Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS.

BACKGROUND: Longer effects of multivitamin-mineral (MVM) supplementation on late-life cognitive function remain untested using in-person, detailed neuropsychological assessments. Furthermore, insufficient evidence exists for healthcare providers to recommend daily MVM supplements to prevent cognitive decline. OBJECTIVES: This study aimed to test MVM effects on cognitive change using in-person, detailed neuropsychological assessments and conduct a meta-analysis within COSMOS (COcoa Supplement and Multivitamin Outcomes Study) cognitive substudies for a robust evaluation of MVM effects on cognition. METHODS: COSMOS is a 2 × 2 factorial trial of cocoa extract (500 mg flavanols/d) and/or a daily MVM supplement for cardiovascular disease and cancer prevention among 21,442 United States adults aged ≥60 y. There were 573 participants in the clinic subcohort of COSMOS (that is, COSMOS-Clinic) who completed all cognitive tests administered at baseline. For the meta-analysis, we included nonoverlapping participants across 3 COSMOS cognitive substudies: COSMOS-Clinic (n = 573); COSMOS-Mind (n = 2158); COSMOS-Web (n = 2472). RESULTS: In COSMOS-Clinic, we observed a modest benefit of MVM compared with placebo on global cognition over 2 y {mean difference [95% confidence interval (CI)] = 0.06 SD units (SU) (-0.003, 0.13)}, with a significantly more favorable change in episodic memory [mean difference (95% CI) = 0.12 SU (0.002, 0.23)] but not in executive function or attention [mean difference (95% CI) = 0.04 SU (-0.04, 0.11)]. The meta-analysis of COSMOS substudies showed clear evidence of MVM benefits on global cognition [mean difference (95% CI) = 0.07 SU (0.03, 0.11); P = 0.0009] and episodic memory [mean difference (95% CI) = 0.06 SU (0.03, 0.10); P = 0.0007]; the magnitude of effect on global cognition was equivalent to reducing cognitive aging by 2 y. CONCLUSIONS: In COSMOS-Clinic, daily MVM supplementation leads to a significantly more favorable 2-y change in episodic memory. The meta-analysis within COSMOS cognitive substudies indicates that daily MVM significantly benefits both global cognition and episodic memory. These findings within the COSMOS trial support the benefits of a daily MVM in preventing cognitive decline among older adults. This trial was registered at COSMOS-clinicaltrials.gov as NCT02422745, at COSMOS-Mind-clinicaltrials.gov as NCT03035201, and at COSMOS-Web-clinicaltrials.gov as NCT04582617.

Long-term Tai Chi practice in older adults is associated with "younger" functional abilities.

Age-related alterations in physiology lead to declines in physical function that are associated with numerous adverse outcomes among older adults. Utilizing a hybrid design, we aimed to understand whether both long-term and short-term Tai Chi (TC) training are associated with age-related decline in physical function in healthy older adults. We first conducted cross-sectional comparisons among TC-naïve older adults (n = 60, 64.2 ± 7.7 years), TC-expert older adults (n = 27, 62.8 ± 7.6 years, 24.5 ± 12 years experience), and TC-naïve younger adults (n = 15, 28.7 ± 3.2 years) to inform long-term effects of TC training on physical function, including single leg stance time with eyes closed, grip strength, Timed Up and Go, maximum walking speed, functional reach, and vertical jump for lower-extremity power. There were significant differences among the three groups on all the six tests. For most functional tests, TC-experts performed better than age-matched TC-naïve controls and were statistically indistinguishable from young healthy adult controls. Long-term TC training was associated with higher levels of physical function in older adults, suggesting a potential preventative healthy aging effect. In the randomized longitudinal trial, TC-naïve subjects were randomized (n = 31 to Tai Chi group, n = 29 to usual care control group) to evaluate the short-term effects of TC over 6 months on all outcomes. TC's short-term impacts on physical function were small and not statistically significant. The impact of short-term training in healthy adults is less clear. Both potential longer-term preventive effects and shorter-term restorative effects warrant further research with rigorous, adequately powered controlled clinical trials.

Effect of cocoa extract supplementation on cognitive function: results from the clinic subcohort of the COSMOS trial.

