Drug prescription appropriateness in hospitalized older patients: 15-year results and lessons from a countrywide register.

The global increase of aging with the related increase of multiple noncommunicable diseases is inevitably accompanied by the associated issue of multimorbidity and polypharmacy. The latter is not without peculiar consequences on health, because it has been shown to be associated with drug-related adverse events, mainly due to poor prescription appropriateness and drug-drug interactions. To contribute to tackle this gigantic problem, a registry of drug dispensation in hospitalized older patient has been initiated in Italy in 2008. Through the last 15 years, data on nearly 11,000 older people have been accrued during their hospital stay in internal medicine and geriatric wards. This review article summarizes the main findings obtained, and how these data contribute to tackle the issue of appropriateness of drug prescription and the need of deprescribing in hospitalized older people affected by the most common noncommunicable diseases.

Bleeding and thrombotic events and intensity of heparin therapy in the two first waves of COVID-19.

A systemic inflammatory response occurs during SARS-CoV2 infection and is associated with hypercoagulability and thrombotic events. From March 2020 in our hospital different dosages of low-molecular weight heparin (LMWH) were introduced according to the level of patient care intensity. Because bleeding episodes occurred in hospitalized COVID-19 patients on heparin, the dosage of LMWH at the end of first wave was tailored on the severity of COVID-19. The aim of this study is to describe bleeding and thrombotic events in patients hospitalized with SARS-CoV2 infection on LMWH therapy in the two waves of COVID-19 and analyze the factors associated with these events. Among 1143 patients enrolled in the COVID-19 Network registry, 912 were included in the analysis, 537 of them admitted during the first wave and 375 during the second. Bleeding events were 30 (3.3%): 22 (2.4%) major and 8 (0.9%) non-major. Arterial and venous thrombotic events were 6 (0.7%) and 24 (2.6%). The incidence of venous thrombotic events was higher in the first than in the second wave (0.29% [95% CI 0.20-0.45] events/day vs. 0.05% [95% CI 0.02-0.16]), with a 71% risk reduction (95% CI 22%-94%). The incidence of bleeding was 0.33% (95% CI 0.22-0.50) vs 0.14% events/day (95% CI 0.07-0.28), with no statistical between-wave difference (HR 0.41 95% CI 0.16-1.08). After adjusting for the competing risks of death and comorbidities, patients in the second wave had lower odds to have thrombotic events than in the first wave (0.24 HR [95% C.I. 0.07-0.89]). In this retrospective study on COVID-19 we found a low rate of hemorrhagic and thrombotic events, that may be explained by the absence in the case material of patients admitted to intensive care unit.

Statins, ACE/ARBs drug use, and risk of pneumonia in hospitalized older patients: a retrospective cohort study.

The aims of this study is to evaluate the association between angiotensin-converting enzyme inhibitor (ACE-I), angiotensin II receptor blocker (ARBs) and/or statin use with the risk of pneumonia, as well as and with in-hospital and short-term outpatient mortality in hospitalized older patients with pneumonia. Patients aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro Politerapuie SIMI-Società Italiana di Medicina Interna) register from 2010 to 2019 were screened to assess the diagnosis of pneumonia and classified on whether or not they were prescribed with at least one drug among ACE-I, ARBs, and/or statins. Further study outcomes were mortality during hospital stay and at 3 months after hospital discharge. Among 5717 cases included (of whom 18.0% with pneumonia), 2915 (51.0%) were prescribed at least one drug among ACE-I, ARBs, and statins. An inverse association was found between treatment with ACE-I or ARBs and pneumonia (OR = 0.79, 95% CI 0.65-0.95). A higher effect was found among patients treated with ACE-I or ARBs in combination with statins (OR = 0.67, 95% CI 0.52-0.85). This study confirmed in the real-world setting that these largely used medications may reduce the risk of pneumonia in older people, who chronically take them for cardiovascular conditions.

Proton Pump Inhibitor Use and the Risk of Cardiovascular Complications and Death in Older Adults with Diabetes: A Population-Based Cohort Study.

