OBJECTIVE: We aimed to evaluate the risk of colorectal adenocarcinoma (CRA) associated with long-term use of proton pump inhibitors (PPIs) in a large nationwide cohort.
METHODS: Retrospective cohort study.
METHODS: This research was conducted at the national level, encompassing the entire population of Sweden.
METHODS: This study utilised Swedish national registries to identify all adults who had ≥180 days of cumulative PPI use between July 2005 and December 2012, excluding participants who were followed up for less than 1 year. A total of 754 118 maintenance PPI users were included, with a maximum follow-up of 7.5 years.
METHODS: Maintenance PPI use (cumulative≥180 days), with a comparator of maintenance histamine-2 receptor antagonist (H2RA) use.
METHODS: The primary outcome measure was the risk of CRA, presented as standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). Subgroup analyses were performed to explore the impact of indications, tumour locations, tumour stages and the duration of follow-up. A multivariable Poisson regression model was fitted to estimate the incidence rate ratios (IRRs) and 95% CIs of PPI versus H2RA use.
RESULTS: Maintenance PPI users exhibited a slightly elevated risk of CRA compared to the general population (SIR 1.10, 95% CI=1.06 to 1.13) for both men and women. Individuals aged 18-39 (SIR 2.79, 95% CI=1.62 to 4.47) and 40-49 (SIR 2.02, 95% CI=1.65 to 2.45) had significantly higher risks than the general population. Right-sided CRA showed a higher risk compared to the general population (SIR 1.26, 95% CI=1.20 to 1.32). There was no significant difference in the risk of CRA between maintenance PPI users and maintenance H2RA users (IRR 1.05, 95% CI=0.87 to 1.27, p<0.05).
CONCLUSIONS: Maintenance PPI use may be associated with an increased risk of CRA, but a prolonged observation time is needed.

OBJECTIVE: This study compared three artificial intelligence (AI) platforms\' potential to identify drug therapy communication competencies expected of a graduating medical doctor.
METHODS: We presented three AI platforms, namely, Poe Assistant©, ChatGPT© and Google Bard©, with structured queries to generate communication skill competencies and case scenarios appropriate for graduating medical doctors. These case scenarios comprised 15 prototypical medical conditions that required drug prescriptions. Two authors independently evaluated the AI-enhanced clinical encounters, which integrated a diverse range of information to create patient-centred care plans. Through a consensus-based approach using a checklist, the communication components generated for each scenario were assessed. The instructions and warnings provided for each case scenario were evaluated by referencing the British National Formulary.
RESULTS: AI platforms demonstrated overlap in competency domains generated, albeit with variations in wording. The domains of knowledge (basic and clinical pharmacology, prescribing, communication and drug safety) were unanimously recognized by all platforms. A broad consensus among Poe Assistant© and ChatGPT© on drug therapy-related communication issues specific to each case scenario was evident. The consensus primarily encompassed salutation, generic drug prescribed, treatment goals and follow-up schedules. Differences were observed in patient instruction clarity, listed side effects, warnings and patient empowerment. Google Bard did not provide guidance on patient communication issues.
CONCLUSIONS: AI platforms recognized competencies with variations in how these were stated. Poe Assistant© and ChatGPT© exhibited alignment of communication issues. However, significant discrepancies were observed in specific skill components, indicating the necessity of human intervention to critically evaluate AI-generated outputs.

BACKGROUND: Critically ill patients are at risk of suboptimal beta-lactam antibiotic (beta-lactam) exposure due to the impact of altered physiology on pharmacokinetics. Suboptimal concentrations can lead to treatment failure or toxicity. Therapeutic drug monitoring (TDM) involves adjusting doses based on measured plasma concentrations and individualising dosing to improve the likelihood of improving exposure. Despite its potential benefits, its adoption has been slow, and data on implementation, dose adaptation and safety are sparse. The aim of this trial is to assess the feasibility and fidelity of implementing beta-lactam TDM-guided dosing in the intensive care unit setting.
METHODS: A beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring (ADAPT-TDM) is a single-centre, unblinded, feasibility randomised controlled trial aiming to enroll up to 60 critically ill adult participants (≥18 years). TDM and dose adjustment will be performed daily in the intervention group; the standard of care group will undergo plasma sampling, but no dose adjustment. The main outcomes include: (1) feasibility of recruitment, defined as the number of participants who are recruited from a pool of eligible participants, and (2) fidelity of TDM, defined as the degree to which TDM as a test is delivered as intended, from accurate sample collection, sample processing to result availability. Secondary outcomes include target attainment, uptake of TDM-guided dosing and incidence of neurotoxicity, hepatotoxicity and nephrotoxicity.
BACKGROUND: This study has been approved by the Alfred Hospital human research ethics committee, Office of Ethics and Research Governance (reference: Project No. 565/22; date of approval: 22/11/2022). Prospective consent will be obtained and the study will be conducted in accordance with the Declaration of Helsinki. The finalised manuscript, including aggregate data, will be submitted for publication in a peer reviewed journal. ADAPT-TDM will determine whether beta-lactam TDM-guided dose adaptation is reproducible and feasible and provide important information required to implement this intervention in a phase III trial.
BACKGROUND: Australian New Zealand Clinical Trials Registry, ACTRN12623000032651.