BACKGROUND: Some prior randomized clinical trials (RCTs) that tested the effects of cocoa extract (CE), a source of flavanols, on late-life cognition have yielded promising findings. A long-term RCT using in-person neuropsychological tests covering multiple cognitive domains may clarify the cognitive effects of CE. OBJECTIVES: To test whether daily supplementation with CE, compared with placebo, produces better cognitive change over 2 y. METHODS: The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a 2 × 2 factorial RCT of CE [500 mg flavanols/d, including 80 mg (-)-epicatechin] and/or a daily multivitamin-mineral supplement for cardiovascular disease and cancer prevention among 21,442 United States adults aged ≥60 y. There were 573 participants in the clinic subcohort of COSMOS (that is, COSMOS-Clinic) who completed all cognitive tests at baseline; of these, 492 completed 2-y follow-up assessments. The primary outcome was global cognition (averaging z-scores across 11 tests). Secondary outcomes were episodic memory and executive function/attention. Repeated measures models were used to compare randomized groups. RESULTS: Participants' mean age (standard deviation) was 69.6 (5.3); 49.2% were females. Daily supplementation with CE, compared with placebo, had no significant effect on 2-y change in global cognition {mean difference [95% confidence interval (CI)]: -0.01 (-0.08, 0.05) standard deviation units (SU)}. CE, compared with placebo, had no significant effects on 2-y change in episodic memory [mean difference (95% CI): -0.01 (-0.13, 0.10) SU] or executive function/attention [mean difference (95% CI): 0.003 (-0.07, 0.08) SU]. Subgroup analyses uncorrected for multiple-testing suggested cognitive benefits of CE supplementation, compared with placebo among those with poorer baseline diet quality. CONCLUSIONS: Among 573 older adults who underwent repeat in-person, detailed neuropsychological assessments over 2 y, daily CE supplementation, compared with placebo, showed no overall benefits for global or domain-specific cognitive function. Possible cognitive benefits of CE among those with poorer diet quality warrant further study. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov with identifier - NCT02422745.

Rationale and design of an ancillary study evaluating the effects of the cocoa flavanol and/or multivitamin interventions on falls and physical performance outcomes in the COcoa Supplement and Multivitamin Outcomes Study (COSMOS).

BACKGROUND: Falls and decreased physical function increase markedly with age and result in injury, hospitalization, and premature death. Emerging studies show potential benefits of supplemental cocoa extract on physical performance, including grip strength and walking speed in older adults. However, there are no large, long-term randomized controlled trials of effects of supplemental cocoa extract on falls, muscle performance, and/or fall-related injuries. METHODS: The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a double-blind, placebo-controlled, 2 × 2 factorial trial investigating effects of supplementation with cocoa extract (500 mg/d, including 80 mg (-)-epicatechin) and/or a multivitamin on prevention of cardiovascular disease and cancer in 21,442 women (≥65 years) and men (≥60 years). COSMOS: Effects on Falls and Physical Performance is an ancillary study to COSMOS that will clarify effects of cocoa extract and/or multivitamin supplementation on falls, physical performance, and incident fracture outcomes in older adults. Injurious fall(s) resulting in healthcare utilization and recurrent falls were regularly assessed by follow-up questionnaires in the overall cohort. Incident fractures were also assessed by annual questionnaires. Circumstances surrounding falls and any fall-related injuries will be confirmed by medical record review. Effects of the interventions on 2-year changes in physical performance measures (grip strength, walking speed, and the Short Physical Performance Battery) will be tested in a clinic sub-cohort (n = 603). CONCLUSION: Results from this ancillary study will determine whether supplemental cocoa extract slows age-related declines in physical performance and decrease injurious and recurrent falls and fall-related injuries and fractures that are major public health problems in older adults.

Acceptance and commitment therapy for episodic migraine: Rationale and design of a pilot randomized controlled trial.

Migraine is a debilitating disorder with limited pharmacological options. Many migraine medications can have intolerable side effects leading patients to seek complementary and integrative health (CIM) approaches for treatment. One option that is growing in popularity and evidence is Acceptance and Commitment Therapy (ACT), a mindfulness-based therapy. The purpose of this paper is to describe how ACT may be an effective modality integrated into the treatment of migraine and to describe the design of a pilot study of ACT for migraine. First, we review the research and the promise of mindfulness therapies for the treatment of migraine. Then, we describe how ACT differs from other mindfulness therapies for migraine and why it can be a promising option for these patients. Finally, we summarize the design of a pilot study designed to determine the feasibility of performing a future fully powered study to determine the effectiveness of ACT on migraine frequency and disability. This pilot study includes unique features, including a remotely-delivered ACT intervention and the measurement of cortisol levels before and after the intervention.

Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial.

BACKGROUND: Cocoa extract is a source of flavanols that favorably influence vascular risk factors in small and short-term trials, yet effects on clinical cardiovascular events are untested. OBJECTIVES: We examined whether cocoa extract supplementation decreases total cardiovascular disease (CVD) among older adults. METHODS: We conducted a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial of cocoa extract supplementation and multivitamins for prevention of CVD and cancer among 21,442 US adults (12,666 women aged ≥65 y and 8776 men aged ≥60 y), free of major CVD and recently diagnosed cancer. The intervention phase was June 2015 through December 2020. This article reports on the cocoa extract intervention. Participants were randomly assigned to a cocoa extract supplement [500 mg flavanols/d, including 80 mg (-)-epicatechin] or placebo. The primary outcome was a composite of confirmed incident total cardiovascular events, including myocardial infarction (MI), stroke, coronary revascularization, cardiovascular death, carotid artery disease, peripheral artery surgery, and unstable angina. RESULTS: During a median follow-up of 3.6 y, 410 participants taking cocoa extract and 456 taking placebo had confirmed total cardiovascular events (HR: 0.90; 95% CI: 0.78, 1.02; P = 0.11). For secondary endpoints, HRs were 0.73 (95% CI: 0.54, 0.98) for CVD death, 0.87 (95% CI: 0.66, 1.16) for MI, 0.91 (95% CI: 0.70, 1.17) for stroke, 0.95 (95% CI: 0.77, 1.17) for coronary revascularization, neutral for other individual cardiovascular endpoints, and 0.89 (95% CI: 0.77, 1.03) for all-cause mortality. Per-protocol analyses censoring follow-up at nonadherence supported a lower risk of total cardiovascular events (HR: 0.85; 95% CI: 0.72, 0.99). There were no safety concerns. CONCLUSIONS: Cocoa extract supplementation did not significantly reduce total cardiovascular events among older adults but reduced CVD death by 27%. Potential reductions in total cardiovascular events were supported in per-protocol analyses. Additional research is warranted to clarify whether cocoa extract may reduce clinical cardiovascular events. This trial is registered at www.clinicaltrials.gov as NCT02422745.

Multivitamins in the prevention of cancer and cardiovascular disease: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial.

BACKGROUND: Although older adults commonly take multivitamin-multimineral (MVM) supplements to promote health, evidence on the use of daily MVMs on invasive cancer is limited. OBJECTIVES: The study objective was to determine if a daily MVM decreases total invasive cancer among older adults. METHODS: We performed a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial of a daily MVM and cocoa extract for prevention of cancer and cardiovascular disease (CVD) among 21,442 US adults (12,666 women aged ≥65 y and 8776 men aged ≥60 y) free of major CVD and recently diagnosed cancer. The intervention phase was from June 2015 through December 2020. This article reports on the MVM intervention. Participants were randomly assigned to daily MVM or placebo. The primary outcome was total invasive cancer, excluding nonmelanoma skin cancer. Secondary outcomes included major site-specific cancers, total CVD, all-cause mortality, and total cancer risk among those with a baseline history of cancer. RESULTS: During a median follow-up of 3.6 y, invasive cancer occurred in 518 participants in the MVM group and 535 participants in the placebo group (HR: 0.97; 95% CI: 0.86, 1.09; P = 0.57). We observed no significant effect of a daily MVM on breast cancer (HR: 1.06; 95% CI: 0.79, 1.42) or colorectal cancer (HR: 1.30; 95% CI: 0.80, 2.12). We observed a protective effect of a daily MVM on lung cancer (HR: 0.62; 95% CI: 0.42, 0.92). The composite CVD outcome occurred in 429 participants in the MVM group and 437 participants in the placebo group (HR: 0.98; 95% CI: 0.86, 1.12). MVM use did not significantly affect all-cause mortality (HR: 0.93; 95% CI: 0.81, 1.08). There were no safety concerns. CONCLUSIONS: A daily MVM supplement, compared with placebo, did not significantly reduce the incidence of total cancer among older men and women. Future studies are needed to determine the effects of MVMs on other aging-related outcomes among older adults. This trial is registered at www.clinicaltrials.gov as NCT02422745.

