Geriatric syndromes and functions in older adults with COVID-19 hospitalized in sub-acute care: a multicenter study.

OBJECTIVE: Alternatives to conventional acute hospitalizations have been particularly useful during the COVID-19 pandemic. However, little is known on the management and outcomes of COVID-19 in older patient admitted to non-acute settings. The main aim of this study was to determine the effect of geriatrics syndromes on functional outcomes in older COVID-19 patients cared in sub-acute units. METHODS: Prospective multicenter observational cohort study of patients aged 65 years and older with COVID-19, admitted to sub-acute units in Italy and Spain. Multivariable logistic regression models were used to test the association between geriatric syndromes and other clinical variables, and the functional status at discharge, defined by a Barthel Index > = 80. RESULTS: A total of 158 patients were included in the study with a median age of 82 [Interquartile Range 81, 83]; of these 102 (65%) patients had a Barthel Index ≥ 80 at discharge. In the main multivariable logistic regression model a higher severity of frailty-measured with the Clinical Frailty Scale-(OR 0.30; CI 0.18-0.47), and the presence of delirium (OR 0.04; CI 0.00-0.35) at admission were associated with lower odds of a higher functional status at discharge. Other variables associated with lower functional status were female gender (OR 0.36; CI 0.13-0.96), and a higher number of comorbidities (OR 0.48; CI 0.26-0.82). CONCLUSION: The study reports a relatively high prevalence of functional recovery for older COVID-19 patients admitted to sub-acute units. Additionally, it underlines the importance of targeting geriatrics syndromes, in particular frailty and delirium, for their possible effects on functional recovery.

Frailty predicts failure to discharge patients home from a subacute-care unit: a 3-year Italian experience.

BACKGROUND: The primary purpose of Subacute Care Units (SCU) is to decongest acute hospital wards and facilitate the return of older patients to home. AIMS: We analyzed the clinical characteristics and outcomes of patients admitted to an Italian SCU, and we explored factors associated with discharge to locations other than home (outcome). METHODS: This retrospective observational cohort study was conducted at a medium-sized suburban hospital, enrolling all patients consecutively admitted to one SCU from October 2017 to February 2020. We collected demographics, cause of admission, comorbidities, cognition, Barthel Index (BI), nutritional status, Clinical Frailty Scale (CFS), length of stay, and discharge destination. Delirium was screened with the 4AT score. We adopted a multivariable conditional logistic regression model to identify the factors associated with the outcome. RESULTS: Frail subjects accounted for 58.6% of 406 patients (mean age 78.2 years, SD 11.6), while 61% were classified as functionally dependent. More than half of patients had relevant comorbidity, approximately 80% had a poor nutritional status, and 25% had pre-existing dementia. The overall prevalence of delirium was 14.5%. Most patients came from a hospital setting; recurrent reasons for admission were infections (70.5%) and heart failure (12.7%). Having a urinary bladder catheter at discharge, being overtly frail (CFS > 8), and low BI score were factors independently associated with not being discharged home. DISCUSSION AND CONCLUSION: The routine assessment of frailty, as expressed by the CFS, may help redirecting the patients eligible for SCU admission.

Adverse Events of Proton Pump Inhibitors: Potential Mechanisms.

OBJECTIVE: We aimed at summarizing current evidence about mechanisms for potentially harmful effects of Proton Pump Inhibitors (PPIs). METHODS: A Pubmed search was performed, and 207 studies concerning the relationship between use of PPIs and cardiovascular diseases, kidney impairment, nutritional disorders, fractures, infections, functional decline, and mortality were selected and reviewed. RESULTS: PPIs may cause potentially harmful effects by several mechanisms, including endothelial dysfunction, hypomagnesemia, drug interactions, reduced absorption of selected nutrients, increased gastric microbiota and small intestine bacterial overgrowth, reduced immune response, tubular-interstitial inflammation, increased bone turnover, accumulation of amyloid in the brain. Clinical and epidemiologic evidence is not consistent in regard to some negative outcomes during PPI treatment. Data from randomized clinical trials seem to deny most of them, but they are usually designed to investigate efficacy of drugs in ideal conditions and are not powered enough to detect adverse events. Besides being at special risk of experiencing negative outcomes during long-term treatment with PPIs, older and complex patients treated with polypharmacy regimens are persistently excluded from randomized clinical trials. Thus, large observational studies involving real-world patients should be considered as an important informative source about potential risks related to PPIs. CONCLUSIONS: Current evidence suggests that use of PPIs may be associated with negative outcomes by eliciting several different pathophysiologic mechanisms. While short-term PPIs could be considered effective and safe in adult patients with acid-related disorders, their long-term and often inappropriate use in patients carrying vulnerability to adverse events and/or high risk of drug-interactions should be avoided.

Multiple hormonal dysregulation as determinant of low physical performance and mobility in older persons.

