International Journal of Clinical Pharmacy最新文献

Introduction: Rational prescribing is challenging due to global antibiotic resistance and widespread polypharmacy. Evidence on effective interventions to improve prescribing practices in MENA is limited.

Aim: This systematic review and meta-analysis evaluated the effectiveness of multifaceted and educational interventions in improving WHO/INRUD prescribing indicators in the Middle East and North Africa (MENA).

Method: We searched PubMed, Scopus, and CINHAL up to June 10, 2025, for experimental studies evaluating the effectiveness of multifaceted interventions on WHO/INRUD prescribing indicators. Searches were supplemented by screening reference lists of relevant reviews, first 20 pages of Google Scholar results, and ResearchRabbit.ai for citation-chaining to identify additional records. Primary outcomes included WHO/INRUD prescribing indicators: average number of drugs per prescription, percentage of encounters with an antibiotic prescribed, percentage of encounters with an injection prescribed, percentage of drugs prescribed by generics, and percentage of drugs prescribed from the essential medicines list. Methodological quality was assessed with the MASTER scale. Meta-analysis used a bias-adjusted inverse-variance heterogeneity model adjusted with quality score. Heterogeneity and publication bias were assessed using I², the Doi plot, and LFK index.

Results: Sixteen studies (seven RCTs, six pre-post, three quasi-experimental) from Iran, UAE, Egypt, Sudan, Lebanon, Saudi Arabia, and Palestine were included. Multifaceted interventions modestly reduced the average number of drugs per prescription (weighted mean difference WMD - 0.10, (95% CI - 0.18 to -0.02; I² = 99.8%). There was a downward trend in the odds of prescriptions with antibiotics (OR 0.65; 95% CI 0.41 to 1.03, I² = 93.5%) and injections (OR 0.93, 95% CI 0.82 to 1.04, I² = 25.3%), though these did not reach statistical significance and confidence intervals included the possibility of no effect. Meta-analysis revealed extreme statistical heterogeneity (I² up to 99.8%), and the GRADE certainty of evidence was low to very low for all outcomes.

Conclusion: Multifaceted interventions in the MENA region demonstrate potential for modest improvements in prescribing indicators, though evidence certainty remains low to very low. With non-significant pooled effects for antibiotics and injections, these exploratory findings suggest that context-specific stewardship and prescribing quality programs can achieve targeted improvements, but also highlight the need for more locally led, rigorous research with longer follow-up to inform policy decisions.

Introduction: With the rising global prevalence of diabetes, traditional hospital-centered healthcare models are becoming increasingly inadequate to meet patients' long-term management needs. Community pharmacy services have the potential to address these gaps. However, systematic research on patient preferences for such services remains limited.

Aim: This study aimed to determine the factors influencing diabetic patients' preferences for community pharmacy service models using a discrete choice experiment (DCE), and to explore how these preferences vary according to glycemic control status.

Method: Attributes and levels of DCE were identified through literature review, expert consultation, and patient pretesting. Six attributes were included: service content, service provider, follow-up program, reduction in cardiovascular events, reduction in hypoglycemic events, and service costs. A mixed orthogonal design generated 18 choice sets, with one scenario serving as reference. The survey was conducted face-to-face with patients with type 2 diabetes attending three community health service centers in Nanjing, China. Conditional logit models were applied to estimate attribute importance and subgroup analyses were performed based on HbA1c levels.

Results: Of the 237 respondents, 190 provided valid responses (response rate: 80.1%). Across the overall sample, the most influential attributes were pharmacy service content (Wald = 389.188, relative attribute importance [RAI] = 4.59), followed by the frequency of hypoglycemic reactions (Wald = 284.155, RAI = 4.19), service cost (Wald = 168.079, RAI = 4.07), reduction in cardiovascular events (Wald = 144.608, RAI = 3.38), service providers (Wald = 142.913, RAI = 3.29), and follow-up programs (Wald = 50.644, RAI = 1.15). Patients preferred drug effectiveness assessments over counselling or adverse reaction monitoring, valued collaborative care involving pharmacists and physicians, and demonstrated willingness to pay approximately ¥20 per session. Subgroup analyses revealed that patients with HbA1c ≤ 8% were more cost-sensitive and favored fixed-interval follow-up, whereas those with HbA1c > 8% preferred individualized follow-up programs and placed less emphasis on service costs.