Design and baseline characteristics of participants in the COcoa Supplement and Multivitamin Outcomes Study (COSMOS).

Background Cocoa extract and multivitamins have been proposed to reduce the risk of cardiovascular disease (CVD) and cancer, respectively. However, few randomized clinical trials have tested their long-term effects on these outcomes. Methods The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a randomized, double-blind, placebo-controlled, 2 × 2 factorial trial of a cocoa extract supplement and a multivitamin supplement to reduce the risk of CVD and cancer. Here we describe the pragmatic, hybrid design of the trial and baseline characteristics of the trial participants. Results The nationwide study population includes 21,442 U.S. women aged ≥65 years and men aged ≥60 years without baseline myocardial infarction (MI), stroke, or a recent (within the past 2 years) cancer diagnosis. Participants were randomized in a 2 × 2 factorial design to one of four groups: (1) cocoa extract (containing 500 mg/d flavanols, including 80 mg (-)-epicatechin) and a multivitamin (Centrum Silver©); (2) cocoa extract and multivitamin placebo; (3) multivitamin and cocoa extract placebo; or (4) both placebos. Randomization successfully distributed baseline demographic, clinical, behavioral, and dietary characteristics across treatment groups. Baseline biospecimens were collected from 6867 participants, with at least one follow-up biospecimen from 2142 participants. The primary outcome for the cocoa extract intervention is total CVD (a composite of MI, stroke, cardiovascular mortality, coronary revascularization, unstable angina requiring hospitalization, carotid artery surgery, and peripheral artery surgery); the primary outcome for the multivitamin intervention is total invasive cancer. Conclusion COSMOS will provide important information on the health effects of cocoa extract and multivitamin supplementation in older U.S. adults. Clinical Trials Registration: clinicaltrials.gov #NCT02422745.

Development of a Novel Intervention (Mindful Steps) to Promote Long-Term Walking Behavior in Chronic Cardiopulmonary Disease: Protocol for a Randomized Controlled Trial.

BACKGROUND: Despite current rehabilitation programs, long-term engagement in physical activity remains a significant challenge for patients with chronic obstructive pulmonary disease (COPD) and heart failure (HF). Novel strategies to promote physical activity in these populations are greatly needed. Emerging literature on the benefits of both mind-body interventions and web-based interventions provide the rationale for the development of the Mindful Steps intervention for increasing walking behavior. OBJECTIVE: This study aims to develop a novel multimodal mind-body exercise intervention through adaptation of an existing web-based physical activity intervention and incorporation of mind-body exercise, and to pilot test the delivery of the new intervention, Mindful Steps, in a randomized controlled feasibility trial in older adults with COPD and/or HF. METHODS: In phase 1, guided by a theoretical conceptual model and review of the literature on facilitators and barriers of physical activity in COPD and HF, we convened an expert panel of researchers, mind-body practitioners, and clinicians to inform development of the novel, multimodal intervention. In phase 2, we are conducting a pilot randomized controlled feasibility trial of the Mindful Steps intervention that includes in-person mind-body exercise classes, an educational website, online mind-body videos, and a pedometer with step-count feedback and goals to increase walking behavior in patients with COPD and/or HF. Outcomes include feasibility measures as well as patient-centered measures. RESULTS: The study is currently ongoing. Phase 1 intervention development was completed in March 2019, and phase 2 data collection began in April 2019. CONCLUSIONS: Through the integration of components from a web-based physical activity intervention and mind-body exercise, we created a novel, multimodal program to impact long-term physical activity engagement for individuals with COPD and HF. This developmental work and pilot study will provide valuable information needed to design a future clinical trial assessing efficacy of this multimodal approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT03003780; https://clinicaltrials.gov/ct2/show/NCT03003780. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/27826.

Tai Chi training's effect on lower extremity muscle co-contraction during single- and dual-task gait: Cross-sectional and randomized trial studies.

