Pharmacoepidemiology

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

Background: Antibiotic resistance represents a growing concern. A new strategy developed to treat severe infections is represented by ceftazidime/avibactam (CZA/AVI). Despite the promising activities against more pathogens, continuous monitoring is required to identify potential antibiotic resistance in clinical practice settings. Therefore, real-world data from pharmacovigilance databases can help to better define the safety profile. Methods: We analyzed all Individual Case Safety Reports (ICSRs) collected in the EudraVigilance database focusing on ICSRs with at least one adverse event (AE) potentially suggestive of drug resistance (DR) and drug ineffectiveness (DI). Results: A total of 654 ICSRs related to CZA/AVI were retrieved from EudraVigilance, of which N = 378 (57.8%) were related to male and N = 230 (35.1%) to adult patients. A total of 80.2% of all AEs were serious but with a positive outcome. Overall, we found N = 129 (19.7%) cases of potential DR or DI after CZA/AVI administration. The majority of CZA/AVI-induced DR or DI occurred in adult male patients. The most frequently reported AEs were “drug ineffective” and “pathogen resistance”. Lastly, CZA/AVI was mostly used for the treatment of “Klebsiella infection” and “Pneumonia”. Conclusions: The present study showed how pharmacovigilance could play a key role in generating evidence about the safety profile of CZA/AVI. Further studies are warranted. Full article

The state of knowledge regarding the teratogenic effects of maternal use of medications during pregnancy is constantly evolving and is often uncertain. Timely access to high-quality information may reduce prolonged harmful exposures, decrease the number of preventable birth defects, empower patients with accurate information about the risks of exposure, and prevent unnecessary patient anxiety and pregnancy termination. In this narrative review, we describe the process by which the teratogenic risk of medications is assessed by experts in medicine, genetics, and epidemiology and how identifiable risks can be effectively communicated to patients. Risk assessment of birth defects in human pregnancy involves collecting and synthesizing available data through a proper and rule-driven evaluation of scientific literature. Expert consensus is a practical approach to determine whether a given exposure produces damage after careful consideration of gestational timing, dose and route of the exposure, maternal and fetal genetic susceptibility, as well as evidence for biological plausibility. The provision of teratogen risk counseling through appropriate interpretation of information and effective knowledge translation to the patient is critical for the prevention of birth defects and maximizing healthy pregnancies. Full article

(1) Background: Although Sri Lanka is a developing country and boasts of having a well-established healthcare system along with good healthcare indices, we are still lagging in certain aspects of healthcare. One such aspect is the deficiencies in guidelines and practices related to the handling of pharmaceutical waste. (2) Methods: This was a qualitative study performed using in-depth interviews with the help of a semi-structured questionnaire conducted among staff who are working at a ministry complex in Galle, Sri Lanka. Data analysis was performed using thematic analysis, (3) Results: There were 40 participants which included 29 (72.5%) females. Three main themes were identified, namely, (I) current knowledge, (II) perceptions, and (III) practices towards storage, disposal, and misuse of pharmaceutical waste. The death of the patient, forgetting, relieving symptoms, and adverse effects were some reasons for the accumulation of unused pharmaceuticals at home. Most of the participants did not believe that the reuse of unused medications can cause various health hazards. Moreover, all participants practiced unsafe methods such as flushing down toilets, pouring into a sink, burning, etc. (4) Conclusions: The incorrect practices and poor knowledge in the handling of pharmaceutical waste and less concern for the environment highlight the need for awareness programs to the general public and establishing proper medication waste management such drug take-back systems. Full article

Dalbavancin, a semi-synthetic lipoglycopeptide with an extended half-life that allows for weekly dosing, is currently approved for the treatment of bacterial skin and soft tissue infections caused by susceptible gram-positive organisms. This case report discusses the successful treatment of septic arthritis with dalbavancin in a 38-year-old obese male. Septic arthritis, commonly caused by Staphylococcus aureus and Streptococcus species, was diagnosed in this patient following a mechanical fall that led to worsening shoulder pain. Given the patient’s morbid obesity and concerns about antibiotic penetration, dalbavancin 1500 mg IV biweekly was chosen for its extended half-life and ease of administration. This case underscores dalbavancin’s efficacy in managing septic arthritis in obese patients, offering a convenient alternative to traditional therapies that require a peripherally inserted central catheter (PICC line), frequent dosing, therapeutic monitoring, and prolonged hospital stays. Despite its higher cost, dalbavancin’s advantages include reduced need for PICC lines, additional staff and resources to monitor therapeutic drug levels, and fewer complications, which can offset some expenses. To our knowledge, this is the first documented case investigating the use of dalbavancin for enterococcal septic arthritis with a biweekly dosing regimen. Full article

