Background:Statins are a cornerstone of therapy to reduce LDL cholesterol and cardiovascular diseases. However, their use may cause adverse events. This umbrella review aims to comprehensively review the safety profile of statin therapy. Methods:PubMed and Embase were searched to identify systematic reviews, scoping reviews, meta-analyses and network meta-analyses on statin safety. Extracted data included study type, data source, number of included studies, search date range, participant numbers, interventions, safety outcomes, results and funding. Risk of bias was assessed using the AMSTAR 2 instrument. Data underwent descriptive statistical analysis. Results:Seventy-two reviews were included, mostly based on clinical trials (70.8%) and observational studies (59.7%). Only 21 (29.2%) reported results for individual statins, with atorvastatin being the most frequently evaluated individual statin (95.2%). Nearly 86% of the reviews were rated as Critically Low in overall confidence. Statins were associated with an increased risk of new-onset diabetes, particularly rosuvastatin and atorvastatin, whereas pitavastatin may be protective. Liver injury/dysfunction and elevated transaminases were observed, along with a small risk of muscle-related symptoms, specifically at higher statin intensity. Rare serious events, such as necrotising myopathy, were reported. Pregnancy studies indicated an increased risk of spontaneous abortion. Conclusion:Although overall statin safety is favourable, the risks of diabetes, liver dysfunction, enzyme elevations and muscle symptoms require consideration, especially with high-intensity therapy or specific statins. Pitavastatin may be a safer option for patients at metabolic risk. Therapy should be tailored to individual patient factors. Further research is needed to clarify rare or inconsistent outcomes.

Aims Once-weekly basal insulins, icodec and efsitora alfa, were developed to improve treatment adherence and glycemic control and appear to be as effective as once-daily degludec in reducing HbA1c in type 1 diabetes (T1DM). However, higher rates of clinically significant hypoglycemias were associated with both once-weekly insulins. This network meta-analysis compares the efficacy and safety of once-weekly and once-daily basal insulins in T1DM.Methods PubMed and Embase were searched (up to April, 2025) to identify phase 3 clinical trials evaluating basal insulins in T1DM (icodec, efsitora alfa, degludec 100, glargine [100 and 300], detemir, and NPH). Change in HbA1c and weight, risk of hypoglycemias (overall and severe), and serious adverse events (AEs) were assessed at week 26 and 52.Results Nineteen studies were included. At week 52, icodec reduced HbA1c more than degludec 100 (-0.17% [95% CrI: -0.28; -0.06]), glargine 100 (-0.17% [95% CrI: -0.32; -0.02]), detemir (-0.17% [95% CrI: -0.32; -0.02]), and NPH (-0.59% [95% CrI: -0.85; -0.34]), while efsitora alfa reduced HbA1c more than NPH (-0.45% [95% CrI: -0.70; -0.19]). Icodec showed a higher overall hypoglycemia risk at week 52 compared with degludec 100 (OR 1.64; 95% CrI 1.07-2.54) and detemir (OR 2.08; 95% CrI 1.01-4.39), but no increased risk of severe hypoglycemias or serious AEs.Conclusions In T1DM, once-weekly basal insulins appear broadly comparable in reducing HbA1c at week 52. Although icodec showed a higher overall hypoglycemia risk, evidence suggests a comparable risk of severe hypoglycemias between treatments.

Background/Objective: Systematic reviews (SRs) with network meta-analysis (NMA) support evidence-based decision-making by enabling both direct and indirect comparisons across multiple interventions. Given the expanding use of Janus kinase (JAK) inhibitors in rheumatoid arthritis (RA), the methodological rigor of SRs with NMA is essential for trustworthy conclusions. This study is aimed at evaluating the methodological quality of SRs with NMA assessing the efficacy and/or safety of JAK inhibitors in RA. Methods: PubMed and Embase were searched for full-text SRs with NMAs evaluating JAK inhibitors as a therapeutic class in RA. Eligible publications were English-language articles reporting efficacy and/or safety outcomes. Narrative reviews, letters, duplicates, reviews focused on a single JAK inhibitor, and reviews without quantitative synthesis were excluded. Three independent reviewers assessed methodological quality using AMSTAR 2. Descriptive statistics were used to summarize findings. Results: Of the 222 records identified, 18 SRs with NMA met the inclusion criteria: 5 focused on efficacy, 5 on safety, and 8 assessed both. The most consistently fulfilled AMSTAR 2 items were a clearly defined PICO question (100%), duplicate study selection (100%), and reporting of conflicts of interest (100%). Common shortcomings included lack of protocol registration (44%), incomplete reporting of the search strategy (39%), and absence of publication bias assessment (50%). Risk-of-bias assessment varied by review focus: all safety reviews complied (100%), compared with 20% of efficacy reviews and 37% of mixed reviews. Conclusions: Most SRs with NMA of JAK inhibitors in RA present relevant methodological limitations, particularly in protocol registration, search reporting, and risk-of-bias assessment. Methodological standards were generally higher in safety-focused reviews, underscoring the need for more consistent and rigorous conduct and reporting, especially in efficacy and mixed reviews, to strengthen confidence in NMA-derived conclusions.