BACKGROUND: The unfavorable effect of proton pump inhibitors (PPIs) on cardiovascular (CV) outcomes and mortality was reported in the general population. We investigated the impact of PPIs on CV outcomes and total mortality in older people with diabetes mellitus (DM) for whom evidence is missing. METHODS: Using administrative health databases of the Lombardy Region, we analyzed the risk of myocardial infarction (MI), ischemic stroke and total mortality in individuals with DM (≥65 years of age) exposed to PPIs in 2015 and followed up to 2021. The outcomes were analyzed using a multivariable-adjusted Cox proportional hazards model to compute hazard ratios (HRs) with 95% confidence intervals (CIs). HRs between PPI users and non-users were also estimated in selected subgroups. A sensitivity analysis was also performed in a 1:1 propensity score matching population. RESULTS: A total of 284,068 patients were included in the analysis (49.4% PPI users, 50.6% non-PPI users). A higher prevalence of comorbidities and medications was reported in PPI users as compared with non-users. During a median follow-up of 6.7 years, the use of PPIs was associated with a higher risk for ischemic stroke (HR 1.14, 95% CI 95% 1.08-1.20), MI (HR 1.36, 95% CI 1.31-1.41) and total mortality (HR 1.24, 95% CI 1.22-1.26). These risks were higher in PPI users regardless of the PPI type. Among sexes, previous CV diseases, and insulin subgroups, the use of PPIs was correlated with a statistically significant increased risk of ischemic stroke in men, in individuals without a history of CV disease, and in those who were not treated with insulin. A significantly higher risk of MI was associated with PPIs for all subgroups, as well as for total mortality, with the exception of patients with a previous history of CV diseases. The sensitivity analysis confirmed the results of the unmatched cohort. CONCLUSIONS: Our findings confirmed an increased risk of CV events and all-cause mortality in a large population of older adults with DM exposed to PPIs. This could have an important impact on public health and costs for National Health Service, therefore a regular assessment of PPI appropriateness is recommended, particularly in this population.

Clinical characteristics and outcomes of vaccinated patients hospitalised with SARS-CoV-2 breakthrough infection: Multi-IPV, a multicentre study in Northern Italy.

BACKGROUND: Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. METHODS: Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson's Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. RESULTS: Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039-0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582-1.703, p = 0.987). CONCLUSIONS: This study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first-booster uptake rates.

Prevalence and Predictors of Post-Acute COVID-19 Symptoms in Italian Primary Care Patients.

BACKGROUND: Despite all the progress in the management of acute COVID-19, it is still not clear why some people continue to experience symptoms after recovery. Using data from a self-administered online survey, we assessed the prevalence and predictors of post-acute COVID-19 in an unselected population followed by GPs. METHODS: Patients ≥18 years with a confirmed COVID-19 diagnosis were included. The survey collected information on demographics, risk factors, COVID-19 course and symptomatology. Fatigue and Quality of Life questionnaires were also administered. Descriptive statistics were used to describe patients' characteristics, stratified as acute and post-acute COVID-19. Logistic regression models were used to assess the association between clinical characteristics and post-acute COVID-19. RESULTS: A total of 1108 surveys were analyzed. Nearly 29% of patients reported post-acute COVID-19. The more persistent symptoms were fatigue, memory and concentration impairment. Adjusted Odds Ratio (OR) showed a significantly higher probability of post-acute COVID-19 for women compared to men (OR 1.9, 95% CI 1.4-2.5), for age >50 years than ≤50 years (OR 1.6, 95% CI 1.2-2.2), for BMI > 25 compared to BMI ≤ 25 (OR 1.6, 95% CI 1.1-2.1) and those with autoimmune diseases, compared to those without (OR 1.8 95% CI 1.1-2.9). In addition, a significant association was found with COVID-19 hospitalization, anxiety and allergies. We found that post-acute COVID-19 patients showed a higher fatigue and a worst quality of life. CONCLUSIONS: These findings suggest the need for tailored personalized strategies to improve the management of patients with post-acute COVID-19.

Development and validation of the Medical Attitudes Towards Deprescribing Questionnaire.

