Combined vitamin D, omega-3 fatty acids, and a simple home exercise program may reduce cancer risk among active adults aged 70 and older : A randomized clinical trial

Objective: The aim of this study was to test the individual and combined benefit of vitamin D, omega-3, and a simple home strength exercise program on the risk of any invasive cancer. Design: The DO-HEALTH trial is a three-year, multicenter, 2 × 2 × 2 factorial design double-blind, randomized-controlled trial to test the individual and combined benefit of three public health interventions. Setting: The trial was conducted between December 2012 and December 2017 in five European countries. Participants: Generally healthy community-dwelling adults ≥70 years were recruited. Interventions: Supplemental 2000 IU/day of vitamin D3, and/or 1 g/day of marine omega-3s, and/or a simple home strength exercise (SHEP) programme compared to placebo and control exercise. Main outcome: In this pre-defined exploratory analysis, time-to-development of any verified invasive cancer was the primary outcome in an adjusted, intent-to-treat analysis. Results: In total, 2,157 participants (mean age 74.9 years; 61.7% women; 40.7% with 25-OH vitamin D below 20 /ml, 83% at least moderately physically active) were randomized. Over a median follow-up of 2.99 years, 81 invasive cancer cases were diagnosed and verified. For the three individual treatments, the adjusted hazard ratios (HRs, 95% CI, cases intervention versus control) were 0.76 (0.49–1.18; 36 vs. 45) for vitamin D3, 0.70 (0.44–1.09, 32 vs. 49) for omega-3s, and 0.74 (0.48–1.15, 35 vs. 46) for SHEP. For combinations of two treatments, adjusted HRs were 0.53 (0.28–1.00; 15 vs. 28 cases) for omega-3s plus vitamin D3; 0.56 (0.30–1.04; 11 vs. 21) for vitamin D3 plus SHEP; and 0.52 (0.28–0.97; 12 vs. 26 cases) for omega-3s plus SHEP. For all three treatments combined, the adjusted HR was 0.39 (0.18–0.85; 4 vs. 12 cases). Conclusion: Supplementation with daily high-dose vitamin D3 plus omega-3s, combined with SHEP, showed cumulative reduction in the cancer risk in generally healthy and active and largely vitamin D–replete adults ≥70 years. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT01745263

Local serial correlation in behavioral states in the mouse

In the mouse, Mus musculus, local (ultradian) serial correlation (LSC) within the sleep and wakefulness states varies significantly as a function of circadian phase. The amplitude of the correlation function is greatest during the active phase of the mouse's diurnal cycle. Additionally, mean LSC (averaged across circadian phase) is significantly positive and monotonically decreasing for a broad range of short lags (1-23 minutes). Thus there is no evidence of positive, periodically occurring peaks in the correlation function separated by patches of small or negative correlations that is characteristic of a rhythmic process of fixed period. These findings challenge the concept that an ultradian oscillator plays a significant role in the temporal control of sleep-wake state. (Author)supported in part by the Office of Naval Research under Grant NR-42-284http://archive.org/details/localserialcorre00richN

Comparative effectiveness of functional tests in fall prediction after hip fracture

Objectives To assess the validity of 4 functional tests in predicting falls within the first year after hip fracture. Design Prospective study of functional tests shortly after hip surgery and incident falls during 12 months' follow-up. Setting and Participants The sample comprised 173 adults with acute hip fracture, aged 65 years and older (79% women, 77% community dwelling, mean age 84.2 years), who participated in a clinical trial of vitamin D or home exercise. Methods We assessed 4 functional tests [Timed Up and Go test (TUG), grip strength, and knee flexor and extensor strength in the nonoperated leg] by trained study physiotherapists at baseline (1-12 days after hip fracture surgery). During 12 months' follow-up, we ascertained all fall events by monthly personal phone calls, a telephone hotline, and a patient diary. Then we compared TUG and strength test performance at baseline between future single fallers, recurrent fallers, and nonfallers over the 12-month follow-up. All analyses adjusted for age, body mass index, gender, 25-hydroxyvitamin D status at baseline, days of follow-up, and treatment allocation (the original trial tested vitamin D treatment and/or a home exercise program). Results Ninety-two of 173 (53%) participants fell and experienced 212 falls. Participants who became recurrent fallers (n = 54) had significantly longer TUG times at baseline than those who did not fall (n = 81) in the following 12 months (mean TUG for recurrent fallers = 71.6 seconds, SD = 8.2 seconds, vs mean TUG for nonfallers = 51.4 seconds, SD = 6.9 seconds; P = .02). There were no significant differences in TUG times between single fallers and nonfallers. For all 3 strength tests, there were no significant differences between single fallers, recurrent fallers, and nonfallers. Conclusions and Implications In this population of frail older adults recruited shortly after hip fracture surgery, only the TUG test discriminated between future recurrent fallers and nonfallers over a 12-month follow-up. Because of the high incidence and serious consequences of falls in older adults after a hip fracture, it is very important to identify practical and clinically related tests to predict repeated falls in the first year after a hip fracture, which is of great public health importance. Keywords Falls functional assessments hip fracture Timed Up and Go test grip strength knee flexor and extensor strengt

