International Journal of Clinical Pharmacy最新文献

Introduction: Predictive models play a critical role in enhancing medication safety in clinical practice. While multiple models for adverse drug reactions (ADRs) in adults have demonstrated potential clinical utility, pediatric-specific predictive models remain understudied, with limited comprehensive evaluation of their methodological quality and reporting standards.

Aim: To map the landscape of existing risk prediction models for ADRs specifically developed or validated for pediatric patients, and to describe their characteristics, methodological quality, and reporting completeness.

Method: A systematic search was conducted in Embase, PubMed, CNKI, Wanfang, VIP, and SinoMed for studies on pediatric ADR prediction models. The information from included studies was evaluated using the Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist, the risk of bias was assessed with the Prediction Model Risk of Bias Assessment Tool (PROBAST), and adherence to Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) guidelines was reviewed. Predictive ability of the included model, including the area under the receiver operating characteristic curve (AuROC), sensitivity, and specificity, was also reported.

Results: Out of 12,667 screened studies, 7 articles (describing 10 models) met the inclusion criteria. Study designs included case-control, nested case-control, prospective cohort, and cross-sectional studies. Logistic regression was the primary modeling method, with one study using machine learning. Common methodological limitations included unreported handling of missing data and univariable predictor screening. Model discrimination (AuROC) ranged from 0.63-0.97, with sensitivity and specificity between 52.02-98.50% and 33.33-98.79%, respectively. TRIPOD adherence varied (62.16-86.49%), with notable reporting deficiencies in blinding, sample size justification, intervention details, model usage instructions, and supplementary materials. No models underwent external validation.

Conclusion: Existing pediatric ADR prediction models are limited by methodological and reporting shortcomings. Future research should focus on rigorous model development and external validation to ensure generalizability across diverse clinical settings.

Introduction: Atrial fibrillation (AF) is a common cardiac arrhythmia with limited options for upstream prevention. While several anti-diabetic drugs have shown cardiovascular benefits, their potential role in modifying AF risk remains unclear.

Aim: This study aimed to evaluate the causal relationship between genetically proxied antidiabetic drug targets and the risk of AF using a drug-target Mendelian randomization (MR) approach.

Method: A two-sample MR analysis was conducted to investigate the association between genetic variants related to antidiabetic drug targets and AF. Thirty-eight FDA-approved glucose-lowering agents were identified, and their targets were extracted from the ChEMBL (Chemical Biology Database and Information System) database. Protein quantitative trait loci (pQTL) data from a large plasma proteome GWAS (Genome-Wide Association Study) were used to construct instrumental variables. Positive control testing was conducted to confirm that the selected drug targets were significantly associated with diabetes, using summary statistics from the UK Biobank, FinnGen, and other GWAS datasets. Causal effects on AF were evaluated using multiple independent GWAS cohorts for replication. MR methods included inverse-variance weighted (IVW), MR-Egger, and weighted median approaches with sensitivity analyses for pleiotropy and heterogeneity.

Results: The alpha-glucosidase inhibitor miglitol was causally associated with a reduced risk of AF. Specifically, miglitol was shown to inhibit lactase (LCT), a protein whose elevated levels were associated with increased AF risk (IVW, OR = 1.013; 95%CI, 1.007-1.018; P = 2.37 × 10⁻⁵). This association was confirmed using MR-Egger and weighted median methods and validated across multiple datasets. Sensitivity analyses did not reveal evidence of pleiotropy or confounding factors, supporting the robustness of the findings.

Conclusion: This study provides novel genetic evidence suggesting that miglitol may reduce AF risk through lactase inhibition. These findings highlight a potential opportunity for drug repurposing for cardiovascular prevention, particularly for clinical pharmacists managing patients with higher risks in cardiovascular outcomes meanwhile with type 2 diabetes. Further mechanistic and clinical studies are warranted to confirm these observations and explore their translational value in practice.

Background: Colorectal cancer and its treatment deeply impact patients' lives. Significant others, often family members, play crucial pre-existing roles in patients' lives and are closely involved in their care. However, there is limited understanding of the patients' treatment journey from the significant others' perspective.

Aim: To explore colorectal cancer patients' experiences with antineoplastic agents from the perspective of significant others over 24 weeks.

Method: This involved a longitudinal qualitative study with 16 significant others nominated by patients with colorectal cancer. Two in-depth interviews were conducted: one at start and another after 24 weeks of treatment. Interviews were audio-recorded, transcribed and thematically analysed by 2 researchers independently.

