Clinical and Prognostic Implications of Estimating Glomerular Filtration Rate by Three Different Creatinine-Based Equations in Older Nursing Home Residents.

Background: According to the international literature, the percentage of nursing home (NH) residents with renal insufficiency is very high, ranging between 22 and 78%. Diminished kidney function represents a risk factor for drug overdosage, adverse drug reactions, end-stage renal disease, disability, morbidity, and mortality. Several studies suggested that screening for chronic kidney disease (CKD) in high-risk and older populations may represent a cost-effective approach to reducing progression to renal failure and CKD mortality. Objective: This study aimed (i) to investigate to what extent CKD may be staged interchangeably by three different creatinine-based estimated glomerular filtration rate (eGFR) equations in a sample of older adults living in long-term care facilities; (ii) to investigate factors explaining differences among eGFR equations; and (iii) to compare the predictivity of different creatinine-based eGFR equations with respect to all-cause mortality. Methods: A total of 522 residents aged 65 years and older participated in a prospective cohort study of 9 long-term care facilities in Calabria. eGFR was calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Berlin initiative study (BIS), and full age spectrum (FAS) equations. Disability in at least one activity of daily living (ADL), depression, cognitive impairment, comorbidity, and malnutrition was considered in the analysis. Statistical analysis was carried out by Bland-Altman analysis, and 2-year mortality was investigated by Kaplan-Meier curves and Cox regression analysis. Results: Depending on the adopted equation, the prevalence of NH residents with impaired renal function (eGFR < 60 ml/min/1.73 m2) ranged between 58.2% for the CKD-EPI and 79.1% for the BIS1 equation. The average difference between BIS and FAS was nearly negligible (0.45 ml/min/1.73 m2), while a significant bias was detected between CKD-EPI and BIS and also between CKD-EPI and FAS (6.21 ml/min/1.73 m2 and 6.65 ml/min/1.73 m2, respectively). Although the eGFR study equations had comparable prognostic accuracy in terms of mortality risk, BIS and FAS were able to reclassify NH residents pertaining to a low-risk group with CKD-EPI, and this reclassification improves the discriminative capacity of CKD-EPI with respect to overall mortality. Conclusion: Despite the relatively good correlation between eGFRs calculated using all adopted equations, the findings in this study reported clearly demonstrated that CKD-EPI and BIS/FAS equations are not interchangeable to assess eGFR among older people and particularly in institutionalized and frail older subjects.

COVID-19 Vaccines: Current and Future Perspectives.

Currently available vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are highly effective but not able to keep the coronavirus disease 2019 (COVID-19) pandemic completely under control. Alternative R&D strategies are required to induce a long-lasting immunological response and to reduce adverse events as well as to favor rapid development and large-scale production. Several technological platforms have been used to develop COVID-19 vaccines, including inactivated viruses, recombinant proteins, DNA- and RNA-based vaccines, virus-vectored vaccines, and virus-like particles. In general, mRNA vaccines, protein-based vaccines, and vectored vaccines have shown a high level of protection against COVID-19. However, the mutation-prone nature of the spike (S) protein affects long-lasting vaccine protection and its effectiveness, and vaccinated people can become infected with new variants, also showing high virus levels. In addition, adverse effects may occur, some of them related to the interaction of the S protein with the angiotensin-converting enzyme 2 (ACE-2). Thus, there are some concerns that need to be addressed and challenges regarding logistic problems, such as strict storage at low temperatures for some vaccines. In this review, we discuss the limits of vaccines developed against COVID-19 and possible innovative approaches.

Unveiling the Burden of Interactions Among Clinical Risk Factors for 1-Year Mortality in Hospitalized Older Patients.

