Mental health services in Gauteng, South Africa: A proxy evaluation using pharmaceutical data.

Background: South African legislation advocates for equitable access to mental healthcare services integrated into general healthcare settings. Mental, neurological, and substance use (MNS) disorders are often comorbid. Pharmacoepidemiology provides indirect evidence of service provision for conditions amenable to medicine treatment. Aim: The study aims to evaluate medicine procurement for MNS disorders at different service levels in the health system. Setting: The Public health sector, Gauteng province formed the setting for the study. Method: A secondary analysis of the Gauteng pharmaceutical database was conducted using Anatomic Therapeutic Chemical (ATC) and defined daily dose (DDD) methodology. Anatomic Therapeutic Chemical classes of medicines for MNS disorders were included. Defined daily doses and costs were calculated per 1000 population served by each facility and service level. Statistical comparisons were made using chi-square testing. Results: General healthcare settings accounted for 90% (R118 638 248) and specialised hospitals for 10% (R13 685 032) of expenditure on medicines for MNS disorders, procuring 94% (n = 49 442 474) and 6% (n = 3 311 528) of DDDs, respectively. Although district clinics procured 60% of DDDs, they procured the least per 1000 population served, whereas district hospitals procured the most. For almost all ATC classes, procurement differed significantly between municipalities at every service level and between specialised hospitals. Conclusion: In Gauteng province, most medicines for MNS disorders are procured by general healthcare services, but access to care may not be equitable. While population coverage at district clinics appears low, district hospitals may experience the greatest care burden. Research regarding quality of care at each service level is recommended. Contribution: This study provides insight into service provision for MNS disorders.

Updated core competencies in pharmacoepidemiology to inform contemporary curricula and training for academia, government, and industry.

PURPOSE: The first paper to specify the core content of pharmacoepidemiology as a profession was published by an ISPE (International Society for Pharmacoepidemiology) workgroup in 2012 (Jones JK et al. PDS 2012; 21[7]:677-689). Due to the broader and evolving scope of pharmacoepidemiology, ISPE considers it important to proactively identify, update and expand the list of core competencies to inform curricula of education programs; thus, better positioning pharmacoepidemiologists across academic, government (including regulatory), and industry positions. The aim of this project was to update the list of core competencies in pharmacoepidemiology. METHODS: To ensure applicability of findings to multiple areas, a working group was established consisting of ISPE members with positions in academia, industry, government, and other settings. All competencies outlined by Jones et al. were extracted from the initial manuscript and presented to the working group for review. Expert-based judgments were collated and used to identify consensus. It was noted that some competencies could contribute to multiple groups and could be directly or indirectly related to a group. RESULTS: Five core domains were proposed: (1) Epidemiology, (2) Clinical Pharmacology, (3) Regulatory Science, (4) Statistics and data science, and (5) Communication and other professional skills. In total, 55 individual competencies were proposed, of which 25 were new competencies. No competencies from the original work were dropped but aggregation or amendments were made where considered necessary. CONCLUSIONS: While many core competencies in pharmacoepidemiology have remained the same over the past 10 years, there have also been several updates to reflect new and emerging concepts in the field.

Geographic variation in sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide-1 receptor agonist use in people with type 2 diabetes in New South Wales, Australia.

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and cardio-renal outcomes for people with type 2 diabetes (T2D). However, geographic and socio-economic variation in use is not well understood. METHODS: We identified 367 829 New South Wales residents aged ≥40 years who dispensed metformin in 2020 as a proxy for T2D. We estimated the prevalence of use of other glucose-lowering medicines among people with T2D and the prevalence of SGLT2i and GLP-1RA use among people using concomitant T2D therapy (i.e. metformin + another glucose-lowering medicine). We measured the prevalence by small-level geography, stratified by age group, and characterized by remoteness and socio-economic status. RESULTS: The prevalence of SGLT2i (29.7%) and GLP-1RA (8.3%) use in people with T2D aged 40-64 increased with geographic remoteness and in areas of greater socio-economic disadvantage, similar to other glucose-lowering medicines. The prevalence of SGLT2i (55.4%) and GLP-1RA (15.4%) among people using concomitant T2D therapy varied across geographic areas, with lower SGLT2i use in more disadvantaged areas and localized areas of high GLP-1RA use (2.5 times the median). Compared with people aged 40-64 years, the prevalence of SGLT2i and GLP-1RA use was lower in older age groups, but with similar patterns of variation across geographic areas. CONCLUSIONS: The prevalence of SGLT2i and GLP-1RA use varied by geography, probably reflecting a combination of system- and prescriber-level factors. Socio-economic variation in GLP-1RA use was overshadowed by localized patterns of prescribing. Continued monitoring of variation can help shape interventions to optimize use among people who would benefit the most.