Conclusion: Patients with diabetes prioritize service quality, outcome-driven care, and multidisciplinary collaboration when selecting community pharmacy services. While hypoglycemia reduction and cost are important across groups, preferences vary according to glycemic control, highlighting the need for tailored patient-centered service models. These findings provide evidence to guide the development of sustainable and responsive community pharmacy services.

Introduction: Direct Healthcare Professional Communications (DHPCs) alert healthcare professionals of important safety information relating to medication(s) and of the need to adapt practices with respect to these. International evidence suggests that their implementation varies in clinical practice. To date, few studies have examined implementation of DHPCs in primary care.

Aim: To examine how general practitioners (GPs) and community pharmacists implement DHPCs in Ireland and their preferences for receiving medication safety updates.

Method: A national cross-sectional survey of GPs and pharmacists in collaboration with the Irish Health Products Regulatory Authority (HPRA), was conducted in June 2024. GPs and CPs were invited to participate via national gatekeepers (Irish College of GPs, Pharmaceutical Society of Ireland). Following piloting, the questionnaire were administered via email using Qualtrics. Data was analysed using R and R Studio.

Results: A total of 277 GPs and 219 pharmacists completed the questionnaire, a response rate of 6% and 8% respectively. Most GPs (n = 227, 82%) and pharmacists (n = 196, 89%) reported DHPCs as their preferred source of medication safety updates. Practice protocols for sharing DPHCs once received differed across the two professional groups. For example, DHPCs were more likely to be disseminated and discussed at a pharmacy practice meeting (n = 64 pharmacists, 29%) compared with GP practice meetings (n = 24 GPs, 9%). More than one-third of GPs (n = 98, 35%) identified time constraints as the most important barrier to DHPC implementation, followed by absence of prescribing notifications on patient electronic health records (EHRs), n = 36 GPs (13%), n = 39 CPs (18%). A total of 257 GPs (93%) and 198 CPs (90%) identified patient EHR prescribing alerts, aligned with DHPC recommendations, integrated at the point of patient care as a preferred way to support implementation.

Conclusion: Surveyed GPs and pharmacists use DHPCs as their primary information source for new medication safety alerts and most reported these communications as very useful. Repeated DHPC communications across different modalities were valued. Barriers to implementation included time constraints and lack of point of care alerts for both GPs and pharmacists. Remote clinical support is acceptable to GPs and pharmacists and may support the implementation of DHPC recommendations to optimise medication safety in primary care.

Background: Mental disorders constitute a major global public health concern, particularly among the working-age population. Their impact extends beyond reduced productivity and long-term economic loss. This study presents a comprehensive assessment of the global burden of mental disorders among working-age adults and compares trends in the three most populous countries, India, China, and the United States, from 1990 to 2021, with projections through 2045.

Aim: To evaluate age-, sex-, and country-specific trends in the prevalence, incidence, and disability-adjusted life years (DALYs) of mental disorders among working-age adults, and to forecast future disease burden using advanced modeling techniques.

Method: Data for individuals aged 15-64 years were derived from the Global Burden of Disease Study 2021. The analysis was stratified by sex, age, country, and type of disorder. Age-standardized prevalence and incidence rates were calculated and temporal trends were quantified using the estimated annual percentage change. Significant inflection points were detected using the Joinpoint regression. Future DALYs (2022-2045) were projected using the Nordpred age-period-cohort model based on historical trends and population forecasts. All analyses were conducted using the R software (version 4.4.3).

