A multidisciplinary approach to improve adherence to medical recommendations in older adults at hospital discharge: The APPROACH study protocol.

INTRODUCTION: Poor comprehension and medication adherence are common in older people, especially after hospitalizations, in case of changes or prescriptions of new therapeutic regimes. This randomized controlled trial aims to evaluate the effectiveness of an integrated approach in improving older individuals' adherence to medical recommendations after hospital discharge. METHODS: Data from an expected sample of 360 older inpatients (and their caregivers) will be collected. Medical recommendations' understanding will be tested before and after the routine explanation received by in-charge physicians. Participants will be randomized in the control (usual care) and intervention group. The intervention consists of educational training by a multidisciplinary team (occupational therapist, dietician, and physician, in consultation with a pharmacologist) at hospital discharge and, after hospital discharge, receiving a phone recall checking for therapy adherence and having the possibility to contact the study team for potential related concerns. After 7 days, medication adherence will be assessed through structured phone interviews comparing ongoing and prescribed medications and by administering the 4-item validated Morisky, Green, Levine scale and the Medication adherence report scale (MARS-5). At 30 and 90 days from discharge, data on medication adherence, falls, rehospitalizations, and vital status will be collected through phone interviews and hospital records. TRIAL REGISTRATION: Registration: NCT05719870 (clinicaltrial.gov). https://classic.clinicaltrials.gov/ct2/show/NCT05719870.

DOACs for Older adults with Atrial Fibrillation and Falls: Results from the prospective single-centre DOAFF study.

INTRODUCTION: Falls are one of the most fearsome events in anticoagulated older adults. The evidence concerning safety of direct oral anticoagulants (DOACs) in falling elderly patients with atrial fibrillation (AF) is still limited. METHODS: We prospectively enrolled consecutive anticoagulant-naïve patients aged 65 years and older, starting anticoagulation with DOACs for AF. The study cohort was stratified in fallers vs. non-fallers, according to the occurrence of at least one fall during the 2-year follow-up and bleeding outcomes were evaluated. RESULTS: We enrolled 524 consecutive patients. Mean age was 80.8 years and they were mostly women (54.0%). Among the study cohort, 148 patients (28.2%) presented at least one fall episode during the study period. After the adjustment for potential confounders, no difference was found between fallers and non-fallers for all the study outcomes: major bleeding [HR: 1.04 (95%CI: 0.58-1.85)], intracranial haemorrhage [HR: 1.63 (95%CI: 0.69-3.80)], clinically relevant non-major bleeding [HR: 1.21 (95%CI: 0.83-1.76)], and all-cause death [HR: 1.51 (95%CI: 0.85-2.69)]. The presence of a prior cerebrovascular event [HR: 2.27 (95%CI: 1.12-4.62); p-value: 0.02] and polypharmacy [HR: 1.60 (95%CI: 1.08-2.39); p-value: 0.02] were the main drivers for major and clinically relevant non-major bleedings, respectively. CONCLUSIONS: Falls in an anticoagulant-naïve population aged 65 years and over starting a DOAC for AF do not increase the bleeding risk. Thus, the presence of falls should not discourage clinicians from prescribing DOACs also in this subset of patients.

Sarcopenic patients "get even": The impact of COVID-19 vaccination on mortality.

BACKGROUND: Coronavirus Disease-2019 (COVID-19), driven by the SARS-CoV-2 virus, has disproportionately affected the elderly, with comorbidities like sarcopenia worsening prognosis. Considering the significant impact of RNA vaccines on survival rates in this population, our objective is to investigate the impact of vaccination on the survival of hospitalized elderly patients with COVID-19, considering the presence or absence of sarcopenia. METHODS: Prospective study conducted on 159 patients aged>65 years from September 2021 to March 2022. Data about clinical and body composition, and mortality at 12-months after discharge were recorded. Sarcopenia was diagnosed according to the 2019 European Consensus criteria. RESULTS: At the twelfth month post-discharge, vaccinated sarcopenic individuals exhibited a mortality risk similar to vaccinated non-sarcopenic individuals, and lower than unvaccinated non-sarcopenic patients. Cox regression analysis, adjusted for age, gender, comorbidity, functional and vaccinal status, showed that the presence of sarcopenia did not significantly impact the risk of death within 12-months post-discharge. DISCUSSION: Vaccination emerges as a protective measure for sarcopenic patients, countering the potential adverse effects of sarcopenia on COVID-19 outcomes, underscoring the importance of immunization in the frail elderly with a call for meticulous monitoring of its benefits. CONCLUSIONS: Our study represents the first attempt to analyze the vaccine's effect on survival in sarcopenic hospitalized older adults with COVID-19. The administration of vaccination to sarcopenic patients proves pivotal, as its omission could lead to notably unfavorable outcomes within this specific population.

