Prevalence of Adverse Drug Reactions in Hospital Among Older Patients with and Without Dementia.

BACKGROUND: Older inpatients with dementia are at an increased risk of an adverse drug reaction (ADR) during hospitalization. OBJECTIVE: To quantify the prevalence of ADRs in older inpatients according to dementia status and ADR definition approach and to identify risk factors of ADRs during hospitalization. METHODS: This was a retrospective cohort study of 2000 inpatients aged ≥ 75 years admitted consecutively to six Sydney hospitals (1 July 2016 to 31 May 2017). Dementia was defined by diagnosis in electronic medical records. ADRs were defined according to two approaches: the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) and classification by a research pharmacist (subset cohort, n = 600). A binary logistic regression was conducted to determine risk factors of ADRs. RESULTS: Among 2000 patients, 25.9% (n = 517) were reported to have dementia. ADRs defined by ICD-10-AM were identified in 8.3% (n = 43) and 14.6% (n = 217) of inpatients with and without dementia respectively (p < 0.001). A total of 13.0% (n = 260) and 12.5% (n = 75) of patients had ADRs defined by ICD-10-AM and a research pharmacist, respectively. Key risk factors of ADRs were longer hospital stay [odds ratio (OR) 1.01, 95% confidence interval (CI) 1.01, 1.02) and a greater number of regular potentially inappropriate medicines (PIMs) on admission (OR 1.17, 95% CI 1.00, 1.38). CONCLUSIONS: ADRs were more prevalent among inpatients without dementia and when assessed by a research pharmacist. Our findings underline the need for improved ADR detection in older inpatients.

The effect of down-titration and discontinuation of heart failure pharmacotherapy in older people: A systematic review and meta-analysis.

The aim of this study was to investigate whether interventions to discontinue or down-titrate heart failure (HF) pharmacotherapy are feasible and associated with risks in older people. A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Electronic databases were searched from inception to 8 March 2023. Randomized controlled trials (RCTs) and observational studies included people with HF, aged ≥50 years and who discontinued or down-titrated HF pharmacotherapy. Outcomes were feasibility (whether discontinuation or down-titration of HF pharmacotherapy was sustained at follow-up) and associated risks (mortality, hospitalization, adverse drug withdrawal effects [ADWE]). Random-effects meta-analysis was performed when heterogeneity was not substantial (Higgins I2 < 70%). Sub-analysis by frailty status was conducted. Six RCTs (536 participants) and 27 observational studies (810 499 participants) across six therapeutic classes were included, for 3-260 weeks follow-up. RCTs were conducted in patients presenting with stable chronic HF. Down-titrating a renin-angiotensin system inhibitor (RASI) in patients with chronic kidney disease was 76% more likely than continuation (risk ratio [RR] 1.76, 95% confidence interval [CI] 1.14-2.73), with no difference in mortality (RR 0.64, 95% CI 0.30-1.64). Discontinuation of beta-blockers were feasible compared to continuation in preserved ejection fraction (RR 1.00, 95% CI 0.68-1.47). Participants were 25% more likely to re-initiate discontinued diuretics (RR 0.75, 95% CI 0.66-0.86). Digoxin discontinuation was associated with 5.5-fold risk of hospitalization compared to continuation. Worsening HF was the most common ADWE. One observational study measured frailty but did not report outcomes by frailty status. The appropriateness and associated risks of down-titrating or discontinuing HF pharmacotherapy in people aged ≥75 years is uncertain. Evaluation of outcomes by frailty status necessitates investigation.

Efficacy and safety of antidepressants for pain in older adults: A systematic review and meta-analysis.