Total serum testosterone and WOMAC pain and function among older men and women with severe knee OA

OBJECTIVES: We investigated if serum total testosterone (T)-level is associated with knee pain and function in men and women with severe knee osteoarthritis (OA). METHODS: We enrolled 272 adults ≥60 years (70.4±4.4 years, 53% women) who underwent unilateral total knee replacement (TKR) due to severe knee OA. Serum T-levels and WOMAC pain and function of the operated and contra-lateral knee were measured at 6-8 weeks after surgery. At the non-operated knee, 56% participants had radiographic knee OA with a Kellgren-Lawrence grade ≥2. Cross-sectional analyses were performed by gender and BMI subgroups using multivariable regression adjusted for age, physical activity and BMI. RESULTS: At the operated knee, higher T-levels were associated with less WOMAC pain in men (B = -0.62; P = 0.046) and women (B = -3.79; P = 0.02), and less WOMAC disability scores in women (B = -3.62; P = 0.02) and obese men (B = -1.99; P = 0.02). At the non-operated knee, T-levels were not associated with WOMAC pain in men or women, but higher T-levels were associated with less disability in women (B = -0.95; P = 0.02). T-levels were inconsistently associated with pain and disability in BMI subgroups among men. Only among obese women, T-levels were inversely associated with radiographic knee OA (OR = 0.10; P = 0.003). CONCLUSIONS: Higher total T-levels were associated with less pain in the operated knee in men and women undergoing TKR and less disability in women. At the non-operated knee, higher T-levels were inconsistently associated with less pain and disability

Effect of Monthly Vitamin D on Chronic Pain Among Community-Dwelling Seniors: A Randomized, Double-Blind Controlled Trial

OBJECTIVE With advancing age, the prevalence of vitamin D deficiency and musculoskeletal pain increases. However, published data on the effectiveness of vitamin D supplementation in reducing chronic pain are inconclusive. The purpose of this study was to test the effect of 3 different monthly doses of vitamin D on chronic pain in seniors 70 years and older with a prior fall event. DESIGN 1-year, double-blind randomized clinical trial. SETTING The trial was conducted in Zurich, Switzerland. Participants were 200 community-dwelling men and women 70 years and older with a prior fall. INTERVENTION Three study groups with monthly treatments were randomized to either a low-dose control group of vitamin D (24,000 IU vitamin D/mo), a high dose of vitamin D (60,000 IU vitamin D/mo), or a combination of calcifediol and vitamin D (24,000 IU vitamin D plus 300 μg calcifediol/mo). MEASUREMENTS The primary endpoint was the change in the mean number of painful areas using the McGill Pain map over 12 months of follow-up. All analyses were adjusted for age, sex, body mass index, 25-hydroxyvitamin (OH)D levels, and pain scores at baseline. A predefined subgroup analysis was performed by baseline 25(OH)D status (<20 vs ≥ 20 ng/mL). RESULTS The mean age of the participants 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. Over 12 months of follow-up, the changes in the mean number of painful areas did not differ significantly among treatment groups (P = .46). However, there was a significant interaction effect between baseline vitamin levels (<20 vs ≥ 20 ng/mL) and treatment (P = .02). Among those who were vitamin D replete at baseline (n = 84), there was a significant difference between treatment groups over time (P = .04), and only seniors in the 24,000-IU vitamin D group had a marginally significant decrease in their total mean pain score (-0.77; 95% CI, -1.56 to 0.01, P = .05), whereas there were no changes in the high-dose groups. Among seniors who were vitamin D deficient at baseline (n = 116), chronic pain did not differ by treatment groups over time (P = .33). CONCLUSION Our results suggest that both starting level of 25(OH)D and monthly treatment dose of vitamin D may be important with respect to chronic pain reduction-with the only benefit seen among vitamin D-replete seniors treated with a monthly dose of 24,000 IU vitamin D

Polypharmacy and Kidney Function in Community-Dwelling Adults Age 60 Years and Older: A Prospective Observational Study

Objectives Information on the impact of polypharmacy on kidney function in older adults is limited. We prospectively investigated the association between intake of total number of drugs or nonsteroidal anti-inflammatory drugs (NSAIDs) and kidney function. Design Our study is a prospective observational analysis of the 2-year Zurich Multiple Endpoint Vitamin D Trial in Knee Osteoarthritis Patients. Setting and participants Of the 273 participants of the original trial, 270 participants (mean age 70.3 ± 6.4 years, 53% women) were included in this observational analysis. Methods The associations between (1) total number of drugs (or NSAIDs) at baseline or (2) cumulative number of drugs (or NASAIDs) repeatedly measured over 24 months and kidney function repeatedly measured over 24 months as estimated glomerular filtration rate (eGFR) were investigated using multivariable-adjusted repeated-measures analysis. Results Per drug at baseline, kidney function decreased by 0.64 mL/min/1.73 m2 eGFR (Beta = −0.64; 95% CI −1.19 to −0.08; P = .024) over 24 months. With every additional drug taken cumulatively over 24 months, kidney function decreased by 0.39 mL/min/1.73 m2 eGFR (Beta = −0.39; 95% CI −0.63 to −0.15; P = .002). In a high-risk subgroup, per NSAID taken cumulatively over 24 months, kidney function declined by 1.21 mL/min/1.73 m2 eGFR (Beta = −1.21; 95% CI −2.35 to −0.07; P = .021). Conclusions and implications For every additional drug prescribed among older adults, our study supports an independent and immediate harmful impact on kidney function. This negative impact seems to be about 3 times greater for NSAIDs compared with an additional average drug

Which method of fall ascertainment captures the most falls in prefrail and frail seniors?

