Manuela Casula

Introduction: Optimizing drug treatments in older adults is essential for improving health outcomes and reducing drug-related issues. Objective: This study aimed to develop an updated and comprehensive explicit indicator of potentially inappropriate medications in older adults, and to evaluate its association with all-cause hospitalization. Methods: Administrative healthcare data from Local Health Units (LHUs) in Lombardy, Italy (2015–2018) were used to identify individuals aged ≥65 years who were exposed to potentially inappropriate medications (PIMs), identified through an explicit criteria-based list. Risk-set matching was used to select unexposed controls, and logistic regression models adjusted for high-dimensional propensity scores were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for all-cause hospitalization within 90 days after the first exposure date. Key findings: Among 641 230 older patients, between 52.8% and 56.3% were exposed to at least one PIM. After matching (128 063 pairs) hospitalization rates were higher among the exposed (8.3%–10.2%) compared with the not exposed (5.1%–6.0%) across the LHUs. Pooled estimates showed an increased risk of hospitalization for those exposed (ORs 1.55, 95% CIs 1.48–1.62), with the highest risk observed in adults aged 65–74 years (1.67, 1.59–1.76) and in women (1.62, 1.55–1.70). Conclusions: Over half of older individuals were exposed to at least one PIM, with a 55% increase in short-term hospitalization risk. These findings highlight the urgent need for improved prescribing practices tailored to older populations.

Background: Medication non‐adherence is common among older adults and represents a major challenge for healthcare systems. Effective interventions are needed to support adherence and inform quality‐improvement efforts. Objective: To assess how medication‐adherence interventions for older adults are currently implemented in Italy and to identify care‐delivery priorities improving quality and feasibility across healthcare settings. Methods: We conducted a mixed‐methods study within the Eldercare project. We administered a national benchmarking survey (May–August 2024) to healthcare professionals and patient representatives from scientific societies, professional orders, public institutions, universities, and patient associations. We ran a nested Strengths, Weaknesses, Opportunities and Threats (SWOT) survey (January–March 2025) with key informants. We summarized quantitative responses, compared distributions across professional roles ( χ ² /Fisher's exact tests), and analyzed SWOT free‐text using a hybrid deductive–inductive Framework Method. Results: In the benchmarking survey ( n = 340), Respondents reported that adherence is mainly addressed during routine consultations (78.5%) and most often relied on direct patient‐provider communication (51.5%). Respondents reported that monitoring is primarily based on clinical data (55.3%) and access to dispensing/prescription data and digital tools was less frequent (generally ≤ 50%). Respondents rated patient‐centered strategies as highly important (e.g., caregiver involvement 94.4%, shared goal setting 90.3%, individual counseling 87.6%), but feasibility ratings were consistently lower. The most frequently reported unmet needs were limited patient awareness (68.8%) and poor coordination among professionals (60.3%). Key barriers included high numbers of daily medicines (69.1%) and lack of clear information on prescribed therapies (64.7%). In the SWOT survey ( n = 14), strengths included continuity and communication, while weaknesses and threats focused on fragmented interprofessional collaboration, limited training, low digitalisation, and scarce financial/institutional support. Conclusions: Medication‐adherence support for older adults in Italy remains largely consultation‐based and variably resourced. Strengthening interprofessional coordination, training, and use of digital/administrative data may help develop more structured and scalable adherence‐support pathways as a quality‐improvement model of care.

Background Falls are a leading cause of hospitalisation among older adults, with substantial impacts on quality of life and healthcare costs. Fall-risk-increasing drugs represent an important risk factor. Objective This study aimed to evaluate the association between fall-risk-increasing drug use and the risk of fall-related hospitalisation. Methods A nested case-control study was conducted using administrative healthcare data from a sample of Italian community-dwelling older adults. Cases included individuals aged ≥65 years hospitalised for fall-related injuries in 2018, matched 1:1 by sex and age with controls who had no fall-related injuries. Fall-risk-increasing drug exposure was assessed by drug class, duration and recency of use. Adjusted odds ratios (aORs) were estimated using logistic regression, controlling for polypharmacy and comorbidities. Results Among 16,118 cases and 16,118 controls (68.77% female, mean age 79.76 years), cases showed a higher prevalence of polypharmacy (five to nine drugs: 42.03 vs 37.16%; ten or more drugs: 7.02 vs 5.44%; p < 0.0001) and multimorbidity (three or more diseases: 6.42 vs 2.82%; p < 0.0001). Fall-risk-increasing drug use was higher in cases (37.70 vs 26.49%, p < 0.0001), with a 51% increased risk of fall-related hospitalisation (aOR 1.51, 95% confidence interval [CI] 1.44–1.59). Opioids (aOR 1.40, 95% CI 1.31–1.50) and antidepressants (aOR 1.45, 95% CI 1.36–1.54) were associated with the highest risk. Prolonged fall-risk-increasing drug exposure (>9 months; aOR 1.69, 95% CI 1.57–1.83) and current exposure (within 30 days before hospitalisation; aOR 1.78, 95% CI 1.68–1.89) showed higher odds. Conclusions Fall-risk-increasing drug use was associated with a higher risk of fall-related hospitalisations in older adults. These findings support the importance of optimising prescribing and managing polypharmacy as potential strategies to improve patient safety and reduce the healthcare burden.

