Effects of vitamin D3, omega-3 s and a simple strength training exercise program on bone health: the DO-HEALTH randomized controlled trial.

INTRODUCTION: Evidence on the effects of Vitamin D, omega-3 s and exercise on aBMD in healthy older adults is limited. We examined whether vitamin D3, omega-3 s, or a simple home-based exercise program (SHEP), alone or in combination, over three years, improve lumbar spine (LS), femoral neck (FN) or total hip (TH) aBMD assessed by DXA. METHODS: aBMD was a secondary outcome in DO-HEALTH, a 3-year, multicenter, double-blind, randomized 2 × 2 × 2 factorial design trial in generally healthy older adults age ≥ 70 years. The study interventions were vitamin D3 (2000IU/d), omega-3 s (1 g/d), and SHEP (3 × 30 min/wk), applied alone or in combination in 8 treatment arms. Mixed effect models were used adjusting for age, sex, BMI, prior fall, study site and baseline level of the outcome. Main effects were assessed in the absence of an interaction between the interventions. Subgroup analyses by sex, physical activity level, dietary calcium intake, serum 25(OH)D levels, and fracture history were conducted. RESULTS: DXA scans were available for 1493 participants (mean age 75 years; 80.4% were physically active, 44% had 25(OH)D levels <20 ng/ml). At the LS and FN sites, none of the treatments showed a benefit. At the TH, vitamin D vs. no vitamin D treatment showed a significant benefit across 3 years (difference in adjusted means [AM]: 0.0035 [95% CI 0.0011, 0.0059] g/cm2). Furthermore, there was a benefit for vitamin D vs. no vitamin D treatment on LS aBMD in the male subgroup of (interaction P = 0.003; ∆AM: 0.0070 [95% CI 0.0007, 0.0132] g/cm2). CONCLUSIONS: Omega-3 and SHEP had no benefit on aBMD in healthy, active and largely vitamin D replete older adults. Our study suggests a small benefit of 2000 IU vitamin D daily on TH aBMD overall and LS aBMD among men, however, effect sizes were very modest and the clinical impact of these findings is unclear.

Vitamin D, omega-3 fatty acids (omega-3 s) and strength training are simple but promising strategies to improve bone health, however, their effect in healthy older adults over a period of three years was unclear. In this study, we examined whether daily vitamin D supplementation (2000 IU/d), daily omega-3 s supplementation (1 g/d) or a simple strength training program performed three times per week, either applied alone (e.g., only vitamin D supplements) or in combination (e.g., vitamin D and omega-3 s supplements) could improve bone density at the spine, hip or femoral neck. We included 1493 healthy older adults from Switzerland, Germany, France and Portugal who were at least 70 years of age and who had not experienced any major health events in the five years before study start. Taking omega-3 s supplements showed no benefit for bone density. Similarly, the simple strength exercise program showed no benefit. In contrast, participants receiving daily vitamin D supplements experienced a benefit at the hip. However, it should be noted that the effect across three years was very small.

Implementation of a Scalable Online Weight Management Programme in Clinical Settings: Protocol for the PROPS 2.0 Programme (Partnerships for Reducing Overweight and Obesity with Patient-Centered Strategies 2.0).

INTRODUCTION: There is an urgent need for scalable strategies for treating overweight and obesity in clinical settings. PROPS 2.0 (Partnerships for Reducing Overweight and Obesity with Patient-Centered Strategies 2.0) aims to adapt and implement the combined intervention from the PROPS Study at scale, in a diverse cross-section of patients and providers. METHODS AND ANALYSIS: We are implementing PROPS 2.0 across a variety of clinics at Brigham and Women's Hospital, targeting enrolment of 5000 patients. Providers can refer patients or patients can self-refer. Eligible patients must be ≥20 years old and have a body mass index (BMI) of ≥30 kg/m2 or a BMI of 25-29.9 kg/m2 plus another cardiovascular risk factor or obesity-related condition. After enrolment, patients register for the RestoreHealth online programme/app (HealthFleet Inc.) and participate for 12 months. Patients can engage with the programme and receive personalized feedback from a coach. Patient navigators help to enrol patients, enter updates in the electronic health record, and refer patients to additional resources. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework is guiding the evaluation. ETHICS AND DISSEMINATION: The Mass General Brigham Human Research Committee approved this protocol. An implementation guide will be created and disseminated, to help other sites adopt the intervention in the future. TRIAL REGISTRATION NUMBER: NCT0555925.