Background: Hospitalized older patients are particularly exposed to adverse health outcomes. Objective: In this study, we aimed at investigating the prognostic interactions between disability in basic activities of daily living (BADL), cognitive impairment, low handgrip strength, anticholinergic cognitive burden (ACB), and depression on 1-year mortality. Setting and Subjects: Our series consisted of 503 older patients discharged from acute care hospitals. Methods: Disability in at least one BADL, ACB, depression, cognitive impairment, and low handgrip strength was considered in the analysis. One-year mortality was investigated by Cox regression analysis and prognostic interactions among study variables were assessed by survival tree analysis. Results: Basic activities of daily living disability, ACB, cognitive impairment, and low handgrip strength were significantly associated with 1-year mortality. Survival tree analysis showed that patients with BADL disability and high ACB carried the highest risk of poor survival [hazard ratio (HR): 16.48 (2.63-74.72)], followed by patients with BADL disability and low ACB (HR: 8.43, 95% CI: 1.85-38.87). Patients with cognitive impairment and no BADL disability were characterized by a lower but still significant risk of mortality (HR: 6.61, 95% CI: 1.51-28.97) and those with high ACB scores and good cognitive and functional performance (HR: 5.28, 95% CI: 1.13-24.55). Conclusion: Basic activities of daily living dependency, cognitive impairment, and ACB score were the three main predictors of 1-year mortality among patients discharged from acute care hospitals; the interaction between BADL dependency and ACB score was found to significantly affect survival. Early identification of such high-risk patients may help tailor targeted interventions to counteract their detrimental effects on prognosis.

Design and methodology of the chronic kidney disease as a dysmetabolic determinant of disability among older people (CKD-3D) study: a multicenter cohort observational study.

BACKGROUND: Chronic kidney disease (CKD) is a common condition in older people and represents a global health issue since it increases the risk of associated comorbidities and all-cause mortality. Furthermore, older people with reduced renal function might be at higher risk for developing functional limitation and disability. Moreover, the current creatinine-based measures of renal function are influenced by several factors in older population. The aims of the CKD-3D project are to perform an observational study to expand the knowledge about CKD-disability relationship and to investigate the use of novel biomarkers of kidney function. METHODS: An observational, multicenter, prospective cohort study will be conducted in 75 + old patients consecutively admitted to acute care wards of geriatric medicine at participating hospitals. The study planned to enroll 440 patients undergoing clinical and laboratory evaluations at baseline and after 12 months. Face-to-face follow-up at 6 months and telephone follow-up at 3 and 9 months will be carried out. Comprehensive Geriatric Assessment (CGA) and the measurement of Cystatin C, Beta-Trace Protein and Beta2-Microglobulin levels will be included. DISCUSSION: This study will provide useful information to prevent CKD-related disability by collecting real-life data over 1-year period. The combined approach of CGA and the investigation of innovative existing biomarkers will make it possible to develop new recommendations and guidelines for a patient-centered approach. It is believed that such a study may lead to an improvement of knowledge on CKD in elderly patients and may also have implications in daily clinical practice and in decision-making process.

The excess mortality risk associated with anticholinergic burden among older patients discharged from acute care hospital with depressive symptoms.

BACKGROUND: The relationship between anticholinergic burden and mortality is controversial, and the impact of anticholinergic burden on prognosis may vary in presence of other conditions common in old age. We aimed at investigating the role of depressive symptoms as potential effect modifiers in the association between anticholinergic burden and 1-year mortality in older patients discharged from hospital. METHODS: Our series consisted of 576 older patients consecutively admitted to seven geriatric and internal medicine acute care wards in the context of a prospective multicenter observational study. Overall anticholinergic burden was assessed by Anticholinergic Cognitive Burden (ACB) score. Depressive symptoms were assessed by 15-item Geriatric Depression Scale (GDS). The study outcome was all-cause mortality during 12-months follow-up. Statistical analysis was carried out by Cox regression analysis. RESULTS: After adjusting for potential confounders, discharge ACB score = 2 or more was significantly associated with the outcome among patients with GDS > 5 (HR = 3.70; 95%CI = 1.18-11.6), but not among those with GDS ≤ 5 (HR = 2.32; 95%CI = 0.90-6.24). The association was confirmed among depressed patients after adjusting for ACB score at 3-month follow-up (HR = 3.58; 95%CI = 1.21-10.7), as well as when considering ACB score as a continuous variable (HR = 1.42; 95%CI = 1.10-1.91). The interaction between ACB score at discharge and BADL dependency was statistically significant (p < .005). CONCLUSIONS: ACB score at discharge may predict mortality among older patients discharged from acute care hospital carrying high GDS score e. Hospital physician should be aware that prescribing anticholinergic medications in such a vulnerable population may have negative prognostic implications.

