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Proton pump inhibitors (PPIs) are widely prescribed medications primarily used to treat gastroesophageal reflux disease, peptic ulcer disease, and upper gastrointestinal bleeding. Despite clear therapeutic benefits in appropriate contexts, widespread overprescribing and extended use without clear indications have prompted significant concerns about associated risks. Accumulating evidence, predominantly from observational studies, suggests that long-term PPI use may lead to complications such as vitamin and mineral deficiencies, increased risks of infections, dysbiosis, renal dysfunction, bone fractures, cardiovascular disease, and certain malignancies. This narrative review not only synthesizes the current evidence surrounding PPI-related harms and existing deprescribing guidelines but also offers a novel perspective on how stewardship principles can be applied to promote responsible PPI prescribing. In particular, we propose a stewardship-oriented deprescribing framework rooted in implementation science, focusing on provider behavior, patient engagement, and health system-level integration. Recognizing these potential harms, evidence-based deprescribing strategies such as tapering, intermittent dosing, and transitions to alternative therapies are critical to mitigate unnecessary patient exposure. Effective implementation of deprescribing requires addressing patient, provider, and institutional barriers through educational initiatives, policy support, and structured monitoring. By promoting judicious PPI prescribing and proactive stewardship practices, clinicians can significantly reduce medication-related harm and improve patient safety. Full article

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly encompassed under nonalcoholic fatty liver disease (NAFLD), is a growing global health burden associated with progression to cirrhosis and hepatocellular carcinoma. Resmetirom, a thyroid hormone receptor-β (THR-β) agonist, and semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), have emerged as promising agents targeting distinct metabolic and inflammatory pathways. This systematic review compares the safety and efficacy of resmetirom and semaglutide in MASLD. Methods: We conducted a comprehensive search of PubMed, Embase, and Google Scholar for randomized controlled trials and clinical studies published between January 2014 and April 2025, following PRISMA guidelines. Studies assessing the efficacy and safety of resmetirom and/or semaglutide in MASLD or NASH were included. Data extraction was performed by two independent reviewers, and a narrative synthesis was undertaken due to the heterogeneity in study design and outcome measures. Results: Fourteen studies encompassing over 4500 patients were analyzed. Resmetirom demonstrated consistent reductions in hepatic fat (≥30% in >50% of patients) and improvements in fibrosis (≥1 stage in up to 26.4% of patients), as evidenced in the MAESTRO-NASH trial. Semaglutide achieved higher rates of NASH resolution (up to 62.9%) without worsening fibrosis, especially among patients with type 2 diabetes or obesity, although fibrosis improvement was less consistently observed. Resmetirom was well tolerated with low discontinuation rates, while semaglutide was associated with more frequent, yet manageable, gastrointestinal adverse events. Conclusions: Both resmetirom and semaglutide show therapeutic potential for MASLD. Resmetirom offers more consistent antifibrotic effects, while semaglutide excels in NASH resolution and metabolic improvement. The absence of direct comparative trials underscores the need for future head-to-head studies to guide tailored treatment strategies in MASLD management. Full article

Objectives: This study aimed to assess the concordance between depression and anxiety case definitions derived from algorithms based on medico-administrative data and structured interviews aligned with the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria in older adults. Methods: We analyzed data from 1405 primary care older adults (≥65 years) from the Étude sur la Santé des Aînés (ESA)-Services cohort (2011–2013) in Quebec, Canada, who had available survey and medico-administrative data. Cases of depression and anxiety were identified using algorithms incorporating combinations of hospitalization records, physician-visit claims, and medication claims for antidepressants or anxiolytics. The agreement was assessed with the kappa statistics (κ), and the algorithms’ sensitivity, specificity, and positive and negative predictive values were calculated using the case definitions derived from the DSM-IV-aligned ESA-Services interviews as the gold standard. Results: Agreements between the algorithms and the interviews were fair (κ: 0.06–0.22) for depression gooand slight (κ: 0.02–0.09) for anxiety. The algorithms had low sensitivity (2–39.7% for depression and 1.4–39.9% for anxiety) but high specificity (84.5–99.6% for depression and 73–99.2% for anxiety), depending on the algorithm. Conclusions: The agreement between algorithms based on administrative data and DSM-IV-aligned interviews for anxiety or depressive disorders was low. The two methods identified older adults with different characteristics. Despite these discrepancies, algorithms with high specificity provide valuable insights into healthcare utilization patterns associated with these disorders. Full article

