Outcomes from hematopoietic stem cell transplantation following treosulfan-based conditioning: A clinical and pharmacokinetic analysis.

BACKGROUND: The aims of this study are to report our experience with treosulfan-based conditioning regimens for patients with non-malignant hematologic conditions, correlating clinical outcomes at different time points post-transplant with treosulfan exposure (AUC). METHODS: This study was a single-center observational study investigating overall survival (OS), disease-free survival (DFS), and event-free survival (EFS) end-points post-transplant. The consequences of treosulfan AUC with respect to toxicity, correction of underlying disease, and long-term chimerism were also explored using pharmacokinetic analysis. RESULTS: Forty-six patients received 49 transplants with treosulfan and fludarabine-based conditioning between 2005 and 2023. Twenty-four patients also received thiotepa. Donor chimerism was assessed on either whole blood or sorted cell lines at different time points post-transplant. Thirty-nine patients received treosulfan pharmacokinetic assessment to evaluate cumulative AUC, with five infants receiving real-time assessment to facilitate daily dose adjustment. OS, DFS, and EFS were 87%, 81%, and 69%, respectively. Median follow-up was 32.1 months (range 0.82-160 months) following transplant. Lower EFS was associated with patient age (<1 year; p = .057) and lower cumulative treosulfan dose (<42 g/m2; p = .003). Stable donor chimerism in B-cell, NK-cell, and granulocyte lineages at 1-year post-transplant were more prevalent in patients receiving thiotepa conditioning. Two infants required daily dose adjustment to treosulfan to avoid high AUC. CONCLUSIONS: Excellent clinical outcomes and stable chimerism were observed in this patient series. The addition of thiotepa conferred no significant toxicity and trended toward sustained ongoing donor engraftment. Correlating treosulfan AUC with long-term patient outcomes is required.

Conscientious objection - a cross-sectional, vignette-based, mixed methods exploration of Australian pharmacists' perspectives.

Background: Conscientious objection (CO) in healthcare is a controversial topic. Some perceive CO as freedom of conscience, others believe their professional duty-of-care overrides personal-perspectives. There is a paucity of literature pertaining to pharmacists' perspectives on CO. Aim: To explore Australian pharmacists' decision-making in complex scenarios around CO and reasons for their choices. Method: A cross-sectional, qualitative questionnaire of pharmacists' perspectives on CO. Vignette-based questions were about scenarios related to medical termination, emergency contraception, IVF surrogacy for a same-sex couple and Voluntary Assisted Dying (VAD) Results: Approximately half of participants (n = 223) believed pharmacists have the right to CO and most agreed to supply prescriptions across all vignettes. However, those who chose not to supply (n = 20.9%), believed it justifiable, even at the risk of patients failing to access treatment. Strong self-reported religiosity had a statistically significant relationship with decisions not to supply for 3 of 4 vignettes. Three emergent themes included: ethical considerations, the role of the pharmacist and training and guidance. Conclusion: This exploratory study revealed perspectives of Australian pharmacists about a lack of guidance around CO in pharmacy. Findings highlighted the need for future research to investigate and develop further training and professional frameworks articulating steps to guide pharmacists around CO.

Health coaching intervention with or without the support of an exercise buddy to increase physical activity of people with chronic low back pain compared to usual care: a feasibility and pilot randomised controlled trial.

BACKGROUND: Exercise buddies (people to exercise together with) might support people with low back pain (LBP) to become active. However, involving buddies in randomised controlled trials (RCT) might challenge recruitment, data collection and follow-up. OBJECTIVES: To explore the feasibility of the intervention, recruitment and data collection approaches and potential effects of a health coaching intervention (focused on physical activity) with or without exercise buddies' support on physical activity of people with chronic LBP versus usual discharge care. DESIGN: Feasibility and pilot RCT. METHODS: Adults (n = 30) discharged from LBP treatment were randomised to the Buddy-Assisted (health coaching intervention with exercise buddy's support), Individual-Only (health coaching only), or usual care groups. Data were collected at baseline, three and six months. The feasibility of trial's procedures was assessed through recruitment rate (acceptable if >70%), data completion rate (acceptable if ≤ 20% missing data), and follow-up rate (successful if ≥ 85%). The intervention's acceptability was assessed via feedback questionnaires. Preliminary effects on physical activity and other outcomes were also explored. RESULTS: Recruitment and baseline data completion were acceptable. However, data collection and follow-up rates post-randomisation were not. 85% of the Buddy-Assisted Group believed the buddies helped them to increase physical activity and would recommend the intervention. 70% of the Individual-Only and Control groups believed exercise buddies would help them to become further active. CONCLUSION: The data collection and follow-up approaches were not successful and need amending before a large-scale RCT. Nonetheless, the buddy-assisted intervention was well-accepted. A future RCT will focus on differences in clinical outcomes. TRIAL REGISTRATION: The study was registered at the Australian New Zealand Clinical Trial Registry (ACTRN12620001118998).