BACKGROUND: Tai Chi (TC) mind-body exercise has been shown to reduce falls and improve balance and gait, however, few studies have evaluated the role of lower extremity muscle activation patterns in the observed benefits of TC on mobility. PURPOSE: To perform an exploratory analysis of the association between TC training and levels of lower extremity muscle co-contraction in healthy adults during walking under single-task (ST) and cognitive dual-task (DT) conditions. METHODS: Surface electromyography of the anterior tibialis and lateral gastrocnemius muscles was recorded during 90 sec trials of overground ST (walking normally) and DT (walking with verbalized serial subtractions) walking. A mean co-contraction index (CCI), across all strides, was calculated based on the percentage of total muscle activity when antagonist muscles were simultaneously activated. A hybrid study design investigated long-term effects of TC via a cross-sectional comparison of 27 TC experts and 60 age-matched TC-naïve older adults. A longitudinal comparison assessed the shorter-term effects of TC; TC-naïve participants were randomly allocated to either 6 months of TC training or to usual care. RESULTS: Across all participants at baseline, greater CCI was correlated with slower gait speed under DT (ß(95% CI) = -26.1(-48.6, -3.7)) but not ST (ß(95% CI) = -15.4(-38.2, 7.4)) walking. Linear models adjusting for age, gender, BMI and other factors that differed at baseline indicated that TC experts exhibited lower CCI compared to TC naives under DT, but not ST conditions (ST: mean difference (95% CI) = -7.1(-15.2, 0.97); DT: mean difference (95% CI) = -10.1(-18.1, -2.4)). No differences were observed in CCI for TC-naive adults randomly assigned to 6 months of TC vs. usual care. CONCLUSION: Lower extremity muscle co-contraction may play a role in the observed benefit of longer-term TC training on gait and postural control. Longer-duration and adequately powered randomized trials are needed to evaluate the effect of TC on neuromuscular coordination and its impact on postural control. TRIAL REGISTRATION: The randomized trial component of this study was registered at ClinicalTrials.gov (NCT01340365).

Perceptions of Chiropractic Care Among Women With Migraine: A Qualitative Substudy Using a Grounded-Theory Framework.

OBJECTIVE: The purpose of this study was to characterize expectations, attitudes, and experiences of individuals with migraine who were randomly assigned to receive chiropractic care delivered within a randomized controlled trial in a hospital-based integrative care center. METHODS: This qualitative substudy was conducted as a part of a 2-arm pilot pragmatic randomized controlled trial investigating a multimodal model of chiropractic care for women with episodic migraine (4-13 migraines per month). Women were randomly assigned to chiropractic care (10 sessions over 14 weeks) plus enhanced usual care vs enhanced usual care alone. Semistructured interviews were conducted at baseline and 14-week follow-up with 15 randomly selected participants from the 29 participants randomized to the chiropractic group. Qualitative analysis was performed by 2 independent reviewers using a constant comparative method of analysis for generating grounded theory. RESULTS: Integrating baseline and follow-up interviews, 3 themes emerged: over the course of treatment with chiropractic care, participants became more aware of the role of musculoskeletal tension, pain, and posture in triggering migraine; participants revised their prior conceptions of chiropractic care beyond spinal manipulation; and participants viewed the chiropractor-patient relationship as an essential and valuable component to effectively managing their migraines. CONCLUSION: In this qualitative study, women with episodic migraine after receiving comprehensive chiropractic care described chiropractic as a multimodal intervention where they learned about musculoskeletal contributions to migraine, discovered new ways to affect their symptoms, and developed a collaborative patient-practitioner relationship. The results of this study provide insights into perceptions of chiropractic care among women with migraine and suggestions for future trials.

Effect of Vitamin D and/or Marine n-3 Fatty Acid Supplementation on Changes in Migraine Frequency and Severity.

BACKGROUND: There is interest in whether supplements, including vitamin D and marine omega-3 (n-3) fatty acids, may be effective migraine prophylaxis. However, few studies have evaluated whether vitamin D or n-3 fatty acid supplementation may reduce migraine frequency or severity. METHODS: Participants in the VITamin D and OmegA-3 TriaL (VITAL) were assigned to vitamin D3 (2000 IU/d) or marine n-3 fatty acid (1 g/d) supplementation in a 2-by-2 factorial design. Lifetime history of migraine was assessed a median of 4.6 years after the start of the trial. Individuals were asked to self-report changes in migraine frequency (no change, more frequent, or less frequent) and severity (no change, more severe, less severe) in the past 5 years. We used χ2 tests to compare proportions of individuals reporting changes in migraine frequency and severity between active and placebo groups. RESULTS: Among the 25,871 participants in VITAL, 1032 participants had a history of probable migraine and provided information on changes in migraine frequency and severity. The percentage of individuals reporting decreases in migraine frequency did not differ between active (69.0%) and placebo vitamin D (68.4%) (P value = 0.54) or between active (67.8%) and placebo n-3 fatty acid (69.6%) (P value = 0.82). Similarly, the percentage of individuals reporting decreases in migraine severity did not differ between active (64.1%) and placebo vitamin D (65.0%) (P value = 0.86) or between active (64.5%) and placebo n-3 fatty acid (64.5%) (P value = 0.96). CONCLUSIONS: Neither vitamin D nor marine n-3 fatty acid supplementation, compared to placebo, affected migraine frequency or severity among middle-aged or older adults.