Association of Antipsychotic Polypharmacy and Two-Year All-Cause Mortality: A Population-Based Cohort Study of 33,221 Italian Continuous Users.

Background: Differences in survival between patients treated with antipsychotic monotherapy vs. polytherapy are debated. This study aimed to examine the association of antipsychotic polytherapy with 2-year all-cause mortality in a population-based cohort. Methods: Data were retrieved from healthcare databases of four local health units of Lombardy, Italy. Subjects aged 18-79 years who received continuous antipsychotic prescriptions in 2018 were identified. Overall survival among patients with antipsychotic monotherapy vs. polytherapy was compared. A multivariate Cox PH model was used to estimate the association between antipsychotic therapy, or antipsychotic use (continuous vs. non-continuous), and all-cause mortality. Adjustments were made for the presence of metabolic disturbances, total antipsychotic dosage amount (olanzapine equivalent doses), age, and sex. Results: A total of 49,875 subjects receiving at least one prescription of antipsychotics during 2018 were identified. Among the 33,221 patients receiving continuative antipsychotic prescriptions, 1958 (5.9%) experienced death from any cause at two years. Patients with continuous antipsychotic use had a 1.13-point increased mortality risk compared with non-continuous users. Patients treated with antipsychotic polytherapy showed an adjusted mortality risk increased by 17% (95% CI: 2%, 33%) compared to monotherapy. Conclusions: The study highlights the potential risks associated with antipsychotic polypharmacy, emphasizing the importance of optimizing drug prescriptions to improve patient safety and reduce mortality rates in individuals receiving antipsychotic therapy.

Prescription opioid dispensing patterns among patients with schizophrenia or bipolar disorder.

BACKGROUND: Patients with schizophrenia (SZ) or bipolar disorder (BD) may have increased risk of complications from prescribed opioids, including opioid-induced respiratory depression. We compared prescription opioid pain medication dispensing for patients with SZ or BD versus controls over 5 years to assess dispensing trends. METHODS: This retrospective, observational study analysed US claims data from the IBM® MarketScan® Commercial and Multi-State Medicaid databases for individuals aged 18-64 years with prevalent SZ or BD for years 2015-2019 compared with age- and sex-matched controls. Baseline characteristics, comorbidities, and medication use were assessed. Proportions of individuals dispensed prescription opioids chronically (ie, ≥70 days over a 90-day period or ≥ 6 prescriptions annually) or nonchronically (≥1 prescription, chronic definition not met) were assessed. RESULTS: In 2019, the Commercial and Medicaid databases contained records for 4773 and 30,179 patients with SZ and 52,780 and 63,455 patients with BD, respectively. Patients with SZ or BD had a higher prevalence of comorbidities, including pain, versus controls in each analysis year. From 2015 to 2019, among commercially insured patients with SZ, chronic opioid-dispensing proportions decreased from 6.1% (controls: 2.7%) to 2.3% (controls: 1.2%) and, for patients with BD, from 11.4% (controls: 2.7%) to 6.4% (controls: 1.6%). Chronic opioid dispensing declined in Medicaid-covered patients with SZ from 15.0% (controls: 14.7%) to 6.7% (controls: 6.0%) and, for patients with BD, from 27.4% (controls: 12.0%) to 12.4% (controls: 4.7%). Among commercially insured patients with SZ, nonchronic opioid dispensing decreased from 15.5% (controls: 16.4%) to 10.7% (controls: 11.0%) and, for patients with BD, from 26.1% (controls: 17.5%) to 20.0% (controls: 12.2%). In Medicaid-covered patients with SZ, nonchronic opioid dispensing declined from 22.5% (controls: 24.4%) to 15.1% (controls: 12.7%) and, for patients with BD, from 32.3% (controls: 25.9%) to 24.6% (controls: 13.6%). CONCLUSIONS: The proportions of individuals dispensed chronic or nonchronic opioid medications each year were similar between commercially and Medicaid-insured patients with SZ versus controls and were higher for patients with BD versus controls. From 2015 to 2019, the proportions of individuals who were dispensed prescription opioids chronically or nonchronically decreased for patients with SZ or BD and controls.