Prevalence of polypharmacy in community-dwelling older adults from seven centres in five European countries: a cross-sectional study of DO-HEALTH.

OBJECTIVE: To investigate the prevalence of polypharmacy and characteristics associated with polypharmacy in older adults from seven European cities. DESIGN: Cross-sectional study of baseline data from DO-HEALTH. SETTING AND PARTICIPANTS: DO-HEALTH enrolled 2157 community-dwelling adults age 70 and older from seven centres in Europe. Participants were excluded if they had major health problems or Mini-Mental State Examination Score <24 at baseline. PRIMARY OUTCOME MEASURES: Extensive information on prescription and over-the-counter medications were recorded. Polypharmacy was defined as the concomitant use of five or more medications, excluding vitamins or dietary supplements. Bivariate and multivariable logistic regression was used to test the association of sociodemographic factors (age, sex, years of education, living situation and city) and health-related indicators (number of comorbidities, cognitive function, frailty status, body mass index (BMI), prior fall, self-rated health and smoking status) with polypharmacy. RESULTS: 27.2% of participants reported polypharmacy ranging from 16.4% in Geneva to 60.8% in Coimbra. In the multivariable logistic regression analyses, older age (OR 1.07; 95% CI 1.04 to 1.10), greater BMI (OR 1.09; 95% CI 1.06 to 1.12) and increased number of comorbidities (OR 2.13; 95% CI 1.92 to 2.36) were associated with polypharmacy. Women were less likely to report polypharmacy than men (OR 0.65; 95% CI 0.51 to 0.84). In comparison to participants from Zurich, participants from Coimbra were more likely to report polypharmacy (OR 2.36; 95% CI 1.56 to 3.55), while participants from Geneva or Toulouse were less likely to report polypharmacy ((OR 0.36; 95% CI 0.22 to 0.59 and OR 0.64; 95% CI 0.42 to 0.96), respectively). Living situation, smoking status, years of education, prior fall, cognitive function, self-rated health and frailty status were not significantly associated with polypharmacy. CONCLUSION: Polypharmacy is common among relatively healthy older adults, with moderate variability across seven European cities. Independent of several confounders, being a woman, older age, greater BMI and greater number of comorbidities were associated with increased odds for polypharmacy. TRIAL REGISTRATION NUMBER: NCT01745263.

Community Outreach for Navajo People Living with Diabetes: Who Benefits Most?

INTRODUCTION: The Community Outreach and Patient Empowerment (COPE) intervention provides integrated outreach through community health representatives (CHRs) to people living with diabetes in Navajo Nation. The aim of this study was to identify groups for whom the intervention had the greatest effect on glycated hemoglobin A1c (HbA1c). METHODS: We analyzed de-identified data extracted from routine health records dated from December 1, 2010, through August 31, 2014, to compare net change in HbA1c among COPE patients and non-COPE patients. We used linear mixed models to assess whether the intervention was modified by age, sex, preferred language, having a primary care provider, baseline HbA1c, or having a mental health condition. RESULTS: Age, having a primary care provider, and baseline HbA1c significantly modified HbA1c levels. Among patients aged 64 or younger, COPE participation was associated with a net decrease in HbA1c of 0.77%; among patients aged 65 or older, the net decrease was 0.49% (P = .03). COPE participation was associated with a steeper decrease in HbA1c among patients without a primary care physician (net decrease, 0.99%) than among patients with a primary care provider (net decrease, 0.57%) (P = .03). COPE patients with a baseline HbA1c >9% had a net decrease of 0.70%, while those with a baseline HbA1c ≤9% had a net decrease of 0.34% (P = .01). We found no significant differences based on sex, preferred language, or having a mental health condition. CONCLUSION: Findings suggest that the COPE intervention was robust and equitable, benefiting all groups living with diabetes in Navajo Nation, but conferring the greatest benefit on the most vulnerable.