Mobility-disability is a common condition in older individuals. Many factors, including the age-related hormonal dysregulation, may concur to the development of disability in the elderly. In fact, during the aging process it is observed an imbalance between anabolic hormones that decrease (testosterone, dehydroepiandrosterone sulphate (DHEAS), estradiol, insulin like growth factor-1 (IGF-1) and Vitamin D) and catabolic hormones (cortisol, thyroid hormones) that increase. We start this review focusing on the mechanisms by which anabolic and catabolic hormones may affect physical performance and mobility. To address the role of the hormonal dysregulation to mobility-disability, we start to discuss the contribution of the single hormonal derangement. The studies used in this review were selected according to the period of time of publication, ranging from 2002 to 2013, and the age of the participants (≥65 years). We devoted particular attention to the effects of anabolic hormones (DHEAS, testosterone, estradiol, Vitamin D and IGF-1) on both skeletal muscle mass and strength, as well as other objective indicators of physical performance. We also analyzed the reasons beyond the inconclusive data coming from RCTs using sex hormones, thyroid hormones, and vitamin D (dosage, duration of treatment, baseline hormonal values and reached hormonal levels). We finally hypothesized that the parallel decline of anabolic hormones has a higher impact than a single hormonal derangement on adverse mobility outcomes in older population. Given the multifactorial origin of low mobility, we underlined the need of future synergistic optional treatments (micronutrients and exercise) to improve the effectiveness of hormonal treatment and to safely ameliorate the anabolic hormonal status and mobility in older individuals.

IGF-1, the cross road of the nutritional, inflammatory and hormonal pathways to frailty.

The decline in functional capacity is a heterogeneous phenomenon in the elderly. An accelerated ageing determines a frail status. It results in an increased vulnerability to stressors for decreased physiological reserves. The early identification of a frail status is essential for preventing loss of functional capacity, and its clinical consequences. Frailty and mobility limitation result from an interplay of different pathways including multiple anabolic deficiency, inflammation, oxidative stress, and a poor nutritional status. However, the age-related decline in insulin-like growth factor 1 (IGF-1) bioactivity deserves special attention as it could represent the ideal crossroad of endocrine, inflammatory, and nutritional pathways to frailty. Several minerals, namely magnesium, selenium, and zinc, appear to be important determinants of IGF-1 bioactivity. This review aims to provide an overview of the potential usefulness of nutrients modulating IGF-1 as potential therapeutic targets in the prevention of mobility limitation occurring in frail older subjects.

SHBG and endothelial function in older subjects.

BACKGROUND: Endothelial dysfunction is predictor of cardiovascular diseases that have different prevalence in men and women before menopause. Sex hormones and sex hormone binding globulin (SHBG), novel risk factors for diabetes and cardiovascular diseases even in older individuals, might explain this difference. However, the relationship between these hormones and endothelial function has never been addressed in the elderly. METHODS AND RESULTS: 430 men and,424 women 70 years older of Prospective Study of the Vasculature in Uppsala Seniors study, with complete data on SHBG, testosterone(T), estradiol(E2), endothelium-independent vasodilation (EIDV), endothelium-dependent vasodilation(EDV), flow-mediated vasodilation (FMD) and the pulse wave analysis (reflection index, RI) were evaluated. Multivariate regression analysis adjusted for confounders was used to assess the relationship between T, E2, SHBG and endothelial function. In men we found a positive relationship between SHBG and EDV (ß ± SE 3.60 ± 0.83, p<0.0001), EIDV (2.42 ± 0.58, p<0.0001) but not with FMD. The relationship between SHBG and EDV and EIDV was maintained after adjustment for sex (1.64 ± 0.47, p<0.001 and 1.79 ± 0.35, p<0.0006, respectively). After adjustment for confounders, the relationship between SHBG and EDV and EIDV was still statistically significant (2.63 ± 0.90 and 1.86 ± 0.63, p = 0.004 for both). In women SHBG and EIDV were positively associated (1.58 ± 0.46; p = 0.0007), and this relationship was independent of sex (1.79 ± 0.35; p<0.001). No significant interaction SHBG * SEX was found for EIDV (p = 0.72). In a combined analysis in two sexes, SHBG and EIDV were positively associated (1.13 ± 0.45; p = 0.01). SHBG was not associated with EDV, FMD and RI. No significant relationship was found between T or E2 and EDV, EIDV, FMD or RI in both sexes. CONCLUSIONS: In older men SHBG, but not T and E2, is positively and independently associated with EDV in resistance arteries. In both sexes, SHBG was positively and independently associated with EIDV.

Proton pump inhibitors and risk of 1-year mortality and rehospitalization in older patients discharged from acute care hospitals.

IMPORTANCE: The use of proton pump inhibitors (PPIs) has rapidly increased during the past several years. However, concern remains about risks associated with their long-term use in older populations. OBJECTIVE: To investigate the relationship between the use of PPIs and the risk of death or the combined end point of death or rehospitalization in older patients discharged from acute care hospitals. DESIGN: We investigated the relationship between PPI use and study outcomes using time-dependent Cox proportional hazards regression in patients 65 years or older discharged from acute care medical wards from April 1 to June 30, 2007. SETTING: Eleven acute care medical wards. PARTICIPANTS: Four hundred ninety-one patients (mean [SD] age, 80.0 [5.9] years). MAIN OUTCOME MEASURES: Mortality and the combined end point of death or rehospitalization. RESULTS The use of PPIs was independently associated with mortality (hazard ratio, 1.51 [95% CI, 1.03-2.77]) but not with the combined end point (1.49 [0.98-2.17]). An increased risk of mortality was observed among patients exposed to high-dose PPIs vs none (hazard ratio, 2.59 [95% CI, 1.22-7.16]). CONCLUSIONS AND RELEVANCE: In older patients discharged from acute care hospitals, the use of high-dose PPIs is associated with increased 1-year mortality. Randomized controlled studies including older frail patients are needed. In the meantime, physicians need to use caution and balance benefits and harms in long-term prescription of high-dose PPIs.