Background: Opioid Use Disorder (OUD) has claimed the lives of many Americans, with rates of overdose steadily rising over the past decade. Despite having highly effective medications to treat this condition, many providers still hesitate to prescribe them. Psychiatric inpatient facilities have a unique opportunity to engage patients with co-occurring disorders in the treatment of OUD; however, significant barriers exist. This study describes a novel OUD–buprenorphine (BUP) consultation service that provides such care to hospitalized psychiatric patients. Methods: This IRB-approved retrospective study reviewed the medical records of 123 hospitalized psychiatric patients who received consultations from the BUP consultation service. Descriptive and comparative statistics were performed. Results: The sample was predominantly male, with significant unemployment and housing instability. Patients were hospitalized for depressive, bipolar, and schizophrenia spectrum disorders. Over 90% of patients were discharged on buprenorphine, with over 50% being connected to specialized substance use services. No increase in the length of stay was found, and no difference in outcomes was observed based on diagnosis or BUP discharge status. Discussion/Conclusions: This novel service was effective in providing OUD treatment to patients with complex co-occurring psychiatric disorders without significantly increasing their length of stay. Despite acute exacerbations in psychiatric illness, patients were able to engage in discussions regarding BUP. While the study was limited in scope, it underscores the feasibility of integrating OUD treatment in the acute psychiatric inpatient setting. Full article

Background: The validated Screening Tool of Older People’s Prescriptions (STOPP) identifies potentially inappropriate prescribing (PIP)—treatments where potential risk outweighs potential benefit. STOPP is particularly important for people aging with HIV and comorbidities, since PIP may exacerbate symptoms and decrease adherence. Methods: We analyzed data from the DC Cohort, a longitudinal cohort of people with HIV (PWH). We applied STOPP criteria to identify PIP among DC Cohort participants aged ≥ 50 years who completed a Patient Reported Outcomes (PROs) survey. All medications prescribed in the 2 years prior to PROs survey completion were considered. Negative binomial models were used to evaluate factors associated with PIP and structural equation modeling was used to evaluate whether symptom burden mediates the relationship between PIP and quality of life. Results: Of 1048 eligible DC Cohort participants, 486 (46%) had at least one PIP. The most common systems implicated were musculoskeletal (23%), analgesic drugs (16%), and the central nervous system (13%). Age, race/ethnicity, HIV transmission factor, social determinants of health, and type of HIV care site were significantly associated with number of PIP in the crude models. In the multivariable model with just demographic variables, the association between age (aIRR: 1.03 (95% CI: 1.02, 1.04)), intravenous drug use (aIRR: 1.68 (95% CI: 1.20, 2.35)), White, non-Hispanic race (aIRR: 0.67 (95% CI: 0.50, 0.92)), site type (aIRR: 0.75 (95% CI: 0.62, 0.92)), and the expected number of PIPs remained significant. In the fully adjusted multivariable model with demographics and SDOH, the association between age, intravenous drug use, White, non-Hispanic race, and expected number of PIPs remained significant. Statistical evidence that symptom burden mediates the relationship between PIP and each of the QOL dimensions was present. Conclusions: Future interventions should work to decrease PIP among these high-risk groups, especially for PIP associated with increased symptom burden. Full article

