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Aim: A systematic review and meta-analysis were performed to evaluate the efficacy of treatments for previously treated advanced biliary tract cancer (BTC) patients. Materials & methods: Databases were searched for studies evaluating treatments for advanced (unresectable and/or metastatic) BTC patients who progressed on prior therapy. Pooled estimates of objective response rate (ORR), median overall survival (OS) and median progression-free survival (PFS) were calculated using random effects meta-analysis. Results: Across 31 studies evaluating chemotherapy or targeted treatment regimens in an unselected advanced BTC patient population, pooled ORR was 6.9%, median OS was 6.6 months and median PFS was 3.2 months. Conclusion: The efficacy of conventional treatments for previously treated advanced BTC patients is poor and could be improved by novel therapies.

Purpose: Although second-line treatments improve survival compared to best supportive care in patients with advanced gastric cancer with disease progression on first-line therapy, prognosis remains poor. A systematic review and meta-analysis were conducted to quantify the efficacy of second-or-later line systemic therapies in this target population., Methods: A systematic literature review (January 1, 2000 to July 6, 2021) of Embase, MEDLINE, and CENTRAL with additional searches of 2019-2021 annual ASCO and ESMO conferences was conducted to identify studies in the target population. A random-effects meta-analysis was performed among studies involving chemotherapies and targeted therapies relevant in treatment guidelines and HTA activities. Outcomes of interest were objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) presented as Kaplan-Meier data. Randomized controlled trials reporting any of the outcomes of interest were included. For OS and PFS, individual patient-level data were reconstructed from published Kaplan-Meier curves., Results: Forty-four trials were eligible for the analysis. Pooled ORR (42 trials; 77 treatment arms; 7256 participants) was 15.0% (95% confidence interval (CI) 12.7-17.5%). Median OS from the pooled analysis (34 trials; 64 treatment arms; 60,350 person-months) was 7.9 months (95% CI 7.4-8.5). Median PFS from the pooled analysis (32 trials; 61 treatment arms; 28,860 person-months) was 3.5 months (95% CI 3.2-3.7)., Conclusion: Our study confirms poor prognosis among patients with advanced gastric cancer, following disease progression on first-line therapy. Despite the approved, recommended, and experimental systemic treatments available, there is still an unmet need for novel interventions for this indication., (© 2023. The Author(s).)

Background: While grip strength (GS) is commonly assessed using a Dynamometer, the Martin Vigorimeter was proposed as an alternative method especially in older adults. However, its reference values for Swiss older adults are missing. We therefore aimed to derive sex- and age-specific GS cut-points for the dominant and non-dominant hand (DH; NDH) using the Martin Vigorimeter. Additionally, we aimed to identify clinically relevant weakness and assess convergent validity with key markers of physical function and sarcopenia in generally healthy Swiss older adults., Methods: This cross-sectional analysis includes baseline data from Swiss participants enrolled in DO-HEALTH, a 3-year randomized controlled trial in community-dwelling adults age 70 + . For both DH and NDH, 4 different definitions of weakness to derive GS cut-points by sex and age category (≤ 75 vs. > 75 years) were used: i) GS below the median of the 1 st quintile, ii) GS below the upper limit of the 1 st quintile, iii) GS below 2-standard deviation (SD) of the sex- and age-specific mean in DO-HEALTH Swiss healthy agers (i.e. individuals without major chronic diseases, disabilities, cognitive impairment or mental health issues) and iv) GS below 2.5-SD of the sex- and age-specific mean in DO-HEALTH Swiss healthy agers. To assess the proposed cut-points' convergent validity, we assessed their association with gait speed, time to complete the 5 Times Sit-To-Stand (5TSTS) test, and present sarcopenia., Results: In total, 976 participants had available GS at the DH (mean age 75.2, 62% women). According to the 4 weakness definitions, GS cut-points at the DH ranged from 29-42 and 25-39 kPa in younger and older women respectively, and from 51-69 and 31-50 kPa in younger and older men respectively. Overall, weakness prevalence ranged from 2.0% to 19.3%. Definitions of weakness using the median and the upper limit of the 1 st GS quintile were most consistently associated with markers of physical performance. Weak participants were more likely to have lower gait speed, longer time to complete the 5TSTS, and sarcopenia, compared to participants without weakness., Conclusions: In generally healthy Swiss older adults, weakness defined by the median or the upper limit of the 1 st GS quintile may serve as reference to identify clinically relevant weakness. Additional research is needed in less healthy populations in order to derive representative population-based cut-points., Trial Registration: ClinicalTrials.gov Identifier: NCT01745263., (© 2023. European Group for Research into Elderly and Physical Activity (EGRIPA).)

