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.

Association of magnesium and vitamin D status with grip strength and fatigue in older adults: a 4-week observational study of geriatric participants undergoing rehabilitation.

BACKGROUND: Low magnesium and vitamin D levels negatively affect individuals' health. AIMS: We aimed to investigate the association of magnesium status with grip strength and fatigue scores, and evaluate whether this association differs by vitamin D status among older participants undergoing geriatric rehabilitation. METHODS: This is a 4-week observational study of participants aged ≥ 65 years undergoing rehabilitation. The outcomes were baseline grip strength and fatigue scores, and 4-week change from baseline in grip strength and fatigue scores. The exposures were baseline magnesium tertiles and achieved magnesium tertiles at week 4. Pre-defined subgroup analyses by vitamin D status (25[OH]D < 50 nmol/l = deficient) were performed. RESULTS: At baseline, participants (N = 253, mean age 75.7 years, 49.4% women) in the first magnesium tertile had lower mean grip strength compared to participants in the third tertile (25.99 [95% CI 24.28-27.70] vs. 30.1 [95% CI 28.26-31.69] kg). Similar results were observed among vitamin D sufficient participants (25.54 [95% CI 22.65-28.43] kg in the first magnesium tertile vs. 30.91 [27.97-33.86] kg in the third tertile). This association was not significant among vitamin D deficient participants. At week 4, no significant associations were observed between achieved magnesium tertiles and change in grip strength, overall and by vitamin D status. For fatigue, no significant associations were observed. CONCLUSIONS: Among older participants undergoing rehabilitation, magnesium status may be relevant for grip strength, particularly among vitamin D sufficient individuals. Magnesium status was not associated with fatigue, regardless of vitamin D status. STUDY REGISTRATION: Clinicaltrials.gov, NCT03422263; registered February 5, 2018.

Association of polypharmacy with cognitive impairment in older trauma patients: a cross-sectional study.

INTRODUCTION: Few if any studies have been conducted to date on the association between polypharmacy and cognitive impairment among older trauma patients. Therefore, we investigated whether polypharmacy is associated with cognitive impairment in trauma patients aged ≥70 years. METHODS: This is a cross-sectional study of patients aged ≥70 years hospitalised due to a trauma-related injury. Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score ≤24 points. Medications were coded according to the Anatomical Therapeutic Chemical classification. Three exposures were examined: polypharmacy (≥5 medications), excessive polypharmacy (≥10 medications), and number of medications. Separate logistic regression models adjusted for age, sex, body mass index (BMI), education, smoking, independent living, frailty, multimorbidity, depression, and type of trauma were used to test the association between the three exposures and cognitive impairment. RESULTS: A total of 198 patients were included (mean age 80.2; 64.7% women and 35.4% men), of which 148 (74.8%) had polypharmacy and 63 (31.8%) had excessive polypharmacy. The prevalence of cognitive impairment was 34.3% overall, 37.2% in the polypharmacy group and 50.8% in the excessive polypharmacy group. More than 80% of participants were taking at least one analgesic. Overall, polypharmacy was not statistically significantly associated with cognitive impairment (odds ratio (OR) 1.20 [95% confidence interval (CI) 0.46 to 3.11]). However, patients in the excessive polypharmacy group were more than two times more likely to have cognitive impairment (OR 2.88 [95% CI 1.31 to 6.37]) even after adjustments for relevant confounders. Similarly, the number of medications was associated with greater odds of cognitive impairment (OR 1.15 [95% CI 1.04 to 1.28]) after adjustments for the same relevant confounders. CONCLUSION: Cognitive impairment is common among older trauma patients, particularly among those in the excessive polypharmacy group. Polypharmacy was not associated with cognitive impairment. Excessive polypharmacy and number of medications, on the other hand, were associated with greater odds of cognitive impairment in older trauma patients.

Association between iron deficiency and hospitalization rate in community-dwelling older adults: A 3-year prospective observational study of DO-HEALTH.

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.

Predictive validity of current sarcopenia definitions (EWGSOP2, SDOC, and AWGS2) for clinical outcomes: A scoping review.