Background: Incretin mimetics, including glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonist) and dipeptidyl peptidase-4 (DPP-4) inhibitors, have been increasingly utilized for glycemic control in patients with type 2 diabetes (T2D). Studies have demonstrated additional improvements in weight loss, cardiovascular health, and renal outcomes. Animal studies have shown an association between GLP-1 receptor agonists and C-cell proliferation and elevated calcitonin, resulting in an FDA black box. Insulin resistance in patients with T2D, along with the use of other glucose control medications, confounds the relationship between incretin mimetics and thyroid cancers. The true effect of incretin mimetics on thyroid cancer remains uncertain and speculative due to this confounding. Methods: This retrospective cohort study compared patients with T2D, who were new users of incretin mimetics, to new users of metformin. Study patients used no other anti-diabetes medications beyond the study medications. The risks of incident thyroid cancer and subsequent thyroidectomy were quantified using Cox proportional hazards regression models fitted with adjustments for demographic and medical covariates over a three-year study period. Medullary thyroid cancer (MTC) and multiple endocrine neoplasia type II (MEN2) cases were quantified. Results: Of the 91,394 patients, 28 incretin mimetic users had a diagnosis of thyroid cancer, and nine of these patients underwent a subsequent thyroidectomy procedure. No incretin mimetic user was diagnosed with MTC or MEN2. There was no statistically significant effect on the overall incretin mimetic category (1.28 aHR, 0.83–1.96), the incretin mimetic subcategories of GLP-1 receptor agonists (1.35 aHR, 0.80–2.29), or DPP-4 inhibitor (0.62 aHR, 0.33–1.17) users in developing thyroid cancer within three years of drug initiation. Similarly, no association was found between the overall incretin mimetic category (1.02 aHR, 0.49–2.10), the subcategories of GLP-1 receptor agonists (1.26 aHR, 0.54–2.96), or DPP-4 inhibitors (0.32 aHR, 0.08–1.37) and a subsequent thyroidectomy. Conclusions: In this real-world cohort study, exposure to incretin mimetics overall or through the incretin mimetic subcategories of GLP-1 receptor agonists and DPP-4 inhibitors was not associated with risks of thyroid cancer or thyroidectomy compared to metformin users. Full article

Objective: The aim of this study was to investigate a possible relationship between the time to onset (TTO) of adverse events following immunization (AEFIs) and recall bias and to compare it between AEFIs of COVID-19 vaccines reported though the spontaneous reporting system (SRS) and those from a cohort event monitoring (CEM) study. Methods: A retrospective study comparing TTO patterns of AEFIs of four COVID-19 vaccines from the SRS and those from a CEM study was performed. Reports concerning AEFIs related to COVID-19 vaccination were used for the study. TTO patterns were stratified for vaccination dose number, perceived burden of the AEFI, and for being pre-defined. Additionally, since menstrual disorders received much media attention, their effect on the TTO pattern was investigated for SRS reports only. Results: A total of 160,613 reports from the SRS and 19,979 from the CEM, containing 755,647 and 103,703 AEFIs, respectively, were included. For AEFIs with a short TTO, no differences in TTO patterns were observed. However, the median TTO for AEFIs from the SRS was lower with increasing TTO duration. There were differences in both median TTO and time to reporting for AEFIs reported before and during episodes of media attention, but no correlation between the two could be found. Conclusions: Based on the performed TTO analyses, recall bias does not seem to be more evident in SRS compared to CEM studies for AEFIs with a short TTO. For AEFIs with a longer TTO, this may be more pronounced. Full article

Background/Objectives: Controversy exists over the use of passive reporting systems, especially the Vaccine Adverse Event Reporting System, in risk assessment. One limitation of these systems is that adverse event (AE) reporting rates cannot be calculated without knowing the number of shots administered or prescriptions in the case of pharmaceuticals. Adverse event reporting rates can be a factor in a risk assessment, though they should not be solely relied on; they can be used to compare the relative safety profiles of different vaccine products or pharmaceuticals. This study introduces the Denominator-Adjusted Rate Estimates of Substance Adverse Events Frequency Evaluation (DARE-SAFE) method to analyze pharmacovigilance reporting rates for vaccines and common pharmaceuticals. Methods: We calculated reporting rates for the top 250 most prescribed drugs in the US Food and Drug Association (FDA) Adverse Event Reporting System and common vaccines in the Vaccine Adverse Events Reporting System. For vaccines, we used USA Centers for Disease Control (CDC) dose data and OpenVAERS reports. For pharmaceuticals, we utilized prescription data from ClinCalc and FAERS reports for 2022. Results: VAERS reporting rates varied significantly across vaccine types. COVID-19 vaccines showed a 63.0 ± 0.6 times higher rate of VAERS deaths per dose and an 18.95 ± 0.02 times higher rate of total adverse event reports per dose compared to influenza vaccines. The ratio of total VAERS reports to deaths for vaccines was 73 ± 4 to 1 (R² = 0.94). For pharmaceuticals, the ratio of total adverse event reports to deaths was 26 ± 2 (R² = 0.46), with a strong correlation between serious adverse events and deaths (ratio 9.1 ± 0.3, R² = 0.79). Conclusions: DARE-SAFE provides a standardized method for comparing reporting rates across different medical products. The observed differences between vaccines and pharmaceuticals, as well as among different vaccine types, warrant further investigation into reporting practices, actual safety profiles, and potential biases in surveillance systems. Full article