(1) Background: Post-acute care (PAC) aims to support functional recovery in older adults after acute hospitalization in order to regain a sufficient level of self-care facilitating their return home. However, the long-term outcomes of PAC are understudied due to challenges in recording a follow-up. We aimed to investigate the feasibility of a 12-month follow-up after PAC in Swiss nursing homes, examining practicability and potential factors influencing participation rate. (2) Methods: Collection of one-year follow-up data among 140 eligible patients after PAC in nursing homes was attempted. Patients were recruited using letters and phone calls between August and December 2017. We compared baseline data of all initial PAC patients with those who declined participation in the follow-up to identify factors potentially influencing participation. (3) Results: Overall mortality at 12 months was 25% ( n = 35 of 140). Of the 105 survivors, 53 (50%) refused participation, 26 (25%) were interviewed, and 26 (25%) were lost to follow-up. Comparison of baseline characteristics between participants and objectors indicated significant statistical differences in Mini-Mental State Examination (MMSE) scores (participants mean of 26.0 [SD 3.92] vs. objectors mean of 23.5 points [SD 4.40], p = 0.015). Further, logistic regression showed statistically significantly greater odds of participation (OR 1.25 [95% CI 1.06-1.48]) for each point increase in MMSE scores. (4) Conclusions: Long-term follow-up studies in older adults after PAC are challenging due to high mortality and dropout rates. Of note, intact cognitive function at baseline was associated with a higher willingness to participate in a follow-up phone interview. The assessment of cognitive function should be considered when estimating the participation rate in older patients.