Integrating community health representatives with health care systems: clinical outcomes among individuals with diabetes in Navajo Nation.

BACKGROUND: We studied the impact of Community Outreach and Patient Empowerment (COPE) intervention to support Community Health Representatives (CHR) on the clinical outcomes of patients living with diabetes in the Navajo Nation extending into the States of Arizona, Utah, and New Mexico. The COPE intervention integrated CHRs into healthcare teams by providing a structured approach to referrals and home visits. METHODS: We abstracted routine clinical data from the Indian Health Service's information system on individuals with diabetes mellitus seen at participating clinical sites from 2010 to 2014. We matched 173 COPE participants to 2880 patients with similar demographic and clinical characteristics who had not participated in COPE. We compared the changes in clinical outcomes between the two groups using linear mixed models. RESULTS: Over the four years of the study, COPE patients had greater improvements in glycosylated hemoglobin (- 0.56%) than non-COPE participants (+ 0.07%) for a difference in differences of 0.63% (95% confidence interval (CI): 0.50, 0.76). Low-density lipoprotein fell more steeply in the COPE group (- 10.58 mg/dl) compared to the non-COPE group (- 3.18 mg/dl) for a difference in differences of 7.40 mg/dl (95%CI: 2.00, 12.80). Systolic blood pressure increased slightly more among COPE (2.06 mmHg) than non-COPE patients (0.61 mmHg). We noted no significant change for body mass index in either group. CONCLUSION: Structured outreach by Community Health Representatives as part of an integrated care team was associated with improved glycemic and lipid levels in the target Navajo population. TRIAL REGISTRATION: Trial registration: NCT03326206. Registered 31 October 2017 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT03326206.

Prognosis of seronegative patients in a large prospective cohort of patients with early inflammatory arthritis.

OBJECTIVE: Rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) are believed to be associated with more severe rheumatoid arthritis; however, studies in early inflammatory arthritis (EIA) have yielded conflicting results. Our study determined the prognosis of baseline ACPA-negative and RF-negative patients. METHODS: Patients enrolled in the Canadian Early Arthritis Cohort had IgM RF and IgG anticyclic citrullinated peptide antibodies 2 (anti-CCP2) measured at baseline. Remission was defined as a Disease Activity Score of 28 joints (DAS28) < 2.6 using logistic regression accounting for confounders at 12-month and 24-month followup. RESULTS: Of the 841 patients, 216 (26%) were negative for both RF and anti-CCP2. Compared to seropositive subjects, seronegative subjects were older (57 ± 15 vs 51 ± 14 yrs), more males proportionately (31% vs 23%), and had shorter length of symptoms (166 ± 87 vs 192 ± 98 days), and at baseline had higher mean swollen joint count (SJC; 8.8 ± 6.8 vs 6.5 ± 5.6), DAS28 (5.0 ± 1.6 vs 4.8 ± 1.5), and erosive disease (32% vs 24%, p < 0.05). Treatment was similar between the 2 groups. At 24-month followup, seronegative compared to seropositive subjects had greater mean change (Δ ± SD) in disease activity measures: ΔSJC counts (-6.9 ± 7.0 vs -5.1 ± 5.9), ΔDAS28 (-2.4 ± 2.0 vs -1.8 ± 1.8), and ΔC-reactive protein (-11.0 ± 17.9 vs -6.4 ± 17.5, p < 0.05). Accounting for confounders, antibody status was not significantly associated with remission. However, at 12-month followup, ACPA-positive subjects were independently more likely to have new erosive disease (OR 2.94, 95% CI 1.45-5.94). CONCLUSION: Although seronegative subjects with EIA have higher baseline DAS28 compared to seropositive subjects, they have a good response to treatment and are less likely to develop erosive disease during followup.

Dietary calcium and serum 25-hydroxyvitamin D status in relation to BMD among U.S. adults.

