often well accepted by patients and increasingly used in the community. METHODS/DESIGN: This multi-phase, mixed methods study will: (1) conduct a retrospective study using information from electronic medical records (EMRs) of a large HMO to identify unique clusters of patients with CMP (e.g., those with differing demographics, histories of pain condition, use of allopathic and CAM health services, and comorbidity profiles) that may be associated with different propensities for A/C utilization and/or differential outcomes associated with such care; (2) use qualitative interviews to explore allopathic providers' recommendations for A/C and patients' decisions to pursue and retain CAM care; and (3) prospectively evaluate health services/costs and broader clinical and functional outcomes associated with the receipt of A/C relative to carefully matched comparison participants receiving traditional CMP services. Sensitivity analyses will compare methods relying solely on EMR-derived data versus analyses supplementing EMR data with conventionally collected patient and clinician data. DISCUSSION: Successful completion of these aggregate aims will provide an evaluation of outcomes associated with the real-world use of A/C services. The trio of retrospective, qualitative, and prospective study will also provide a clearer understanding of the decision-making processes behind the use of A/C for CMP and a transportable methodology that can be applied to other health care settings, CAM treatments, and clinical populations. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01345409.

The TOTS community intervention to prevent overweight in American Indian toddlers beginning at birth: a feasibility and efficacy study.

Excess weight gain in American Indian/Alaskan native (AI/AN) children is a public health concern. This study tested (1) the feasibility of delivering community-wide interventions, alone or in combination with family-based interventions, to promote breastfeeding and reduce the consumption of sugar-sweetened beverages; and (2) whether these interventions decrease Body Mass Index (BMI)-Z scores in children 18-24 months of age. Three AI/AN tribes were randomly assigned to two active interventions; a community-wide intervention alone (tribe A; n = 63 families) or community-wide intervention containing a family component (tribes B and C; n = 142 families). Tribal staff and the research team designed community-tailored interventions and trained community health workers to deliver the family intervention through home visits. Feasibility and acceptability of the intervention and BMI-Z scores at 18-24 months were compared between tribe A and tribes B & C combined using a separate sample pretest, posttest design. Eighty-six percent of enrolled families completed the study. Breastfeeding initiation and 6-month duration increased 14 and 15%, respectively, in all tribes compared to national rates for American Indians. Breastfeeding at 12 months was comparable to national data. Parents expressed confidence in their ability to curtail family consumption of sugar-sweetened beverages. Compared to a pretest sample of children of a similar age 2 years before the study begun, BMI-Z scores increased in all tribes. However, the increase was less in tribes B & C compared to tribe A (-0.75, P = 0.016). Family, plus community-wide interventions to increase breastfeeding and curtail sugar-sweetened beverages attenuate BMI rise in AI/AN toddlers more than community-wide interventions alone.

Dental caries in American Indian toddlers after a community-based beverage intervention.

OBJECTIVE/SETTING: The Toddler Overweight and Tooth Decay Prevention Study (TOTS) was an overweight and early childhood caries (ECC) project in the Pacific Northwest. It targeted American Indian (AI) toddlers from birth, to effect changes in breastfeeding and sweetened beverage consumption. DESIGN/INTERVENTION/PARTICIPANTS: The intervention cohort was children born in three communities during 12 months; expectant mothers were identified through prenatal visits, and recruited by tribal coordinators. The local comparison cohorts were children in those communities who were aged 18-30 months at study start. A control longitudinal cohort consisted of annual samples of children aged 18-30 months in a fourth community, supplying secular trends. OUTCOME MEASURES: d1-2mfs was used to identify incident caries in intervention, comparison, and control cohorts after 18-to-30 months of follow-up in 2006. RESULTS: No missing or filled teeth were found. For d1t, all three intervention cohorts showed statistically significant downward intervention effects, decreases of between 0.300 and 0.631 in terms of the fraction of affected mouths. The results for d2t were similar but of smaller magnitudes, decreases of between 0.342 and 0.449; these results met the .05 level for significance in two of three cases. In light of an estimated secular increase in dental caries in the control site, all three intervention cohorts showed improvements in both d1t and d1t. CONCLUSION: Simple interventions targeting sweetened beverage availability (in combination with related measures) reduced high tooth decay trends, and were both feasible and acceptable to the AI communities we studied.

A preliminary path analysis of expectancy and patient-provider encounter in an open-label randomized controlled trial of spinal manipulation for cervicogenic headache.

