Effects of testosterone and vitamin D on fall risk in pre-frail hypogonadal men: a factorial design RCT.

OBJECTIVE: To test whether transdermal testosterone at a dose of 75 mg per day and/or monthly 24'000 IU Vitamin D reduces the fall risk in pre-frail hypogonadal men aged 65 and older. DESIGN: 2 × 2 factorial design randomized controlled trial, follow up of 12 months. METHODS: Hypogonadism was defined as total testosterone <11.3 nmol/L and pre-frailty as ≥1 Fried- frailty criteria and/or being at risk for falling at the time of screening. The primary outcomes were number of fallers and the rate of falls, assessed prospectively. Secondary outcomes were appendicular lean mass (ALM), sit-to-stand, gait speed, and the short physical performance test battery. Analyses were adjusted for age, BMI, fall history and the respective baseline measurement. RESULTS: We aimed to recruit 168 men and stopped at 91 due to unexpected low recruitment rate (1266 men were pre-screened). Mean age was 72.2 years, serum total testosterone was 10.8 ± 3.0 nmol/l, and 20.9% had 25(OH)D levels below 20 ng/mL. Over 12 months, 37 participants had 72 falls. Neither the odds of falling nor the rate of falls were reduced by testosterone or by vitamin D. Testosterone improved ALM compared to no testosterone (0.21 kg/m2 [0.06, 0.37]), and improved gait speed (0.11 m/s, [0.03, 0.20]) compared to placebo. CONCLUSION: Transdermal testosterone did not reduce fall risk but improved ALM and gait speed in pre-frail older men. Monthly vitamin D supplementation had no benefit.

Effects of vitamin D, omega-3 and a simple strength exercise programme in cardiovascular disease prevention: The DO-HEALTH randomized controlled trial.

BACKGROUND: The effects of non-pharmaceutical interventions in the prevention of cardiovascular diseases (CVD) in older adults remains unclear. Therefore, the aim was to investigate the effect of 2000 IU/day of vitamin D3, omega-3 fatty acids (1 g/day), and a simple home strength exercise program (SHEP) (3×/week) on lipid and CVD biomarkers plasma changes over 3 years, incident hypertension and major cardiovascular events (MACE). METHODS: The risk of MACE (coronary heart event or intervention, heart failure, stroke) was an exploratory endpoint of DO-HEALTH, incident hypertension and change in biomarkers were secondary endpoints. DO-HEALTH is a completed multicentre, randomised, placebo-controlled, 2 × 2 × 2 factorial design trial enrolling 2157 Europeans aged ≥70 years. RESULTS: Participants' median age was 74 [72, 77] years, 61.7% were women, 82.5% were at least moderately physically active, and 40.7% had 25(OH)D < 20 ng/mL at baseline. Compared to their controls, omega-3 increased HDL-cholesterol (difference in change over 3 years: 0.08 mmol/L, 95% CI 0.05-0.10), decreased triglycerides (-0.08 mmol/L, (95%CI -0.12 to -0.03), but increased total- (0.15 mmol/L, 95%CI 0.09; 0.2), LDL- (0.11 mmol/L, 0.06; 0.16), and non-HDL-cholesterol (0.07 mmol/L, 95%CI 0.02; 0.12). However, neither omega-3 (adjustedHR 1.00, 95%CI 0.64-1.56), nor vitamin D3 (aHR 1.37, 95%CI 0.88-2.14), nor SHEP (aHR 1.18, 95%CI 0.76-1.84) reduced risk of MACE or incident hypertension compared to control. CONCLUSION: Among generally healthy, active, and largely vitamin D replete, older adults, treatment with omega-3, vitamin D3, and/or SHEP had no benefit on MACE prevention. Only omega-3 supplementation changed lipid biomarkers, but with mixed effects. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT01745263.

Enrollment And Characteristics Of Dual-Eligible Medicare And Medicaid Beneficiaries In Integrated Care Programs.