Background: Antibiotic resistance presents a global challenge. Community awareness of antibiotic use has not been studied extensively in Saudi Arabia. This study aimed to assess public awareness of the appropriate use and indications of antibiotics in Riyadh, Saudi Arabia. Furthermore, the responses were compared across gender and age groups. Methods: We conducted a cross-sectional study between September 2022 and October 2022, including adult participants from Riyadh. The questionnaires were distributed via electronic channels and included sections about participants’ sociodemographic data and behavior concerning antibiotic use. Results: This study included 453 respondents. There were 281 (62%) female and 172 (38%) male respondents. Most respondents were between 46 and 55 years (n = 111; 24.5%) and above 56 years (n = 134; 29.6%). Two hundred seventy-two (60%) were college/university graduates, and 113 (24.9%) were at the secondary school level. Most participants (n = 410; 90.5%) were not affiliated with or working in the health sector. One hundred thirty-nine (30.7%) participants used an antibiotic within the past six months, and 171 (37.7%) kept antibiotics at room temperature. Most participants (n = 380; 83.9%) completed the treatment plan as prescribed. Sixty-eight percent of respondents stopped taking antibiotics when they felt better, and 11.5% believed antibiotics can treat bacterial and viral infections. The responses were compared between patients of both genders and patients aged ≤55 years or older. The comparison indicated that females tended to store antibiotics as instructed by the manufacturer (p = 0.004) and disposed of the remaining antibiotics immediately after completing the treatment (p < 0.001). Furthermore, the indications for antibiotic use differed between the genders, with no difference between the age groups. Participants > 55 years tended to complete the treatment plan (p = 0.007) and continued taking antibiotics at the same time and dose as prescribed (p = 0.002). Conclusions: This study’s findings suggest that public health authorities should implement awareness intervention programs to educate the Riyadh community on the proper use of antibiotics, with target interventions for specific gender and age groups. This study’s findings should be interpreted in the context of the Riyadh community and the potential biases of cross-sectional studies. Full article

Background: Despite widespread consensus on the need to reduce benzodiazepine (BZD) use in older adults, prescription rates in the U.S. have paradoxically increased over the past few decades. Objective: We examined (1) the characteristics of the BZD adverse reaction cases in patients aged 50 and older that were admitted to a healthcare facility (HCF) and experienced major effects/death, and (2) the associations between the concomitant use of opioids and/or antidepressants and HCF admission and major effects/death among BZD cases. Methods: We used the 2015–2022 National Poison Data System (NPDS), which contained data from 55 America’s Poison Centers. We fitted two multivariable logistic regression models to examine the associations between the co-use of opioids and/or antidepressants and HCF admission and major effects/death. Results: Of the BZD cases that were examined (N = 1979), 14.9% or 295 cases were admitted to healthcare facilities, and 8.5% of those who were followed up (77 out of 893 cases) experienced major effects or death. The number of co-used substances, co-use of opioids and antidepressants, atypical antipsychotics, anticonvulsants, muscle relaxants, and Gabapentin were associated with greater odds of healthcare admission. Co-use of opioids and healthcare admission were associated with greater odds of major effects/death. Conclusions: Adverse reactions and healthcare admissions are likely to be prevented when healthcare providers limit and carefully monitor BZD prescribing, especially for those who are on other medications, including prescription opioids and antidepressants. Full article

