The latest medical research on Clinical Pharmacology

Despite developing a polypharmacy core outcome set (COS) in primary care, it is not clear how these outcomes should be measured.

To select outcome measurement instruments (OMIs) for a COS targeting appropriate polypharmacy in older patients in primary care.

Following the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guideline, OMIs were identified from a Cochrane review focusing on appropriate polypharmacy. The quality of OMIs was assessed using a published checklist. Subsequently, two rounds of Delphi questionnaires were conducted via the SoGoSurvey® platform, engaging stakeholders (researchers, clinicians and journal editors specialising in geriatric primary care) to achieve consensus on OMIs using a scale encompassing "agree", "disagree", or "unsure". Consensus was achieved if 70% or more participants chose "agree" and 15% or fewer chose "disagree."

The quality of 20 OMIs identified from the Cochrane review was evaluated. Seven OMIs were selected based on meeting the COSMIN guideline's minimum requirements. Out of 188 potential participants, 57 (30.3%) consented to participate. Rounds 1 and 2 of Delphi exercises were completed by 50 respondents, achieving agreement on three OMIs: 'number of serious adverse drug reactions (ADRs)' (98%), 'number of deaths' (76%), and 'number of patients who fell' (70%) for measuring 'serious ADRs,' 'mortality,' and 'falls,' respectively. No agreement was reached for 'medication appropriateness,' 'medication side-effects,' 'quality of life,' and 'medication regimen complexity.'

OMIs were selected for a limited number of outcomes in the polypharmacy COS. Future research should identify suitable OMIs for the remaining four outcomes.

Proton pump inhibitors (PPIs) are commonly prescribed for treating upper gastrointestinal hemorrhage, eradicating Helicobacter pylori, and stress ulcer prophylaxis, among other digestive system diseases. Recent case reports provided limited evidence of a correlation between PPIs and drug reactions with eosinophilia and systemic symptoms (DRESS). However, there is currently no established association between PPIs and DRESS.

This research aimed to identify the associations between PPIs and DRESS using the US Food and Drug Administration Adverse Events Reporting System (FAERS) database.

A retrospective investigation of DRESS associated with six PPIs used FAERS data from Q1 2004 to Q3 2023. Data mining algorithms were used to identify adverse events in the FAERS database that met the following criteria: (1) proportional reporting ratio (PRR) ≥ 2; (2) reporting odds ratio (ROR) > 1; (3) 95% confidence interval (CI) of ROR > 1; (4) Chi-square (χ2) ≥ 4 and case count ≥ 3.

There were 495 reports of PPI-related DRESS, including pantoprazole (174, 35.2%), omeprazole (103, 20.8%), lansoprazole (103, 20.8%), esomeprazole (101, 20.4%), rabeprazole (8, 1.6%), and dexlansoprazole (6, 1.2%). The results indicated a significant association of three PPIs (pantoprazole, omeprazole, and lansoprazole) with DRESS. The sensitivity analysis demonstrated that only pantoprazole remained significantly associated with DRESS after 10 concomitant drugs had been removed (ROR: 3.00, PRR: 2.99, and information component [IC]: 1.57).

This study identified the signals suggesting a potential association between DRESS and six PPIs. However, more investigation of epidemiological data is required to validate of these conclusions.

Provision of take-home naloxone (THN) and overdose education reduces opioid-related mortality. In Australia, from July 2022, all Australian community pharmacies were eligible to supply naloxone for free through the national THN Program.

This study aimed to identify naloxone stocking rates and correlates of stocking naloxone across Australian pharmacies.

Data were collected from a representative sample of Australian pharmacists in Victoria, New South Wales, Queensland and Western Australia via an online survey. Data collected included pharmacy and pharmacist characteristics and services offered within the pharmacy, including needle and syringe programs, opioid agonist treatment (OAT) and stocking naloxone. Binary probit regression analysis was used to identify correlates of stocking naloxone after controlling for key covariates.

Data from 530 pharmacists were analysed. In total, 321 pharmacies (60.6%) reported stocking naloxone. Chain pharmacies and pharmacies that provided OAT had a greater probability of stocking naloxone (B = 0.307, 95%CI: [0.057, 0.556], and B = 0.543, 95%CI: [0.308, 0.777] respectively). Most (61.7%) pharmacists felt comfortable discussing overdose prevention with patients who use prescription opioids, and this comfort was associated with a higher probability of stocking naloxone (B = 0.392, 95%CI: 0.128, 0.655). Comfort discussing overdose prevention with people who use illicit opioids was lower (49.4%) and was not associated with stocking naloxone.

There is scope to increase stocking of naloxone and comfort with overdose prevention, particularly through addressing comfort working with higher risk groups such as people who use illicit opioids.

Tirzepatide was approved to treat type 2 diabetes and obesity, but its efficacy and safety in patients without diabetes has not been investigated.

This meta-analysis aimed to evaluate the efficacy and safety of tirzepatide compared to placebo in overweight or obese patients without diabetes.

PubMed, Embase and Cochrane were searched on January 18, 2024. Randomized controlled trials (RCTs) that used tirzepatide in overweight or obese adults without diabetes were included. Efficacy outcomes included the proportion of participants achieving weight loss targets, changes in body weight (%), body mass index (BMI), waist circumference (WC), and blood pressure (BP). Safety outcomes were commonly reported adverse events. Standardized mean differences (SMD) or odds ratios (OR) with 95% confidence intervals (CIs) were used for continuous and dichotomous outcomes, respectively.

Three RCTs with 3901 participants were included. Tirzepatide was associated with increased proportion of participants achieving weight loss targets, reduced body weight (SMD - 1.61, 95% CI - 2.20 to - 1.02), BMI (SMD - 2.13, 95% CI - 3.08 to - 1.18), WC (SMD - 0.91, 95% CI - 1.14 to - 0.69), and BP versus placebo. However, the risk of adverse events such as nausea (OR 4.26, 95% CI 2.60 to 3.81), vomiting (OR 8.35, 95% CI 5.19 to 13.45), and diarrhea (OR 3.57, 95% CI 2.80 to 4.57) was significantly higher for tirzepatide versus placebo.

Tirzepatide significantly reduced weight and improved metabolic markers among overweight or obese without diabetes. However, increased adverse events highlights the need for benefits versus risks assessment before initiation and continuous monitoring.