Efficacy and safety of direct oral anticoagulants in older adults with atrial fibrillation: a prospective single-centre cohort study.

INTRODUCTION: Direct oral anticoagulants (DOACs) are underused in the elderly, regardless the evidence in their favour in this population. METHODS: We prospectively enrolled anticoagulant-naïve patients aged ≥ 75 years who started treatment with DOACs for atrial fibrillation (AF) and stratified them in older adults (aged 75-84 years) and extremely older adults (≥ 85 years). Thrombotic and hemorrhagic events were evaluated for 12 months follow-up. RESULTS: We enrolled 518 consecutive patients. They were mostly aged 75-84 years (299 patients; 57.7%) vs. ≥ 85 years (219 patients; 42.3%). Extremely older adults showed higher incidence of all the endpoints (systemic cardioembolism [HR 3.25 (95% CI 1.71-6.18)], major bleeding [HR 2.75 (95% CI 1.77-4.27)], and clinically relevant non-major bleeding [HR 2.13 (95% CI 1.17-3.92)]) vs. older adults during the first year after starting anticoagulation. In patients aged ≥ 85 years, no difference in the aforementioned endpoints was found between those receiving on-label vs. off-label DOACs. In the extremely older adults, chronic kidney disease, polypharmacy, use of antipsychotics, and DOAC discontinuation correlated with higher rates of thrombotic events, whereas a history of bleeding, Charlson Index ≥ 6, use of reduced DOAC dose, absence of a caregiver, use of non-steroidal anti-inflammatory drugs (NSAIDs), and HAS-BLED score ≥ 3 were associated with major bleedings. CONCLUSIONS: Naïve patients aged ≥ 85 who started a DOAC for AF are at higher risk of thrombotic and bleeding events compared to those aged 75-84 years in the first year of therapy. History of bleeding, HAS-BLED score ≥ 3 and use of NSAIDs are associated with higher rates of major bleeding.

Can the Multidimensional Prognostic Index (MPI) be a predictive instrument for mortality in older adult liver transplant candidates?

PURPOSE: The most recent guidelines recommend that selection of liver transplant recipient patients be guided by a multidimensional approach that includes frailty assessment. Different scales have been developed to identify frail patients and determine their prognosis, but the data on older adult candidates are still inconclusive. The aim of this study was to compare the accuracy of the Liver Frailty Index (LFI) and the Multidimensional Prognostic Index (MPI) as predictors of mortality in a cohort of older people patients being evaluated for liver transplantation. METHODS: This retrospective study was conducted on 68 patients > 70 years being followed at the University Hospital of Padua in 2018. Clinical information on each patient, Model For End-Stage Liver Disease (MELD), Body Mass Index (BMI), Activities of Daily Living (ADL), Mini Nutritional Assessment (MNA), LFI, MPI, and date-of-death, were recorded. The observational period was 3 years. RESULTS: We studied 68 individuals (25 women), with a mean age 72.21 ± 1.64 years. Twenty-five (36.2%) patients died during the observational period. ROC curve analysis showed both MPI and LFI to be good predictors of mortality (AUC 0.7, p = 0.007, and AUC 0.689, p = 0.015, respectively). MELD (HR 1.99, p = 0.001), BMI (HR 2.34, p = 0.001), and poor ADL (HR 3.34, p = 0.04) were risk factors for mortality in these patients, while male sex (HR 0.1, p = 0.01) and high MNA scores (HR 0.57, p = 0.01) were protective factors. CONCLUSION: Our study confirmed the prognostic value of MPI in older adult patients awaiting liver transplantation. In this cohort, good nutritional status and male sex were protective factors, while high MELD and BMI scores and poor functional status were risk factors.

Clinical trial on the effects of oral magnesium supplementation in stable-phase COPD patients.