Results: Five themes were identified: Patients' perceptions and knowledge of the illness and treatment, the healthcare system in relation to the illness and treatment, patients' involvement in treatment decision-making and their experience of medicine-taking, medicine and illness-related impact on patients and others and personal support structures. Significant others observed that patients initially viewed treatment as curative but later perceived as means to extend life-expectancy. While significant others considered that concerns about aesthetics were initially prominent for the patient, fatigue and peripheral neuropathy became most impactful effects. They considered patients' experiences with cancer services to remain overall positive, particularly regarding personalised support from nurse navigators. Significant others noted that early establishment of support network was crucial for fostering resilience throughout the treatment journey.

Conclusion: This study provides insights from significant others highlighting the complex evolution of patients' experiences and importance of establishing a personalised support network early in treatment journey.

Introduction: Polypharmacy is a growing public health concern, yet its association with area-level socioeconomic deprivation in England has been under-explored.

Aim: To investigate whether socioeconomic deprivation, measured by the Index of Multiple Deprivation (IMD), is associated with polypharmacy among adults.

Method: We analysed cross-sectional data from the 2021 Health Survey for England, including 1705 adults aged 16+ who completed nurse visits and reported prescribed medication use in the past week. Polypharmacy was defined as the use of five or more prescribed medications. IMD scores were categorised into quintiles (least to most deprived). Multivariable logistic regression estimated adjusted odds ratios (ORs) with 95% confidence intervals (CIs), controlling for age, sex, ethnicity, multimorbidity, obesity, smoking, alcohol use, and GP visit frequency. A polynomial contrast test assessed linear trends, and adjusted predicted probabilities were calculated to illustrate the deprivation-polypharmacy gradient.

Results: In the fully adjusted model, adults residing in the most deprived IMD quintile had significantly higher odds of polypharmacy (OR 1.82; 95% CI 1.09-3.04; p = 0.022) compared to those living in the least deprived areas. No statistically significant associations were observed for intermediate quintiles. A polynomial contrast test confirmed a significant linear trend across IMD levels (p = 0.010), indicating that the odds of polypharmacy increased progressively with greater area-level deprivation. This gradient was further illustrated by adjusted predicted probabilities, which rose from 18.3% (95% CI 15.3-21.3%) in the least deprived quintile to 24.6% (95% CI 20.1-29.2%) in the most deprived (p < 0.001).

Conclusion: Socioeconomic deprivation is independently associated with polypharmacy, even after adjusting for multimorbidity and other confounders, highlighting persistent health inequalities within England's healthcare system. Targeted strategies, including regular medication reviews and enhanced access to care in deprived communities, may help mitigate risks and promote equity in prescribing practices.

Introduction: Vancomycin is a glycopeptide antibiotic commonly prescribed to treat severe gram-positive infections; however, it has a narrow therapeutic range and potentially induces nephrotoxicity following overdosing. Most studies have revealed that renal function is the main factor influencing vancomycin clearance. However, the effects of cardiac insufficiency, which usually occurs early following surgery and can cause changes in the pharmacokinetics of various drugs, likely due to decreased cardiac output, on vancomycin metabolism are poorly understood.

Aim: This study aimed to establish a vancomycin population pharmacokinetic model in patients undergoing cardiac surgery and simultaneously explore the effects of renal and cardiac functions on vancomycin pharmacokinetics.

Method: Three hundred twenty patients treated with vancomycin were enrolled. The patients' vancomycin treatment history, specific vancomycin administration and sampling times, and laboratory test results were obtained from the electronic medical records. The data were analyzed using nonlinear mixed effects modeling. Model accuracy and robustness were evaluated with a goodness-of-fit plot, bootstrap resampling, and visual predictive checks. The vancomycin dosage strategy was simulated with a virtual patient using the pharmacokinetic parameters of the established model in different clinical scenarios.

Results: A one-compartment model was used to determine vancomycin pharmacokinetics. The estimated clearance (CL) and distribution volume (V) of vancomycin were 3.22 L/h and 88.3 L, respectively. The interindividual variabilities in CL and V were 26.0% and 48.9%, respectively, while the corresponding interoccasion variabilities were 8.9% and 13.6%. CL decreased as serum creatinine (Scr), cystatin C (CysC) and N-terminal pro-B-type natriuretic peptide levels increased. V decreased as the CysC levels and neutrophil counts increased but increased with age. The highest percentage of the within 24-h target area under the concentration curve (400-650 mg*h/L) for the virtual patient across the different clinical scenarios was 52.4-65.2%.

Conclusion: A vancomycin population pharmacokinetic model was established for cardiac surgery patients. Both renal and cardiac functions have confirmed effects on vancomycin pharmacokinetics.