Multimodal chiropractic care for migraine: A pilot randomized controlled trial.

BACKGROUND: Spinal manipulation may reduce migraine frequency, but effects of multimodal chiropractic care on migraine frequency have not been evaluated. METHODS: We conducted a pilot randomized controlled trial comparing multimodal chiropractic care + enhanced usual care (MCC+) versus enhanced usual care alone (EUC) among adult women with episodic migraine. EUC was comprised of usual medical care and migraine education literature. MCC+ participants received 10 sessions of chiropractic care over 14 weeks. Primary aims evaluated feasibility of recruitment, retention, protocol adherence, and safety. Change in migraine days was a secondary aim. RESULTS: Of 422 patients screened, 61 were randomized over 20 months. Fifty-seven (93%) completed daily migraine logs during the intervention, 51 (84%) completed final follow-up, and 45 (74%) completed all assessments. Twenty-four of 29 MCC+ participants (83%) attended > 75% of the chiropractic sessions. Ninety-eight non-serious adverse events were reported by 26 participants (43%) with 39 events among 11 EUC participants and 59 events among 15 MCC+ participants. MCC+ participants experienced greater reductions in migraine days (-2.9 days for MCC+ vs. -1.0 days for EUC, difference = -1.9; 95% confidence interval: -3.5, -0.4). CONCLUSIONS: Pre-specified feasibility criteria were not met, but deficits were remediable. Preliminary data support a definitive trial of MCC+ for migraine. TRIAL REGISTRATION: This study is registered at Clinicaltrials.gov (NCT03177616).

Effect of vitamin D and/or omega-3 fatty acid supplementation on stroke outcomes: A randomized trial.

BACKGROUND AND PURPOSE: Among stroke patients, low serum 25-hydroxyvitamin D predicts poor outcomes. In mice, higher omega-3 (n-3) fatty acid intake diminishes brain damage after stroke. In this study, we tested whether vitamin D or n-3 fatty acids supplementation prior to stroke reduces the risk of functional limitations and physical disability after stroke. METHODS: We used data from VITAL (the VITamin D and OmegA-3 TriaL) which randomized middle-aged and older men and women without cardiovascular disease to vitamin D3 (2000 IU/day) and/or marine n-3 fatty acids (1 g/day) and followed them for incident stroke events. Individuals experiencing a non-fatal stroke were mailed questionnaires assessing functional limitations (the physical performance scale adapted from Nagi) and physical disability (the modified Katz Activities of Daily Living and Rosow-Breslau Functional Health scales). We used logistic regression to analyze associations between randomized treatment and limitations on each scale. RESULTS: A total of 290 individuals experienced their first stroke during the trial, of whom 197 stroke survivors completed the stroke outcomes questionnaire a median of 1.4 years after diagnosis. We observed no associations between randomized treatment to vitamin D and functional limitations (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.52, 1.97) or physical disability (Rosow-Breslau scale: OR 0.92, 95% CI 0.50, 1.67; Katz scale: OR 1.03, 95% CI 0.31, 3.42). Those randomized to n-3 fatty acids had a non-significantly lower risk of functional limitations (OR 0.55, 95% CI 0.28, 1.09) and physical disability (Rosow-Breslau scale: OR 0.56, 95% CI 0.31, 1.02; Katz sclae: OR 0.32, 95% CI 0.50, 1.67). CONCLUSION: Vitamin D or omega-3 fatty acid supplementation prior to stroke did not result in significantly improved post-stroke outcomes.

Development and Implementation of the Integrative Toolbox for Headache Management.