Integrated care programs (ICPs) are meant to make Medicare and Medicaid coverage for dual-eligible beneficiaries work more seamlessly. Evidence is limited on ICP enrollment trends and the characteristics of dual-eligible beneficiaries who enroll in these programs-specifically, the Program of All-Inclusive Care for the Elderly, Medicare Advantage (MA) Fully Integrated Dual-Eligible Special Needs Plans, and state demonstration Medicare-Medicaid plans. Using national data, we evaluated changes in ICP enrollment between 2013 and 2020 and compared the demographic characteristics of beneficiaries in these programs relative to the characteristics of beneficiaries not in them. The proportion of dual-eligible beneficiaries in ICPs increased from 2.0 percent in 2013 to 9.4 percent in 2020. However, nonintegrated or partially integrated coordination-only MA plans experienced the plurality of growth in enrollment of dual-eligible beneficiaries. Relative to non-ICP fee-for-service Medicare, beneficiaries in ICPs were more likely to be Black and Hispanic versus White and were less likely to be rural, younger, or disabled. Policy makers should diligently monitor growth in ICPs and less integrated dual-eligible plans in MA while also evaluating their impact on equity, spending, and quality of care.

Association of Dance-Based Mind-Motor Activities With Falls and Physical Function Among Healthy Older Adults: A Systematic Review and Meta-analysis.

Importance: Falls increase morbidity and mortality in adults 65 years and older. The role of dance-based mind-motor activities in preventing falls among healthy older adults is not well established. Objective: To assess the effectiveness of dance-based mind-motor activities in preventing falls. Data Sources: Systematic search included the PubMed, Embase, Cochrane Library, Web of Science, CINAHL, PsychINFO, Abstracts in Social Gerontology, AgeLine, AMED, and Scopus databases from database inception to February 18, 2018, using the Medical Subject Headings aged 65 and older, accidental falls, and dancing. Study Selection: This systematic review and meta-analysis included 29 randomized clinical trials that evaluated a dance-based mind-motor activity in healthy older adults with regard to fall risk, fall rate, or well-established measures of physical function in the domains of balance, mobility, and strength. The included studies targeted participants without comorbidities associated with higher fall risk. Dance-based mind-motor activities were defined as coordinated upright mind-motor movements that emphasize dynamic balance, structured through music or an inner rhythm (eg, breathing) and distinctive instructions or choreography, and that involve social interaction. Data Extraction and Synthesis: Standardized independent screening, data extraction, and bias assessment were performed. Data were pooled using random-effects models. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Main Outcomes and Measures: Primary outcomes were risk of falling and rate of falls. For the secondary end points of physical function (balance, mobility, and strength), standardized mean differences (SMDs) were estimated and pooled (Hedges g). Results: In this systematic review and meta-analysis of 29 randomized clinical trials, dance-based mind-motor activities were significantly associated with reduced (37%) risk of falling (risk ratio, 0.63; 95% CI, 0.49-0.80; 8 trials, 1579 participants) and a significantly reduced (31%) rate of falls (incidence rate ratio, 0.69; 95% CI, 0.53-0.89; 7 trials, 2012 participants). In addition, dance-based mind-motor activities were significantly associated with improved physical function in the domains of balance (standardized mean difference [SMD], 0.62; 95% CI, 0.33-0.90; 15 trials, 1476 participants), mobility (SMD, -0.56; 95% CI, -0.81 to -0.31; 13 trials, 1379 participants), and lower body strength (SMD, 0.57; 95% CI, 0.23-0.91; 13 trials, 1613 participants) but not upper body strength (SMD, 0.18; 95% CI, -0.03 to 0.38; 4 trials, 414 participants). Conclusion and Relevance: Among healthy older adults, dance-based mind-motor activities were associated with decreased risk of falling and rate of falls and improved balance, mobility, and lower body strength. This type of activity may be useful in preventing falls in this population.

Effect of daily 2000 IU versus 800 IU vitamin D on blood pressure among adults age 60 years and older: a randomized clinical trial.