A higher calcium intake is still the primary recommendation for the prevention of osteoporosis, whereas vitamin D deficiency is often not addressed. To study the relative importance of dietary calcium intake and serum 25-hydroxyvitamin D [25(OH)D] status in regard to hip BMD, 4958 community-dwelling women and 5003 men >/=20 yr of age from the U.S. NHANES III population-based survey were studied. Calcium supplement users and individuals with a prior radius or hip fracture were excluded. We calculated standardized means for BMD by quartiles of sex-specific calcium intake for three 25(OH)D categories (<50, 50-74, and 75+ nM) among men and women, separately controlling for other important predictors of BMD. A higher calcium intake was significantly associated with higher BMD (p value for trend: p = 0.005) only for women with 25(OH)D status <50 nM, whereas calcium intake beyond the upper end of the lowest quartile (>566 mg/d) was not significantly associated with BMD at 25(OH)D concentrations >50 nM. Among men, there was no significant association between a higher calcium intake beyond the upper end of the lowest quartile (626 mg/d) and BMD within all 25(OH)D categories. Among both sexes, BMD increased stepwise and significantly with higher 25(OH)D concentrations (<50, 50-74, 75+ nM; p value for trend: women < 0.0001; men = 0.0001). Among men and women, 25(OH)D status seems to be the dominant predictor of BMD relative to calcium intake. Only women with 25(OH)D concentrations <50 nM seem to benefit from a higher calcium intake.

Racial segregation and disparities in breast cancer care and mortality.

BACKGROUND: Questions have existed as to whether residential segregation is a mediator of racial/ethnic disparities in breast cancer care and breast cancer mortality, or has a differential effect by race/ethnicity. METHODS: Data from the Surveillance, Epidemiology, and End Results-Medicare database on white, black, and Hispanic women aged 66 to 85 years with breast cancer were examined for the receipt of adequate breast cancer care. RESULTS: Blacks were less likely than whites to receive adequate breast cancer care (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.71-0.86). Individuals, both black and white, who lived in areas with greater black segregation were less likely to receive adequate breast cancer care (OR, 0.73; 95% CI, 0.64-0.82). Black segregation was a mediator of the black/white disparity in breast cancer care, explaining 8.9% of the difference. After adjustment, adequate care for Hispanics did not significantly differ from whites, but individuals, both Hispanic and white, who lived in areas with greater Hispanic segregation were less likely to receive adequate breast cancer care (OR, 0.73; 95% CI, 0.61-0.89). Although Blacks experienced greater breast cancer mortality than whites, black segregation did not substantially mediate the black-white disparity in survival, and was not significantly associated with mortality (hazards ratio, 1.03; 95% CI, 0.87-1.21). Breast cancer mortality did not differ between Hispanics and whites. CONCLUSIONS: Among seniors, segregation mediates some of the black-white disparity in breast cancer care, but not mortality. Individuals who live in more segregated areas are less likely to receive adequate breast cancer care.

Racial segregation and disparities in cancer stage for seniors.

BACKGROUND: Disparities in cancer survival may be related to differences in stage. Segregation may be associated with disparities in stage, particularly for cancers for which screening promotes survival. OBJECTIVES: The objective of the study was to examine whether segregation modifies racial/ethnic disparities in stage. DESIGN: The design of the study was analysis of Surveillance, Epidemiology, and End Results Medicare data for seniors with breast, colorectal, lung, and prostate cancer (n = 410,870). MEASUREMENTS AND MAIN RESULTS: The outcome was early- versus late-stage diagnosis. Area of residence was categorized into 4 groups: low segregation/high income (potentially the most advantaged), high segregation/high income, low segregation/low income, and high segregation/low income (possibly the most disadvantaged). Blacks were less likely than whites to be diagnosed with early-stage breast, colorectal, or prostate cancer, regardless of area. For colorectal cancer, the black/white disparity was largest in low-segregation/low-income areas (black/white odds ratio [OR] of early stage 0.51) and smallest in the most segregated areas (ORs 0.71 and 0.74, P < .005). Differences in disparities in stage by area category were not apparent for breast, prostate, or lung cancer. Whereas there were few Hispanic-white differences in early-stage diagnosis, the Hispanic/white disparity in early-stage diagnosis of breast cancer was largest in low-segregation/low-income areas (Hispanic/white OR of early stage 0.54) and smallest in high-segregation/low-income areas (OR 0.96, P < .05 compared to low-segregation/low-income areas). CONCLUSIONS: Disparities in stages for cancers with an established screening test were smaller in more segregated areas.