IntroductionReimbursement appraisals of medicines should emphasize outcomes clinically relevant to patients and clinicians. This study aims to characterize the outcomes selected in oncology reimbursement appraisal reports in Portugal.MethodsA cross-sectional analysis of public INFARMED pharmacotherapeutic appraisal reports for oncology medicines published in 2023-2024 was conducted. For each included report, we extracted efficacy and safety outcomes, their clinical relevance rating (critical/important), whether data were presented for analysis, and which outcomes were prioritized in the final decision rationale. Descriptive statistics were employed.ResultsFifty-four oncology reimbursement appraisals met the inclusion criteria. Overall survival was rated critical in 52/54 reports (96.3%) and prioritized in 29 (53.7%). Progression-free survival was rarely rated critical (n = 2, 3.7%) and was more often deemed important (n = 49, 90.7%), being prioritized in 15 (27.8%) reports. Quality of life was rated as critical in 52 (96.3%) reports but prioritized in only one (1.8%) decision. For safety, grade 3 to 4 AEs and mortality were graded as critical in 51 (94.4%) reports each, followed by discontinuation due to AEs (n = 50, 92.6%), although none of the appraisals prioritized safety outcomes in the final reimbursement decision.ConclusionsOverall survival predominates as the most influential outcome in Portuguese oncology drug reimbursement decisions. Progression-free survival is frequently used as a practical surrogate. Although quality of life and safety outcomes are commonly prioritized during scope-setting, they are not consistently reflected in decision rationales, underscoring the need to strengthen outcome reporting and evidence generation to better inform patient-centered reimbursement decisions.

Observational studies have evaluated the risk of acute pancreatitis associated with drugs acting on the Renin-Angiotensin-Aldosterone System (RAAS) but reported conflicting results. This meta-analysis aims to investigate the risk of acute pancreatitis associated with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). PubMed and Embase were searched for observational studies. A random-effects model was used to pool odds ratios (ORs). A sensitivity analysis explored the robustness of the initial findings according to study design, treatment duration, dose, age, active substance, and Risk of Bias scores. Main results were re-analyzed using the Knapp-Hartung method and Bayesian random-effects. Eleven observational studies were included. ACE inhibitors increased the risk of acute pancreatitis (OR 1.33; 95% CI 1.12-1.58; I² = 93%), whereas ARBs did not (OR 0.82; 95% CI 0.80-0.83; I² = 0%). Few studies presented disaggregated results for the sensitivity analyses, but most estimates were consistent with the initial findings. The Knapp-Hartung method and Bayesian random-effects meta-analyses yielded similar results. The incidence rate of acute pancreatitis among patients treated with ACE inhibitors was 0.98 cases per 1,000 person-years, while for ARBs it was 0.71 cases per 1,000 person-years. These results suggest that ACE inhibitors increase the risk of acute pancreatitis, in contrast to the effect of ARBs. Healthcare professionals should be aware of the potential risk of pancreatitis when managing patients receiving these medications.