There is no consensus on the most reliable method of ascertaining falls among the elderly. Therefore, we investigated which method captured the most falls among prefrail and frail seniors from 2 randomized controlled trials conducted in Zurich, Switzerland: an 18-month trial (2009–2010) including 200 community-dwelling prefrail seniors with a prior fall and a 12-month trial (2005–2008) including 173 frail seniors with acute hip fracture. Both trials included the same methods of fall ascertainment: monthly active asking, daily self-report diary entries, and a call-in hotline. We compared numbers of falls reported and estimated overall and positive percent agreement between methods. Prefrail seniors reported 499 falls (fall rate = 2.5/year) and frail seniors reported 205 falls (fall rate = 1.4/year). Most falls (81% of falls in prefrail seniors and 78% in frail seniors) were reported via active asking. Among prefrail seniors, diaries captured an additional 19% of falls, while the hotline added none. Among frail seniors, the hotline added 16% of falls, while diaries added 6%. The positive percent agreement between active asking and diary entries was 100% among prefrail seniors and 88% among frail seniors. While monthly active asking captures most falls in both groups, this method alone missed 19% of falls in prefrail seniors and 22% in frail seniors. Thus, a combination of active asking and diaries for prefrail seniors and a combination of active asking and a hotline for frail seniors is warranted

Which Method of Fall Ascertainment Captures the Most Falls in Prefrail and Frail Seniors?

There is no consensus on the most reliable method of ascertaining falls among the elderly. Therefore, we investigated which method captured the most falls among prefrail and frail seniors from 2 randomized controlled trials conducted in Zurich, Switzerland: an 18-month trial (2009-2010) including 200 community-dwelling prefrail seniors with a prior fall and a 12-month trial (2005-2008) including 173 frail seniors with acute hip fracture. Both trials included the same methods of fall ascertainment: monthly active asking, daily self-report diary entries, and a call-in hotline. We compared numbers of falls reported and estimated overall and positive percent agreement between methods. Prefrail seniors reported 499 falls (fall rate = 2.5/year) and frail seniors reported 205 falls (fall rate = 1.4/year). Most falls (81% of falls in prefrail seniors and 78% in frail seniors) were reported via active asking. Among prefrail seniors, diaries captured an additional 19% of falls, while the hotline added none. Among frail seniors, the hotline added 16% of falls, while diaries added 6%. The positive percent agreement between active asking and diary entries was 100% among prefrail seniors and 88% among frail seniors. While monthly active asking captures most falls in both groups, this method alone missed 19% of falls in prefrail seniors and 22% in frail seniors. Thus, a combination of active asking and diaries for prefrail seniors and a combination of active asking and a hotline for frail seniors is warranted

Health-Related Quality of Life and Functional Status Are Associated with Cardiac Status and Clinical Outcome in Children with Cardiomyopathy

To measure the health-related quality of life (HRQOL) and functional status of children with cardiomyopathy and to determine whether they are correlated with sociodemographics, cardiac status, and clinical outcomes. Parents of children in the Pediatric Cardiomyopathy Registry completed the Child Health Questionnaire (CHQ; age ≥ 5 years) and Functional Status II (Revised) (age ≤ 18 years) instruments. Linear and Cox regressions were used to examine hypothesized associations with HRQOL. The 355 children evaluated at ≥ 5 years (median 8.6 years) had lower functioning (CHQ Physical and Psychosocial Summary Scores 41.7 ± 14.4 and 47.8 ± 10.7) than that of healthy historical controls. The most extreme CHQ domain score, Parental Impact-Emotional, was one SD below normal. Younger age at diagnosis and smaller left ventricular end-diastolic dimension z score were associated independently with better physical functioning in children with dilated cardiomyopathy. Greater income/education correlated with better psychosocial functioning in children with hypertrophic and mixed/other types of cardiomyopathy. In the age ≥ 5 year cohort, lower scores on both instruments predicted earlier death/transplant and listing for transplant in children with dilated and mixed/other types of cardiomyopathy (P < .001). Across all ages (n = 565), the Functional Status II (Revised) total score was 87.1 ± 16.4, and a lower score was associated with earlier death/transplant for all cardiomyopathies. HRQOL and functional status in children with cardiomyopathy is on average impaired relative to healthy children. These impairments are associated with older age at diagnosis, lower socioeconomic status, left ventricular size, and increased risk for death and transplant. Identification of families at risk for functional impairment allows for provision of specialized services early in the course of disease. ClinicalTrials.gov: NCT00005391