OBJECTIVE: The purpose of this article was to present a preliminary model to identify the effects of expectancy of treatment success and the patient-provider encounter (PPE) on outcomes in an open-label randomized trial. METHODS: Eighty participants with chronic cervicogenic headache (CGH) were randomized to 4 groups: 2 levels of treatment dose (8 or 16) and 2 levels of therapy from a chiropractor (spinal manipulation or light massage). Providers were instructed to have equal enthusiasm for all care. Structural equation modeling with standardized path coefficients (beta) was used in a path analysis to identify the effects of patient expectancy and the PPE on CGH pain. The model included monthly pain from baseline to 12 weeks. Expectancy and PPE were evaluated on Likert scales. The patient-provider encounter was measured as patient perception of chiropractor enthusiasm, confidence, and comfort with care. RESULTS: Baseline patient expectancy was balanced across groups. The PPE measures were balanced across groups and consistent over the 8-week treatment period. Treatment and baseline pain had the strongest effects on pain outcomes (|beta| = .46-.59). Expectations had little effect on pain (abs value(beta) < .15). The patient-provider encounter had a weak effect on pain (abs value(beta)= .03-.27) and on subsequent confidence in treatment success (abs value(beta)= .09 and .12). CONCLUSIONS: Encouraging equipoise in the PPE and balancing expectancy across treatment groups may protect against some confounding related to the absence of blinding in a randomized controlled trial of pain. In this trial, their effects were found to be small relative to the effects of treatment and baseline values.

Influence of stressors on breast cancer incidence in the Women's Health Initiative.

OBJECTIVE: To examine associations among life events stress, social support, and breast cancer incidence in a cohort of postmenopausal women. DESIGN AND MAIN OUTCOME MEASURE: Women's Health Initiative observational study participants, breast cancer free at entry, who provided assessment of stressful life events, social support, and breast cancer risk factors, were prospectively followed for breast cancer incidence (n = 84,334). RESULTS: During an average of 7.6 years of follow-up, 2,481 invasive breast cancers were diagnosed. In age-adjusted proportional hazards models, 1 stressful life event was associated with increased risk, but risk decreased with each additional stressful life event. After adjustment for confounders the decreasing risk was not significant. Stressful life events and social support appeared to interact in relation to breast cancer risk such that women who had greater number of stressful life events and low social support had a decreased risk of breast cancer. CONCLUSIONS: This study found no independent association between stressful life events and breast cancer risk. The results are compatible with a more complex model of psychosocial factors interacting in relation to breast cancer risk.

Using a website to build community and enhance outcomes in a group, multi-component intervention promoting healthy diet and exercise in adolescents.

OBJECTIVE: This article describes website use and behavioral outcomes in a multi-component lifestyle intervention promoting healthy diet and exercise. METHODS: A 2-year randomized clinical trial to improve bone density in 228 adolescent girls, the intervention included a website designed to enhance intervention adherence, retention of participants, and behavioral outcomes. Measures included diet and exercise recalls, surveys, and web-usage data. RESULTS: Website use was associated with increases in calcium intake (ss = 69.72, p =.01, ES = 0.15) and high-impact activity (ss = 10.93, p =.04, ES =.13). Use of web pages related to behavioral feedback and communications was not significantly associated with behavioral outcomes. The most visited website pages had content related to incentive points, caption contests, and fun facts. CONCLUSIONS: Web elements of a multi-component intervention may promote retention and engagement in target behaviors. Such websites may be most acceptable to adolescent participants if they blend fun and behavioral elements, rather than exclusively focusing on behavioral changes.

Pilot study of dietary influences on mammographic density in pre- and postmenopausal Hispanic and non-Hispanic white women.

OBJECTIVE: The extent to which modifiable dietary factors may account for some of the variability demonstrated in mammographic density across ethnic groups is unknown. The purpose of this study was to provide pilot data describing the relationship between dietary variables and mammographic density in pre- and postmenopausal Hispanic and non-Hispanic white (NHW) women (N=238) ranging in age from 41 to 50 years (premenopausal only) or 56 to 70 years (postmenopausal only). DESIGN: Using a cross-sectional design, computer-assisted density assessments were performed on mammograms of both breasts and averaged for analysis. The Arizona Food Frequency Questionnaire was used to estimate dietary intake. RESULTS: Study participants were well educated and overweight, with mean mammographic densities ranging from 20.25% for postmenopausal Hispanic women to 46.94% for premenopausal NHW women. Hispanic women reported higher energy intake than NHW women, but energy-adjusted intake of other nutrients was generally comparable. There was preliminary evidence of ethnic variability in diet-mammographic density associations. Among premenopausal Hispanic women, density was inversely associated with dairy, calcium, and vitamin D intakes (P

Electronic medical records and prevention quality: the prevention index.