Ventricular tachycardia poses a significant therapeutic challenge. It can manifest over a spectrum from minimal palpitation symptoms to sudden cardiac death. This makes large-scale trials on the treatment of ventricular tachycardia difficult to perform. The mechanism of ventricular tachycardia must also be understood before embarking on treatment. Patients with or without structural heart disease will have different mechanisms for the onset and propagation of these arrhythmias. Catheter ablation is an established management option for ventricular tachycardia; however, it is not always successful and anti-arrhythmic medications are often necessary to control these life-threatening arrhythmias. Although anti-arrhythmics can suppress ventricular tachycardias they also carry side effects. In certain substrates, some of these medications can exacerbate arrhythmias or heart failure. For these reasons, a multifaceted approach to treating ventricular tachycardia is necessary. This paper is a comprehensive review of the comprehensive management strategies for ventricular tachycardia. Anti-arrhythmic medications have an important role and their use in various cardiomyopathies and channelopathies is reviewed in detail. We also review the promising effects of gene therapy and artificial intelligence on different substrates for ventricular tachycardia. Full article

The future directions in leveraging real-world evidence (RWE) and real-world data (RWD) in the field of lymphoma, as compared to traditional experimental clinical trials, are poised to significantly impact research methodologies, treatment strategies, and patient care. Current methods of clinical trials involve a well-controlled design and patient selection bias. Integrating RWE and RWD with experimental clinical trials offers a multifaceted approach to understanding lymphoma and enhancing patient outcomes. In this review, we discuss how RWE has helped shape lymphoma clinical trials, and we compare and evaluate evidence obtained from real-world lymphoma studies/databases with that obtained from clinical trials. We also discuss methods for utilizing surrogate endpoints to facilitate clinical trials and expedite drug development. RWE can be leveraged to bridge the gap between data obtained from clinical trial populations and the broader patient population encountered in clinical practice, by highlighting differences in outcomes and the need for effective treatment strategies across diverse patient groups. Full article

Aims: The aim of this study was to explore the suspected adverse drug reaction (ADR) data of five licensed statins in the UK: atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin. A secondary aim was to determine if there are any associations between the polypharmacological properties of the statins and their associated muscle-related side effects. Methods: The chemical database of bioactive molecules with drug-like properties, European Molecular Biology Laboratory (ChEMBL), was used to obtain data on the pharmacological interactions of statins with human proteins. The Medicines and Healthcare Products Regulatory Agency’s (MHRA) Yellow Card scheme was used to obtain reports of suspected ADRs from 2018 to 2022. The OpenPrescribing database was used to obtain the prescribing rates for statistical interpretation. Results: The study found no significant difference between the statins association with suspected ADRs across all organ classes (X², p > 0.05). Fluvastatin was found to have a higher incidence of ADRs/100,000 R_x across multiple system organ classes. Conclusions: No significant difference was found between the suspected ADR incidence of the statins across all system organ classes. Full article

Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea in the United States. Tigecycline has been proposed as a potential treatment for CDI, though limited clinical data exist to support this practice. The objective of this study was to determine if the provision of tigecycline provides a clinically meaningful benefit to inpatients with CDI. This study was a retrospective chart review enrolling inpatients receiving treatment for CDI. Patients were divided into cohorts depending on whether they received a standard antibiotic therapy regimen for CDI or an antibiotic treatment regimen that included tigecycline. The primary outcome was clinical recovery at the time of hospital discharge. A total of 39 and 22 patients were included in the standard antibiotic therapy and tigecycline groups, respectively. ATLAS (Age, Treatment, Leukocyte, Albumin, Serum creatinine) scores at the time of CDI diagnosis were similar between the two groups, though patients in the tigecycline groups were more likely to represent a recurrent episode of CDI. There was no difference in the rate of clinical recovery at the time of hospital discharge between the standard antibiotic therapy and tigecycline groups (38.5% vs. 36.4%, p = 0.8710). These data do not support the routine use of tigecycline for the treatment of CDI, though interpretation is limited due to baseline differences between groups and the retrospective, observational nature of this study. Full article