Purpose: The purpose of this study was to evaluate clinical outcomes of standard therapies in previously treated, advanced colorectal cancer (CRC) patients., Methods: A systematic literature review was conducted in Embase, MEDLINE, and CENTRAL databases (January 2000-July 2021), annual oncology conferences (2019-2021), and clinicaltrials.gov to identify studies evaluating the use of licensed interventions in second-line or later settings. The primary outcome of interest was objective response rate (ORR) and secondary outcomes included progression-free survival (PFS) and overall survival (OS). ORR was pooled using the Freeman-Tukey double arcsine transformation. For survival outcomes, published Kaplan-Meier curves for OS and PFS were digitized to re-construct individual patient-level data and pooled following the methodology described by Combescure et al. (2014)., Results: Twenty-three trials evaluating standard chemotherapies with or without targeted therapies across 4,791 advanced CRC patients contributed to our meta-analysis. In the second-line setting, the random effects pooled estimate of ORR was 22.4% (95% confidence interval (CI): 18.0, 27.1), median PFS was 7.0 months (95% CI: 6.4, 7.4), and median OS was 14.9 months (95% CI: 13.6, 16.1). In the third-line or later setting, the random effects pooled estimate of ORR was 1.7% (95% CI: 0.8, 2.7), median PFS was 2.3 months (95% CI: 2.0, 2.8), and median OS was 8.2 months (95% CI: 7.1, 9.1)., Conclusion: Standard treatments have limited efficacy in the second-line or later setting with worsening outcomes in later lines. Given the global burden of CRC, further research into novel and emerging therapeutic options following treatment failure is needed., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Ageing trajectories range from delayed ageing with extended health to accelerated ageing, with an increased risk of frailty. We evaluated the prevalence and prospective change between health states among community-dwelling European older adults., Methods: This prospective study is a secondary analysis of DO-HEALTH, a randomized trial that included adults aged 70 years and older across 5 European countries. Healthy agers (HA) fulfilled the Nurses' Health Study healthy ageing criteria and accelerated agers were non-HA being at least pre-frail according to the Fried frailty criteria. We assessed the proportion of participants changing between health states over 4 assessments and evaluated the odds of changing to a more favourable category. To increase reliability and avoid regression to the mean, we averaged the first 2 years and compared them to the average of the last 2 years., Results: Of 2,157 participants, 12.4% were excluded for meeting both healthy ageing and pre-frailty criteria simultaneously. Among the remaining 1,889 participants (mean age 75.1 years, 60.9% female), 23.1% were initially HA, 44.4% were non-HA but not pre-frail, and 32.6% were pre-frail or frail. Subsequently, 65.3% remained in the same health state, 12.0% improved to a healthier state, and 22.8% progressed to a less advantageous state. After adjusting for sex, study centre, treatment, and body mass index, each year of age was associated with 6% lower odds of improving health states. Women had 35% higher odds than men of following a disadvantageous trajectory., Conclusion: We observed dynamic trajectories of ageing where transitioning to a healthier state became less likely with advancing age and among women., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Iron deficiency (ID) is associated with negative health outcomes in older adults. However, data on the impact of ID on the number of hospitalizations and length of hospital stay (LOS) is lacking., Objective: To explore the associations between baseline ID and the number of hospitalizations and between baseline ID and at least one LOS ≥5 days in community-dwelling older adults., Methods: This is a secondary observational analysis of a randomized controlled trial including 2157 community-dwelling adults aged ≥70 years without major diseases at baseline. The main exposure was defined as ID (soluble transferrin receptor [sTfR] concentrations >28.1 nmol/L) at baseline. The primary outcome was the number of hospitalizations over a 3-year follow-up. The secondary outcome was having at least one LOS ≥5 days over the study period among individuals with one or more hospitalizations. Interaction between ID and anemia (hemoglobin <130 g/L for men and <120 g/L for women) was also investigated., Results: Baseline sTfR concentration was determined in 2141 participants (median age 74.0 years). At 3 year, 1497 hospitalizations were reported with an incidence rate of hospitalization of 0.26 per person-year (95% CI: 0.24, 0.28). Overall, baseline ID was associated with a 24% increased incidence rate of hospitalization (incidence rate ratio: 1.24; 95% CI: 1.05, 1.45) over 3 years. This association was independent of anemia status at baseline since the interaction between ID and anemia at baseline was not significant. Moreover, ID was not significantly associated with having a LOS ≥5 days (OR: 1.40; 95% CI: 1.00, 1.97) among participants with at least one hospitalization over 3 years., Conclusions: ID is associated with increased hospitalization rate and not associated with LOS ≥5 days among generally healthy older adults. Efforts to minimize ID in older adults may improve overall health and optimize healthcare costs., (Copyright © 2022. Published by Elsevier Inc.)