Aims: Current proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (the monoclonal antibodies evolocumab and alirocumab, and the siRNA inclisiran) require parenteral administration, which may limit long-term adherence. Orally active PCSK9 inhibitors could improve convenience and treatment accessibility. This meta-analysis evaluates LDL-C reduction and other lipid changes reported in randomized controlled trials (RCTs) of oral PCSK9 inhibitors. Methods and results: RCTs comparing oral PCSK9 inhibitors with placebo and reporting LDL-C changes were identified through PubMed, EMBASE, Web of Science, CENTRAL, and ClinicalTrials.gov up to November 2025. Pooled mean percentage changes in lipid parameters were calculated using random- and fixed-effects models. Serious adverse events (SAEs) were analysed using risk ratios (RRs) with 95% confidence intervals (CIs). Five RCTs on three different molecules (enlicitide, NNC0385-0434, and laroprovstat), including a total of 3295 participants with hypercholesterolaemia receiving stable doses of background lipid-lowering therapy prior to study initiation, met the inclusion criteria. Treatment durations ranged from 8 to 24 weeks. Pooled analysis showed a significant LDL-C reduction of –59.31% (95% CI –62.33 to –56.28) compared with placebo. Additional lipid parameters also improved: apolipoprotein B (−49.53%, 95% CI –54.19 to –44.79), non-HDL cholesterol (−55.41%, 95% CI −57.35 to −53.48), and lipoprotein(a) (−22.74%, 95% CI −26.67 to −18.81). The pooled RR for SAEs was 0.84 (95% CI 0.68–1.03; P = 0.41), indicating no increased risk vs. placebo. Conclusion: Oral PCSK9 inhibitors demonstrate potent LDL-C–lowering efficacy, comparable to parenteral PCSK9i, with favourable effects on other atherogenic lipids and a reassuring short-term safety profile.

Background: Elevated low-density lipoprotein cholesterol (LDL-C) is a causal driver of atherosclerotic cardiovascular disease (ASCVD). Although current European guidelines recommend intensive LDL-C lowering strategies in high, very high, and extreme cardiovascular risk patients, real-world data consistently show suboptimal goal achievement. Aim and Methods: The TRAP-HC study aims to evaluate real-world treatment patterns, LDL-C goal attainment, and adherence to lipid-lowering therapies (LLTs) in patients with hypercholesterolemia, including familial hypercholesterolemia (FH), at high, very high, and extreme cardiovascular risk over a 1-year follow-up. TRAP-HC is a multicenter, prospective, longitudinal, observational study conducted across up to 15 lipid clinics within the Italian LIPIGEN network. Approximately 2,500 adult patients will be enrolled and followed for one year. The primary endpoint will be the change in LDL-C levels and achievement of guideline-recommended LDL-C goals. Secondary endpoints will include adherence, treatment intensification patterns, and patient-reported attitudes toward therapy. Conclusion: TRAP-HC will provide contemporary real-world evidence on lipid management in high-risk populations and identify gaps between guideline recommendations and clinical practice.

Aims: Inhibition of angiopoietin-like protein 3 (ANGPTL3) has been proposed as a promising approach to reduce residual cardiovascular risk. We conducted a meta-analysis of randomized controlled trials (RCTs) to provide a comprehensive evaluation of the metabolic effects of ANGPTL3 inhibitors. Methods: Databases (PubMed, EMBASE, Web of Science, CENTRAL, ClinicalTrials.gov) were searched from inception to July 2025. Eligible studies were RCTs comparing ANGPTL3 inhibitors against placebo. Outcomes included triglycerides (TG), LDL-C, apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), very-low-density lipoprotein cholesterol (VLDL-C), apolipoprotein A1 (ApoA1), apolipoprotein C3 (ApoC3), lipoprotein(a) (Lp(a)), remnant cholesterol (RC), ANGPTL3 and C-reactive protein (CRP). Pooled estimates of percentage change from baseline were obtained using fixed- and random-effects models. Subgroup analysis was performed based on the mechanism of action: monoclonal antibodies (mAbs, evinacumab), antisense oligonucleotides (ASOs, vupanorsen), and small interfering RNAs (siRNA, zodasiran and solbinsiran). Results: Nine RCTs (1254 participants) were included. ANGPTL3 inhibition significantly reduced TG (−47.1%), LDL-C (−21.6%), ApoB (−19.9%), non-HDL-C (−31.5%), TC (−32.8%), VLDL-C (−40.6%), and RC (−72.7%). Modest but consistent reductions were also observed in Lp(a) (−11.5%), ApoA1 (−18.3%), and ApoE (−16.4%). ANGPTL3 inhibitors markedly reduced circulating ANGPTL3 protein (−70.7%), with no significant effect on high-sensitivity CRP. Subgroup analyses demonstrated greater reductions in LDL-C, ApoB, non-HDL-C, and TC with evinacumab compared to the other groups, whereas small interfering RNAs produced more pronounced VLDL-C lowering compared with vupanorsen. Conclusion: ANGPTL3 inhibition offers broad lipid-lowering benefits, with particularly marked reductions in TG-rich lipoproteins.

Atherogenic dyslipidemia is a condition characterized by high lipid levels that promote the development of atherosclerosis. While the clinical manifestations of atherosclerosis typically manifest in adulthood, early vascular damage can be identified in children and adolescents. Dyslipidemia is not uncommon in childhood and adolescence, and its development depends on the interaction between genetic and environmental factors. Forms caused by genetic defects tend to manifest earlier and usually require drug treatment. Forms caused by unhealthy lifestyles and eating habits tend to manifest later and often only require dietary and behavioural treatment. The review describes the most common primary forms, diagnostic criteria and treatment options, both pharmacological and non-pharmacological, emphasizing the differences and specificities of dyslipidemia in children compared to adults. The review’s objective is also to provide a clinically focused summary of the current evidence on atherogenic dyslipidemia in children and adolescents.