Association between statin use and the risk for idiopathic pulmonary fibrosis and its prognosis: a nationwide, population-based study.

Given the pleiotropic effects of statins beyond their lipid-lowering effects, there have been attempts to evaluate the role of statin therapy in IPF, but they have shown inconclusive results. Data from the National Health Insurance Service (NHIS) database of South Korea were used to investigate the effects of statin therapy on IPF. The IPF cohort consisted of a total of 10,568 patients who were newly diagnosed with IPF between 2010 and 2017. These patients were then matched in a 1:3 ratio to 31,704 subjects from a control cohort without IPF, with matching based on age and sex. A case-control study was performed to evaluate the association between statin use and the risk for IPF, and the multivariable analysis revealed that statin use was associated with a lower risk for IPF (adjusted OR 0.847, 95% CI 0.800-0.898). Using the IPF cohort, we also evaluated whether statin use at the time of diagnosis was associated with future clinical outcomes. The statin use at the time of IPF diagnosis was associated with improved overall survival (adjusted HR 0.779, 95% CI 0.709-0.856). Further prospective studies are needed to clarify the role of statin therapy in IPF.

Evaluating the effect of inequalities in oral anti-coagulant prescribing on outcomes in people with atrial fibrillation.

Aims: Whilst anti-coagulation is typically recommended for thromboprophylaxis in atrial fibrillation (AF), it is often never prescribed or prematurely discontinued. The aim of this study was to evaluate the effect of inequalities in anti-coagulant prescribing by assessing stroke/systemic embolism (SSE) and bleeding risk in people with AF who continue anti-coagulation compared with those who stop transiently, permanently, or never start. Methods and results: This retrospective cohort study utilized linked Scottish healthcare data to identify adults diagnosed with AF between January 2010 and April 2016, with a CHA2DS2-VASC score of ≥2. They were sub-categorized based on anti-coagulant exposure: never started, continuous, discontinuous, and cessation. Inverse probability of treatment weighting-adjusted Cox regression and competing risk regression was utilized to compare SSE and bleeding risks between cohorts during 5-year follow-up. Of an overall cohort of 47 427 people, 26 277 (55.41%) were never anti-coagulated, 7934 (16.72%) received continuous anti-coagulation, 9107 (19.2%) temporarily discontinued, and 4109 (8.66%) permanently discontinued. Lower socio-economic status, elevated frailty score, and age ≥ 75 were associated with a reduced likelihood of initiation and continuation of anti-coagulation. Stroke/systemic embolism risk was significantly greater in those with discontinuous anti-coagulation, compared with continuous [subhazard ratio (SHR): 2.65; 2.39-2.94]. In the context of a major bleeding event, there was no significant difference in bleeding risk between the cessation and continuous cohorts (SHR 0.94; 0.42-2.14). Conclusion: Our data suggest significant inequalities in anti-coagulation prescribing, with substantial opportunity to improve initiation and continuation. Decision-making should be patient-centred and must recognize that discontinuation or cessation is associated with considerable thromboembolic risk not offset by mitigated bleeding risk.

Power to the People: Why person-generated health data is important for pharmacoepidemiology.

Person-generated health data (PGHD) are valuable to study outcomes relevant to everyday living, to obtain information not otherwise available, for long-term follow-up and in situations where decisions cannot wait for traditional clinical research to be completed. While there is no dispute that these data are subject to bias, insights gained may be better than an information void, provided the biases are understood and acknowledged. People will share information known uniquely to them about exposures that may affect drug tolerance, safety and effectiveness, e.g., using non-prescription and complementary medications, alcohol, tobacco, illicit drugs, exercise, etc. Patients may be the best source of safety information when long-term follow-up is needed, e.g., the 5-15-year follow-up required for some gene therapies. Validation studies must be performed to evaluate what people can accurately report and when supplementary confirmation information is needed. But PGHD has already proven valuable in quantifying and contrasting COVID-19 vaccine benefits and risks, and for evaluating disease transmission and the accuracy of COVID-19 testing. Going forward, PGHD will be used for patient-measured and patient-relevant outcomes, including regulatory purposes, and will be linked to broader health data networks using tokenization, becoming a mainstay for signals about risks and benefits for diverse populations.