Patients with migraine are interested in integrative therapies and overall wellness. They also suffer from social isolation as they try to manage a chronic medical condition. We implemented a three-part workshop structured as a group visit that teaches multiple integrative therapies from specialists and offers a chance for shared support and learning.

The Impact of Spinal Manipulation on Migraine Pain and Disability: A Systematic Review and Meta-Analysis.

BACKGROUND: Several small studies have suggested that spinal manipulation may be an effective treatment for reducing migraine pain and disability. We performed a systematic review and meta-analysis of published randomized clinical trials (RCTs) to evaluate the evidence regarding spinal manipulation as an alternative or integrative therapy in reducing migraine pain and disability. METHODS: PubMed and the Cochrane Library databases were searched for clinical trials that evaluated spinal manipulation and migraine-related outcomes through April 2017. Search terms included: migraine, spinal manipulation, manual therapy, chiropractic, and osteopathic. Meta-analytic methods were employed to estimate the effect sizes (Hedges' g) and heterogeneity (I2 ) for migraine days, pain, and disability. The methodological quality of retrieved studies was examined following the Cochrane Risk of Bias Tool. RESULTS: Our search identified 6 RCTs (pooled n = 677; range of n = 42-218) eligible for meta-analysis. Intervention duration ranged from 2 to 6 months; outcomes included measures of migraine days (primary outcome), migraine pain/intensity, and migraine disability. Methodological quality varied across the studies. For example, some studies received high or unclear bias scores for methodological features such as compliance, blinding, and completeness of outcome data. Due to high levels of heterogeneity when all 6 studies were included in the meta-analysis, the 1 RCT performed only among chronic migraineurs was excluded. Heterogeneity across the remaining studies was low. We observed that spinal manipulation reduced migraine days with an overall small effect size (Hedges' g = -0.35, 95% CI: -0.53, -0.16, P < .001) as well as migraine pain/intensity. CONCLUSIONS: Spinal manipulation may be an effective therapeutic technique to reduce migraine days and pain/intensity. However, given the limitations to studies included in this meta-analysis, we consider these results to be preliminary. Methodologically rigorous, large-scale RCTs are warranted to better inform the evidence base for spinal manipulation as a treatment for migraine.

Integrating Chiropractic Care Into the Treatment of Migraine Headaches in a Tertiary Care Hospital: A Case Series.

This case series illustrates an integrated model of care for migraine that combines standard neurological care with chiropractic treatment. For each patient, we describe the rationale for referral, diagnosis by both the neurologist and chiropractor, the coordinated care plan, communication between the neurologist and chiropractor based on direct face-to-face "hallway" interaction, medical notes, team meetings, and clinical outcomes. Findings are evaluated within the broader context of the multicause nature of migraine and the impact of integrative chiropractic. Suggestions for future areas of research evaluating integrative approaches are discussed.

Multivitamin Use and the Risk of Cardiovascular Disease in Men.

BACKGROUND: Although multivitamins are widely used by US adults, few prospective studies have investigated their association with the long- and short-term risks of cardiovascular disease (CVD). OBJECTIVE: The aim of this study was to investigate how multivitamin use is associated with the risk of CVD in initially healthy men at baseline. METHODS: We studied 18,530 male physicians aged ≥40 y from the Physicians' Health Study I cohort who were free of CVD and cancer at baseline (1982). All men provided a wide range of self-reported lifestyle and clinical factors plus intake of selected foods and dietary supplements. Cox proportional hazards models were used to calculate multivariable-adjusted HRs (95% CIs). RESULTS: During a mean follow-up of 12.2 y (total of 225,287 person-years), there were 1697 incident cases of major CVD (defined as nonfatal myocardial infarction, nonfatal stroke, and CVD death). In multivariable-adjusted analyses, no significant associations were observed among baseline multivitamin users compared with nonusers for the risk of major CVD events (HR: 0.94; 95% CI: 0.84, 1.05), whereas a self-reported duration of ≥20 y at baseline was associated with lower risk (HR: 0.56; 95% CI: 0.35, 0.90; P-trend = 0.05). Baseline multivitamin use was also significantly inversely associated with the risk of cardiac revascularization (HR: 0.86; 95% CI: 0.75, 0.98). Baseline use of multivitamins was not significantly associated with other CVD endpoints. CONCLUSION: In this long-term prospective study in initially healthy men, multivitamin use for ≥20 y was associated with a lower risk of major CVD events.