Therapeutic drug monitoring of liposomal amphotericin B in children. Are we there yet? A systematic review.

INTRODUCTION: Therapeutic drug monitoring (TDM) is a tool that supports personalized dosing, but its role for liposomal amphotericin B (L-amb) is unclear. This systematic review assessed the evidence for L-amb TDM in children. OBJECTIVES: To evaluate the concentration-efficacy relationship, concentration-toxicity relationship and pharmacokinetic/pharmacodynamic (PK/PD) variability of L-amb in children. METHODS: We systematically reviewed PubMed and Embase databases following PRISMA guidelines. Eligible studies included L-amb PK/PD studies in children aged 0-18 years. Review articles, case series of 600 mg·h/L for nephrotoxicity. L-amb doses of 2.5-10 mg/kg/day were reported to achieve Cmax/MIC > 25 using an MIC of 1 mg/L. CONCLUSIONS: While significant PK variability was observed in children, evidence to support routine L-amb TDM was limited. Further studies on efficacy and toxicity benefits are required before routine TDM of L-amb can be recommended.

Opioid analgesics for nociceptive cancer pain: A comprehensive review.

Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo-controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate-certainty to low-certainty evidence). Nonsteroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate-to-severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.

Comparison of capecitabine concentrations determined by microsampling versus plasma concentrations for therapeutic drug monitoring: a pilot study.

OBJECTIVES: Therapeutic drug monitoring allows personalized dosing of chemotherapy, but is not well established for capecitabine. The aim of this study was to compare the concentrations of capecitabine and its metabolites obtained simultaneously by microsampling with plasma sampling and their acceptability to patients. METHODS: Adults taking capecitabine for cancer had paired (duplicate) microsampling at steady state (hour 2 post dose) using Mitra® devices and venous blood samples for analysis. Capecitabine and metabolites were measured using a validated mass spectrometry assay. Correlation between the sampling methods was determined. Patients' preferences were elicited using a Likert numeric rating scale and pain by a Visual Analog Scale (range, 0-10). KEY FINDINGS: Capecitabine concentrations from 10 patients (60 paired samples) by microsampling and plasma sampling were highly correlated (Pearson correlation: 0.97, Coefficients of determination: 0.94, P < 0.0001). Capecitabine concentrations in capillary sampling were consistently lower than the paired plasma concentration (median capecitabine capillary/plasma concentration ratio = 2851/3846 µg/l 75%). The agreement between sampling matrices showed a 28% bias (95% Cl, 4.02-52.00). Participant ratings showed microsampling was the preferred method by all 10 patients. Most participants reported no pain with microsampling (median 0, range 0-1). CONCLUSION: Capecitabine concentration measured by microsampling and plasma sampling were highly correlated, but consistently lower in microsampling. Microsampling was the preferred method with minimal pain.

Clinical Observation, Management and Function Of low back pain Relief Therapies (COMFORT): A cluster randomised controlled trial protocol.