Results: Globally, the overall burden of mental disorders remained relatively stable from 1990 to 2021; however, substantial heterogeneity was observed across sex, age groups and countries. Females consistently demonstrated a higher prevalence of depressive and anxiety disorders, whereas males exhibited higher rates of schizophrenia, attention deficit/hyperactivity disorder, and autism spectrum disorders. In the United States, both the prevalence and incidence increased markedly for most mental disorders, whereas China and India showed overall declining trends. Age-stratified analyses revealed a high disease burden among adolescents and young adults, alongside a pronounced and continuing increase in the middle-aged and older populations. Projections through 2045 suggest a further rise in DALYs, particularly among females and individuals aged 50-54 years, indicating a worsening global burden of mental disorders.

Conclusion: This study provides the most detailed, age-stratified evaluation of mental disorder burden among working-age populations to date. The findings highlight persistent gender and regional disparities and demonstrate the urgent need for scalable, culturally sensitive mental health interventions, workforce-based support systems, and the integration of mental health care into primary and occupational health frameworks.

Introduction: Mental disorders represent a significant global burden, with a high proportion of depressive disorders. Antidepressants (ADs) are the most prescribed drugs for treating mental disorders, with broad indications, e.g. depression, anxiety disorders, and off-label use.

Aim: This study assesses current and historical changes in AD consumption in 25 European countries, predicts future developments, and further analyses ATC subgroup consumption in 13 countries.

Method: Consumption data for ADs (ATC code N06A) were collected from the OECD Data Explorer. Subgroup data came from publicly available sources. The time span covered is 1980 to 2024. Changes in defined daily doses per 1000 population per day (DID) were analysed, and projections to 2030 were made using Auto Regressive Integrated Moving Average models. Treatment coverage for depressive disorder prevalence was also calculated.

Results: In 2023, AD consumption ranged from 26.3 DID (Latvia) to 164.7 DID (Iceland). Use increased in nearly all countries, except Luxembourg (- 0.3 DID between 2013 and 2022). Increases ranged from + 5.9% (Austria) to + 157.8% (Latvia). Forecasts predict further increases in most countries (+ 0.1 to + 80.9%), with decreases projected for Hungary, Austria, the UK, and Luxembourg (- 3.4 to - 21.7%). Selective serotonin reuptake inhibitors (SSRIs) are the most used subgroup, with mixed developments. The second most used is miscellaneous, with growing shares in most countries. Non-selective monoamine reuptake inhibitors (NSMRIs) are declining, while monoamine oxidase inhibitors (MAO-Is) and monoamine oxidase A inhibitors (MAOA-Is) have very low shares. Northern Europe shows the highest AD use versus Eastern Europe the lowest. All regions primarily use SSRIs. Northern Europe has a higher miscellaneous share, while Eastern Europe uses more NSMRIs.

Conclusion: AD use has increased and is projected to continue rising in most countries, with changing subgroup preferences. The dominance of SSRIs reflects first-line treatment recommendations. Increased miscellaneous use may indicate more individualised treatment and better tolerability. NSMRIs are declining due to adverse effects, and MAO-Is as well as MAOA-Is are rarely used due to safety concerns. Prescribing patterns vary across regions, influenced by health systems, cultural differences, stigma, and healthcare resources.

Introduction: Casimersen is an antisense oligonucleotide used to treat patients with Duchenne muscular dystrophy (DMD), with mutations amenable to exon 45 skipping. However, real-world safety data are limited.

Aim: This study used the Food and Drug Administration Adverse Event Reporting System (FAERS) database to describe post-marketing adverse event reporting patterns associated with casimersen, identify disproportionality signals at the preferred term level, and characterize their onset patterns and affected organ systems.

Method: FAERS reports from 2004 to 2024 involving casimersen were extracted, deduplicated, and coded using the Medical Dictionary for Regulatory Activities (MedDRA). Disproportionality analyses were performed using four validated algorithms: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Empirical Bayesian Geometric Mean (EBGM). Signals that met all four criteria were considered statistically significant. Time-to-onset and subgroup analyses according to age and sex were also performed.

