Risks and benefits of oral modified-release compared with oral immediate-release opioid use after surgery: a systematic review and meta-analysis.

Prescription of modified-release opioids for acute postoperative pain is widespread despite evidence to show their use may be associated with an increased risk of adverse effects. This systematic review and meta-analysis aimed to examine the available evidence on the safety and efficacy of modified-release, compared with immediate-release, oral opioids for postoperative pain in adults. We searched five electronic databases from 1 January 2003 to 1 January 2023. Published randomised clinical trials and observational studies on adults who underwent surgery which compared those who received oral modified-release opioids postoperatively with those receiving oral immediate-release opioids were included. Two reviewers independently extracted data on the primary outcomes of safety (incidence of adverse events) and efficacy (pain intensity, analgesic and opioid use, and physical function) and secondary outcomes (length of hospital stay, hospital readmission, psychological function, costs, and quality of life) up to 12 months postoperatively. Of the eight articles included, five were randomised clinical trials and three were observational studies. The overall quality of evidence was low. Modified-release opioid use was associated with a higher incidence of adverse events (n = 645, odds ratio (95%CI) 2.76 (1.52-5.04)) and worse pain (n = 550, standardised mean difference (95%CI) 0.2 (0.04-0.37)) compared with immediate-release opioid use following surgery. Our narrative synthesis concluded that modified-release opioids showed no superiority over immediate-release opioids for analgesic consumption, length of hospital stay, hospital readmissions or physical function after surgery. One study showed that modified-release opioid use is associated with higher rates of persistent postoperative opioid use compared with immediate-release opioid use. None of the included studies reported on psychological function, costs or quality of life.

Impact of modified-release opioid use on clinical outcomes following total hip and knee arthroplasty: a propensity score-matched cohort study.

Modified-release opioids are often prescribed for the management of moderate to severe acute pain following total hip and knee arthroplasty, despite recommendations against their use due to increasing concerns regarding harm. The primary objective of this multicentre study was to examine the impact of modified-release opioid use on the incidence of opioid-related adverse events compared with immediate-release opioid use, among adult inpatients following total hip or knee arthroplasty. Data for total hip and knee arthroplasty inpatients receiving an opioid analgesic for postoperative analgesia during hospitalisation were collected from electronic medical records of three tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events during hospital admission. Patients who received modified with or without immediate-release opioids were matched to those receiving immediate-release opioids only (1:1) using nearest neighbour propensity score matching with patient and clinical characteristics as covariates. This included total opioid dose received. In the matched cohorts, patients given modified-release opioids (n = 347) experienced a higher incidence of opioid-related adverse events overall, compared with those given immediate-release opioids only (20.5%, 71/347 vs. 12.7%, 44/347; difference in proportions 7.8% [95%CI 2.3-13.3%]). Modified-release opioid use was associated with an increased risk of harm when used for acute pain during hospitalisation after total hip or knee arthroplasty.

How to design a study to evaluate therapeutic drug monitoring in infectious diseases?

BACKGROUND: Therapeutic drug monitoring (TDM) is a tool to personalize and optimize dosing by measuring the drug concentration and subsequently adjusting the dose to reach a target concentration or exposure. The evidence to support TDM is however often ranked as expert opinion. Limitations in study design and sample size have hampered definitive conclusions of the potential added value of TDM. OBJECTIVES: We aim to give expert opinion and discuss the main points and limitations of available data from antibiotic TDM trials and emphasize key elements for consideration in design of future clinical studies to quantify the benefits of TDM. SOURCES: The sources were peer-reviewed publications, guidelines and expert opinions from the field of TDM. CONTENT: This review focuses on key aspects of antimicrobial TDM study design: describing the rationale for a TDM study, assessing the exposure of a drug, assessing susceptibility of pathogens and selecting appropriate clinical endpoints. Moreover we provide guidance on appropriate study design. IMPLICATIONS: This is an overview of different aspects relevant for the conduct of a TDM study. We believe that this paper will help researchers and clinicians to design and conduct high-quality TDM studies.

Contraindicated drug-drug interactions associated with oral antimicrobial agents prescribed in the ambulatory care setting in the United States.

OBJECTIVES: Antimicrobial agents are commonly used in ambulatory care settings. Our objective was to examine national-level patterns of contraindications between oral antibacterial or antifungal agents and patients' other oral medications in the US ambulatory care setting. METHODS: This cross-sectional study included multiple year pooled data (2003-2011) from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey (NHAMCS Outpatient Department). Visits by adults (age ≥18 years) in ambulatory settings in the United States who were prescribed oral antibacterial or antifungal agents were evaluated for potential drug-drug interaction (DDI) contraindications. Findings with relative standard error >30% or unweighted sample size <30 were not reported because these were deemed unreliable estimates. RESULTS: From 2003 to 2011, there were 1 235 000 outpatient visits (proportion = 0.52%; 95% confidence interval (CI), 0.29-0.74) in which a patient was prescribed an antimicrobial agent associated with a contraindicated DDI. The most prevalent antimicrobials with contraindicated combination among outpatients were simultaneous use of macrolide-containing products (erythromycin or clarithromycin) with statin medication-containing products (simvastatin or lovastatin) (841 864 visits, proportion = 1.91%; 95% CI, 0.96-2.86). The next most common combination was use of fluoroquinolones with antiarrhythmic agents (amiodarone, sotalol, quinidine or procainamide) (365 622 visits, proportion = 0.19%; 95% CI, 0.06-0.32). CONCLUSIONS: Providers should be aware of potential contraindicated DDIs when prescribing antibiotics, especially macrolides and fluoroquinolones.

Effect of epinephrine on survival after cardiac arrest: a systematic review and meta-analysis.

The use of epinephrine is currently recommended as a treatment option for patients with cardiac arrest. The primary objective of this systematic review was to determine if epinephrine use during cardiac arrest is associated with improved survival to hospital discharge. MEDLINE, EMBASE, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, International Pharmaceutical Abstracts, and Biological Abstracts (BIOSIS Previews), and bibliographies of previous systematic reviews. Studies involving patients with cardiac arrest that compared epinephrine to no epinephrine (or placebo) with regard to survival to hospital discharge or 30-day survival. Randomized controlled trials (RCTs) and observational studies were included. The results were stratified into three groups: 1) RCTs, 2) observational studies with unadjusted data (observational-U), and 3) observational studies with adjusted data using multivariate analysis (observational-A). There were a total of 10 studies included in the systematic review and nine studies were included in the meta-analysis. The association between epinephrine use and survival to hospital discharge, grouped by study type was not significant for RCTs (OR 2.33, 95% CI 0.85 to 6.40; p=0.10; I2=0.00%) or observational-U studies (OR 1.17, 95% CI 0.67 to 2.07; p=0.58; I2=76.68%). But epinephrine was associated with decreased survival in observational-A studies (OR 0.43, 95% CI 0.40 to 0.48; P<0.01; I2=0.00%). Epinephrine use during cardiac arrest is not associated with improved survival to hospital discharge. Observational studies with a lower-risk for bias suggest that it may be associated with decreased survival.