BACKGROUND: Observational studies report higher blood pressure (BP) among individuals with lower 25-hydroxyvitamin D concentration. Whether dosage of vitamin D supplementation has a differential effect on BP control remains unclear. OBJECTIVE: The study aimed to determine if daily vitamin D supplementation with 2000 IU is more effective than 800 IU for BP control among older adults. METHODS: This randomized, double-blind, ancillary trial of the Zurich Multiple Endpoint Vitamin D Trial in Knee Osteoarthritis enrolled adults aged ≥60 y who underwent elective surgery due to severe knee osteoarthritis. Participants were randomly assigned to receive high dose (2000 IU) or standard dose (800 IU) daily vitamin D3 for 24 mo. Outcomes included daytime and 24-h mean systolic BP. BP variability and serum 25-hydroxyvitamin D concentration were examined in a post hoc and observational analysis. RESULTS: Of the 273 participants randomly assigned, 250 participants completed a follow-up 24-h ambulatory BP monitoring (mean age: 70.4 ± 6.4 y; 47.2% men). The difference in daytime mean systolic BP reduction between the 2000 IU (n = 123) and 800 IU (n = 127) groups was not statistically significant (-2.75 mm Hg vs. -3.94 mm Hg; difference: 1.18 mm Hg; 95% CI: -0.68, 3.05; P = 0.21), consistent with 24-h mean systolic BP. However, systolic BP variability was significantly reduced with 2000 IU (average real variability: -0.37 mm Hg) compared to 800 IU vitamin D3 (0.11 mm Hg; difference: -0.48 mm Hg; 95% CI: -0.94, -0.01; P = 0.045). Independent of group allocation, maximal reductions in mean BP were observed at 28.7 ng/mL of achieved serum 25-hydroxyvitamin D concentrations. CONCLUSIONS: While daily 2000 IU and 800 IU vitamin D3 reduced mean systolic BP over 2 y to a small and similar extent, 2000 IU reduced mean systolic BP variability significantly more compared with 800 IU. However, without a placebo control group we cannot ascertain whether vitamin D supplementation effectively reduces BP.This trial was registered at www.clinicaltrials.gov as NCT00599807.

Long-term Risk of Colorectal Cancer and Related Death After Adenoma Removal in a Large, Community-based Population.

BACKGROUND & AIMS: The long-term risks of colorectal cancer (CRC) and CRC-related death following adenoma removal are uncertain. Data are needed to inform evidence-based surveillance guidelines, which vary in follow-up recommendations for some polyp types. Using data from a large, community-based integrated health care setting, we examined the risks of CRC and related death by baseline colonoscopy adenoma findings. METHODS: Participants at 21 medical centers underwent baseline colonoscopies from 2004 through 2010; findings were categorized as no-adenoma, low-risk adenoma, or high-risk adenoma. Participants were followed until the earliest of CRC diagnosis, death, health plan disenrollment, or December 31, 2017. Risks of CRC and related deaths among the high- and low-risk adenoma groups were compared with the no-adenoma group using Cox regression adjusting for confounders. RESULTS: Among 186,046 patients, 64,422 met eligibility criteria (54.3% female; mean age, 61.6 ± 7.1 years; median follow-up time, 8.1 years from the baseline colonoscopy). Compared with the no-adenoma group (45,881 patients), the high-risk adenoma group (7563 patients) had a higher risk of CRC (hazard ratio [HR] 2.61; 95% confidence interval [CI] 1.87-3.63) and related death (HR 3.94; 95% CI 1.90-6.56), whereas the low-risk adenoma group (10,978 patients) did not have a significant increase in risk of CRC (HR 1.29; 95% CI 0.89-1.88) or related death (HR 0.65; 95% CI 0.19-2.18). CONCLUSIONS: With up to 14 years of follow-up, high-risk adenomas were associated with an increased risk of CRC and related death, supporting early colonoscopy surveillance. Low-risk adenomas were not associated with a significantly increased risk of CRC or related deaths. These results can inform current surveillance guidelines for high- and low-risk adenomas.

Effect of Monthly High-Dose Vitamin D on Mental Health in Older Adults: Secondary Analysis of a RCT.