Oxycodone initiation in Australia (2014-2018): Sociodemographic factors and preceding health service use.

AIMS: Oxycodone is the most commonly prescribed strong opioid in Australia. This study describes health service antecedents and sociodemographic factors associated with oxycodone initiation. METHODS: Population-based new user cohort study linking medicine dispensings, hospitalizations, emergency department visits, medical services and cancer notifications from New South Wales (NSW) for 2014-2018. New users had no dispensings of any opioid in the preceding year. We analysed health service use in the 5 days preceding initiation and proportion of people on treatment over 1 year and fitted an area-based, multivariable initiation model with sociodemographic covariates. RESULTS: Oxycodone accounted for 30% of opioid initiations. Annually, 3% of the NSW population initiated oxycodone, and 5-6% were prevalent users; the new user cohort comprised 830 963 people. Discharge from hospital (39.3%), therapeutic procedures (21.4%) and emergency department visits (19.7%) were common; a hospital admission for injury (6.0%) or a past-year history of cancer (7.2%) were less common. At 1 year after initiation, 4.6% of people were using oxycodone. In the multivariable model, new use of oxycodone increased with age and was higher for people outside major cities, for example, an incidence rate ratio of 1.43 (95% confidence interval 1.36-1.51) for inner regional areas relative to major cities; there was no evidence of variation in rates of new use by social disadvantage. CONCLUSION: About half of new oxycodone use in NSW was preceded by a recent episode of hospital care or a therapeutic procedure. Higher rates of oxycodone initiation in rural and regional areas were not explained by sociodemographic factors.

Association between prolactin increasing antipsychotic use and the risk of breast cancer: a retrospective observational cohort study in a United States Medicaid population.

Introduction: Results of retrospective studies examining the relationship between prolactin increasing antipsychotics and incident breast cancer have been inconsistent. This study assessed the association between use of high prolactin increasing antipsychotics (HPD) and the incidence of breast cancer using best practices in pharmacoepidemiology. Methods: Using administrative claims data from the MarketScan Medicaid database, schizophrenia patients initiating antipsychotics were identified. Those initiating HPD were compared with new users of non/low prolactin increasing drugs (NPD). Two definitions of breast cancer, two at-risk periods, and two large-scale propensity score (PS) adjustment methods were used in separate analyses. PS models included all previously diagnosed conditions, medication use, demographics, and other available medical history. Negative control outcomes were used for empirical calibration. Results: Five analysis variants passed all diagnostics for sufficient statistical power and balance across all covariates. Four of the five variants used an intent-to-treat (ITT) approach. Between 4,256 and 6,341 patients were included in each group for the ITT analyses, and patients contributed approximately four years of follow-up time on average. There was no statistically significant association between exposure to HPD and risk of incident breast cancer in any analysis, and hazard ratios remained close to 1.0, ranging from 0.96 (95% confidence interval 0.62 - 1.48) to 1.28 (0.40 - 4.07). Discussion: Using multiple PS methods, outcome definitions and at-risk periods provided robust and consistent results which found no evidence of an association between use of HPD and risk of breast cancer.

A comparison of four self-controlled study designs in an analysis of COVID-19 vaccines and myocarditis using five European databases.