INTRODUCTION AND OBJECTIVES:This study aimed to evaluate the impact of the COVID-19 pandemic on healthcare provided to patients with arterial hypertension in Portugal. METHODS:The pre-pandemic and pandemic periods were compared using publicly available data on performance and health outcome indicators from the Portuguese National Health Service (NHS). Pre-pandemic data were modeled to project hypothetical scenarios without a pandemic using an exponential smoothing algorithm, and then compared with data collected during the COVID-19 pandemic. A cohort model was developed to estimate the number of all-cause deaths and years of life lost (YLL) due to the reduction in blood pressure (BP) monitoring and in BP records <150/90 mmHg during the first two years of the pandemic. Microsoft Excel® was used for statistical analyses. RESULTS:There was a 26.4% relative reduction in the number of patients with hypertension under 65 years of age with at least one BP measurement, and a 21.8% relative reduction in the proportion of patients with BP <150/90 mmHg during the first two years of the pandemic. The model projections were 176 additional deaths and 3287 YLL among the Portuguese population of patients with hypertension. CONCLUSIONS:The disruption in BP testing in Portugal during the pandemic increased hypertension-associated morbidity and mortality, with significant YLL. The long-term implications of impaired monitoring of patients with hypertension should be assessed, and proactive strategies implemented to mitigate the increase in hypertension morbidity and mortality associated with the COVID-19 pandemic.

Background Cervical cancer is a major concern to women’s health, being the fourth most common cancer worldwide. A great percentage of these cancer is consequence of an HPV infection, namely from specific genotypes such as 16/18. Portuguese screening program subjects women to a reflex cytology triage every 5 years. Aptima® HPV is a screening test which presents better specificity than other tests which are used in Portugal (Hybrid Capture® 2 and Cobas® 4800) and still have a comparable sensitivity. The present study aims to estimate the number of diagnostic tests and costs that are avoided using Aptima® HPV compared to the use of two other tests, Hybrid Capture® 2 and Cobas® 4800, within the cervical cancer screening programme in Portugal. Methods A model, consisting of a decision-tree, was developed to represent the full Portuguese screening program for cervical cancer. This model is used to compare the costs resulting from using Aptima® HPV test versus the other tests used in Portugal, during 2 years. Other outcomes such as the number of additional tests and exams were also computed. This comparison considers the performance of each test (sensitivity and specificity) and assumes an equal price for every test compared. Results Cost savings resulting from the use of Aptima® HPV are estimated at approximately €382 million versus Hybrid Capture® 2 and €2.8 million versus Cobas® 4800. Moreover, Aptima® HPV prevents 265,443 and 269,856 additional tests and exams when compared with Hybrid Capture® 2 and Cobas® 4800. Conclusions The use of Aptima® HPV resulted in lower costs as well as less additional test and exams. These values result from the greater specificity of Aptima® HPV, which signals less false positive cases and consequently avoids carrying out additional tests.

INTRODUCTION:Potential associations between Chronic Obstructive Pulmonary Disease (COPD) and osteoporosis have been studied, but areas of uncertainty remain. OBJECTIVE:This scoping review aimed to identify the published evidence on the epidemiological relationships between COPD and osteoporosis. METHODS:Experimental and observational evidence evaluating relationships between COPD and osteoporosis on epidemiology, clinical manifestations, risk factors (RFs), therapeutic management and quality of life (QoL) was searched on PubMed and Embase (until May 2023). The studies were categorized according to their objectives and characteristics. Data were analyzed using descriptive statistics. RESULTS:Ninety-nine studies were selected, namely 33 (33%) reporting epidemiologic measures, 11 (11%) clinical manifestations, 74 (75%) RFs (45 ones, of which body mass index [BMI; n = 22 studies], corticosteroids' use [n = 20], and COPD severity [n = 15] were the most studied), 7 (7%) therapeutic management, and 3 (3%) QoL. Twenty-seven (27.6%) studies evaluated ≥2 domains. Most studies followed a cross-sectional design (n = 37; 37.4%). Eighty-nine studies (90%) assessed patients with COPD at baseline and studied its relationship with osteoporosis. CONCLUSION:There are well-established features linking COPD and osteoporosis, including shared RFs, such as smoking, elderly, physical inactivity, or low BMI. Others deserve clarification, including the impact of COPD severity, or the use of inhaled corticosteroids on the incidence of osteoporosis and fractures, as well as the value of performing routine imaging tests, or prescribing anti-resorptive medications in COPD to prevent osteoporotic-related outcomes. QoL studies are also lacking. Investigating such issues is needed to propose clinical guidelines for managing osteoporosis in patients with COPD.