Background and Aim: Iron deficiency is associated with increased morbidity and mortality in older adults. However, data on its prevalence and incidence among older adults is limited. The aim of this study was to investigate the prevalence and incidence of iron deficiency in European community-dwelling older adults aged ≥ 70 years., Methods: Secondary analysis of the DO-HEALTH trial, a 3-year clinical trial including 2157 community-dwelling adults aged ≥ 70 years from Austria, France, Germany, Portugal and Switzerland. Iron deficiency was defined as soluble transferrin receptor (sTfR) > 28.1 nmol/L. Prevalence and incidence rate (IR) of iron deficiency per 100 person-years were examined overall and stratified by sex, age group, and country. Sensitivity analysis for three commonly used definitions of iron deficiency (ferritin < 45 μg/L, ferritin < 30 μg/L, and sTfR-ferritin index > 1.5) were also performed., Results: Out of 2157 participants, 2141 had sTfR measured at baseline (mean age 74.9 years; 61.5% women). The prevalence of iron deficiency at baseline was 26.8%, and did not differ by sex, but by age (35.6% in age group ≥ 80, 29.3% in age group 75-79, 23.2% in age group 70-74); P < 0.0001) and country (P = 0.02), with the highest prevalence in Portugal (34.5%) and the lowest in France (24.4%). As for the other definitions of iron deficiency, the prevalence ranged from 4.2% for ferritin < 30 µg/L to 35.3% for sTfR-ferritin index > 1.5. Occurrences of iron deficiency were observed with IR per 100 person-years of 9.2 (95% CI 8.3-10.1) and did not significantly differ by sex or age group. The highest IR per 100 person-years was observed in Austria (20.8, 95% CI 16.1-26.9), the lowest in Germany (6.1, 95% CI 4.7-8.0). Regarding the other definitions of iron deficiency, the IR per 100 person-years was 4.5 (95% CI 4.0-4.9) for ferritin < 45 µg/L, 2.4 (95% CI 2.2-2.7) for ferritin < 30 µg/L, and 12.2 (95% CI 11.0-13.5) for sTfR-ferritin index > 1.5., Conclusions: Iron deficiency is frequent among relatively healthy European older adults, with people aged ≥ 80 years and residence in Austria and Portugal associated with the highest risk., (© 2022. The Author(s).)

Background: The longitudinal association between iron deficiency and inflammatory biomarkers levels has not been fully explored among relatively healthy older adults., Aims: To assess whether iron deficiency at baseline and at any yearly follow-up time point, with or without anemia, was associated with changes from baseline in high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) levels over 3 years., Methods: This is a post-hoc observational analysis of DO-HEALTH, a double-blind, randomized controlled trial including 2157 European community-dwelling adults age 70+. The outcomes were changes from baseline in hs-CRP and IL-6 levels, measured at 12, 24, and 36 months of follow-up. Iron deficiency was defined by soluble transferrin receptor levels > 28.1 nmol/L and baseline anemia by hemoglobin levels < 130 g/L for men and < 120 g/L for women., Results: In total, 2141 participants were included in the analyses (mean age: 74.9 years, 61.5% of women, 26.8% with iron deficiency). Baseline iron deficiency was associated with greater increase in IL-6 levels (mean difference in change: 0.52 ng/L, 95%CI 0.03-1.00, P = .04) over 3 years. Iron deficiency at any yearly time point was associated with higher increases in hs-CRP (mean difference in change: 1.62 mg/L, 95%CI 0.98-2.26, P < .001) and IL-6 levels (mean difference in change: 1.33 ng/L, 95%CI 0.87-1.79, P < .001) over 3 years. No significant interaction between iron deficiency and anemia was found, suggesting that the results are independent of the anemic status., Conclusions: These findings suggest that iron deficiency may play a role in low-grade chronic inflammation among relatively healthy older adults., (© 2021. The Author(s).)

Background: Frailty is a geriatric syndrome associated with multiple negative health outcomes. However, its prevalence varies by population and instrument used. We investigated frailty and pre-frailty prevalence by 5 instruments in community-dwelling older adults enrolled to a randomized-controlled trial in 5 European countries., Methods: Cross-sectional baseline analysis in 2,144 DO-HEALTH participants recruited from Switzerland, Austria, France, Germany, and Portugal with complete data for frailty. Frailty status was assessed by the Physical Frailty Phenotype [PFP], SOF-Frailty Index [SOF-FI], FRAIL-Scale, SHARE-Frailty Instrument [SHARE-FI], and a modified SHARE-FI, and compared by country, age, and gender. Logistic regression was used to determine relevant factors associated with frailty and pre-frailty., Results: Mean age was 74.9 (±4.4) years, 61.6% were women. Based on the PFP, overall frailty and pre-frailty prevalence was 3.0% and 43.0%. By country, frailty prevalence was highest in Portugal (13.7%) and lowest in Austria (0%), and pre-frailty prevalence was highest in Portugal (57.3%) and lowest in Germany (37.1%). By instrument and overall, frailty and pre-frailty prevalence was highest based on SHARE-FI (7.0% / 43.7%) and lowest based on SOF-FI (1.0% / 25.9%). Frailty associated factors were residing in Coimbra (Portugal) [OR 12.0, CI 5.30-27.21], age above 75 years [OR 2.0, CI 1.17-3.45], and female gender [OR 2.8, CI 1.48-5.44]. The same three factors predicted pre-frailty., Conclusions: Among relatively healthy adults age 70 and older enroled to DO-HEALTH, prevalence of frailty and pre-frailty differed significantly by instrument, country, gender, and age. Among instruments, the highest prevalence of frailty and pre-frailty was documented by the SHARE-FI and the lowest by the SOF-FI., Competing Interests: The authors declare no conflict of interest in regard to this work.