INTRODUCTION: The aim of this study was to assess the possible extent of bias due to violation of a core assumption (event-dependent exposures) when using self-controlled designs to analyse the association between COVID-19 vaccines and myocarditis. METHODS: We used data from five European databases (Spain: BIFAP, FISABIO VID, and SIDIAP; Italy: ARS-Tuscany; England: CPRD Aurum) converted to the ConcePTION Common Data Model. Individuals who experienced both myocarditis and were vaccinated against COVID-19 between 1 September 2020 and the end of data availability in each country were included. We compared a self-controlled risk interval study (SCRI) using a pre-vaccination control window, an SCRI using a post-vaccination control window, a standard SCCS and an extension of the SCCS designed to handle violations of the assumption of event-dependent exposures. RESULTS: We included 1,757 cases of myocarditis. For analyses of the first dose of the Pfizer vaccine, to which all databases contributed information, we found results consistent with a null effect in both of the SCRI and extended SCCS, but some indication of a harmful effect in a standard SCCS. For the second dose, we found evidence of a harmful association for all study designs, with relatively similar effect sizes (SCRI pre = 1.99, 1.40 - 2.82; SCRI post 2.13, 95 %CI - 1.43, 3.18; standard SCCS 1.79, 95 %CI 1.31 - 2.44, extended SCCS 1.52, 95 %CI = 1.08 - 2.15). Adjustment for calendar time did not change these conclusions. Findings using all designs were also consistent with a harmful effect following a second dose of the Moderna vaccine. CONCLUSIONS: In the context of the known association between COVID-19 vaccines and myocarditis, we have demonstrated that two forms of SCRI and two forms of SCCS led to largely comparable results, possibly because of limited violation of the assumption of event-dependent exposures.

Sociodemographic disparities in sodium-glucose cotransporter-2 inhibitor use among US kidney transplant recipients: An observational study of real-world pharmacy records.

BACKGROUND: Recent clinical trials demonstrate benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with chronic kidney disease, but data on use in kidney transplant (KTx) recipients are limited. METHODS: We examined a novel database linking SRTR registry data for KTx recipients (2000-2021) with outpatient fill records from a large pharmaceutical claims warehouse (2015-2021). Adult (≥18 years) KTx recipients treated with SGLT2i were compared to those who received other noninsulin diabetes medications without SGLT2i. Characteristics associated with SGLT2i use were quantified by multivariable logistic regression (adjusted odds ratio, 95%LCLaOR95%UCL). RESULTS: Among 18 988 KTx recipients treated with noninsulin diabetes agents in the study period, 2224 filled an SGLT2i. Mean time from KTx to prescription was 6.7 years for SGLT2i versus 4.7 years for non-SGLT2i medications. SGLT2i use was more common in Asian adults (aOR, 1.091.311.58) and those aged > 30-59 years (compared with 18-30 years) or with BMI > 35 kg/m2 (aOR, 1.191.411.67), and trended higher with self-pay status. SGLT2i use was lower among KTx recipients who were women (aOR, .79.87.96), Black (aOR, .77.881.00) and other (aOR, .52.751.07) race, publicly insured (aOR, .82.921.03), or with less than college education (aOR, .78.87.96), and trended lower in those age 75 years and older. SGLT2i use in KTx patients increased dramatically in 2019-2021 (aOR, 5.015.636.33 vs. prior years). CONCLUSION: SGLT2i use is increasing in KTx recipients but varies with factors including race, education, and insurance. While ongoing study is needed to define risks and benefits of SGLT2i use in KTx patients, attention should also focus on reducing treatment disparities related to sociodemographic traits.

Increased risk of hypocalcemia with decreased kidney function in patients prescribed bisphosphonates based on real-world data from the MID-NET® in Japan: a new-user cohort study.

BACKGROUND: In the post-marketing stage, cases of hypocalcemia associated with bisphosphonate preparations (BPs) have been reported in patients with decreased kidney function, despite warning against use of BPs in such patients in the package insert (PI) of Japan. The purpose of this study was to investigate the safety of BPs in patients with decreased kidney function. METHODS: The cohort study was conducted in patients with osteoporosis and newly prescribed bisphosphonate utilizing real-world data from MID-NET® in Japan. The adjusted hazard ratios (aHRs) for hypocalcemia (a corrected serum Ca level < 8.00 mg/dL) relative to the normal group were calculated in each decreased kidney function group (mild, moderate or severe group). RESULTS: A total of 14,551 patients were included in the analysis, comprising 2,601 (17.88%) with normal (eGFR ≥ 90 mL/min/1.73m2), 7,613 (52.32%) with mild (60 ≤ eGFR < 90 mL/min/1.73m2), 3,919 (26.93%) with moderate (30 ≤ eGFR < 60 mL/min/1.73m2), and 418 (2.87%) with severe kidney function (eGFR < 30 mL/min/1.73m2). The aHRs (95% confidence interval) for hypocalcemia were 1.85 (0.75-4.57), 2.30 (0.86-6.21), and 22.74 (8.37-61.78) in the mild, moderate, and severe groups, respectively. The increased risk of hypocalcemia depending on kidney function was also observed even when calculating the aHR for each specific BP such as alendronate sodium hydrate, minodronic acid hydrate, and sodium risedronate hydrate. Furthermore, similar results were obtained in the sensitivity analysis by altering the outcome definition to a 20% or more reduction in corrected serum Ca level from the baseline, as well as when focusing on patients with more than one laboratory test result per 30 days during the follow-up period. CONCLUSIONS: These findings suggest that the risk of hypocalcemia during BP prescription is higher in patients with decreased kidney function, particularly those with severely decreased kidney function. The quantitative real-world evidence on the safety risk of BPs obtained in this study has led to the PI revision describing a relationship between hypocalcemia risk and decreased kidney function as a regulatory action in Japan and will contribute to promoting the proper use of BPs with appropriate risk management in clinical practice.