Results: Among 21,964,449 FAERS reports, 598 listed casimersen as the primary suspect, predominantly in males (98.5%) and patients aged < 18 years (62.0%). The median time to AE onset was 253 days (range, 101-490 days). Twenty-one System Organ Classes (SOCs) were implicated, including injury, poisoning, procedural complications (n = 377), vascular disorders (n = 85), product issues (n = 80), and social circumstances (n = 13). Using all four algorithms, 30 significantly preferred terms (PTs) were identified, encompassing heterogeneous reporting categories, including clinically oriented terms as well as administration-related, medication use, and non-specific descriptors, such as product dose omission, poor venous access, proteinuria, hematuria, chromaturia, underdose, illness, and infusion-site extravasation.

Conclusion: This study characterized post-marketing adverse event reporting patterns associated with casimersen using FAERS data. By summarizing the preferred term-level reporting distributions, affected organ system categories, and time-to-onset characteristics, the findings provide a descriptive overview of real-world reporting patterns following casimersen use. These results may inform post-marketing pharmacovigilance activities and support hypothesis generation in future studies.

Primary care is critical for supporting health, yet access to family physicians and nurse practitioners is less than ideal in many countries. One solution to improve access to primary care is to expand the scope of practice for other primary healthcare professionals, such as pharmacists. Building on this approach, some countries have created community pharmacy care clinics to further improve access to primary care services provided by pharmacists working to full scope of practice. As the role of pharmacists in primary care increases and community pharmacy care clinics become more prevalent, it is important to assess the effect on health service utilization and health outcomes. While the emergency department visit rate is a widely accepted indicator for access to primary care, there is currently no framework to evaluate the impact of pharmacists on emergency department visits. Frameworks based on International Classification of Diseases codes provide health services researchers with a standardized approach to present and analyze administrative health data. In this commentary, we describe the development of a framework to identify and classify emergency department visits that may be impacted by pharmacists providing primary care services in a community pharmacy care clinic. The framework covers three mutually exclusive groups of conditions: a subset of primary care sensitive conditions that can be managed by community pharmacists, conditions attributable to an adverse medication event, and conditions attributable to medically appropriate referrals to an emergency department. The conditions included within these groups provide a broad overview of potential benefits and unintended harms that may occur when pharmacists are involved in providing primary care services. This framework can be used to characterize changes in health service utilization and health outcomes that may occur as pharmacists become more actively involved in providing primary care services.

Introduction: Regulatory reviews in 2023-2024 reignited concern about possible suicidality with Glucagon-like peptide-1 (GLP-1) receptor agonists used for weight management. While clinical trials and real-world studies have not confirmed an increased risk, comparative post-marketing analyses across all anti-obesity agents are scarce.

Aim: To compare disproportional reporting of suicidality-related adverse events among GLP-1/dual incretin versus non-GLP-1 anti-obesity drugs in the FDA Adverse Event Reporting System (FAERS).

Method: We conducted a retrospective disproportionality study using FAERS (January 2012-February 2025). Reports submitted from the United States with the study drug listed as primary suspect were retrieved via openFDA. Suicidality terms were predefined (MedDRA Preferred Terms: suicidal ideation, suicide attempt, completed suicide). Reporting Odds Ratios (RORs) with 95% confidence intervals (CIs) were calculated for each drug and at class level (GLP-1/dual incretin vs non-GLP-1). Haldane-Anscombe corrections were applied where needed.

Results: Among approximately 78,000 anti-obesity reports, 207 (approximately 0.3%) involved suicidality-related events. For semaglutide, RORs were 1.39 (95% CI 0.99-1.94) for suicidal ideation, 1.38 (0.46-4.15) for suicide attempt, and 1.72 (0.62-4.74) for completed suicide, none statistically significant. Liraglutide showed ROR 1.01 (0.66-1.55) for suicidal ideation and 18.11 (6.96-47.15) for completed suicide based on 14 cases. Tirzepatide yielded RORs below unity for all outcomes. Naltrexone/bupropion showed elevated disproportional reporting for suicidal ideation (ROR 3.84; 95% CI 2.89-5.12) and suicide attempt (ROR 4.11; 95% CI 1.62-10.45.

Conclusion: GLP-1 and dual-incretin agents did not show disproportionality signals for suicidal ideation or suicide attempt. A statistically significant disproportionality signal for completed suicide was observed for liraglutide; however, this estimate was based on few cases and displayed wide confidence intervals, warranting cautious interpretation. These findings support an overall neutral psychiatric safety profile for incretin-based therapies while underscoring the need for continued monitoring of rare events such as completed suicide.