Polypharmacy and inappropriate prescriptions in the elderly are widely discussed themes in scientific literature. Although more and more studies showed the safety and feasibility of deprescribing strategies, these are not implemented in clinical practice. In order to measure the attitudes of Italian doctors towards deprescribing and address their awareness, experiences, difficulties in applying these strategies and potential suggestions, we aimed to develop and validate a questionnaire, the Medical Attitudes Towards Deprescribing Questionnaire (MATD-Q). Between November 2017 and October 2018 an e-mail was sent to internists, geriatricians and general practitioners, to invite them to connect to a platform and answer to the questionnaire, consisting in 38 items (with a five level score) and five questions. After 2-3 weeks, a second e-mail was sent for a second completion of the questionnaire. Test-retest reliability was assessed by means of the intraclass correlation coefficient (ICC). The correlations between items were assessed by means of Pearson linear correlation coefficients and Cronbach Alpha was used to assess internal consistency. A total of 77 questionnaires completed twice were collected. By a principal component analysis we defined a smaller set of variables (n = 12), which resulted to be representative of the 38-item questionnaire.The final version of the questionnaire we developed (MATDQ-12), after validation in other cohorts, could be a useful tool to measure the efficacy of educational interventions aimed at improving the attitude of physicians towards deprescribing strategies with the final goal to allow their implementation in clinical practice.

Nursing Home Organization Mealtimes and Staff Attitude Toward Nutritional Care: A Multicenter Observational Study.

OBJECTIVES: The aims of this study were to investigate the practices of registered nurses and nurse aides at mealtimes in nursing homes (NHs) and to evaluate the attitudes of health care staff toward the nutritional care of older people. DESIGN: This is a multicenter cross-sectional study. SETTING AND PARTICIPANTS: The study involved a convenience sample of NH health care staff: physicians, registered nurses, and nurse aides. METHODS: Data were collected on characteristics of the dining environment, organizational and nutritional care practices, staff-resident ratio, and staff activities during meals, using 2 questionnaires and staff attitudes were assessed with Staff Attitudes to Nutritional Nursing Care Geriatric Scale (SANN-G). Total score ranges from 18 to 90 points, with the following cutoffs: ≥72, positive attitude; ≤54, negative; and 55-71 points, neutral attitude. RESULTS: A total of 1267 workers from 29 NHs in northern Italy participated in the study. The most common nutritional assessment tool used by nurses was the Malnutrition Universal Screening Tool. A median of 4.0 and 4.2 people (family caregivers, volunteers and staff) were present for feeding support, respectively, at lunch and dinner. A median of 2.5 and 2.0 staff members at lunch and at dinner, respectively, fed residents. Overall, 1024 health care workers responded to SANN-G of which 21.9% showed a negative attitude, 57.2% neutral, and 20.9% a positive attitude. Nurse aides (190/714) showed worse attitudes compared with registered nurses (20/204) and physicians (2/36); differences were statistically significant. Overall, the best attitudes were toward "habits," "interventions," and "individualization" of nutritional care. Staff who had received nutritional training (29.2%) had best attitudes. CONCLUSIONS AND IMPLICATIONS: The results suggest that NHs should ensure adequate staff-resident ratio during meals, involving trained volunteers and relatives. Moreover, health professionals' knowledge and attitude toward nutritional care should be improved through continuous training.

The role of immune suppression in COVID-19 hospitalization: clinical and epidemiological trends over three years of SARS-CoV-2 epidemic.

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients >17 years that were hospitalized for COVID-19 at the "Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico" in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8-20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p < 0.001) and be vaccinated (37% vs. 12.7%, p < 0.001). We evaluated the contribution of immune suppression to hospitalization during the various stages of the epidemic and investigated whether immune suppression contributed to severe outcomes and death, also considering the vaccination status of the patients. The proportion of immune suppressed patients among all hospitalizations (initially stable at <20%) started to increase around December 2021, and remained high (30-50%). This change coincided with an increase in the proportions of older patients and patients with co-morbidities and with a decrease in the proportion of patients with severe outcomes. Vaccinated patients showed a lower proportion of severe outcomes; among non-vaccinated patients, severe outcomes were more common in immune suppressed individuals. Immune suppression was a significant predictor of severe outcomes, after adjusting for age, sex, co-morbidities, period of hospitalization, and vaccination status (OR: 1.64; 95% CI: 1.23-2.19), while vaccination was a protective factor (OR: 0.31; 95% IC: 0.20-0.47). However, after November 2021, differences in disease outcomes between vaccinated and non-vaccinated groups (for both immune suppressed and immune competent subjects) disappeared. Since December 2021, the spread of the less virulent Omicron variant and an overall higher level of induced and/or natural immunity likely contributed to the observed shift in hospitalized patient characteristics. Nonetheless, vaccination against SARS-CoV-2, likely in combination with naturally acquired immunity, effectively reduced severe outcomes in both immune competent (73.9% vs. 48.2%, p < 0.001) and immune suppressed (66.4% vs. 35.2%, p < 0.001) patients, confirming previous observations about the value of the vaccine in preventing serious disease.