Background: V114 (15-valent pneumococcal conjugate vaccine [PCV15]) and a 20-valent PCV (PCV20) are approved for adults (≥18 years) in the United States. We present methodologies to indirectly compare immune responses to V114 versus PCV20., Research Design and Methods: Indirect treatment comparison and matching-adjusted indirect comparison (MAIC) were performed to estimate opsonophagocytic activity (OPA) geometric mean titer (GMT) ratios of V114/PCV20 at 30 days post-vaccination with PCV13 as common comparator for 13 serotypes (STs) shared with a 13-valent PCV (PCV13) among pneumococcal vaccine-naïve adults aged ≥60 years. Data from three V114 studies were pooled (V114, N = 2,196; PCV13, N = 843). In the MAIC analysis, data were reweighted, matching participant age and sex in NCT03760146 (PCV20, N = 1,507; PCV13, N = 1,490)., Results: The lower bound of V114/PCV20 OPA GMT ratio for all PCV13 STs is greater than the prespecified  0.5 non-inferiority margin and those for five PCV13 STs (3, 6A, 6B, 18C, and 23F) are greater than the prespecified 1.2 superiority margin. V114 was associated with 77% greater OPA GMT for ST3 versus PCV20., Conclusion: V114 was non-inferior to PCV20 for all PCV13 STs and statistically superior for five PCV13 STs.