BACKGROUND AND AIMS: COPD is a common chronic condition in older age that impacts on daily activities and quality of life. Previous studies suggest that magnesium deficit in COPD patients affects bronco-obstruction, inflammation, and physical performance. We investigated whether oral magnesium supplementation in stable-phase COPD patients improves lung function, physical performance, and quality of life. METHODS: We conducted a double-blind randomized-controlled clinical study with 49 participants divided into two groups: one given 300 mg/day of magnesium citrate (n = 25) and the other one sachet/day of a placebo (n = 24). The following parameters were assessed at baseline and after 3 and 6 months: lung function (spirometry), physical performance (handgrip strength, lower limb strength, six-minute walk test), inflammation (e.g., C-reactive protein, CRP), disease-related symptoms, and quality of life (St George's Respiratory Questionnaire, EuroQoL-5D, the Modified British Medical Research Council Questionnaire). RESULTS: Linear mixed models revealed significantly lower CRP values in the intervention group than in the placebo group at the 6 month follow-up (ß = - 3.2, 95% CI - 6.0, - 0.4, p = 0.03). Moreover, the maximum work for flexion tended to increase in both groups between the 3 and the 6 month assessments, especially in the placebo group. No significant differences within and between groups over the study period were observed for the other parameters tested. CONCLUSIONS: Although the established minimum sample size was not reached, our results suggests that oral magnesium supplementation may have a potential anti-inflammatory role. On the other hand, it does not seem to substantially influence lung function, physical performance, and quality of life in COPD patients. TRIAL REGISTRATION: The study is registered in clinicaltrial.gov (Trial Registration: NCT02680769, 13 June 2016, retrospectively registered).

Association of body surface area with fat mass, free fat mass and total weight in healthy individuals, and implications for the dosage of cytotoxic drugs.

BACKGROUND & AIMS: In oncology, the dosage of anti-neoplastic drugs is generally adapted to the patient's body surface area (BSA). We investigated the potential differences between BSA and body weight (BW) in estimating the variability in body composition among individuals, especially older adults. MATERIALS AND METHODS: The study population included 322 community-dwelling individuals with different age and sex: 45 adult men (AM, age 18-65 years), 86 older men (OM, age >65 years), 54 adult women (AW, age 18-65 years), and 137 older women (OW, age >65 years). For each participant, we estimated the body composition with dual-energy X-ray absorptiometry, and we calculated the BSA using the DuBois and DuBois formula. The strength of relationships between fat free mass (FFM) and fat mass (FM) with BSA, BW, and BMI were expressed as correlation (r) and determination coefficients (R2). RESULTS: Most of the included sample was normal weight (45.7%) or overweight (41.9%). FFM demonstrated a stronger association with BSA than with BW or BMI in all age/sex groups, with r ranging from 0.831 to 0.924 (p < 0.001 for all) and R2 from 0.691 to 0.853. Conversely, BW and BMI were more strongly related to FM than BSA, especially in women. For such relationship, BW, in particular, showed r ranging from 0.793 to 0.924 (p < 0.001 for all). CONCLUSIONS: This study suggests that BSA may be more appropriately used to estimate FFM, compared with BW. Instead, alternative parameters should be considered to estimate FM in patients at risk for adverse effects of lipophilic drugs, especially in older age.

The Impact of Smoking on Bone Metabolism, Bone Mineral Density and Vertebral Fractures in Postmenopausal Women.

BACKGROUND: Smoking is recognized among the risk factors for osteoporosis, but only few studies have comprehensively explored its influence on bone metabolism and strength. We aimed to evaluate smoking effects on calcium-phosphate metabolism, bone mineral density (BMD) and fracture risk in postmenopausal women. METHODS: Our sample included 1067 postmenopausal women who arrived to our osteoporosis outpatient clinic. Anamnestic data, smoking habits (categorized as never, former, and current; and by smoking intensity and duration), biochemical parameters, lumbar/femoral BMD, and presence of vertebral fractures were recorded. In a subsample of 357 women, the changes in BMD after a 2-yr follow-up period were also assessed. RESULTS: Current smokers had shorter reproductive age, lower body mass index, and higher prevalence of heavy alcohol consumption than former/never smokers. They also had lower PTH values and weaker linear association between serum vitamin D and parathyroid hormone (current ß = -0.11[SE = 0.004]; former ß = -0.14[SE = 0.01]; never ß = -0.20[SE = 0.003]; p < 0.01 for all). Baseline BMD did not reflect differences based on smoking habits, duration or intensity. However, after 2 years, only current smokers significantly worsened in femural BMD. After adjustment for confounders, the chance of having sustained vertebral fractures at the first evaluation increased by 74% (95% confidence interval:1.07-2.83) in current compared with never smokers, especially among heavy smokers. CONCLUSIONS: Smoking may negatively affect bone by inhibiting vitamin D-parathyroid hormone axis, reducing estrogen exposure, promoting risky health behaviors, and accelerating bone loss, especially at the femur. No significant differences were observed in these outcomes among former smokers, suggesting that quitting smoking has beneficial effects on bone health.