Background/Objectives: Direct oral anticoagulants (DOACs), when compared to the Vitamin K antagonist (VKA) warfarin, exhibit greater safety and effectiveness. However, DOACs may still have potential drug–drug interactions that result in major bleeding events. There is a paucity of studies on medications that have pharmacodynamic interactions with DOACs, such as selective serotonin reuptake inhibitors (SSRIs). This study evaluates the potential major bleeding risk associated with the concomitant use of SSRIs among nonvalvular atrial fibrillation (NVAF) patients who were receiving DOACs. Methods: Adult patients receiving DOACs with consecutive NVAF diagnoses were identified from the Penn State Health Electronic Health Records from 2013 to 2023. These patients were then checked for exposure (i.e., concomitant use of SSRIs). The outcome was time to the first occurrence of a major bleeding event, with a follow-up from the first DOAC prescription until a major bleeding event, death, or end of follow-up. This retrospective cohort study used a Cox cause-specific proportional hazard model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with inverse probability of treatment weighting to adjust for measurable confounding factors (e.g., demographics, comorbidities, comedications). Results: A total of 8657 NVAF patients who were receiving DOACs were identified. The mean age was 70.3 ± 11.95 years, and females comprised 39.8% of the study population. The baseline CHA2DS2-VASc score was 3.77 ± 1.76, and the HAS-BLED score was 2.98 ± 1.27. Among these patients, 2649 (30.6%) were co-prescribed with SSRIs. The unadjusted hazard ratio for SSRIs was 0.87 (95% CI: 0.76–0.99) and the adjusted hazard ratio was 0.68 (95% CI: 0.59–0.78). Conclusions: In patients with NVAF receiving DOACs, concomitant use of SSRIs was not associated with a higher risk of major bleeding. Full article

Background/Objectives: Despite an improved knowledgebase, effective intervention, and guidelines, many patients with depression do not receive adequate treatment and treatment discontinuation and non-response are common. It was intended to explore the challenges clinicians face while managing depression in their clinical practice and their suggestions for solutions. Methods: It was an online survey of 137 psychiatrists in 18 countries including both high and low economies, using a pre-designed questionnaire; with both quantitative and qualitative measures. Results: Antidepressant prescribing appeared close to the evidence-based guidelines. There was frequent use of other medications alongside antidepressants since treatment initiation. There were many challenges in managing depression, such as treatment non-response, resistance, and discontinuation; side effects, mostly sexual problems; inadequate psychological intervention; availability and affordability of treatment modalities; comorbidities, especially substance use and personality disorders; stigma; and lack of education and training. Suggested approaches for solutions included personalized treatment, quicker follow-up, psychoeducation, blending psychological intervention into routine clinical practice, improving continuity of care, and preventing treatment discontinuation. Support from governments for improving access, making interventions affordable, and providing socio-occupational support is essential. Training and development of professionals, public education providing information, and dealing with stigma are still relevant. Conclusions: The results indicated a need for reviewing current practices in managing depression, optimizing it with available resources, and preventing treatment discontinuation, and non-response. Making treatment available and affordable, public education fighting stigma to improve treatment acceptability, and research addressing gaps in interventions, especially for treatment resistance and psychotherapy are other approaches that may improve depression management. Full article