INTRODUCTION: Low back pain (LBP) is commonly treated with opioid analgesics despite evidence that these medicines provide minimal or no benefit for LBP and have an established profile of harms. International guidelines discourage or urge caution with the use of opioids for back pain; however, doctors and patients lack practical strategies to help them implement the guidelines. This trial will evaluate a multifaceted intervention to support general practitioners (GPs) and their patients with LBP implement the recommendations in the latest opioid prescribing guidelines. METHODS AND ANALYSIS: This is a cluster randomised controlled trial that will evaluate the effect of educational outreach visits to GPs promoting opioid stewardship alongside non-pharmacological interventions including heat wrap and patient education about the possible harms and benefits of opioids, on GP prescribing of opioids medicines dispensed. At least 40 general practices will be randomised in a 1:1 ratio to either the intervention or control (no outreach visits; GP provides usual care). A total of 410 patient-participants (205 in each arm) who have been prescribed an opioid for LBP will be enrolled via participating general practices. Follow-up of patient-participants will occur over a 1-year period. The primary outcome will be the cumulative dose of opioid dispensed that was prescribed by study GPs over 1 year from the enrolment visit (in morphine milligram equivalent dose). Secondary outcomes include prescription of opioid medicines, benzodiazepines, gabapentinoids, non-steroidal anti-inflammatory drugs by study GPs or any GP, health services utilisation and patient-reported outcomes such as pain, quality of life and adverse events. Analysis will be by intention to treat, with a health economics analysis also planned. ETHICS AND DISSEMINATION: The trial received ethics approval from The University of Sydney Human Research Ethics Committee (2022/511). The results will be disseminated via publications in journals, media and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12622001505796.

What is the most effective and safest Non-steroidal anti-inflammatory drug for treating osteoarthritis in patients with comorbidities?

INTRODUCTION: Understanding what the most effective and safe non-steroidal anti-inflammatory drug (NSAID) is for managing osteoarthritis (OA) is complicated. OA is prevalent worldwide and people living with OA commonly have multiple comorbidities. The efficacy and safety of NSAIDs in a patient are influenced by their intrinsic and extrinsic factors. Current guidelines recommend the lowest dose for the shortest duration, monitoring patients for risk factors and comorbidities but generally do not specify, which NSAID is most suitable for a patient with specific comorbidities. AREAS COVERED: This paper looks at the mechanism of action of all NSAIDs and reviews the current literature concerning their safety in patients with and without comorbidities. Relevant publications were identified by searching PubMed and Cochrane Library using key terms. The search was conducted from inception to 18 July 2023 and included results published before 18 July 2023. The search results and their references were then manually reviewed. EXPERT OPINION: In the paper, we determine whether the current practice of 'lowest dose for shortest duration' is in fact the best approach for prescribing NSAIDs and identify which NSAIDs are most suitable given a patient's risk factors and comorbidities. Our aim is to help guide health professionals in recommending the most suitable NSAID for each patient.

General practitioners' decision-making process to prescribe pain medicines for low back pain: a qualitative study.

BACKGROUND: Pain medicines are widely prescribed by general practitioners (GPs) when managing people with low back pain (LBP), but little is known about what drives decisions to prescribe these medicines. OBJECTIVES: The aim of this study was to investigate what influences GPs' decision to prescribe pain medicines for LBP. DESIGN: Qualitative study with in-depth interviews. SETTING: Australian primary care. PARTICIPANTS: We interviewed 25 GPs practising in Australia experienced in managing LBP (mean (SD) age 53.4 (9.1) years, mean (SD) years of experience: 24.6 (9.3), 36% female). GPs were provided three vignettes describing common LBP presentations (acute exacerbation of chronic LBP, subacute sciatica and chronic LBP) and were asked to think aloud how they would manage the cases described in the vignettes. DATA ANALYSIS: We summarised GP's choices of pain medicines for each vignette using content analysis and used framework analysis to investigate factors that affected GP's decision-making. RESULTS: GPs more commonly prescribed opioid analgesics. Anticonvulsants and antidepressants were also commonly prescribed depending on the presentation described in the vignette. GP participants made decisions about what pain medicines to prescribe for LBP largely based on previous experiences, including their own personal experiences of LBP, rather than guidelines. The choice of pain medicine was influenced by a range of clinical factors, more commonly the patient's pathoanatomical diagnosis. While many adhered to principles of judicious use of pain medicines, polypharmacy scenarios were also common. Concerns about drug-seeking behaviour, adverse effects, stigma around opioid analgesics and pressure from regulators also shaped their decision-making process. CONCLUSIONS: We identified several aspects of decision-making that help explain the current profile of pain medicines prescribed for LBP by GPs. Themes identified by our study could inform future implementation strategies to improve the quality use of medicines for LBP.

International pharmacy survey of peripheral vasopressor infusions in critical care (INFUSE).