BACKGROUND: The Prevention Index is a methodology for using electronic medical records to identify and evaluate practice variations in the delivery of preventive care. METHODS: The Prevention Index was used to evaluate the provision of 10 recommended adult preventive services using electronic medical record data for the years 1999 through 2002 among the 450,000 members of a large Northwest integrated care system. The analyses were conducted in 2005. The Prevention Index determines the proportion of person-time that is covered using consensus guidelines as a standard of care. It is analyzed at the population level and produces quality measures at the individual, practice, clinic, and system levels. The Prevention Index also removes diagnostic services in evaluating preventive care. RESULTS: Overall, about 47% of recommended person-time was actually covered by the services in 2002. For nine services with care guidelines, the percent of covered person-time ranged from 19% for chlamydia screening to 80% for blood pressure screening. The percent of recommended person-time covered by these preventive services varied widely across clinical practices. From 17% to 53% of preventive screening tests were delivered for non-screening purposes. CONCLUSIONS: There are wide variations across clinical practices in the adherence to standard prevention guidelines, and also wide variations across different recommended clinical services. The Prevention Index methodology may allow the identification of the source of these variations, allowing system corrections and other remedial actions to be applied precisely and efficiently.

Researching complementary and alternative treatments--the gatekeepers are not at home.

BACKGROUND: To explore the strengths and weaknesses of conventional biomedical research strategies and methods as applied to complementary and alternative medicine (CAM), and to suggest a new research framework for assessing these treatment modalities. DISCUSSION: There appears to be a gap between published studies showing little or no efficacy of CAM, and reports of substantial clinical benefit from patients and CAM practitioners. This "gap" might be partially due to the current focus on placebo-controlled randomized trials, which are appropriately designed to answer questions about the efficacy and safety of pharmaceutical agents. In an attempt to fit this assessment strategy, complex CAM treatment approaches have been dissected into standardized and often simplified treatment methods, and outcomes have been limited. Unlike conventional medicine, CAM has no regulatory or financial gatekeeper controlling their therapeutic "agents" before they are marketed. Treatments may thus be in widespread use before researchers know of their existence. In addition, the treatments are often provided as an integrated 'whole system' of care, without careful consideration of the safety issue. We propose a five-phase strategy for assessing CAM built on the acknowledgement of the inherent, unique aspects of CAM treatments and their regulatory status in most Western countries. These phases comprise: 1. Context, paradigms, philosophical understanding and utilization 2. Safety status 3. Comparative effectiveness. 4. Component efficacy 5. Biological mechanisms. SUMMARY: Using the proposed strategy will generate evidence relevant to clinical practice, while acknowledging the absence of regulatory and financial gatekeepers for CAM. It will also emphasize the important but subtle differences between CAM and conventional medical practice.

The importance of early phase research.

Early phase research in complementary and alternative medicine (CAM) is especially important because of the large influence it has on the subsequent expenditure of money and effort in particular areas of CAM therapies. The culture of biomedical research has, however, blurred the distinction between early and late-phase research, and this has distorted the very distinct aims of these two activities. The purpose of this paper is to reaffirm the critical role of early phase CAM research and to encourage CAM researchers to value and conduct early phase studies for their proper purposes.

Conceptualization and analysis of mechanistic studies.

Much recent attention has been given to the priority for doing "mechanistic studies" of complementary and alternative medicine (CAM) modalities. A preference for such studes has been clearly indicated by the National Center for Complementary and Alternative Medicine program of funding for CAM research. It is, however, difficult to find canons by which "mechanistic" studies should be analyzed, and even harder to find a good definition of "mechanism." Social scientists have well-developed ways of approaching these issues, but their methods suffer from a fatal flaw, the ecologic mechanistic fallacy. Basic scientists fare even worse, often conducting mechanistic studies that may have no plausible mechanistic content, and that also commit the ecologic mechanistic fallacy. More methodological work on the concept of mechanism is needed at a fundamental level.

The pluses and minuses of interactions.

An important idea in biomedicine is that some factors can moderate the effects of others. In statistical terms this is called interaction, and it occurs when products of variables are introduced into linear models. Although interactions are clinically important, the statistical models are sometimes misunderstood. In one common misuse, treatment effects are obtained from the wrong place in linear model statistical output, and portrayed in a manner that can reverse their true roles. The issues are laid out here in a straightforward manner to assist alternative medicine researchers in avoiding this kind of mistake and recognizing when it is committed in the literature. It is also emphasized that there are situations in which interactions might be the central issue in a study, and it is illustrated how this might handled.

Randomized trial of two mind-body interventions for weight-loss maintenance.