OBJECTIVES: To test the effect of monthly high-dose vitamin D supplementation on mental health in pre-frail older adults. DESIGN: Ancillary study of a 1-year double-blind randomized clinical trial conducted in Zurich, Switzerland. SETTING AND PARTICIPANTS: A total of 200 community-dwelling adults 70 years and older with a prior fall event in the last year. Participants were randomized to receive 24 000 IU vitamin D3 (considered standard of care), 60 000 IU vitamin D3 , or 24 000 IU vitamin D3 plus 300 µg calcifediol per month. MEASURES: The primary end point was the Mental Component Summary (MCS) of the SF-36. Secondary end points were the SF-36 Mental Health (MH) subscale and the Geriatric Depression Scale (GDS-15). RESULTS: Participants' mean age was 78 years (67% women), and 58% were vitamin D deficient (<20 ng/mL). Over time, primary and secondary end points did not differ significantly among the three treatment groups or in subgroups by vitamin D status at baseline. Given the lack of a true placebo group, we explored in a predefined observational analysis the change in mental health scales by achieved 25(OH)D levels at 12 months. After adjusting for confounders, participants achieving the highest 25(OH)D quartile (Q) at 12 months (44.7-98.9 ng/mL) had the greatest improvements in MCS (Q4 = 0.79 vs Q1 = -2.9; p = .03) and MH scales (Q4 = 2.54 vs Q1 = -3.07; p = .03); these associations were strongest among participants who were vitamin D deficient at baseline. No association was found for GDS (p = .89). CONCLUSIONS: For mental health, our study suggests no benefit of higher monthly doses of vitamin D3 compared with the standard monthly dose of 24 000 IU. However, irrespective of vitamin D treatment dose, achieving higher 25(OH)D levels at 12-month follow-up was associated with a small, clinically uncertain but statistically significant improvement in mental health scores.

Effect of 800 IU Versus 2000 IU Vitamin D3 With or Without a Simple Home Exercise Program on Functional Recovery After Hip Fracture: A Randomized Controlled Trial.

OBJECTIVES: To evaluate 2 simple strategies, vitamin D3 and a home exercise program, in functional recovery during the first year after hip fracture. DESIGN: Secondary analysis of a factorial clinical trial. Patients were randomly allocated to 800 IU (standard of care) or 2000 IU vitamin D3 and a daily instruction of a simple home exercise program (SHEP) or standard physiotherapy alone during acute care. SETTING AND PARTICIPANTS: Acute hip fracture patients aged ≥65 years, after hip fracture surgery, admitted to a large hospital in Zurich, Switzerland. MEASURES: Three objective measures of lower extremity function were assessed at baseline and 6 and 12 months, with the Timed Up and Go test (TUG) as the primary endpoint, and knee flexor and extensor strength, and a self-reported physical function score (PF-10) as secondary endpoints. Linear mixed model regression analyses were based on intention to treat, adjusting for baseline function, time, age, sex, and baseline 25-hydroxyvitamin D level. RESULTS: We enrolled 173 patients (79.2% women; mean age 84 years; 77.5% living at home). A significant interaction was found between vitamin D3 dose and SHEP for TUG (P = .045). Thus, findings compared the standard of care reference arm with 800 IU vitamin D3 without SHEP to 3 interventions arms (800 IU vitamin D3+SHEP; 2000 IU vitamin D3 without SHEP; 2000 IU vitamin D3+SHEP). For TUG, over 12 months the 800 IU vitamin D3+SHEP group performed significantly better than the standard-of-care group (13.8 vs 19.5 seconds; P = .01). Findings for knee flexor strength were in line with TUG results and approached significance (P = .07), whereas knee extensor strength and PF-10 did not differ by treatments. CONCLUSIONS/IMPLICATIONS: For functional recovery after hip fracture, combining home exercise with 800 IU vitamin D3 is superior to no home exercise or 2000 IU vitamin D3. None of the interventions improved subjective physical functioning.

Recovery after unilateral knee replacement due to severe osteoarthritis and progression in the contralateral knee: a randomised clinical trial comparing daily 2000 IU versus 800 IU vitamin D.

OBJECTIVE: To test whether daily high-dose vitamin D improves recovery after unilateral total knee replacement. METHODS: Data come from a 24-month randomised, double-blind clinical trial. Adults aged 60 and older undergoing unilateral joint replacement due to severe knee osteoarthritis were 6-8 weeks after surgery randomly assigned to receive daily high-dose (2000 IU) or standard-dose (800 IU) vitamin D3. The primary endpoints were symptoms (Western Ontario and McMaster Universities Arthritis Index pain and function scores) assessed at baseline, 6, 12, 18 and 24 months in both knees, and the rate of falls over 24 months. The secondary outcomes were sit-to-stand performance, gait speed, physical activity and radiographic progression in the contralateral knee. RESULTS: We recruited 273 participants, 137 were randomised to receive 2000 IU and 136 were randomised to receive 800 IU vitamin D per day. 2000 IU vitamin D increased 25-hydroxyvitamin D levels to 45.6 ng/mL and 800 IU vitamin D to 37.1 ng/mL at month 24 (p<0.0001). While symptoms improved significantly in the operated knee and remained stable in the contralateral knee over time, none of the primary or secondary endpoints differed by treatment group over time. The rate of falls over 24 months was 1.05 with 2000 IU and 1.07 with 800 IU (p=0.84). 30.5% of participants in the 2000 IU and 31.3% of participants in the 800 IU group had radiographic progression in the contralateral knee over 24 months (p=0.88). CONCLUSIONS: Our findings suggest that a 24-month treatment with daily 2000 IU vitamin D did not show greater benefits or harm than a daily standard dose of 800 IU among older adults undergoing unilateral total knee replacement.