PURPOSE: The primary objective was to determine the proportion of hospitals that administered norepinephrine peripheral vasopressor infusions (PVIs) in critically ill adult patients. Secondary objectives were to describe how norepinephrine is used such as the maximum duration, infusion rate and concentration, and to determine the most common first-line PVI used by country. MATERIALS AND METHODS: An international multi-centre cross-sectional survey study was conducted in adult intensive care units in Australia, US, UK, Canada, and Saudi Arabia. RESULTS: Critical care pharmacists from 132 institutions responded to the survey. Norepinephrine PVIs were utilised in 86% of institutions (n = 113/132). The median maximum duration of norepinephrine PVIs was 24 h (IQR 24-24) (n = 57/113). The most common maximum norepinephrine PVI rate was between 11 and 20 µg/min (n = 16/113). The most common maximum norepinephrine PVI concentration was 16 µg/mL (n = 60/113). Half of the institutions had a preference to administer another PVI over norepinephrine as a first-line agent (n = 66/132). The most common alternative PVI used by country was: US (phenylephrine 41%, n = 37/90), Canada (dopamine 31%, n = 5/16), UK (metaraminol 82%, n = 9/11), and Australia (metaraminol 89%, n = 8/9). CONCLUSIONS: There is variability in clinical practice regarding PVI administration in critically ill adult patients dependent on drug availability and local institutional recommendations.

Opioid analgesia for acute low back pain and neck pain (the OPAL trial): a randomised placebo-controlled trial.

BACKGROUND: Opioid analgesics are commonly used for acute low back pain and neck pain, but supporting efficacy data are scarce. We aimed to investigate the efficacy and safety of a judicious short course of an opioid analgesic for acute low back pain and neck pain. METHODS: OPAL was a triple-blinded, placebo-controlled randomised trial that recruited adults (aged ≥18 years) presenting to one of 157 primary care or emergency department sites in Sydney, NSW, Australia, with 12 weeks or less of low back or neck pain (or both) of at least moderate pain severity. Participants were randomly assigned (1:1) using statistician-generated randomly permuted blocks to guideline-recommended care plus an opioid (oxycodone-naloxone, up to 20 mg oxycodone per day orally) or guideline-recommended care and an identical placebo, for up to 6 weeks. The primary outcome was pain severity at 6 weeks measured with the pain severity subscale of the Brief Pain Inventory (10-point scale), analysed in all eligible participants who provided at least one post-randomisation pain score, by use of a repeated measures linear mixed model. Safety was analysed in all randomly assigned eligible participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000775516). FINDINGS: Between Feb 29, 2016, and March 10, 2022, 347 participants were recruited (174 to the opioid group and 173 to the placebo group). 170 (49%) of 346 participants were female and 176 (51%) were male. 33 (19%) of 174 participants in the opioid group and 25 (15%) of 172 in the placebo group had discontinued from the trial by week 6, due to loss to follow-up and participant withdrawals. 151 participants in the opioid group and 159 in the placebo group were included in the primary analysis. Mean pain score at 6 weeks was 2·78 (SE 0·20) in the opioid group versus 2·25 (0·19) in the placebo group (adjusted mean difference 0·53, 95% CI -0·00 to 1·07, p=0·051). 61 (35%) of 174 participants in the opioid group reported at least one adverse event versus 51 (30%) of 172 in the placebo group (p=0·30), but more people in the opioid group reported opioid-related adverse events (eg, 13 [7·5%] of 174 participants in the opioid group reported constipation vs six [3·5%] of 173 in the placebo group). INTERPRETATION: Opioids should not be recommended for acute non-specific low back pain or neck pain given that we found no significant difference in pain severity compared with placebo. This finding calls for a change in the frequent use of opioids for these conditions. FUNDING: National Health and Medical Research Council, University of Sydney Faculty of Medicine and Health, and SafeWork SA.

An evaluation of the quality of Annona muricata leaf products.

OBJECTIVES: Annona muricata, also known as graviola, is traditionally used for the treatment of a range of disorders including cancer. Interest in A. muricata use has increased in recent years. This study investigated the quality and safety of a selection of commercially available A. muricata leaf products. METHODS: Seven commercially available products were purchased via online shopping sites. Each product was assessed for quality indicators including weight variation, quantification of the bioactive constituent annonacin, presence of annonaceous acetogenins and contaminants. The samples were evaluated by thin-layer chromatography, high-performance liquid chromatography, liquid chromatography-mass spectroscopy, low-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Microbial analysis was carried out in accordance with the British Pharmacopoeia. Heavy metals were analysed by inductive coupled plasma mass spectrometry. KEY FINDINGS: Of the seven products analysed, one product contained less than half of the content stated on the label. The labelled dosage recommendation varied between products. There was a high variation in annonacin concentration (1.05-3.09 mg/g) and the presence of annonaceous acetogenins. One of the products was found to have a total aerobic microbial count above the United States Pharmacopoeia limit. CONCLUSIONS: The variation in the indicators of quality and safety of commercially available A. muricata leaf products tested have implications for clinicians and people living with cancer who use these herbal products.