Background: Infliximab (IFX), a monoclonal antibody that neutralizes tumor necrosis factor-α, is widely used as a biologic treatment for Crohn's disease (CD). Despite its established efficacy, a substantial proportion of patients develop subtherapeutic IFX trough concentrations (< 3 μg/mL), leading to diminished clinical response and treatment failure. Early identification of high-risk individuals remains challenging due to the multifactorial nature of IFX pharmacokinetics.

Aim: This study integrated Least Absolute Shrinkage and Selection Operator (LASSO)-based variable selection with multivariable logistic regression to identify CD patients at risk for subtherapeutic IFX trough levels during induction.

Method: A total of 347 patients diagnosed with CD who commenced IFX induction therapy at the Sixth Affiliated Hospital of Sun Yat-sen University from January to December 2023 were retrospectively reviewed in this study. Comprehensive demographic, clinical, and biochemical data were retrieved from electronic records. Variable selection was performed using the Least Absolute Shrinkage and Selection Operator (LASSO), after which a multivariable logistic model was developed. Model discrimination, calibration and clinical usefulness were assessed through the area under the receiver operating characteristic curve (AUC), calibration curves, decision curve analysis (DCA) and clinical impact curves (CIC).

Results: Of the 347 participants, 148 (42.7%) exhibited subtherapeutic IFX trough concentrations. LASSO and multivariable logistic analyses identified four independent predictors: older age at diagnosis (> 40 years), elevated anti-drug antibody levels, higher erythrocyte sedimentation rate and reduced albumin (P < 0.05). The model demonstrated an AUC of 0.737 (95% CI 0.684-0.790), with a bootstrap-adjusted AUC of 0.726 (95% CI 0.697-0.739) based on 1000 resamples. Calibration demonstrated close alignment with observed outcomes, validated by a non-significant Hosmer-Lemeshow test (χ² = 8.447, P = 0.391). DCA and CIC analyses indicated meaningful clinical utility.

Conclusion: The proposed LASSO-logistic regression model demonstrates promising predictive performance for identifying subtherapeutic IFX exposure in CD patients. By leveraging readily available clinical data, it enables early risk stratification and individualized therapeutic decision-making, thereby facilitating more effective treatment optimization.

Introduction: The effectiveness of infliximab in Crohn's disease is often compromised by immunogenicity. Oral low-dose methotrexate may offer a promising strategy to optimize infliximab therapy, yet its real-world effectiveness and safety remain uncertain.

Aim: This study aimed to compare the effectiveness and safety of infliximab plus oral low-dose methotrexate versus infliximab monotherapy.

Method: In this single-center retrospective cohort study, 119 patients with Crohn's disease received either infliximab monotherapy (n = 99) or combination therapy with oral low-dose methotrexate (10-15 mg/week; n = 20). The primary outcome was endoscopic remission (Simple Endoscopic Score for Crohn's Disease ≤ 2) at week 26. Propensity score methods, including nearest-neighbor matching and inverse probability of treatment weighting, were used to adjust for confounding. Conditional and weighted logistic regression were used to estimate treatment effects.

Results: After propensity score adjustment, combination therapy was associated with a significantly higher rate of endoscopic remission (aOR 3.70, 95% CI 1.16-11.75; P = 0.027). No significant differences were observed in endoscopic response or clinical outcomes. In a pharmacokinetic subgroup, combination therapy resulted in numerically higher infliximab trough concentrations and no detectable anti-drug antibodies (0% vs. 16.7%). Higher trough concentrations were associated with endoscopic remission (P = 0.033). The incidence of elevated liver enzymes was higher in the combination group (20.0% vs. 4.0%), but this difference was not statistically significant after adjustment (P = 0.058).

Conclusion: In patients with Crohn's disease, oral low-dose methotrexate combined with infliximab was associated with significantly improved endoscopic remission at week 26 compared to infliximab monotherapy, without a statistically significant increase in adverse events.