Objectives: To assess if baseline iron deficiency, with or without anemia, is associated with incident infections over 3 years among community-dwelling older adults., Design: Prospective secondary analysis of DO-HEALTH, a 3-year randomized, double-blind controlled trial., Setting and Participants: 2157 community-dwelling adults age 70+ from 5 European countries with good cognitive function and mobility and no major health events in the 5 years prior to enrollment Measurements: Incident infections, their severity and type were recorded every 3 months throughout the 3-year follow-up. Iron deficiency was defined as soluble transferrin receptor (sTfR) levels > 28.1 nmol/l and anemia as hemoglobin levels < 120 g/l for women and 130 g/l for men. We applied negative binomial mixed effects regression models with random effects for countries, and controlling for treatment allocation, age, sex, body mass index, polypharmacy, number of comorbidities, smoking status, living situation, alcohol intake, frailty status, and physical activity levels. A pre-defined stratified analysis was performed to explore if the associations between iron deficiency and infections were consistent by baseline anemia status., Results: In total, 2141 participants were included in the analyses (mean age 74.9 years, 61.5% of women, 26.8% with iron deficiency). Across all participants, baseline iron deficiency was not associated with incident overall infections, but was associated with a 63% greater rate of incident severe infections requiring hospitalization (incidence rate ratio [IRR] 1.63, 95% Confidence Interval [CI] 1.11-2.41, p=0.01). This association was more pronounced among the 2000 participants who did not have anemia at baseline (IRR=1.80, 95% CI 1.20-2.69, p=0.005)., Conclusion: Based on this prospective study among generally healthy European community-dwelling older adults, iron deficiency was not associated with the incidence rate of overall infections but may increase the incidence of severe infections. Intervention studies are needed to prove the causality of this observation., Competing Interests: DRS reports personal fees from Danube University of Krems, US Department of Defense, European Society of Anesthesiology, Korean Society for Patient Blood Management, Korean Society of Anesthesiologists, Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis, Bayer AG, Zürich, B. Braun Melsungen AG, Boehringer Ingelheim GmbH, Bristol-Myers-Squibb, CSL Behring GmbH, Celgene International II Sàrl, Daiichi Sankyo AG, Haemonetics, Instrumentation Laboratory (Werfen), LFB Biomédicaments, Merck Sharp and Dohme, PAION Deutschland GmbH, Pharmacosmos A/S, Pfzer AG, Pierre Fabre Pharma, Portola Schweiz GmbH, Roche Diagnostics International Ltd, Sarstedt AG and Co., Shire Switzerland GmbH, Tem International GmbH, Vifor Pharma, Vifor (International) AG, Zuellig Pharma Holdings. DRS’s academic department is receiving grant support from the Swiss National Science Foundation, the Swiss Society of Anesthesiology and Reanimation (SGAR), the Swiss Foundation for Anesthesia Research, Vifor SA and Vifor (International) AG. DRS is co-chair of the ABC-Trauma Faculty, sponsored by unrestricted educational grants from Novo Nordisk Health Care AG, CSL Behring GmbH, LFB Biomédicaments, and Octapharma AG. LA is currently an employee of MSD, Switzerland. As part of the DO-HEALTH independent and investigator-initiated clinical trial, HABF reports as the PI of the DOHEALTH trial, grants from European Commission, from University of Zurich, from NESTEC, from PFIZER Consumer Healthcare, from Streuli Pharma, plus nonfinancial support from DSM Nutritional Products and nonfinancial support from Roche Diagnostics. Further, Prof. Bischoff-Ferrari reports speaker fees from Wild, Pfzer, Vifor, Mylan, Roche Diagnostics, and independent and investigator-initiated grants from Pfizer and from Vifor. All other authors declare no competing interests.

Background: Acute geriatric treatment is a type of early rehabilitation for hospitalized seniors to maintain personal autonomy and to avoid nursing home placement., Objective: The aim of the study was to describe the changes of mobility and functional independence of older trauma patients during acute geriatric treatment., Material and Methods: This study analyzed admission and discharge assessment data from 164 patients in the geriatric department with fall-related injuries. Mobility and performance in activities of daily living were assessed using the short physical performance battery (SPPB), gait speed and Barthel index. We analyzed changes in mobility from admission to discharge (t-test) and examined differences in mobility between patients returning home and those admitted to long-term care (age-adjusted and gender-adjusted linear regression model)., Results: Patients improved their mobility measured by the SPPB by 1.8 points ± 2.1 points, gait speed by 0.10 ± 0.14 m/s and the Barthel index by 13 ± 16 points, all p < 0.001). The number of patients not able to walk decreased from 43% to 14% (p = 0.003). Of the community-dwelling patients 73% were discharged either directly back home or after rehabilitation outside the hospital as a transitional solution., Conclusion: In the context of acute geriatric treatment older trauma patients significantly improved their mobility and performance. The majority of patients could return home., (© 2020. The Author(s).)