Anticholinergic Burden is Associated With Increased Mortality in Older Patients With Dependency Discharged From Hospital.

OBJECTIVES: To determine whether anticholinergic burden may predict differently 1-year mortality in older patients discharged from acute care hospitals with or without dependency in basic activities of daily living (BADL). DESIGN: Prospective observational study. SETTING AND PARTICIPANTS: Our series consisted of 807 patients aged 65 years or older consecutively discharged from 7 acute care geriatric wards throughout Italy between June 2010 and May 2011. MEASURES: Overall anticholinergic burden was assessed by the anticholinergic cognitive burden (ACB) score. Dependency was rated by BADL, and dependency in at least 1 BADL was considered as a potential mediator in the analysis. The study outcome was all-cause mortality during 12-months of follow-up. RESULTS: Patients included in the study were aged 81.0 ± 7.4 years, and 438 (54.3%) were female. During the follow-up period, 177 out of 807 participants (21.9%) died. After adjusting for potential confounders, discharge ACB score = 2 or more was significantly associated with the outcome among patients with dependency in at least 1 BADL [hazard ratio (HR) 2.25 95% confidence (CI) 1.22‒4.14], but not among independent ones (HR 1.06 95% CI 0.50‒2.34). The association was confirmed among dependent patients after adjusting for the number of lost BADL at discharge (HR 2.20 95% CI 1.18‒4.04) or ACB score at 3-month follow-up (HR 2.18 95% CI 1.20‒3.98), as well as when considering ACB score as a continuous variable (HR 1.28 95% CI 1.11‒1.49). The interaction between ACB score at discharge and BADL dependency was highly significant (P < .001). CONCLUSIONS/IMPLICATIONS: ACB score at discharge may predict mortality among older patients discharged from an acute care hospital carrying at least 1 BADL dependency. Hospital physicians should be aware that prescribing anticholinergic medications in this population may have negative prognostic implications and they should try to reduce anticholinergic burden at discharge whenever possible.

Anticholinergic burden and 1-year mortality among older patients discharged from acute care hospital.

AIM: The association between anticholinergic burden and mortality is controversial. We aimed to investigate whether the anticholinergic cognitive burden (ACB) score predicts 1-year mortality in older patients discharged from acute care hospitals. METHODS: Our series consisted of 807 hospitalized patients aged ≥65 years. Patients were followed up for 12 months after discharge. All-cause mortality was the outcome of the study. The ACB score at discharge (0, 1, ≥2) and increasing ACB score from admission to discharge (no increase, +1, +2 or more) were calculated and used as exposure variables. Cox proportional hazards models adjusted for potential confounders were used for the analysis. Interactions between the ACB score and cognitive impairment or history of falls were also investigated. RESULTS: During the follow-up period, 177 out of 807 participants (21.9%) died. After adjusting for potential confounders, a discharge ACB score of ≥2 (HR 1.69, 95% CI 1.09-2.65) was significantly associated with the outcome, whereas the association between increasing ACB score of +2 or more and mortality was weaker (HR 1.30, 95% CI 0.95-1.92). The interaction between the ACB score at discharge or increasing ACB score and cognitive impairment was statistically significant (P = 0.003 and P = 0.004, respectively), whereas that between the ACB score and falls was not. CONCLUSIONS: The ACB score at discharge and, to a lesser extent, an increasing ACB score during hospital stay are associated with an increased risk of 1-year mortality in older patients discharged from hospital. Such an association is stronger among patients with cognitive impairment. Geriatr Gerontol Int 2018; 18: 705-713.

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.