Post-recovery impact of the second and third SARS-CoV-2 infection waves on healthcare resource utilization in Lombardy, Italy.

The administrative claims database of the Italian region Lombardy, the first in Europe to be hit by the SARS-CoV-2 pandemic, was employed to evaluate the impact on healthcare resource utilization following recovery from the second (mainly alpha-related variant) and third (delta-related) infection waves. 317,164 individuals recovered from the infection and became negative after the second wave, 271,180 after the third. Of them, 1571 (0.5%) and 1575 (0.6%) died in the first 6 post-negativization months. In the remaining cases (315,593 after the second wave and 269,605 after the third), hospitalizations, attendances to emergency rooms and outpatient visits were compared with those recorded in the same pre-pandemic time periods in 2019. Dispensation of drugs as well as of imaging, and functional and biochemical diagnostic tests were also compared as additional proxies of the healthcare impact of the SARS-CoV-2 infection waves. Following both waves, hospitalizations, attendances at emergency rooms, and outpatient visits were similar in number and rates to the pre-pandemic periods. However, there was an increased dispensation a number of drugs and diagnostic tests, particularly those addressing the cardiorespiratory and blood systems. In a large region such as Lombardy taken as a relevant model because early and severely hit by the SARS-CoV-2 pandemic, the post-COVID burden on healthcare facilities was mildly relevant in cases who recovered from the second and third infection waves regarding such pivotal events as deaths, hospitalizations, and need for emergency room and outpatient visits, but was high regarding the dispensation of some drug classes and types of diagnostic tests.

Prescribing trends of glucose-lowering drugs in older adults from 2010 to 2021: A population-based study of Northern Italy.

AIMS: To describe glucose-lowering drugs prescribing pattern in a large population of older diabetics from 2010 to 2021. METHODS: Using linkable administrative health databases, we included patients aged 65-90 years treated with glucose-lowering drugs. Prevalence rate of drugs was collected within each study year. A stratified analysis by gender, age and coexistence of cardiovascular disease (CVD) was conducted. RESULTS: A total of 251 737 and 308 372 patients were identified in 2010 and 2021, respectively. Use of metformin (68.4% to 76.6%), DPP-4i (1.6% to 18.4%), GLP-1-RA (0.4% to 10.2%), SGLT2i (0.6% to 11.1%) increased, while sulfonylureas (53.6% to 20.7%) and glinides (10.5% to 3.5%) decreased over time. Metformin, glitazones, GLP1-RA, SGLT2i and DPP4i (except for 2021) usage decreased with aging, in contrast to sulfonylureas, glinides and insulin. The coexistence of CVD was associated with a higher prescription of glinides, insulin, DPP-4i, GLP1-RA and SGLT2i, particularly in 2021. CONCLUSIONS: We found a significant increase in the prescriptions of GLP-1 RA and SGLT2i in older diabetics, mainly in those with CVD. However, drugs without CV benefits including sulfonylureas and DPP-4i continued to be highly prescribed in older patients. There is still room to improve the management in this population according to recommendations.

Two years of SARS-CoV-2 pandemic and COVID-19 in Lombardy, Italy.

Lombardy, the largest and most densely populated Italian region, was severely hit in February 2020 by the first pandemic wave of SARS-CoV-2 and associated COVID-19. Since then, additional infection waves spread in the region. The aim of this study was to compare the first with the subsequent waves using the administrative database of the Lombardy Welfare directorate. In the time frames of the four 2020-2022 waves, the absolute number of infected cases, sites of management and crude mortality rate associated with SARS-CoV-2 positivity were extracted from the database. Infected cases progressively increased in the region by approximately 5-fold in the second versus the first wave, 4-fold in the third and 20-fold during the most recent wave mainly associated with the omicron variant. The crude death decreased from 18.7% in the first to 2% in the second and third wave to reach a 0.3% nadir at the time of the fourth wave. This study confirms that in Lombardy outcomes of public health and health-care relevance such as deaths and number of hospitalizations declined dramatically across the four virus waves and reached very low values in 2022 when, at variance with the first three SARS-CoV-2 waves, the majority of infected cases had been previously vaccinated.