Background: The paediatric use of ophthalmic chloramphenicol in New Zealand (NZ) is relatively high; however, little more is known about its utilisation, including whether this is equitable. This study aimed to describe chloramphenicol utilisation in NZ children aged five years and under, by patient ethnicity, socioeconomic deprivation, and urban/non-urban domicile. Methods: This analysis included every publicly subsidised chloramphenicol dispensing received from birth to five years of age, for every child born in NZ in 2013. Cumulative proportion of first exposure, dispensing rate per person-year, and seasonality of dispensing were quantified. These were calculated following stratification by ethnicity, socioeconomic deprivation quintile, and urban/non-urban health district. For cumulative proportion of first exposure, odds ratios (OR) were calculated and multivariate logistic regression was performed. For dispensing rate, incidence rate ratios (IRR) were calculated and zero-inflated Poisson regression was performed. Results: Almost one-quarter of NZ children received their first dispensing within the first year of life. By five years of age, 55.2% of children had received their first dispensing. By five years of age, children of Pacific ethnicity, those in the highest deprivation quintile, and in those non-urban health districts had lower odds of receiving chloramphenicol (adjusted OR 0.90, 0.79, and 0.81, respectively, all p < 0.001). In contrast, children of Māori ethnicity had higher odds (adjusted OR 1.99, p < 0.001). Māori and Pacific ethnicity, and residence in non-urban health districts, were associated with fewer dispensings (adjusted IRR 0.88, 0.75 and 0.87, all p < 0.001). In contrast, deprivation quintile was not significantly associated with dispensing rate. Conclusion: Chloramphenicol utilisation is prevalent among NZ children, and utilisation may be lower among children of Pacific ethnicity and those in non-urban areas Full article

Adverse drug reactions (ADRs) are frequent and represent a significant healthcare burden. ADRs are a potentially avoidable contributor to excess unscheduled hospital admissions, higher morbidity, mortality, and healthcare costs. The objective of this review is to examine the epidemiology of ADRs in older multimorbid adults and to explore strategies for ADR prevention. ADRs in this population are often linked to commonly prescribed medications, including anticoagulants, antiplatelet agents, insulin, and non-steroidal anti-inflammatory drugs, but ADRs and adverse drug events (ADEs) in fact encompass a much broader range of culprit drugs. Age-related factors such as changes in pharmacokinetics and pharmacodynamics, multimorbidity, polypharmacy, and frailty have been associated with ADR occurrences. Various strategies have been proposed to prevent ADRs in different clinical settings, such as structured routine medication review and the use of bespoke software applications to identify potentially inappropriate prescriptions and drug interactions. Although these approaches have demonstrated some improvement in the quality of prescribing, there is still a lack of consistent evidence regarding their effectiveness in preventing ADRs. The nuanced and often intricate complexities associated with older patients’ pharmacotherapy necessitate a comprehensive approach to attenuate the impact of ADRs within this growing section of most populations globally. Full article

Buprenorphine is a safe and effective medication to treat opioid use disorder (OUD) in pregnant patients and is intended to be continued throughout pregnancy, delivery, and at least the one-year postpartum period. However, delivery often involves the need for acute pain management with opioid medications, such as after a cesarean section. For patients receiving buprenorphine, the provision of prescription opioids may negatively impact OUD treatment outcomes; however, not optimally managing acute pain may also impede OUD treatment benefit. Evidence is needed to disentangle the impacts of opioid prescription provision and methods of pain management in the immediate postpartum period on OUD treatment trajectories, ultimately to inform clinical guidelines tailored to the unique needs of pregnant and postpartum people receiving buprenorphine. Accordingly, this study took an initial step towards this goal to conduct a secondary analysis of a retrospective cohort of pregnant patients taking buprenorphine for OUD at the time of delivery (n = 142) to determine whether receipt of an opioid prescription at birth hospitalization discharge was associated with the time of buprenorphine discontinuation within the 12 months following delivery. Among the sample, 26% (n = 37) were prescribed an opioid at the time of birth hospitalization discharge. The number of weeks post-delivery until buprenorphine discontinuation occurred was shorter amongst patients who were prescribed an opioid (median 11 weeks) compared to patients who were not prescribed an opioid (median 39 weeks; p < 0.001 by Mann–Whitney U test). However, a Cox regression model reported that receipt of an opioid prescription following delivery did not significantly increase the hazard ratio for buprenorphine discontinuation. In other words, OUD patients not prescribed an opioid at birth hospitalization discharge continued their buprenorphine for a longer median duration after delivery compared to their counterparts who received prescription opioids; yet, this finding did not reach statistical significance when taking into account additional clinical variables. The findings indicate how further research is warranted to inform evidence-based post-delivery pain practices for postpartum OUD treatment patients. Full article