OBJECTIVE: Regain of weight after initial weight loss constitutes a major factor contributing to the escalating obesity epidemic. The objective of this study was to determine the feasibility and clinical impact of two mind-body interventions for weight-loss maintenance. DESIGN: Randomized, balanced, controlled trial. SETTING: Large-group model health maintenance organization. PARTICIPANTS: Overweight and obese adults were recruited to a 12-week behavioral weight-loss program. Participants meeting threshold weight loss and attendance requirements were eligible for randomization. INTERVENTIONS: The three weight-loss maintenance interventions were qigong (QI), Tapas Acupressure Technique (TAT (registered trademark of Tapas Fleming, L.Ac.), and a self-directed support (SDS) group as an attention control. OUTCOMES: The main outcome measure was weight loss maintenance at 24 weeks postrandomization. Patient interviews explored additional benefits of the interventions, as well as barriers and facilitators to compliance. RESULTS: Eighty-eight percent (88%) of randomized patients completed the study. There were no significant study-related adverse events. At 24 weeks, the TAT group maintained 1.2 kg more weight loss than the SDS group did (p = 0.09), and 2.8 kg more weight loss than the QI group did (p = 0.00), only regaining 0.1 kg. A separation test (0.05 level, 0.95 power) indicated that TAT merits further study. A secondary analysis revealed that participants reporting a previous history of recurrent unsuccessful weight loss were more likely to regain weight if assigned to the SDS arm, but this effect was suppressed in both the QI and TAT groups (p = 0.03). Although QI participants reported important general health benefits, the instruction sequence was too brief, given the complexity of the intervention. CONCLUSIONS: TAT warrants further research for weight-loss maintenance. Any further research on qigong should use a modification of our protocol.

Electronic medical record reminder improves osteoporosis management after a fracture: a randomized, controlled trial.

OBJECTIVES: Osteoporosis treatment rates after a fracture are low. This study evaluated methods to increase guideline-recommended osteoporosis care postfracture. DESIGN: Participants were randomly assigned to usual care or one of two interventions. Analysis of primary outcomes used electronic data and linear regression. SETTING: A Pacific Northwest nonprofit health maintenance organization. PARTICIPANTS: Female patients aged 50 to 89 who suffered a fracture in 1999 and had not received bone mineral density (BMD) measurement or medication for osteoporosis (n=311) and their primary care providers (n=159). INTERVENTION: Patient-specific clinical guideline advice to the primary care provider delivered by electronic medical record (EMR) message or electronic reminder to the provider plus an educational letter mailed to the patient. MEASUREMENTS: BMD measurement and osteoporosis medication. RESULTS: At 6 months, provider reminder resulted in 51.5% of patients receiving BMD measurement or osteoporosis medication, provider reminder plus patient education resulted in 43.1%, and usual care resulted in 5.9% (P<.001). The effect of provider advice combined with patient education was not significantly different from provider advice alone (P=.88). Patients aged 60 to 69 were 18% (95% confidence interval=3-34) more likely to receive BMD measurement or an osteoporosis medication than those aged 80 to 89. CONCLUSION: Patient-specific postfracture advice to the provider through an EMR message significantly increased BMD measurement and osteoporosis medication. As EMRs become more widespread, this intervention could improve osteoporosis management for many postfracture patients. Future research should identify barriers to and facilitators of care for older, high-risk patients.

Youth: a health plan-based lifestyle intervention increases bone mineral density in adolescent girls.

OBJECTIVE: To test the efficacy of a health plan-based lifestyle intervention to increase bone mineral density in adolescent girls. DESIGN: Two-year randomized, controlled trial. SETTING: Large health maintenance organization. PARTICIPANTS: Girls 14 to 16 years old with body mass index below the national median. Intervention Behavioral intervention (bimonthly group meetings, quarterly coaching telephone calls, and weekly self-monitoring) designed to improve diet and increase physical activity. MAIN OUTCOME MEASURES: Total bone mineral density was measured by dual-energy x-ray absorptiometry. Behavioral outcomes included intake of calcium, vitamin D, soda, and fruits and vegetables; high-impact and strength-training physical activity; measures of strength and fitness; and biomarkers (osteocalcin and naltrexone). RESULTS: Compared with control subjects, girls in the intervention group had significantly higher bone mineral density in the spine and trochanter regions during the first study year, which was maintained during the second study year. The naltrexone biomarker demonstrated a greater relative decrease in the intervention group compared with the control group, with nonsignificant changes in osteocalcin consistent with more bone building in the intervention group. Participants in the intervention group reported significantly greater consumption of calcium in both study years, vitamin D in the first year, and fruits and vegetables in both years. We found no effect on soda consumption or target exercise rates. CONCLUSIONS: A comprehensive health care-based lifestyle intervention can effectively improve dietary intake and increase bone mineral gains in adolescent girls. To our knowledge, this study is the first to significantly improve bone mass in adolescent girls in a non-school-based intervention. Trial Registration ClinicalTrials.gov Identifier: NCT00067600.