Background/Objectives: This systematic review aimed to identify a comprehensive list of potential opioid-related indicators from the published literature to assess prescribing safety in any setting. Methods: Studies that reported prescribing indicators from 1990 to 2019 were retrieved from a previously published systematic review. A subsequent search was conducted from seven electronic databases to identify additional studies from 2019 to June 2024. Potential opioid safety prescribing indicators were extracted from studies that reported prescribing indicators of non-injectable opioids prescribed to adults with concerns about the potential risk of harm. The retrieved indicators were split by each opioid, and duplicates were removed. The identified indicators were categorized by the type of problem, medication, patient condition/disease, and the risk of the indicators. Results: A total of 99 unique opioid-specific prescribing indicators were identified from 53 included articles. Overall, 42 (42%) opioid prescribing indicators focused on a specific class of opioids. Pethidine, tramadol, and fentanyl were the most frequently reported drugs (n = 22, 22%). The indicators account for six types of problems: medication inappropriate for the population (n = 20), omission (n = 8), inappropriate duration (n = 10), inadequate monitoring (n = 2), drug–disease interaction (n = 26), and drug–drug interaction (n = 33). Of all the indicators, older age (over 65) is the most common risk factor (n = 38, 39%). Central nervous system-related adverse effects are the risk of concern for the 28 (29%) indicators associated with drug–drug interactions. Furthermore, five of the six ’omission’ indicators are related to ’without using laxatives’. Conclusions: This review identified a comprehensive set of indicators for flagging patients at high risk of opioid-related harm, thereby supporting informed decision-making in optimizing opioid utilization. However, further research is essential to validate these indicators and evaluate their feasibility across diverse healthcare settings. Full article

Background/Objectivses: Antibiotic consumption patterns in remote urban areas of the Amazon region are poorly understood. This study aimed to analyze antibiotic use in the adult population of Coari, a municipality in Amazonas, Brazil. Methods: A cross-sectional study was conducted between October and November 2021 in the urban area of Coari. 394 adults were interviewed using a structured questionnaire. Data on antibiotic use, sociodemographic factors, health service access, and self-reported illnesses were collected. Poisson regression was used to estimate prevalence ratios and identify factors associated with antibiotic use. Results: The prevalence of antibiotic use was 14.7% (n = 58). The most frequently used antibiotics were azithromycin (26.9%), cefalexin (20.9%), amoxicillin (19.4%), and ciprofloxacin (13.9%). Up to 34.5% of antibiotic use was conducted without a prescription, especially among adults aged 18 to 39 (59.1%). The main health problems that led to self-medication were COVID-19 (28.6%), urinary infection (14.3%), sore throat (37.5%), and intestinal infection (60.0%). Factors associated with antibiotic use included age 18 to 39 (adjusted PR = 3.73; CI = 1.37–10.09), having a family member hospitalized (adjusted PR = 2.61; CI = 1.39–4.89), having contracted COVID-19 (adjusted PR = 2.41; CI = 1.40–4.15), and frequency of visits by the community health agent to the home (adjusted PR = 0.35 CI = 0.15–0.81). Conclusions: The high use of broad-spectrum antibiotics (Watch), particularly azithromycin, for potentially inappropriate indications highlights the need to improve the management of antibiotic use in remote regions of Brazil. Community health agents, as key professionals between health services and the community, can play a key role in promoting the rational use of antibiotics and combating antimicrobial resistance in the Brazilian Amazon context. Full article

Background/Objectives: Functional dyspepsia is associated with abdominal pain and nausea, which leads to reduced quality of life, loss of productivity, and economic loss for patients. Itopride hydrochloride (itopride) stimulates the gastrointestinal smooth muscles, thereby promoting gastric emptying. It has been shown to significantly improve symptoms in patients with functional dyspepsia without severe side effects. Itopride has been available in Vietnam for many years; however, the cost-effectiveness of the drug has not been established. The aim of this study is to estimate the cost-effectiveness of itopride for the treatment of functional dyspepsia in Vietnam. Methods: A 3-stage Markov model with the following health states—controlled functional dyspepsia, uncontrolled functional dyspepsia, and dead—was developed. Functional dyspepsia was used to assess itopride over 10 years using 8-week cycles. A broader Vietnamese societal perspective was assumed for the analysis. Input was retrieved from the literature and through local clinical input from physicians in Vietnam. Output was reported as an incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALY). A GDP/capita threshold (very cost-effective: 1 × GDP = Vietnamese Dong (VND) 64.1 M, cost-effective: 3 × GDP = VND 192.2 M) was used as recommended by the WHO in Vietnam. One-way and probabilistic sensitivity analyses were performed. Results: Itopride use resulted in an additional 0.28 QALYs at an extra cost of VND 11.2 M. This resulted in an ICER of VND 39.7 M per QALY, which is lower than the threshold of VND 192.2 M. One-way sensitivity analyses showed that the ICER was sensitive to varying the efficacy VND 31.8 M to VND 88.3 M), cost of itopride (ICER: VND 43.1 M to VND 56.5 M), and the health utility values (ICER: VND 45.2 M to VND 55.3 M). More than 80% of the simulations in the probabilistic sensitivity analysis were cost-effective at the 1 × GDP (VND 64.1 M) threshold, and 91.3% were cost-effective at the 3 × GDP (VND 192.2 M) threshold. Conclusion: This study shows that itopride hydrochloride is a very cost-effective treatment for functional dyspepsia in Vietnam, with the ICER (VND 39.7 M/QALY) being even lower than the 1 × GDP (VND 64.1 M) threshold. Full article