In this cross-sectional descriptive study conducted in the Ratnapura district, Sri Lanka, we assessed the affordability of oral pediatric anti-infective medicines (OPAIMs). Using a modified WHO/HAI medicinal price methodology, we examined the availability, median price ratios (MPRs), mean percentage difference, and affordability of the standard treatment of the originator brand (OB) and lowest-priced generic (LPG) OPAIMs in 30 private and 2 state-owned pharmacies. The study revealed disparities in availability, with only 50% of private pharmacies offering all 11 medicinal drugs in their generic form. The MPRs of OPAIMs for OB and LPG varied, with three drugs exceeding the financially acceptable MPR of 2 (albendazole, amoxicillin, and erythromycin). The standard treatment with LPGs costs between 0.17 and 0.85 and between 0.06 and 0.28 days’ wages for the lowest daily salary of the private sector and unskilled public employees, respectively. We identified erythromycin and albendazole as having less than 50% availability in their generic form in private pharmacies. To address these findings, we recommend frequent pricing revisions based on exchange rates and associated costs, coupled with the establishment of a transparent scientific criterion to subsidize essential medicines deemed “unaffordable.” Failure to implement such measures amidst economic crises may adversely impact financial access to essential medications. Full article

Background: Hypertension is frequently studied in epidemiological studies that have been conducted using retrospective observational data, either as an outcome or a variable. However, there are few validation studies investigating the accuracy of hypertension phenotyping algorithms in aggregated electronic health record (EHR) data. Methods: Utilizing a centralized repository of inpatient EHR data from Singapore for the period of 2019–2020, a new algorithm that incorporates both diagnostic codes and medication details (Diag+Med) was devised. This algorithm was intended to supplement and improve the diagnostic code-only model (Diag-Only) for the classification of hypertension. We computed various metrics (sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)) to assess the algorithm’s effectiveness in identifying hypertension on 2813 chart-reviewed records. This pool was composed of two patient cohorts: a random sampling of all inpatient admissions (Random Cohort) and a targeted group with atrial fibrillation diagnoses (AF Cohort). Results: The Diag+Med algorithm was more sensitive at detecting hypertension patients in both cohorts compared to the Diag-Only algorithm (83.8 and 87.6% vs. 68.2 and 66.5% in the Random and AF Cohorts, respectively). These improvements in sensitivity came at minimal costs in terms of PPV reductions (88.2 and 90.3% vs. 91.4 and 94.2%, respectively). Conclusion: The combined use of diagnosis codes and specific antihypertension medication exposure patterns facilitates a more accurate capture of patients with hypertension in a database of aggregated EHRs from diverse healthcare institutions in Singapore. The results presented here allow for the bias correction of risk estimates derived from observational studies involving hypertension. Full article

Although statins have served as the cornerstone for pharmacological lowering of lipid levels in atherosclerotic cardiovascular disease (ASCVD) risk reduction, many patients are unable to achieve target doses of statin medication due to side effects or target levels of cholesterol reduction on statin monotherapy. The landscape of lipid-lowering strategies has expanded in recent years, with the emergence of therapies that make use of small interfering RNA (siRNA) and antisense oligonucleotides, in addition to traditional small-molecule agents. Non-statin therapies that have shown promising results in randomized controlled trials include adenosine triphosphate-citrate lyase inhibitors, proprotein convertase subtilisin/kexin 9 (PCSK9)-inhibiting antibodies and siRNA, omega-3 polyunsaturated fatty acids, and lipoprotein(a) gene-inhibiting siRNA and ASOs, in addition to older therapies such as ezetimibe. In contrast, cholesteryl ester transfer protein (CETP) inhibitors have shown less promising results in randomized trials. The purpose of this narrative review is to summarize the evidence for these medications, with a focus on phase III randomized trials. Full article