Application of physiologically based pharmacokinetic modeling to understand real-world outcomes in patients receiving imatinib for chronic myeloid leukemia.

We aimed to use physiologically based pharmacokinetic (PBPK) modeling and simulation to predict imatinib steady-state plasma exposure in patients with chronic myeloid leukemia (CML) to investigate variability in outcomes. A validated imatinib PBPK model (Simcyp Simulator) was used to predict imatinib AUCss , Css,min and Css,max for patients with CML (n = 68) from a real-world retrospective observational study. Differences in imatinib exposure were evaluated based on clinical outcomes, (a) Early Molecular Response (EMR) achievement and (b) occurrence of grade ≥3 adverse drug reactions (ADRs), using the Kruskal-Wallis rank sum test. Sensitivity analyses explored the influence of patient characteristics and drug interactions on imatinib exposure. Simulated imatinib exposure was significantly higher in patients who achieved EMR compared to patients who did not (geometric mean AUC0-24,ss 51.2 vs. 42.7 µg h mL-1 , p < 0.05; Css,min 1.1 vs. 0.9 µg mL-1 , p < 0.05; Css,max 3.4 vs. 2.8 µg mL-1 , p < 0.05). Patients who experienced grade ≥3 ADRs had a significantly higher simulated imatinib exposure compared to patients who did not (AUC0-24,ss 56.1 vs. 45.9 µg h mL-1 , p < 0.05; Css,min 1.2 vs. 1.0 µg mL-1 , p < 0.05; Css,max 3.7 vs. 3.0 µg mL-1 , p < 0.05). Simulations identified a range of patient (sex, age, weight, abundance of hepatic CYP2C8 and CYP3A4, α1 -acid glycoprotein concentrations, liver and kidney function) and medication-related factors (dose, concomitant CYP2C8 modulators) contributing to the inter-individual variability in imatinib exposure. Relationships between imatinib plasma exposure, EMR achievement and ADRs support the rationale for therapeutic drug monitoring to guide imatinib dosing to achieve optimal outcomes in CML.

The smallest worthwhile change on function from a self-management intervention for non-persistent low back pain.

PURPOSE: To determine: (1) the smallest change in function patients would need to see following a self-management intervention for low back pain (LBP) to consider it worthwhile; (2) the association between patient-related factors and the magnitude of the smallest worthwhile change. METHODS: A cross-sectional analysis of 212 participants of the TEXT4myBACK randomised trial was conducted. At baseline, participants nominated the smallest change in function (0-30 scale) following a self-management program they would need to reach to consider it worthwhile. A multivariate regression model estimated the effects of demographic, comorbidities, lifestyle and LBP-related factors on the smallest worthwhile change estimates. RESULTS: On average, people with LBP need to experience an improvement of at least 9.4 points (SD: 5.7) in function to consider a self-management intervention worthwhile. Only baseline function severity was significantly associated with the smallest worthwhile estimate (-0.60; 95%CI - 0.76, - 0.44). CONCLUSION: On average, an improvement of 9.4 points (or 31%) in function is considered by people with LBP as the smallest change that makes self-management worthwhile. Those with lower levels of function needed to experience greater improvements.

Influence of age on pharmacokinetics of capecitabine and its metabolites in older adults with cancer: a pilot study.