Circulating Biomarkers of Dairy Fat and Risk of Incident Diabetes Mellitus Among Men and Women in the United States in Two Large Prospective Cohorts.

BACKGROUND: In prospective studies, the relationship of self-reported consumption of dairy foods with risk of diabetes mellitus is inconsistent. Few studies have assessed dairy fat, using circulating biomarkers, and incident diabetes mellitus. We tested the hypothesis that circulating fatty acid biomarkers of dairy fat, 15:0, 17:0, and t-16:1n-7, are associated with lower incident diabetes mellitus. METHODS AND RESULTS: Among 3333 adults aged 30 to 75 years and free of prevalent diabetes mellitus at baseline, total plasma and erythrocyte fatty acids were measured in blood collected in 1989 to 1990 (Nurses' Health Study) and 1993 to 1994 (Health Professionals Follow-Up Study). Incident diabetes mellitus through 2010 was confirmed by a validated supplementary questionnaire based on symptoms, diagnostic tests, and medications. Risk was assessed by using Cox proportional hazards, with cohort findings combined by meta-analysis. During mean±standard deviation follow-up of 15.2±5.6 years, 277 new cases of diabetes mellitus were diagnosed. In pooled multivariate analyses adjusting for demographics, metabolic risk factors, lifestyle, diet, and other circulating fatty acids, individuals with higher plasma 15:0 had a 44% lower risk of diabetes mellitus (quartiles 4 versus 1, hazard ratio, 0.56; 95% confidence interval, 0.37-0.86; P-trend=0.01); higher plasma 17:0, 43% lower risk (hazard ratio, 0.57; 95% confidence interval, 0.39-0.83; P-trend=0.01); and higher t-16:1n-7, 52% lower risk (hazard ratio, 0.48; 95% confidence interval, 0.33-0.70; P-trend <0.001). Findings were similar for erythrocyte 15:0, 17:0, and t-16:1n-7, although with broader confidence intervals that only achieved statistical significance for 17:0. CONCLUSIONS: In 2 prospective cohorts, higher plasma dairy fatty acid concentrations were associated with lower incident diabetes mellitus. Results were similar for erythrocyte 17:0. Our findings highlight the need to better understand the potential health effects of dairy fat, and the dietary and metabolic determinants of these fatty acids.

Monthly High-Dose Vitamin D Treatment for the Prevention of Functional Decline: A Randomized Clinical Trial.

IMPORTANCE: Vitamin D deficiency has been associated with poor physical performance. OBJECTIVE: To determine the effectiveness of high-dose vitamin D in lowering the risk of functional decline. DESIGN, SETTING, AND PARTICIPANTS: One-year, double-blind, randomized clinical trial conducted in Zurich, Switzerland. The screening phase was December 1, 2009, to May 31, 2010, and the last study visit was in May 2011. The dates of our analysis were June 15, 2012, to October 10, 2015. Participants were 200 community-dwelling men and women 70 years and older with a prior fall. INTERVENTIONS: Three study groups with monthly treatments, including a low-dose control group receiving 24,000 IU of vitamin D3 (24,000 IU group), a group receiving 60,000 IU of vitamin D3 (60,000 IU group), and a group receiving 24,000 IU of vitamin D3 plus 300 µg of calcifediol (24,000 IU plus calcifediol group). MAIN OUTCOMES AND MEASURES: The primary end point was improving lower extremity function (on the Short Physical Performance Battery) and achieving 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months. A secondary end point was monthly reported falls. Analyses were adjusted for age, sex, and body mass index. RESULTS: The study cohort comprised 200 participants (men and women ≥ 70 years with a prior fall). Their mean age was 78 years, 67.0% (134 of 200) were female, and 58.0% (116 of 200) were vitamin D deficient (<20 ng/mL) at baseline. Intent-to-treat analyses showed that, while 60,000 IU and 24,000 IU plus calcifediol were more likely than 24,000 IU to result in 25-hydroxyvitamin D levels of at least 30 ng/mL (P = .001), they were not more effective in improving lower extremity function, which did not differ among the treatment groups (P = .26). However, over the 12-month follow-up, the incidence of falls differed significantly among the treatment groups, with higher incidences in the 60,000 IU group (66.9%; 95% CI, 54.4% to 77.5%) and the 24,000 IU plus calcifediol group (66.1%; 95% CI, 53.5%-76.8%) group compared with the 24,000 IU group (47.9%; 95% CI, 35.8%-60.3%) (P = .048). Consistent with the incidence of falls, the mean number of falls differed marginally by treatment group. The 60,000 IU group (mean, 1.47) and the 24,000 IU plus calcifediol group (mean, 1.24) had higher mean numbers of falls compared with the 24,000 IU group (mean, 0.94) (P = .09). CONCLUSIONS AND RELEVANCE: Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/mL of 25-hydroxyvitamin D, they had no benefit on lower extremity function and were associated with increased risk of falls compared with 24,000 IU. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01017354.