Background: Immuno-oncology has transformed cancer treatment, with immune checkpoint inhibitors (ICIs) like pembrolizumab playing a key role. While highly effective, these therapies can also cause immune-related adverse events. This study examines the incidence and characteristics of hepatobiliary adverse events (AEs) linked to pembrolizumab, using data from the FDA Adverse Event Reporting System (FAERS). Objective: To investigate the rates of hepatobiliary AEs linked to pembrolizumab, providing insights into the risks of liver and biliary system damage in patients prescribed pembrolizumab. Methods: This study utilized the FAERS database via OpenVigil 2.1. Adverse events (AEs) related to pembrolizumab were identified and compared to those associated with other drugs. Reporting odds ratios (RORs) were calculated to assess the likelihood of hepatobiliary AEs in pembrolizumab-treated patients. Results: In total, 594 hepatic AEs and 181 biliary AEs were identified. Significant hepatic AEs included elevated ALT (ROR 3.00, 95% CI: 2.685–3.351), hepatotoxicity (ROR 6.436, 95% CI: 5.72–7.242), and hepatic cytolysis (ROR 15.721, 95% CI: 13.854–17.84). Immune-mediated hepatitis exhibited the highest ROR of 346.716 (95% CI: 303.568–395.997). For biliary AEs, cholangitis (ROR 19.597, 95% CI: 16.852–22.791) and sclerosing cholangitis (ROR 24.735, 95% CI: 19.888–30.763) were the most prominent. Conclusions: Pembrolizumab is associated with a significant risk of hepatobiliary adverse events, particularly immune-mediated hepatitis and cholangitis. The elevated RORs for these conditions highlight the importance of close monitoring and managing liver and biliary functions in patients undergoing pembrolizumab checkpoint blockade. These findings emphasize the need for personalized treatment strategies to mitigate risks and optimize outcomes in cancer immunotherapy, especially for those with preexisting hepatobiliary conditions. Full article

Doxycycline is a semi-synthetic antibiotic in the tetracycline family. The three common subtypes of tetracyclines include naturally occurring, semi-synthetic, and new agents. Each subtype shares specific commonalities but is substantially different in various clinical applications. The mechanism of antimicrobial activity is the same across subtypes. The structural changes to the core naphthacene ring do not alter the mechanism of action but are thought to alter the rates of adverse effects and mechanisms of resistance. Tetracyclines as a class are known to cause fixed drug eruptions, but the majority of these adverse effects were associated with naturally occurring tetracyclines. Semi-synthetic tetracyclines have limited reports of fixed drug eruptions. Here, we present a case of fixed drug eruption in a patient who previously had multiple treatment courses with doxycycline. The case involves the use of doxycycline not for the treatment of an infection but as postexposure prophylactic (PEP) antibiotic therapy to prevent the acquisition of a sexually transmitted infection. Doxycycline PEP has been shown to reduce the rate of bacterial sexually transmitted infection in men who have sex with men (MSM). Doxycycline PEP is a single dose taken orally within 24–72 h of unprotected sexual intercourse. The dosing structure allows for ease of adherence but also repeatedly exposes individuals to doxycycline, putting them at risk for adverse events such as fixed drug eruptions, as illustrated by this case report. Full article