Paternal use of selective serotonin reuptake inhibitors and adverse health outcomes: A nationwide cohort study on 13,547 exposed children.

BACKGROUND: The use of selective serotonin reuptake inhibitors (SSRIs) has increased over time. Several studies indicate that paternal use of medication may adversely affect the developing fetus. Only a few studies have investigated the association between preconceptional paternal exposure to SSRIs and the risks of adverse health outcomes in children. OBJECTIVES: This study aimed to assess adverse birth outcomes and adverse early life events in children fathered by men using SSRIs prior to conception. MATERIALS AND METHODS: All live-born singleton children born in Denmark from 1997 until 2019 and their parents were included. The exposed cohort comprised all children fathered by men using SSRIs 3 months prior to conception and the unexposed cohort comprised all other children. We estimated the odds ratios for adverse birth outcomes: small for gestational age (SGA), preterm birth, low Apgar score, and major congenital malformations. Furthermore, we estimated the hazard ratios for adverse early life events of infections and hospitalizations within 1 year from birth. We also examined adverse birth outcomes and the adverse early life events according to SSRI subgroups. RESULTS: There was a statistically significantly increased odds ratio 1.15 (confidence interval, CI: 1.06-1.23) for preterm birth. No significant results were found for SGA, low Apgar score, and major congenital malformations. The adjusted hazard ratios for hospitalizations and infections were 1.06 (CI: 1.02-1.11) and 1.02 (CI: 0.97-1.07), respectively. There was a statistically significantly increased odds ratio for preterm birth with respect to the SSRI subgroups citalopram and escitalopram, and for hospitalizations with respect to citalopram. DISCUSSION AND CONCLUSION: Although the risks of certain adverse birth and adverse early life outcomes were statistically significantly increased, the ratios were small and may have limited clinical importance. Paternal use of SSRI was in general safe in the preconceptual period.

Potentially inappropriate prescribing for people with dementia in ambulatory care: a cross-sectional observational study.

BACKGROUND: Studies have shown that potentially inappropriate prescribing (PIP) is highly prevalent among people with dementia (PwD) and linked to negative outcomes, such as hospitalisation and mortality. However, there are limited data on prescribing appropriateness for PwD in Saudi Arabia. Therefore, we aimed to estimate the prevalence of PIP and investigate associations between PIP and other patient characteristics among PwD in an ambulatory care setting. METHODS: A cross-sectional, retrospective analysis was conducted at a tertiary hospital in Saudi Arabia. Patients who were ≥ 65 years old, had dementia, and visited ambulatory care clinics between 01/01/2019 and 31/12/2021 were included. Prescribing appropriateness was evaluated by applying the Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) criteria. Descriptive analyses were used to describe the study population. Prevalence of PIP and the prevalence per each STOPP criterion were calculated as a percentage of all eligible patients. Logistic regression analysis was used to investigate associations between PIP, polypharmacy, age and sex; odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Analyses were conducted using SPSS v27. RESULTS: A total of 287 PwD were identified; 56.0% (n = 161) were female. The mean number of medications prescribed was 9.0 [standard deviation (SD) ± 4.2]. The prevalence of PIP was 61.0% (n = 175). Common instances of PIP were drugs prescribed beyond the recommended duration (n = 90, 31.4%), drugs prescribed without an evidence-based clinical indication (n = 78, 27.2%), proton pump inhibitors (PPIs) for > 8 weeks (n = 75, 26.0%), and acetylcholinesterase inhibitors with concurrent drugs that reduce heart rate (n = 60, 21.0%). Polypharmacy was observed in 82.6% (n = 237) of patients and was strongly associated with PIP (adjusted OR 24.1, 95% CI 9.0-64.5). CONCLUSIONS: Findings have revealed a high prevalence of PIP among PwD in Saudi Arabia that is strongly associated with polypharmacy. Future research should aim to explore key stakeholders' experiences and perspectives of medicines management to optimise medication use for this vulnerable patient population.