OBJECTIVE: To provide an initial understanding of problems and potential solution strategies for part-time clinical pharmacist work in China, and provide references for the training of part-time clinical pharmacists.
METHODS: The study was conducted in a tertiary teaching hospital in China, and the project lasted 6 months. Phenomenological methods were used to guide the research design. Research data were obtained by conducting one-to-one semistructured interviews with part-time clinical pharmacists, and interview data were coded and analysed through thematic analysis.
RESULTS: A total of 21 pharmacists were interviewed in a semistructured manner, and the results showed that following problems exist in the work of part-time clinical pharmacists: the existing professional knowledge is not adequate to meet the demands of clinical service; the career orientation of part-time clinical pharmacists is not clear; lack of professional self-confidence in clinical pharmacy practice; there is no suitable entry point to carry out pharmacy service work; it is difficult to communicate effectively, and for in addition, 17 potential solution strategies are proposed for the current problems, which can provide reference for the development of part-time clinical pharmacists\' work.
CONCLUSIONS: The work performed by part-time clinical pharmacists is currently immature and the strategies derived from this study may serve as potential solutions to resolve the part-time clinical pharmacy practice challenges.

BACKGROUND: Fibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current drugs used to treat fibromyalgia provide meaningful benefit to only 30-60% of treated individuals. Combining two or more different drugs is common in clinical practice with the expectation of better efficacy, tolerability or both; however, further research is needed to identify which combinations actually provide added benefit. Thus, we are planning a clinical trial to evaluate melatonin (MLT)-pregabalin (PGB) combination in participants with fibromyalgia.
METHODS: This will be a single-centre, double-blind, randomised, double-dummy, three-period, crossover trial comparing a MLT-PGB combination to each monotherapy in 54 adult participants satisfying the 2016 American College of Rheumatology criteria for fibromyalgia. Participants will receive maximally tolerated doses of MLT, PGB and MLT-PGB combination for 6 weeks. The primary outcome will be daily pain intensity (0-10); secondary outcomes will include the Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events and other measures. Analysis of the primary and secondary outcomes will involve a linear mixed model with sequence, period, treatment, the first-order carryover and baseline pain score as fixed effects and participant as a random effect to test whether there are any treatment differences among three treatments and to estimate the least square mean of the mean daily pain intensity for each treatment, adjusting for carryover as well as period effects (ie, stability of pain levels).
BACKGROUND: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN #18278231, has been granted ethical approval by the Queen\'s University Health Sciences Research Ethics Board (Queen\'s HSREB Protocol #6040998) and is currently under review for a Clinical Trial Application to Health Canada Natural and Non-prescription Health Products Directorate. All participants will provide written informed consent prior to trial participation. Following trial completion, results will be disseminated in one or more biomedical journal publications and presented at one or more scientific meetings.
BACKGROUND: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN18278231.

OBJECTIVE: We studied the pharmacokinetics and exposure-response relationships of the brentuximab vedotin (BV) antibody-drug conjugate (ADC) and unconjugated monomethyl auristatin E in haematologic malignancies.
METHODS: This population pharmacokinetic analysis included data from five adult and three paediatric studies. Exposures in virtual adult and paediatric populations following BV 1.8 mg/kg (maximum 180 mg) intravenously every 3 weeks were simulated. Clinical endpoints included overall response rate, grade ≥2 peripheral neuropathy (PN) and grade ≥3 neutropenia.
RESULTS: BV ADC exhibited linear pharmacokinetics, well-described by a three-compartment model, with body weight being the only significant covariate for exposure. Monomethyl auristatin E exhibited time-varying formation rate. Simulated steady-state BV ADC exposures in patients aged 12 to <18 years were similar to those of adult patients, but 23%-38% lower in patients aged 2 to <12 years. Despite lower exposure, clinical activity was observed with BV 1.8 mg/kg every 3 weeks in those aged 2 to <12 years (overall response rate: 2 to <12 years, 60%; 12 to <18 years, 43%). In adult, but not paediatric patients, increased BV ADC exposures were associated with grade ≥2 PN and grade ≥3 neutropenia occurrence.
CONCLUSIONS: BV pharmacokinetics in adult and paediatric patients were consistent. BV ADC exposures were lower in patients aged 2 to <12 years vs. ≥12 years, but no apparent clinically relevant differences in efficacy, grade ≥2 PN or grade ≥3 neutropenia were observed. These data support body weight-based dosing of BV in patients irrespective of age; thus, dose adjustment in those 2 to <12 years does not appear warranted.