Impact of a group mind/body intervention on pregnancy rates in IVF patients.

OBJECTIVE: To determine if women who were randomized to a mind/body program before starting their first IVF cycle would have higher pregnancy rates than control subjects. DESIGN: Randomized, controlled, prospective study. SETTING: Private academically affiliated infertility center. PATIENT(S): A total of 143 women aged≤40 years who were about to begin their first IVF cycle. INTERVENTION(S): Subjects were randomized to a ten-session mind/body program (MB) or a control group and followed for two IVF cycles. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate. RESULT(S): Only 9% of the MB participants had attended at least one-half of their sessions at cycle 1 start. Pregnancy rates for cycle 1 were 43% for all subjects; 76% of the MB subjects had attended at least one-half of their sessions at cycle 2 start. Pregnancy rates for cycle 2 were 52% for MB and 20% for control. CONCLUSION(S): MB participation was associated with increased pregnancy rates for cycle 2, prior to which most subjects had attended at least half of their sessions.

A randomized trial of three psychosocial treatments for the symptoms of rheumatoid arthritis.

OBJECTIVE: To assess and compare the benefits of 3 psychosocial treatments for rheumatoid arthritis (RA). METHODS: RA patients were randomized to cognitive-behavior therapy (CBT), relaxation response training (RR), or arthritis education (AE). All treatment was conducted in groups. Follow-up occurred immediately after treatment and 6 and 12 months later. Pain, other RA symptoms, role impairment, and psychological distress were assessed with standardized self-report questionnaires. Arthritis severity and activity were assessed with a joint examination, erythrocyte sedimentation rate, grip strength, and walking time. An intent-to-treat analytic strategy was employed. Linear regression was used to establish treatment effect on pain and other RA symptoms, while adjusting for sociodemographic and clinical variables. RESULTS: One hundred sixty-eight patients were randomized. Pain improved significantly at 12 months in the RR and AE groups and showed a nonsignificant positive trend with CBT. Other RA symptoms improved significantly with CBT and AE and showed a nonsignificant trend with RR. There were no significant differences in the outcomes across the 3 treatment groups. When the results for all 3 groups were aggregated, significant benefits were found for pain, other RA symptoms, self-care activities, and social activities. Effect sizes ranged between 0.26 and 0.35. CONCLUSIONS: These 3 psychosocial treatments were beneficial, with treatment effect sizes in the small to moderate range. The effects appeared immediately after treatment and were generally sustained at long-term follow-up. These benefits were achieved over and above those resulting from medical management. These treatments constitute an effective augmentation to standard medical therapy for RA patients.

Substance use and survival after treatment for chronic myelogenous leukemia (CML) or myelodysplastic syndrome (MDS).