Influence of Incomplete Death Information on Cumulative Risk Estimates in United States Claims Data.

Administrative claims databases often do not capture date or fact of death, so studies using these data may inappropriately treat death as a censoring event-equivalent to other withdrawal reasons-rather than a competing event. We examined 1-, 3-, and 5-year inverse-probability-of-treatment-weighted cumulative risks of a composite cardiovascular outcome among 34,527 initiators of telmisartan (exposure) and ramipril (referent) ages ≥55 in Optum claims from 2003 to 2020. Differences in cumulative risks of the cardiovascular endpoint due to censoring of death (cause-specific), as compared to treating death as a competing event (sub-distribution), increased with greater follow-up time and older age, where event and mortality risks were higher. Among ramipril users (selected results), 5-year cause-specific and sub-distribution cumulative risk estimates per 100, respectively, were 16.4 (95% CI 15.3, 17.5) and 16.2 (95% CI 15.1, 17.3) among ages 55-64 (difference=0.2) and were 43.2 (95% CI 41.3, 45.2) and 39.7 (95% CI 37.9, 41.4) among ages ≥75 (difference=3.6). Plasmode simulation results demonstrated the differences in cause-specific versus sub-distribution cumulative risks to increase with increasing mortality rate. We suggest researchers consider the cohort's baseline mortality risk when deciding whether real-world data with incomplete death information can be used without concern.

Evaluation of adherence to antipsychotics: A real-world data study using four different dosing assumptions.

AIMS: This study aimed to assess the frequency of dosing inconsistencies in prescription data and the effect of four dosing assumption strategies on adherence estimates for antipsychotic treatment. METHODS: A retrospective cohort, which linked prescription and dispensing data of adult patients with ≥1 antipsychotic prescription between 2015-2016 and followed up until 2019, in Catalonia (Spain). Four strategies were proposed for selecting the recommended dosing in overlapping prescription periods for the same patient and antipsychotic drug: (i) the minimum dosing prescribed; (ii) the dose corresponding to the latest prescription issued; (iii) the highest dosing prescribed; and (iv) all doses included in the overlapped period. For each strategy, one treatment episode per patient was selected, and the Continuous Medication Availability measure was used to assess adherence. Descriptive statistics were used to describe results by strategy. RESULTS: Of the 277 324 prescriptions included, 76% overlapped with other prescriptions (40% with different recommended dosing instructions). The number and characteristics of patients and treatment episodes (18 292, 18 303, 18 339 and 18 536, respectively per strategy) were similar across strategies. Mean adherence was similar between strategies, ranging from 57 to 60%. However, the proportion of patients with adherence ≥90% was lower when selecting all doses (28%) compared with the other strategies (35%). CONCLUSION: Despite the high prevalence of overlapping prescriptions, the strategies proposed did not show a major effect on the adherence estimates for antipsychotic treatment. Taking into consideration the particularities of antipsychotic prescription practices, selecting the highest dose in the overlapped period seemed to provide a more accurate adherence estimate.

Sodium-glucose cotransporter-2 inhibitors and the risk of atrial fibrillation in patients with type 2 diabetes: a population-based cohort study.