Dehydroepiandrosterone sulfate and fall risk in older people: Sex differences in the Pro.V.A. longitudinal study.

BACKGROUND: The effect of dehydroepiandrosterone sulfate (DHEA-S) on fall risk in older age is still unclear, as is the effect of sex on any relationship between the two. Our aim was to evaluate the association between DHEA-S and the risk of falls and risk of recurrent falls in community-dwelling older men and women. METHODS: We included 1949 (781 M, 1168 F) older adults enrolled in the Progetto Veneto Anziani study. Baseline serum DHEA-S levels were analyzed by immunoassay. The number of falls reported in the year preceding the 4.4-year follow-up assessment was collected. The association between DHEA-S and falls was analyzed by multinomial logistic regression, adjusting for potential confounders and considering death as alternative outcome. RESULTS: After the follow-up, 548 (36.8%) individuals reported at least one fall in the previous year, and 214 (14.4%) reported ≥2 falls (recurrent falls). Each 1-standard deviation (SD) increase in log-transformed DHEA-S level reduced the odds of experiencing at least one fall by 9% (95%CI:0.88-0.95), and the risk of recurrent falls by 16% (95%CI:0.79-0.89). The highest DHEA-S tertile was 27% (95%CI:0.65-0.83) less likely to experience recurrent falls than the lowest tertile. The analyses, stratified by sex, suggested a strong association between DHEA-S and the fall risk for women (OR = 0.91; 95%CI:0.87-0.95 for at least one fall; OR = 0.83, 95%CI:0.78-0.89 for recurrent falls per each 1-SD increase in log-transformed DHEA-S); non-significant results were observed among men. CONCLUSIONS: Higher levels of DHEA-S are associated with a lower risk of falls and recurrent falls in older people, especially women.

Parathormone, vitamin D and the risk of atrial fibrillation in older adults: A prospective study.

BACKGROUND & AIMS: Vitamin D and parathormone (PTH) have been associated with cardiovascular outcomes, but their impact on atrial fibrillation (AF) onset is still unclear. We explored the influence of serum 25-hydroxyvitamin D (25[OH]D) and PTH on AF risk in older adults. METHODS AND RESULTS: Data come from 2418 participants enrolled in the Progetto Veneto Anziani study. Serum 25(OH)D and intact PTH were measured using radioimmunoassay and two-site immunoassay, respectively. The associations between 25(OH)D, PTH and adjudicated AF cases over 4-years were explored by Cox regression. Over the follow-up, 134 incident cases of AF were assessed. The incidence rate of the sample was 13.5 (95%CI 11.4-15.9) per 1000 person-years, and was higher among those with high PTH levels (high: 16.4 [95%CI 11.3-24.0] per 1000 person-years), especially when associated to low 25(OH)D (20.3 [95%CI 12.9-32.3] per 1000 person-years). At Cox regression, only high PTH was significantly associated to an increased risk of AF (HR = 1.90, 95%CI 1.27-2.84). A marginal significant interaction (p = 0.06) was found between 25[OH]D and PTH concentrations in influencing AF risk. When exploring the risk of AF for combined categories of 25(OH)D and PTH, we found that those with high PTH and low 25(OH)D levels had an AF risk twice as high as that of people with normal values (HR = 2.09, 95%CI 1.28-3.42). CONCLUSION: The risk of AF may be increased by high PTH levels, especially when associated with 25(OH)D deficiency. The identification and treatment of high PTH or vitamin D deficiency may thus contribute to lower the risk of AF.

Magnesium and healthy aging.

Magnesium (Mg) is relatively stable in the intracellular compartment, although decreases linearly with advancing age. This begs the question as to whether Mg could be used as biomarker of aging. A biomarker of aging is a biological parameter of an organism that, in the absence of disease, better predicts functional capability at a later age than the chronological age. Bone and muscle Mg content might be useful biomarkers, but the need for biopsies and the heterogeneous distribution of Mg in bones and muscles strongly limit the application of these methods in clinical practice. Similar considerations can be made for urinary Mg assessment, particularly after a loading test. Markers of Mg in blood seem fairly unreliable as biomarkers of aging since they are strongly dependent upon renal function, do not reflect the intracellular Mg status, and, in some investigations, are within normal ranges although other Mg parameters are not. Other investigations (e.g. nuclear magnetic resonance with fluorescent probes) seem to be promising, but their availability remains limited.