Calcium intake and hip fracture risk in men and women: a meta-analysis of prospective cohort studies and randomized controlled trials.

BACKGROUND: The role of total calcium intake in the prevention of hip fracture risk has not been well established. OBJECTIVE: The objective of the study was to assess the relation of calcium intake to the risk of hip fracture on the basis of meta-analyses of cohort studies and clinical trials. RESULTS: In women (7 prospective cohort studies, 170,991 women, 2,954 hip fractures), there was no association between total calcium intake and hip fracture risk [pooled risk ratio (RR) per 300 mg total Ca/d = 1.01; 95% CI: 0.97, 1.05]. In men (5 prospective cohort studies, 68,606 men, 214 hip fractures), the pooled RR per 300 mg total Ca/d was 0.92 (95% CI: 0.82, 1.03). On the basis of 5 clinical trials (n = 5666 women, primarily postmenopausal, plus 1074 men) with 814 nonvertebral fractures, the pooled RR for nonvertebral fractures between calcium supplementation (800-1600 mg/d) and placebo was 0.92 (95% CI: 0.81, 1.05). On the basis of 4 clinical trials with separate results for hip fracture (6,504 subjects with 139 hip fractures), the pooled RR between calcium and placebo was 1.64 (95% CI:1.02, 2.64). Sensitivity analyses including 2 additional small trials with <100 participants or per-protocol results did not substantially alter results. CONCLUSIONS: Pooled results from prospective cohort studies suggest that calcium intake is not significantly associated with hip fracture risk in women or men. Pooled results from randomized controlled trials show no reduction in hip fracture risk with calcium supplementation, and an increased risk is possible. For any nonvertebral fractures, there was a neutral effect in the randomized trials.

The safety of oral antifungal treatments for superficial dermatophytosis and onychomycosis: a meta-analysis.

PURPOSE: We estimated the absolute risks of treatment termination and incidence of adverse liver outcomes among all commonly used oral antifungal treatments for superficial dermatophytosis and onychomycosis. METHODS: MEDLINE, EMBASE, and Cochrane Library were searched to identify randomized and nonrandomized controlled trials, case series, and cohort studies published before December 31, 2005. Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. Treatment arms with the same regimen in terms of drug, type (continuous or intermittent), and dosage were combined to estimate the risk of an outcome of interest. RESULTS: We identified 122 studies with approximately 20,000 enrolled patients for planned comparison. The pooled risks (95% confidence intervals) of treatment discontinuation resulting from adverse reactions for continuous therapy were 3.44% (95% confidence interval [CI], 2.28%-4.61%) for terbinafine 250 mg/day; 1.96% (95% CI, 0.35%-3.57%) for itraconazole 100 mg/day; 4.21% (95% CI, 2.33%-6.09%) for itraconazole 200 mg/day; and 1.51% (95% CI, 0%-4.01%) for fluconazole 50 mg/day. For intermittent therapy, the pooled risks were as follows: pulse terbinafine: 2.09% (95% CI, 0%-4.42%); pulse itraconazole: 2.58% (95% CI, 1.15%-4.01%); intermittent fluconazole 150 mg/week: 1.98% (95% CI, 0.05%-3.92%); and intermittent fluconazole 300 to 450 mg/week: 5.76% (95% CI, 2.42%-9.10%). The risk of liver injury requiring termination of treatment ranged from 0.11% (continuous itraconazole 100 mg/day) to 1.22% (continuous fluconazole 50 mg/day). The risk of having asymptomatic elevation of serum transaminase but not requiring treatment discontinuation was less than 2.0% for all treatment regimens evaluated. CONCLUSION: Oral antifungal therapy against superficial dermatophytosis and onychomycosis, including intermittent and continuous terbinafine, itraconazole, and fluconazole, was associated with a low incidence of adverse events in an immunocompetent population.