BACKGROUND: Diabetes and depression are among the 10 biggest health burdens globally. They often coexist and exhibit a strong bidirectional relationship. Depression leads to decreased adherence to self-care activities. This impacts glycaemic control and worsens type 2 diabetes mellitus (T2D). Both conditions have a synergistic effect and lead to greater complications, hospitalisations, healthcare expenditure and a worse quality of life. There is no consensus on managing people with comorbid T2D and depression. Bupropion is an efficacious antidepressant with many properties suitable for T2D with depression, including a favourable metabolic profile, persistent weight loss and improvement in sexual dysfunction. We will assess the efficacy and safety of add-on bupropion compared with standard care in people with T2D and mild depression. This study can give valuable insights into managing the multimorbidity of T2D and depression. This can help mitigate the health, social and economic burden of both these diseases.
METHODS: This cross-over randomised controlled trial will recruit people with T2D (for 5 years or more) with mild depression. They will be randomised to add-on bupropion and standard care. After 3 months of treatment, there will be a washout period of 1 month (without add-on bupropion while standard treatment will continue). Following this, the two arms will be swapped. Participants will be assessed for glycosylated haemoglobin, adherence to diabetes self-care activities, lipid profile, urine albumin-to-creatinine ratio, autonomic function, sexual function, quality of life and adverse events.
BACKGROUND: The Institutional Ethics Committee at All India Institute of Medical Sciences, Jodhpur has approved this study (AIIMS/IEC/2022/4172, 19 September 2022). We plan to disseminate the research findings via closed group discussions at the site of study, scientific conferences, peer-reviewed published manuscripts and social media.
BACKGROUND: CTRI/2022/10/046411.

OBJECTIVE: To assess antibiotic prescribing practice and its determinants among outpatient prescriptions dispensed to the elderly population.
METHODS: A prescription-based, cross-sectional study.
METHODS: Six community chain pharmacies in Asmara, Eritrea.
METHODS: All outpatient prescriptions dispensed to the elderly population (aged 65 and above) in the six community chain pharmacies in Asmara, Eritrea.
METHODS: Data were collected retrospectively, between 16 June 2023 and 16 July 2023. Antibiotic prescribing practice was assessed using the 2023 World Health Organization (WHO) Access, Watch and Reserve (AWaRe) classification system. Descriptive statistics and logistic regression were performed using IBM SPSS (V.26.0). P values less than 0.05 were considered as significant.
RESULTS: Of the 2680 outpatient prescriptions dispensed to elderly population, 35.8% (95% CI: 34.0, 37.6) contained at least one antibiotic. Moreover, a total of 1061 antibiotics were prescribed to the elderly population. The most commonly prescribed antibiotics were ciprofloxacin (n=322, 30.3%) and amoxicillin/clavulanic acid (n=145, 13.7%). The Access category accounted for the majority of antibiotics (53.7%) with 32.1% from the Watch category. Prescriber qualification (Adjusted Odds Ratio (AOR)= 0.60, 95% CI: 0.44, 0.81) and polypharmacy (AOR= 2.32, 95% CI: 1.26, 4.27) were significant determinants of antibiotic prescribing in the elderly population. Besides, sex (AOR=0.74, 95% CI: 0.56, 0.98), prescriber qualification (AOR=0.49, 95% CI: 0.30 to0.81) and level of health facility (AOR 0.52, 95% CI 0.34 to 0.81) were significant determinants of a Watch antibiotic prescription.
CONCLUSIONS: Antibiotics were prescribed to a considerable number of the elderly population, with more than half of them falling into the Access category. Further efforts by policy-makers are needed to promote the use of Access antibiotics while reducing the use of Watch antibiotics to mitigate risks associated with antimicrobial resistance.

暂无摘要。

暂无摘要。