BACKGROUND: Patients' substance use problems are a particularly understudied aspect of psychosocial variables in cancer treatment. OBJECTIVES: The specific hypothesis tested was that lifetime substance use disorders increased the risk of adverse outcome, in the context of other psychosocial and clinical characteristics demonstrated in other studies to have an impact on treatment outcome. METHOD: Prospective cohort study of 106 adults with chronic myelogenous leukemia or primary myelodysplastic syndrome. None satisfied criteria for current substance abuse or dependence, but the lifetime rates of substance use disorders in this sample were 28% for alcohol, 12% for cannabis, and 9% for cocaine. RESULTS: Participants received treatment as directed by their physicians, and were followed until death or the end of the study (median 1.5 years). Twenty-eight died. Multivariate survival analysis identified three predictors of outcome: lifetime cocaine use, associated with a six-fold increased risk of death (p = .04), and two protective variables, baseline hemoglobin (p = .002) and estimated intelligence quotient (IQ) (p = .04). CONCLUSION: The results of this study highlight the potential significance of substance use disorders, and lifetime cocaine diagnoses in particular, on treatment outcome for people with chronic myelogenous leukemia or myelodysplastic syndrome. Whereas neither lifetime alcohol nor cannabis use were associated with survival on either the univariate or multivariate models of survival, lifetime cocaine diagnoses were associated with significant six-fold increased risk of death (p = .04).

Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials.

BACKGROUND: Antifracture efficacy with supplemental vitamin D has been questioned by recent trials. METHODS: We performed a meta-analysis on the efficacy of oral supplemental vitamin D in preventing nonvertebral and hip fractures among older individuals (> or =65 years). We included 12 double-blind randomized controlled trials (RCTs) for nonvertebral fractures (n = 42 279) and 8 RCTs for hip fractures (n = 40 886) comparing oral vitamin D, with or without calcium, with calcium or placebo. To incorporate adherence to treatment, we multiplied the dose by the percentage of adherence to estimate the mean received dose (dose x adherence) for each trial. RESULTS: The pooled relative risk (RR) was 0.86 (95% confidence interval [CI], 0.77-0.96) for prevention of nonvertebral fractures and 0.91 (95% CI, 0.78-1.05) for the prevention of hip fractures, but with significant heterogeneity for both end points. Including all trials, antifracture efficacy increased significantly with a higher dose and higher achieved blood 25-hydroxyvitamin D levels for both end points. Consistently, pooling trials with a higher received dose of more than 400 IU/d resolved heterogeneity. For the higher dose, the pooled RR was 0.80 (95% CI, 0.72-0.89; n = 33 265 subjects from 9 trials) for nonvertebral fractures and 0.82 (95% CI, 0.69-0.97; n = 31 872 subjects from 5 trials) for hip fractures. The higher dose reduced nonvertebral fractures in community-dwelling individuals (-29%) and institutionalized older individuals (-15%), and its effect was independent of additional calcium supplementation. CONCLUSION: Nonvertebral fracture prevention with vitamin D is dose dependent, and a higher dose should reduce fractures by at least 20% for individuals aged 65 years or older.

Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: a 3-year randomized controlled trial.

BACKGROUND: A recent meta-analysis found that cholecalciferol (vitamin D) should reduce falls by more than 20%. However, little is known about whether supplemental cholecalciferol plus calcium citrate malate will lower the long-term risk of falling in men, active older individuals, and older individuals with higher 25-hydroxyvitamin D levels. METHODS: We studied the effect of 3-year supplementation with cholecalciferol-calcium on the risk of falling at least once in 199 men and 246 women 65 years or older and living at home. Individuals received 700 IU of cholecalciferol plus 500 mg of calcium citrate malate per day or placebo in a randomized double-blind manner. Subjects were classified as less physically active if physical activity was below the median level. Low 25-hydroxyvitamin D levels were classified as those below 32 ng/mL (<80 nmol/L). RESULTS: In 3 years, 55% of women and 45% of men reported at least 1 fall. Mean +/- SD baseline 25-hydroxyvitamin D levels were 26.6 +/- 12.7 ng/mL (66.4 +/- 31.7 nmol/L) in women and 33.2 +/- 14.2 ng/mL (82.9 +/- 34.9) in men. Cholecalciferol-calcium significantly reduced the odds of falling in women (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.30-0.97), but not in men (OR, 0.93; 95% CI, 0.50-1.72). Fall reduction was most pronounced in less active women (OR, 0.35; 95% CI, 0.15-0.81). Baseline 25-hydroxyvitamin D level did not modulate the treatment effect. CONCLUSIONS: Long-term dietary cholecalciferol-calcium supplementation reduces the odds of falling in ambulatory older women by 46%, and especially in less active women by 65%. Supplementation had a neutral effect in men independent of their physical activity level.