Introduction: Pharmacist prescribing is expanding across care settings, supported by pharmacists' expertise in pharmacology, therapeutics, disease management, and medication optimization. In settings where pharmacists can prescribe, patients and providers report positive outcomes. However, limited research has examined pharmacist prescribing in dialysis centers.

Aim: This study explored patient and clinician perspectives on potential pharmacist prescribing in the outpatient hemodialysis unit at Toronto General Hospital, University Health Network (TGH-UHN) in Toronto, Canada.

Method: Semi-structured, one-on-one interviews were conducted with English-speaking adults receiving hemodialysis, and clinicians, including nephrologists, pharmacists, dietitians, and nurse practitioners in the outpatient hemodialysis unit at TGH-UHN. Patient interviews focused on experiences receiving and filling prescriptions, interactions with pharmacists in the hemodialysis unit, and views on potential pharmacist prescribing in the unit. Clinician interviews explored the strengths and limitations of the current prescribing process in the hemodialysis unit, pharmacists' role in the unit, perceived benefits and challenges of potential pharmacist prescribing, and strategies for implementation. Participants were recruited through convenience sampling until data saturation was reached. Interviews were audio-recorded, transcribed, and analyzed thematically using an inductive approach.

Results: Eleven patients and 11 clinicians (six nephrologists, two pharmacists, two dietitians, and one nurse practitioner) were interviewed in June and July 2025. Reported challenges of the current prescribing process included communication gaps and delays in care, while accessibility of prescribers and interdisciplinary collaboration were identified as strengths. Pharmacists were recognized as valuable care team members for their expertise in medication management and rapport with patients. Anticipated benefits of pharmacist prescribing included improved medication optimization, workflow efficiency, timely care, and pharmaco-economic savings. Limited prescribing knowledge among some pharmacists was noted as a barrier. Implementation considerations included a collaborative approach, maintaining physician oversight, restricting prescribing to specific clinical areas, phased rollout, patient and clinician buy-in, adequate resources, and clearly defined roles and communication.

Conclusion: Patients and clinicians were generally supportive of potential pharmacist prescribing in the hemodialysis unit, contingent on several considerations for implementation. Interviews with additional stakeholders in other dialysis care settings could further inform strategies for broader adoption.

Introduction: The integration of learning from continuing professional development (CPD) activities into practice is shaped by behavioral, organizational, and broader system-level factors. However, there is scarce research utilizing theory to provide a comprehensive understanding of prevalent behavioral determinants.

Aim: To investigate key behavioral determinants that influence CPD participants' implementation of learning into their practice following participation in CPD activities.

Method: Eleven semi-structured interviews were conducted with healthcare professionals 4-6 weeks after they participated in a live, interactive CPD workshop. Interview questions were guided by the COM-B model to elucidate behavioral determinants; emerging themes were subsequently mapped to the COM-B domains. Recommended interventions were derived to optimize CPD outcomes using the Behavior Change Wheel (BCW).

Results: All participants (n = 11) reported applying their CPD learning in practice, either partially or fully). Analysis revealed that while Capability, Opportunity, and Motivation were all perceived to influence implementation, Motivation was an important driver, with professional responsibility and satisfaction from positive patient outcomes were also perceived to influence behavior. Opportunity was particularly challenging in community pharmacy settings due to time constraints, workload, and organizational factors. These findings informed targeted recommendations to optimize CPD implementation.

Conclusion: This study highlights the complex interplay of behavioral determinants that are perceived to influence the translation of CPD learning into routine clinical practice. Effective CPD programs should incorporate strategies to address setting-specific barriers-such as time constraints, emotional pressures, and organizational support to foster motivation and facilitate sustained practice change. Tailoring CPD design to these behavioral determinants can improve the integration of learning into practice and ultimately enhance patient care.

Introduction: Venous thromboembolism (VTE) is the leading cause of preventable hospital deaths. Adults hospitalised with psychiatric illness vary in their risk of VTE, and therefore in their likelihood of benefiting from thromboprophylaxis. There is a paucity of evidence-based practice guidelines addressing VTE prophylaxis for this population despite recognition of additional VTE risk factors in this population.

Aim: To develop an evidence-based guideline on VTE prophylaxis for patients hospitalised with psychiatric illness using Grading of Recommendations, Assessment, Development and Evaluation (GRADE).

Method: An international, multidisciplinary, guideline panel including clinical experts, methodologists, and a patient partner was recruited by invitation. Panelists were selected based on methodological and clinical expertise on this subject. Panel members were diverse in geography (from Ireland, the United Kingdom, France, and Canada), expertise and gender. The panel was composed of four advanced specialist psychiatric pharmacists, four consultant haematologists, four consultant psychiatrists, one advanced nurse practitioner in psychiatry, one advanced nurse practitioner in anticoagulation, a methodologist with expertise using GRADE, and a patient partner with lived experience of VTE. The panel prioritised two clinical questions and related population, interventions, outcomes, and secondary analyses according to their importance for patients. GRADE was used to assess certainty of evidence and to move from evidence to risk-stratified recommendations.