Over the last 3 years new definitions of sarcopenia by the Sarcopenia Definition and Outcome Consortium (2020, SDOC), European Working Group on Sarcopenia in Older People (2019, EWGSOP2) and Asian Working Group on Sarcopenia (2019, AWGS2) have been proposed. The objective of this scoping review was to explore predictive validity of these current sarcopenia definitions for clinical outcomes. We followed the PRISMA checklist for scoping reviews. Based on a systematic search performed by two independent reviewers of databases (Pubmed and Embase) articles comparing predictive validity of two or more sarcopenia definitions on prospective clinical outcomes published since January 2019 (the year these definitions were introduced) were included. Data were extracted and results collated by clinical outcomes and by sarcopenia definitions, respectively. Of 4493 articles screened, 11 studies (mean age of participants 77.6 (SD 5.7) years and 50.0% female) comprising 82 validity tests were included. Overall, validity tests on the following categories of clinical outcomes were performed: fracture (n = 40, assessed in one study), mortality (n = 18), function (n = 11), institutionalization (n = 7), falls (n = 4), and hospitalization (n = 2). Thereby, EWGSOP2 was investigated in 15 validity tests (18.3%) on all categories of clinical outcomes, whereas SDOC was investigated in four validity tests (4.9%) in one study on fractures in men only, and none of the validity tests investigated predictive validity by the AWGS2. However, we were not able to pool the data using a meta-analytic approach due to important methodological heterogeneity between the studies. We identified various definitions of clinical outcomes that were used to test predictive validity of sarcopenia definitions suggesting that an agreement on an operational definition of a clinical outcome is key to advance in the field of sarcopenia. Moreover, data on predictive validity using the sarcopenia definitions by the SDOC and AWGS2 are still scarce and lacking, respectively. In a next step, prospective studies including both women and men are needed to compare predictive validity of current sarcopenia definitions on defined key clinical outcomes.

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.

Prevalence and incidence of iron deficiency in European community-dwelling older adults: an observational analysis of the DO-HEALTH trial.

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.

Effects of vitamin D, omega-3 fatty acids, and a simple home strength exercise program on fall prevention: the DO-HEALTH randomized clinical trial.

BACKGROUND: The roles of vitamin D, omega-3 fatty acids, and home exercise on fall prevention among generally healthy and active older adults are unclear. OBJECTIVES: We tested the effects of daily supplemental vitamin D, daily supplemental marine omega-3s fatty acids, and a simple home exercise program (SHEP), alone or in combination, on the incidences of total and injurious falls among generally healthy older adults. METHODS: We performed a 2 × 2 × 2 factorial-design randomized controlled trial among 2157 community-dwelling adults aged 70 years and older, who had no major health events in the 5 years prior to enrolment, recruited from Switzerland, Germany, Austria, France, and Portugal between December 2012 and November 2014. Participants were randomly assigned to supplementation with 2000 international units/day of vitamin D3 and/or 1 g/day of marine omega-3s, and/or a SHEP compared with placebo and/or control exercise over 3 years. The primary endpoint for the present fall analysis was the incidence rate of total falls. Falls were recorded prospectively throughout the trial. Since there were no interactions between treatments, the main effects are reported based on a modified intent-to-treat analysis. RESULTS: Of 2157 randomized participants, 1900 (88%) completed the study. The mean age was 74.9 years, 61.7% were women, 40.7% had a serum 25-hydroxyvitamin D concentration < 20 ng/ml, and 83% were at least moderately physically active. In total, 3333 falls were recorded over a median follow-up of 2.99 years. Overall, vitamin D and the SHEP had no benefit on total falls, whilst supplementation with omega-3s compared to no omega-3 supplementation reduced total falls by 10% (incidence rate ratio = 0.90; 95% CI, 0.81-1.00; P = 0.04). CONCLUSIONS: Among generally healthy, active, and vitamin D-replete older adults, omega-3 supplementation may have a modest benefit on the incidence of total falls, whilst a daily high dose of vitamin D or a SHEP had no benefit.

Iron deficiency and biomarkers of inflammation: a 3-year prospective analysis of the DO-HEALTH trial.

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.

DO-HEALTH: Vitamin D3 - Omega-3 - Home exercise - Healthy aging and longevity trial - Design of a multinational clinical trial on healthy aging among European seniors.