Lower use of hospice by cancer patients who live in minority versus white areas.

BACKGROUND: Although hospice care can alleviate suffering at the end of life for patients with cancer, it remains underutilized, particularly by African Americans and Hispanics. OBJECTIVE: To examine whether the racial composition of the census tract where an individual resides is associated with hospice use. DESIGN: Retrospective analysis of the Surveillance, Epidemiology, and End Results-Medicare file for individuals dying from breast, colorectal, lung, or prostate cancer (n = 70,669). MEASUREMENTS: Hospice use during the 12 months before death. RESULTS: Hospice was most commonly used by individuals who lived in areas with fewer African-American and Hispanic residents (47%), and was least commonly used by individuals who lived in areas with a high percentage of African-American and Hispanic residents (35%). Hispanics (odds ratio 0.51, 95% confidence interval 0.29-0.91) and African Americans (0.56, 0.44-0.71) were less likely to use hospice if they lived in a census tract with a high percentage of both African Americans and Hispanics than if they lived in a low minority tract. African Americans and whites were less likely to receive hospice care if they lived in a census tract with a high percentage of Hispanics than if they lived in a low minority area. CONCLUSIONS: Increasing hospice use may require interventions to improve the delivery of hospice care in minority communities.

Kinin B1 receptor expression on multiple sclerosis mononuclear cells: correlation with magnetic resonance imaging T2-weighted lesion volume and clinical disability.

BACKGROUND: We have previously shown that the inducible kinin B(1) receptor is expressed on T lymphocytes during relapses and progression in multiple sclerosis. OBJECTIVE: To evaluate the correlation between the expression of B1 receptor on peripheral blood mononuclear cells derived from patients who have multiple sclerosis with serial, clinical magnetic resonance imaging and immunological study-derived measures. DESIGN: Using frozen samples obtained from a high-frequency magnetic resonance imaging-immunological study, we analyzed B1 receptor messenger RNA (mRNA) expression in peripheral blood-derived mononuclear cells serially collected from 6 patients with multiple sclerosis and 8 healthy control subjects by semiquantitative radioactive duplex reverse transcriptase-polymerase chain reaction amplification. Time-course kinin B1-actin mRNA ratios were subsequently compared with corresponding clinical magnetic resonance imaging and immune parameters. RESULTS: The time-course kinin B1-actin mRNA ratio correlated positively with the Expanded Disability Status Scale index (P<.001), occurrence of clinical relapse (P = .02), volume of lesion on T2-weighted images (P<.003) and interleukin 2 receptor and major histocompatibility complex class II expression on CD4+ lymphocytes, but not with gadolinium-enhancing lesions. The time-course kinin B1-actin mRNA ratios were 5 to 25 times lower in samples derived from healthy controls. CONCLUSION: The correlation of kinin B1 receptor mRNA levels with dynamic clinical and magnetic resonance imaging measures suggests that expression of this receptor can serve as an index of disease activity in multiple sclerosis.

Impact of social functioning and vitality on preference for life in patients with Parkinson's disease.

The determinants of preference for life in patients with Parkinson's disease are not well known. We assessed the effect of functional status on the preference for life as measured by the time trade-off method with a 10-year life span. Our survey was based on a random sample of 1,200 patients from the Japanese Association of Patients with Parkinson's Disease. Patients' demographics, clinical information, and functional status as measured by the MOS Short Form 36 were considered independent variables. The response rate was 63.5%. Linear regression showed that men had a significantly stronger preference for current health than women (by 10.4 months on a scale of 10 years). Patients with higher physical functioning, social functioning, and vitality had significantly higher preferences for life (each 10-point improvement in physical or social functioning led to a 1.5-month increment in preference for current health; a 10-point improvement in vitality led to a 3-month increment). Longer duration of disease and advanced Hoehn and Yahr stage were significantly associated with a lower preference for current health (by 0.5 months/year of disease and by 2.6 months/stage). Interventions that target social functioning and vitality may be beneficial to preference for life.