BACKGROUND: Capecitabine is an oral chemotherapy prodrug of 5-fluorouracil (5-FU) with unpredictable toxicity, especially in older adults. The aim of this study was to evaluate the pharmacokinetics (PK) of capecitabine and its metabolites in younger adults (< 70 years) and older adults (≥ 70 years) receiving capecitabine for solid cancer. METHODS: Eligible participants receiving capecitabine had 2 venous samples collected on day 14 of cycle 1 and cycle 2 of their treatment. Capecitabine and metabolite concentrations were determined using liquid chromatography with tandem mass spectrometry. A Bayesian estimation approach was used to generate individual estimates of PK parameters for 5-FU. A linear mixed-effect analysis of variance (ANOVA) model was used to compare dose-normalised log-transformed PK parameters between age groups. Correlations were determined by linear regression and logistic regression analyses. RESULTS: Of the total 26 participants, 58% were male with a median age of 67 years (range, 37-85) with 54% aged < 70 years and 46% aged ≥ 70 years. Participants aged ≥ 70 years, compared to those aged < 70 years, had a greater 5-FU exposure based on area under the concentration-time curve (AUC) of 17% (90% CI 103-134%; 0.893 vs. 0.762 mg h/L) and 14% increase in maximal concentration, Cmax (90% CI 82.1-159%; 0.343 vs. 0.300 mg/L). The 5-FU Cmax was positively associated with time up and go (TUG) (Pearson's correlation 0.77, p = 0.01), but not other geriatric assessment domains or severe toxicity. CONCLUSION: 5-FU exposure was significantly increased in older adults compared to younger adults receiving equivalent doses of capecitabine, and is a possible cause for increased toxicity in older adults.

Deprescribing to optimise health outcomes for frail older people: a double-blind placebo-controlled randomised controlled trial-outcomes of the Opti-med study.

BACKGROUND: potentially harmful polypharmacy is very common in older people living in aged care facilities. To date, there have been no double-blind randomised controlled studies of deprescribing multiple medications. METHODS: three-arm (open intervention, blinded intervention and blinded control) randomised controlled trial enrolling people aged over 65 years (n = 303, noting pre-specified recruitment target of n = 954) living in residential aged care facilities. The blinded groups had medications targeted for deprescribing encapsulated while the medicines were deprescribed (blind intervention) or continued (blind control). A third open intervention arm had unblinded deprescribing of targeted medications. RESULTS: participants were 76% female with mean age 85.0 ± 7.5 years. Deprescribing was associated with a significant reduction in the total number of medicines used per participant over 12 months in both intervention groups (blind intervention group -2.7 medicines, 95% CI -3.5, -1.9, and open intervention group -2.3 medicines; 95% CI -3.1, -1.4) compared with the control group (-0.3, 95% CI -1.0, 0.4, P = 0.053). Deprescribing regular medicines was not associated with any significant increase in the number of 'when required' medicines administered. There were no significant differences in mortality in the blind intervention group (HR 0.93, 95% CI 0.50, 1.73, P = 0.83) or the open intervention group (HR 1.47, 95% CI 0.83, 2.61, P = 0.19) compared to the control group. CONCLUSIONS: deprescribing of two to three medicines per person was achieved with protocol-based deprescribing during this study. Pre-specified recruitment targets were not met, so the impact of deprescribing on survival and other clinical outcomes remains uncertain.

Prevalence of Nonsteroidal Antiinflammatory Drugs Prescribed for Osteoarthritis: A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVE: Our systematic review aimed to investigate the proportion of participants with osteoarthritis who were prescribed nonsteroidal antiinflammatory drugs (NSAIDs) by their health care provider. METHODS: Electronic databases were searched for observational studies reporting NSAID prescribing to participants with diagnosed osteoarthritis of any region. Risk of bias was assessed using a tool designed for observational studies measuring prevalence. Random and fixed-effects meta-analysis was used. Meta-regression investigated study-level factors associated with prescribing. The overall evidence quality was assessed using Grading of Recommendations Assessment, Development, and Evaluation criteria. RESULTS: Fifty-one studies were included, published between 1989 and 2022, with 6,494,509 participants. The mean age of participants was 64.7 years (95% confidence interval [95% CI] 62.4, 67.0; n = 34 studies). Most studies were from Europe and Central Asia (n = 23 studies), and North America (n = 12 studies). Most studies were judged to be at low risk of bias (75%). Heterogeneity was eliminated when removing studies with a high risk of bias, to give a pooled estimate of NSAIDs prescribing to participants with osteoarthritis of 43.8% (95% CI 36.8, 51.1; moderate quality of evidence). Meta-regression determined that prescribing was associated with year (decreased prescribing over time; P = 0.05) and geographic region (P = 0.03; higher in Europe and Central Asia and in South Asia than in North America) but not with clinical setting. CONCLUSION: Data from over 6.4 million participants with osteoarthritis between 1989 and 2022 indicate that NSAID prescribing has decreased over time and that prescribing differs between geographic locations.