DO-HEALTH is a multi-center clinical trial among 2157 community-dwelling European men and women age 70 and older. The 2x2x2 randomized-control factorial design trial tested the individual and additive benefit, as well as the cost-effectiveness, of 3 interventions: vitamin D 2000 IU/day, omega-3 fatty acids 1000 mg/day (EPA + DHA, ratio 1:2), and a 30-minute 3 times/week home exercise (strength versus flexibility). Each treatment tested has shown considerable prior promise from mechanistic studies, small clinical trials, or large cohort studies, in the prevention of common age-related chronic diseases, but definitive data are missing. DO-HEALTH will test these interventions in relation to 6 primary endpoints (systolic and diastolic blood pressure, non-vertebral fractures, Short Physical Performance Battery score, the Montreal Cognitive Assessment, and risk of infections), plus several secondary endpoints explored in ancillary studies (i.e. rate of any falls and injurious falls, joint pain, oral health, quality of life, and incident frailty). As the 3 interventions have distinct mechanisms of action for each of the 6 primary endpoints, a maximum benefit is expected for their additive benefit as a "multi-modal" intervention. The trial duration is 3 years with in-person contacts with all participants at 4 clinical visits and by quarterly phone calls. Baseline and follow-up blood samples were collected in all participants to measure changes in 25-hydroxyvitamin D and poly-unsaturated fatty acid concentrations. Our objective was to test interventions that are expected to promote healthy aging and longer life expectancy and that can be easily and safely implemented by older community-dwelling adults.

Effect of Vitamin D Supplementation, Omega-3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults: The DO-HEALTH Randomized Clinical Trial.

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.

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.

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.

Clinical practice guidelines for surgical antimicrobial prophylaxis: Qualitative appraisals and synthesis of recommendations.

RATIONALE, GOALS, AND OBJECTIVES: Clinical practice guidelines (CPGs) for preoperative care have been developed for surgical antimicrobial prophylaxis (SAP). The objective of this study was to synthetize recommendations for SAP based on best-evaluated CPGs. METHODS: A systematic literature search for documents related to SAP, published between January 2011 and December 2016, was conducted on MEDLINE (PubMed), EMBASE, and specific CPG websites. Three reviewers independently assessed the rigour of development and editorial independence of CPGs based on domains 3 and 6 of the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument. CPGs with domain 3 scores of 50% and greater were selected for synthesis of recommendations. Two reviewers independently extracted CPG recommendations from among these documents. A third reviewer performed the synthesis of recommendations. RESULTS: The search retrieved 363 documents, of which 29 CPGs were appraised using AGREE II. Only eight (28%) scored 50% and greater in domain 3. Most CPGs addressed topics related to preoperative care, including SAP. No conflicting recommendations were found, and most recommendations were based on clinical practice. The only recommendation for which there was a difference among CPGs was with respect to the time to initiate the administration of antibiotics (1 hour before or close to the time of the surgical incision). Four CPGs provide recommendations that demonstrate concern about inadequate SAP prolongation. CONCLUSION: Several CPGs for SAP were developed without the desired methodological rigour or transparency. Synthesis of recommendations for best-evaluated CPGs provides a broad approach owing to the complementarity of the recommendations.

Cost analysis of pharmaceutical care provided to HIV-infected patients: an ambispective controlled study.

BACKGROUND: Studies have shown that pharmaceutical care can result in favorable clinical outcomes in human immunodeficiency virus (HIV)-infected patients, however, few studies have assessed the economic impact. The objective of this study was to evaluate the clinical and economic impact of pharmaceutical care of HIV-infected patients. METHODS: A controlled ambispective study was conducted in Brazil from January 2009 to June 2012. Patients were allocated to either intervention or control group. The control group was followed according to standard care while the intervention group was also followed by a pharmacist at each physician appointment for one year. Effectiveness outcomes included CD4+ count, viral load, absence of co-infections and optimal immune response, and economic outcomes included expenses of physician and pharmaceutical appointments, laboratory tests, procedures, and hospitalizations, at six months and one year. RESULTS: Intervention and control groups included 51 patients each. We observed significant decreases in total pharmacotherapy problems during the study. At six months, the intervention group contained higher percentages of patients without co-infections and of patients with CD4+ >500 cells/mm(3). None of the differences between intervention and control group considering clinical outcomes and costs were statistically significant. However, at one year, the intervention group showed higher percentage of better clinical outcomes and generated lower spending (not to procedures). An additional health care system daily investment of US$1.45, 1.09, 2.13, 4.35, 1.09, and 0.87 would be required for each additional outcome of viral load <50 copies/ml, absence of co-infection, CD4+ >200, 350, and 500 cells/mm(3), and optimal immune response, respectively. CONCLUSION: This work demonstrated that pharmaceutical care of HIV-infected patients, for a one-year period, was able to decrease the number of pharmacotherapy problems. However, the clinical outcomes and the costs did not have statistical difference but showed higher percentage of better clinical outcomes and lower costs for some items.