Multivitamin use and cardiovascular disease in a prospective study of women.

BACKGROUND: Although multivitamins are widely used, there are limited prospective studies investigating their association with both long- and short-term risk of cardiovascular disease (CVD). OBJECTIVE: The objective was to investigate how multivitamin use is associated with the long- and short-term risk of CVD. DESIGN: A prospective cohort study was conducted of 37,193 women from the Women's Health Study aged ≥45 y and free of CVD and cancer at baseline who were followed for an average of 16.2 y. At baseline, women self-reported a wide range of lifestyle, clinical, and dietary factors. Women were categorized into 1) no current use and 2) current use of multivitamins. Duration and updated measures over the course of the follow-up to address short-term effects were also considered. Women were followed for major CVD events, including myocardial infarction (MI), stroke, and CVD death. RESULTS: During the follow-up, 1493 incident cases of CVD [defined as myocardial infarction (MI), stroke, and CVD death] occurred. In multivariable analyses, multivitamin use compared with no use was not associated with major CVD events (HR: 1.01; 95% CI: 0.89, 1.15), MI (HR: 1.04; 95% CI: 0.84, 1.27), stroke (HR: 0.99; 95% CI: 0.83, 1.18), or CVD death (HR: 1.10; 95% CI: 0.84, 1.45). A nonsignificant inverse association was observed between baseline multivitamin use and major CVD events among women aged ≥70 y (P-interaction = 0.04) and those consuming <3 servings/d of fruit and vegetables (P-interaction = 0.01). When updating information on multivitamin use during the course of follow-up, no associations were observed for major CVD events (HR: 0.91; 95% CI: 0.82, 1.02), MI (HR: 0.89; 95% CI: 0.74, 1.06), stroke (HR: 0.91; 95% CI: 0.78, 1.06), and CVD death (HR: 0.91; 95% CI: 0.71, 1.16). CONCLUSIONS: In this study of middle-aged and elderly women, neither baseline nor time-varying multivitamin use was associated with the long-term risk of major CVD events, MI, stroke, cardiac revascularizations, or CVD death. Additional studies are needed to clarify the role of multivitamins on CVD.

Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials.

OBJECTIVE: To evaluate the effect of vitamin E supplementation on incident total, ischaemic, and haemorrhagic stroke. DESIGN: Systematic review and meta-analysis of randomised, placebo controlled trials published until January 2010. DATA SOURCES: Electronic databases (Medline, Embase, Cochrane Central Register of Controlled Trials) and reference lists of trial reports. Selection criteria Randomised, placebo controlled trials with ≥1 year of follow-up investigating the effect of vitamin E on stroke. Review methods and data extraction Two investigators independently assessed eligibility of identified trials. Disagreements were resolved by consensus. Two different investigators independently extracted data. Risk ratios (and 95% confidence intervals) were calculated for each trial based on the number of cases and non-cases randomised to vitamin E or placebo. Pooled effect estimates were then calculated. RESULTS: Nine trials investigating the effect of vitamin E on incident stroke were included, totalling 118 765 participants (59 357 randomised to vitamin E and 59 408 to placebo). Among those, seven trials reported data for total stroke and five trials each for haemorrhagic and ischaemic stroke. Vitamin E had no effect on the risk for total stroke (pooled relative risk 0.98 (95% confidence interval 0.91 to 1.05), P=0.53). In contrast, the risk for haemorrhagic stroke was increased (pooled relative risk 1.22 (1.00 to 1.48), P=0.045), while the risk of ischaemic stroke was reduced (pooled relative risk 0.90 (0.82 to 0.99), P=0.02). There was little evidence for heterogeneity among studies. Meta-regression did not identify blinding strategy, vitamin E dose, or morbidity status of participants as sources of heterogeneity. In terms of absolute risk, this translates into one additional haemorrhagic stroke for every 1250 individuals taking vitamin E, in contrast to one ischaemic stroke prevented per 476 individuals taking vitamin E. CONCLUSION: In this meta-analysis, vitamin E increased the risk for haemorrhagic stroke by 22% and reduced the risk of ischaemic stroke by 10%. This differential risk pattern is obscured when looking at total stroke. Given the relatively small risk reduction of ischaemic stroke and the generally more severe outcome of haemorrhagic stroke, indiscriminate widespread use of vitamin E should be cautioned against.