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2Is) have demonstrated effects beyond glucose-lowering, leading to their approval for treating chronic heart failure (HF) in Japan. This study examines prescription trends for SGLT2Is in patients with diabetes versus those without diabetes, focusing on their backgrounds and HF treatment status of patients without diabetes who received SGLT2I after an HF diagnosis. Methods: Using data from DeSC Healthcare Inc., we analyzed patients aged 65 and above who received their first SGLT2I prescription between October 2014 and February 2023. Patients were classified into SGLT2I-treated diabetic and non-diabetic groups. We analyzed the annual prescription trends and compared the characteristics of both groups who started SGLT2I between 2022 and 2023. Additionally, we assessed the timing of SGLT2I initiation and the use of concomitant HF treatment in patients without diabetes after HF diagnosis. Results: The proportion of patients without diabetes receiving their first SGLT2I prescription has increased since 2021. Patients without diabetes receiving SGLT2Is were older, likely owing to aging-related diseases. In patients without a confirmed diabetes diagnosis, SGLT2I was most frequently initiated at the time of HF diagnosis. Mineralocorticoid receptor antagonists (MRAs) are the most common concomitant HF medications. The increase in SGLT2I prescriptions for patients without diabetes receiving SGLT2I since 2021, particularly in older individuals, suggests that SGLT2I is being initiated either at the time of HF diagnosis or in a stepwise manner. Conclusion: In Japan, MRA is commonly used as a concomitant medication in patients without diabetes receiving SGLT2I. Full article

Background/Objectives: Several drugs used to treat prostate cancer have been reported to cause cardiovascular adverse events, and this study sought to identify the real-world risk. Methods: This study utilized real-world data from the FAERS to analyze the association between prostate cancer treatment and cardiovascular adverse events. It evaluated men treated with LHRH agonists and antagonists, antiandrogens, androgen synthesis inhibitors, and PARP inhibitors from 2003 to 2023. This study included patients treated with leuprolide, goserelin, triptorelin, degarelix, relugolix, bicalutamide, flutamide, apalutamide, nilutamide, abiraterone, enzalutamide, olaparib, rucaparib, talazoparib, and niraparib. The main outcome measure was the reported odds ratio (ROR) of adverse cardiovascular event associated with these treatments. Results: Among the 4,049,329 unique adverse event reports, 4391 cardiovascular events were identified. Leuprolide (ROR 0.481, 95% CI: 0.423–0.547), triptorelin (ROR 0.527, 95% CI: 0.305–0.909), enzalutamide (ROR 0.393, 95% CI: 0.341–0.452), and olaparib (ROR 0.145, 95% CI: 0.054–0.386) reduced the risk of myocardial infarction. Goserelin increased the risk of myocardial infarction (ROR 2.235, 95% CI: 1.367–3.654). Degarelix and relugolix both increased the risk of heart failure (ROR 3.136, 95% CI: 2.186–4.497), and enzalutamide was associated with an increased risk of heart failure (ROR 1.305, 95% CI: 1.135–1.501). Bicalutamide increased the risk of unstable angina (ROR 3.019, 95% CI: 1.621–5.622) and heart failure (ROR 3.730, 95% CI: 3.085–4.510). Niraparib increased the risk of hypertension (ROR 4.154, 95% CI: 1.709–10.092). Conclusions: These findings underscore the need for clinicians to monitor cardiac complications in patients undergoing these therapies. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a potent therapeutic option for the management of obesity, demonstrating exceptional efficacy in several large-scale clinical trials. Despite their promising therapeutic outcomes, the rising popularity of these agents raises significant concerns, particularly regarding their off-label use by individuals seeking weight loss for aesthetic reasons rather than addressing underlying metabolic health conditions. This article critically evaluates the efficacy and safety of GLP-1 RAs in obesity management. Additionally, it explores the economic implications and ethical challenges associated with the increasing demand for GLP-1 RAs. By addressing these dimensions, this article aims to facilitate informed and responsible decision-making in clinical practice, highlighting the need for individualized patient assessments and careful consideration of both short- and long-term safety risks. Full article