Results: The panel made three recommendations: a strong recommendation against parenteral pharmacological prophylaxis for patients at low risk of VTE (moderate-certainty evidence); a conditional recommendation in favour of parenteral pharmacological prophylaxis in high-risk patients (low-certainty evidence); and a strong recommendation against graduated compression stockings in patients at high risk of VTE with a contraindication to parenteral pharmacological prophylaxis (low-certainty evidence).

Conclusion: Clinicians should not use parenteral pharmacological prophylaxis in adults hospitalised with psychiatric illness at low risk of VTE; and should consider using parenteral pharmacological prophylaxis for high-risk adults with no contraindications. Graduated compression stockings are not recommended in high-risk patients when parenteral pharmacological prophylaxis is contraindicated. These GRADE- based recommendations offer one of the first evidence-based practice guidelines for thromboprophylaxis decisions in psychiatric in-patient settings.

Introduction: Drug recalls occur regularly with some resulting in medication switches for patients. Limited research into this topic suggests that drug recalls can lead to anxiety and unrest for patients which in turn can affect confidence in and use of medication. In this context, a better understanding of patient perceptions and communication preferences is essential to adequately handle drug recalls and ensure continued medication adherence and trust.

Aim: The aim of this study was to elucidate patients' experiences, perceptions, and preferences regarding drug recalls.

Method: This qualitative study comprised focus group discussions with patients that experienced a drug recall, recruited through pharmacies from distinct locations in the Netherlands. We aimed to conduct at least two focus groups, each comprising a minimum of six participants. Audio recordings were transcribed verbatim and analyzed using a thematic analysis approach.

Results: It was found that patients had limited knowledge of drug recall procedures, often confused them with shortages, and struggled to interpret associated risks. Communication was frequently perceived as unclear, triggering varied emotional responses and, in some cases, reduced trust in and use of medications. Patients preferred pharmacist-led, personalized communication tailored to recall urgency, and emphasized the importance of shared decision-making, particularly during medication substitutions.

Conclusion: Drug recalls cause a range of emotions in patients, leading to reduced confidence and use of medication in some patients. Preferences centered on understandable, transparent, and personalized communication led by pharmacists. The findings of this study emphasize the importance of embedding patient engagement and tailored communication within pharmacovigilance systems to maintain trust and support shared decision-making during drug recalls.

Introduction: Warfarin initiation strategies vary, with some clinicians using either a fixed-dose or loading-dose regimen to achieve therapeutic anticoagulation. However, evidence comparing their effectiveness in multiethnic Asian populations without genotype-guided dosing remains limited.

Aim: To compare a fixed-dose regimen with a 3-day loading-dose regimen in terms of international normalized ratio (INR) stability and time in the therapeutic range (TTR) over 12 months in a multiethnic atrial fibrillation (AF) cohort. We also aimed to evaluate the relationship between the time to initial INR stabilization and the subsequent anticoagulation quality.

Method: This multicenter, retrospective cohort study included 780 warfarin-naïve patients with AF from two tertiary hospitals (2010 to 2022). Patients were grouped by the initiation strategy: fixed-dose (n = 501) or 3-day loading-dose (n = 279). The primary outcome was the TTR at 3, 6, and 12 months. The association between time to INR stabilization and TTR was assessed using Spearman's correlation, and a General Linear Model (GLM) was used to adjust for comprehensive demographic and clinical confounders.

Results: The time to initial INR stabilization showed a strong inverse correlation with TTR across all time points (Spearman's r = -0.600 to -0.710; p < 0.001). Although the unadjusted analysis suggested that the INR stabilized faster in the loading-dose group (mean: 111.8 vs. 138.6 days; p < 0.001), this difference became insignificant after accounting for confounding factors (adjusted mean: 94.1 vs 104.1 days; p = 0.248). Similarly, adjusted means of TTRs did not differ significantly between regimens at 3, 6, or 12 months.

Conclusion: The choice between fixed-dose and loading-dose warfarin initiation strategies does not independently influence long-term anticoagulation control. Instead, time to initial INR stabilization is the strongest predictor of TTR quality over 12 months. Clinical efforts should prioritize early and intensive INR monitoring in settings without genotype-guided dosing, as both baseline characteristics and the ongoing clinical management likely determine anticoagulation outcomes.