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have a direct cardiac effect that is likely to be independent of its glucose lowering renal effect. Previous research has shown that SGLT2-is mitigate heart failure and prevent arrhythmic cardiac death. Our objective is to determine whether SGLT-2is reduce atrial fibrillation (AF) in comparison to other second-to third-line antidiabetic drugs in type 2 diabetes. METHODS AND RESULTS: We conducted a population-based, new-user active comparator cohort study using data from the UK Clinical Practice Research Datalink. We identified a cohort of patients initiating a new antidiabetic drug class between January 2013 and September 2020. This cohort included patients initiating their first ever non-insulin antidiabetic drug, as well as those who switched to or added-on an antidiabetic drug class not previously used in their treatment history. Individuals with a diagnosis of AF or atrial flutter at any time before cohort entry were excluded. Cox regression analysis with time-dependent covariates was used to estimate hazard ratios (HRs) and 95% confidence intervals (95%-CIs) of AF comparing SGLT-2-is with other second-to third-line antidiabetic drugs. Stratified analyses were performed according to sex, diabetes duration (<5 or ≥5 years), body mass index (BMI), HbA1c, and presence of heart failure. The cohort comprised 142,447 patients. SGLT-2is were associated with a statistically significant reduced hazard of AF compared to other second-to third-line antidiabetic drugs (adjusted HR:0.77[95%-CI:0.68-0.88]). This reduced risk was present in both sexes but was more prominently among women (adjusted HRwomen:0.60[95%-CI:0.45-0.79]; HRmen:0.85[95%-CI:0.73-0.98]; P-value interaction:0.012). There was no evidence for effect modification when stratifying on duration of diabetes, body mass index, HbA1c, or presence of heart failure. CONCLUSION: SGLT-2is were associated with a reduced risk of AF in patients with type 2 diabetes compared to other second-to third-line antidiabetic drugs. This reduced risk occurs in both sexes but more prominently among women.

Diuretic drug utilization in neonates: a French prescription database analysis.

Background: The use of diuretics is extremely common in infants cared for in neonatal wards, despite the lack of proven efficacy for many conditions. The main objective of this study was to assess the rate of diuretics exposure in a multicenter French cohort. The secondary objectives were to describe the evolution of this exposure over time, the indications, the prescription practices, and the exposure rates among centers. Methods: An observational study was conducted in 40 Level 3 French neonatal intensive care units using the same computerized order-entry system. Neonates hospitalized between January 2017 to December 2021 with a corrected age between 24 and 44 weeks of gestation at admission were eligible. Results: A total of 86,032 patients were included. The exposure rate was 8.5%, more specifically 29.4% for children born at < 32 weeks of gestation and 3.7% for neonates born at term. There was no significant variation over the study period, but the exposure ranged from 2.4% to 26.5% depending on the center. The main drugs prescribed were furosemide, spironolactone and dopamine with a diuretic purpose. The main indications were "fluid retention," and to a lesser extent "bronchopulmonary dysplasia" and "post-transfusion." For furosemide, the first exposure occurred in mean at 16.5 (±17.8) days of life, mean duration of exposure was 6.2 (±9.5) days, and the cumulative dose was in mean 10.7 (23.9) mg/kg. Conclusion: Diuretic prescription practices vary between centers. The administration of these drugs is often non-evidence based, doses and duration of treatment easily exceed toxic thresholds.

Polypharmacy and risk of fractures in older adults: A systematic review.

BACKGROUND: Fractures have serious health consequences in older adults. While some medications are individually associated with increased risk of falls and fractures, it is not clear if this holds true for the use of many medications (polypharmacy). We aimed to identify what is known about the association between polypharmacy and the risk of fractures in adults aged ≥65 and to examine the methods used to study this association. METHODS: We conducted a systematic review with narrative synthesis of studies published up to October 2023 in PubMed, Embase, CINAHL, PsychINFO, Cochrane Library, Web of Science, and the grey literature. Two independent reviewers screened titles, abstracts, and full texts, then performed data extraction and quality assessment. RESULTS: Among the 31 studies included, 11 different definitions of polypharmacy were used and were based on three medication counting methods (concurrent use 15/31, cumulative use over a period 6/31, daily average 3/31, and indeterminate 7/31). Overall, polypharmacy was frequent and associated with higher fracture risk. A dose-response relationship between increasing number of medications and increased risk of fractures was observed. However, only seven studies adjusted for major confounders (age, sex, and chronic disease). The quality of the studies ranged from poor to high. CONCLUSIONS: Polypharmacy appears to be a relevant modifiable risk factor for fractures in older individuals that can easily be used to identify those at risk. The diversity of medication calculation methods and definitions of polypharmacy highlights the importance of a detailed methodology to understand and compare results.