Introduction: Early identification of frailty by clinical instruments or accumulation of deficit indexes can contribute to improve healthcare for older adults, including the prevention of negative outcomes in acute care. However, conflicting evidence exists on how to best capture frailty in this setting. Simultaneously, the increasing utilisation of electronic health records (EHRs) opens up new possibilities for research and patient care, including frailty., Methods and Analysis: The Swiss Frailty Network and Repository (SFNR) primarily aims to develop an electronic Frailty Index (eFI) from routinely available EHR data in order to investigate its predictive value against length of stay and in-hospital mortality as two important clinical outcomes in a study sample of 1000-1500 hospital patients aged 65 years and older. In addition, we will examine the correlation between the eFI and a test-based clinical Frailty Instrument to compare both concepts in Swiss older adults in acute care settings. As a Swiss Personalized Health Network (SPHN) driver project, our study will report on the characteristics and usability of the first nationwide eFI in Switzerland connecting all five Swiss University Hospitals' Geriatric Departments with a representative sample of patients aged 65 years and older admitted to acute care., Ethics and Dissemination: The study protocol was approved by the competent ethics committee of the Canton of Zurich (BASEC-ID 2019-00445). All acquired data will be handled according to SPHN's ethical framework for responsible data processing in personalised health research. Analyses will be performed within the secure BioMedIT environment, a national infrastructure to enable secure biomedical data processing, an integral part of SPHN., Trial Registration Number: NCT04516642., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Frail older adults with ongoing care needs often require post-acute care (PAC) following acute hospitalization when not eligible for specific rehabilitation. Long-term outcomes of PAC in this patient group have not been reported for Switzerland so far. In the present report, we investigated 12-month mortality in regard to frailty status upon admission to PAC in a nursing home setting. In our sample of 140 patients (mean age 84 [±8.6] years) 4.3% were robust, 37.1% were pre-frail, 54.3% were frail and 4.3% were missing frailty status. Mortality at 12-months follow-up stratified by baseline frailty was 0% (robust), 11.5% (pre-frail) and 31.6% (frail). Kaplan-Meier analysis stratified by frailty status showed a decreased probability of 12-months survival for frail individuals compared to their pre-frail and robust counterparts (P = 0.0096). Being frail was associated with more than 4-fold increased odds of death at follow-up (OR 4.19; 95% CI 1.53-11.47)., Competing Interests: The authors declare no conflict of interest.

Importance: The benefits of vitamin D, omega-3 fatty acids, and exercise in disease prevention remain unclear., Objective: To test whether vitamin D, omega-3s, and a strength-training exercise program, alone or in combination, improved 6 health outcomes among older adults., Design, Setting, and Participants: Double-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial among 2157 adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status. Patients were recruited between December 2012 and November 2014, and final follow-up was in November 2017., Interventions: Participants were randomized to 3 years of intervention in 1 of the following 8 groups: 2000 IU/d of vitamin D3, 1 g/d of omega-3s, and a strength-training exercise program (n = 264); vitamin D3 and omega-3s (n = 265); vitamin D3 and exercise (n = 275); vitamin D3 alone (n = 272); omega-3s and exercise (n = 275); omega-3s alone (n = 269); exercise alone (n = 267); or placebo (n = 270)., Main Outcomes and Measures: The 6 primary outcomes were change in systolic and diastolic blood pressure (BP), Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates (IRs) of nonvertebral fractures and infections over 3 years. Based on multiple comparisons of 6 primary end points, 99% confidence intervals are presented and P < .01 was required for statistical significance., Results: Among 2157 randomized participants (mean age, 74.9 years; 61.7% women), 1900 (88%) completed the study. Median follow-up was 2.99 years. Overall, there were no statistically significant benefits of any intervention individually or in combination for the 6 end points at 3 years. For instance, the differences in mean change in systolic BP with vitamin D vs no vitamin D and with omega-3s vs no omega-3s were both -0.8 (99% CI, -2.1 to 0.5) mm Hg, with P < .13 and P < .11, respectively; the difference in mean change in diastolic BP with omega-3s vs no omega-3s was -0.5 (99% CI, -1.2 to 0.2) mm Hg; P = .06); and the difference in mean change in IR of infections with omega-3s vs no omega-3s was -0.13 (99% CI, -0.23 to -0.03), with an IR ratio of 0.89 (99% CI, 0.78-1.01; P = .02). No effects were found on the outcomes of SPPB, MoCA, and incidence of nonvertebral fractures). A total of 25 deaths were reported, with similar numbers in all treatment groups., Conclusions and Relevance: Among adults without major comorbidities aged 70 years or older, treatment with vitamin D3, omega-3s, or a strength-training exercise program did not result in statistically significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function. These findings do not support the effectiveness of these 3 interventions for these clinical outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT01745263.

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.

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., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)