AIMS: In many countries, pain is the most common indication for use of antidepressants in older adults. We reviewed the evidence from randomized controlled trials on the efficacy and safety of antidepressants, compared to all alternatives for pain in older adults (aged ≥65 years). METHODS: Trials published from inception to 1 February 2024, were retrieved from 13 databases. Two independent reviewers extracted data on study and participant characteristics, primary efficacy (pain scores, converted to 0-100 scale) and harms. Estimates for efficacy were pooled using a random effects model and reported as difference in means and 95% CI. Quality of included trials was assessed using the Cochrane risk of bias tool. RESULTS: Fifteen studies (n = 1369 participants) met the inclusion criteria. The most frequently studied antidepressants were duloxetine and amitriptyline (6/15 studies each). Pain related to knee osteoarthritis was the most studied (6/15 studies). For knee osteoarthritis, antidepressants did not provide a statistically significant effect for the immediate term (0-2 weeks), (-5.6, 95% confidence interval [CI]: -11.5 to 0.3), but duloxetine provided a statistically significant, albeit a very small effect in the intermediate term, (≥6 weeks and <12 months), (-9.1, 95% CI: -11.8 to -6.4). Almost half (7/15) of the studies reported increased withdrawal of participants in the antidepressant treatment group vs. the comparator group due to adverse events. CONCLUSIONS: For most chronic painful conditions, the benefits and harms of antidepressant medicines are unclear. This evidence is predominantly from trials with sample sizes of <100, have disclosed industry ties and classified as having unclear or high risk of bias.

Efficacy and safety of an oral complementary medicine combination in people with symptomatic knee osteoarthritis: Protocol for the double-blind, randomized, placebo-controlled ATLAS trial.

Objective: To investigate the efficacy and safety of an oral complementary medicine combination formulation relative to placebo, on changes in pain intensity from baseline to week 12, in people with knee osteoarthritis (OA). Design: A placebo-controlled, double-blind, two-arm, superiority, phase II, Randomized Controlled Trial (RCT) (ACTRN12623000380695). We will recruit 82 participants (∼41 per arm), aged ≥40 years, with a clinical diagnosis of symptomatic knee OA and radiographic change on x-ray (Kellgren-Lawrence Grade ≥2). Participants will be randomly allocated to receive either a complementary medicine formulation containing a daily dose of Boswellia serrata extract (Boswellin® Super, 250 â€‹mg/day), pine bark extract (Fenoprolic™ 70 Organic 100 â€‹mg/day), curcumin (500 â€‹mg/day), piperine (5 â€‹mg/day), and methylsulfonylmethane (MSM, 1500 â€‹mg/day), or placebo, for 12-weeks. The primary endpoint will be change from baseline in average knee pain intensity at 12-weeks (visual analogue scale). Secondary endpoints will include change in knee pain from baseline to 12-weeks in the Knee Injury and Osteoarthritis Outcome Score (KOOS), global assessment of disease activity, global rating of change, and health-related quality of life (AQoL-8D). Ethics and dissemination: This protocol has been approved by the University of Sydney Human Research Ethics Committee (#2021/877). Dissemination will occur through lay summaries, infographics, conference abstracts, oral presentations, theses, and scientific publications. Conclusion: This RCT will provide credible evidence about the efficacy and safety of this complementary medicine combination and inform updates to international clinical practice standards on the use of complementary medicines in the management of symptomatic knee OA.

Preferred format and strategies for seeking and trusting online health information: a survey of cardiology outpatient attendees across three New Zealand hospitals.

Introduction The volume and quality of online health information requires consumers to be discerning. Aim This study aimed to explore consumer Internet use for health information, preferred format and what factors helped them to trust the source. Methods A cross-sectional study was conducted in 2016-2017 with adults attending three cardiology outpatient clinic sites using a short paper-based survey. The survey included questions regarding online health information use and perceived trustworthiness with opportunities for free text responses. Survey data were summarised with key questions adjusted by age group, gender and ethnicity using logistic regression. Results Of the 708 respondents (51% women, 66% aged 45-74 years, 16% Maori, 12% Pacific), 73% had sought health information online (64% in the previous 12 months), commonly for medication side effects, their health condition and self-help. Most (65%) were successful, although Pacific respondents reported a lower likelihood of search success compared to Europeans. Younger age groups were more concerned about information quality. Fact sheets (80%) were the most popular format and for all ethnic groups, followed by short videos (31%) and discussion groups (23%). Trusting online information required many strategies with 72% wanting health professionals to recommend websites. Discussion Online health information seeking is a norm for consumers, with simple fact sheets being the preferred format to build knowledge and skills. With the rising tide of misinformation, health portal providers need to offer accurate and easy-to-read fact sheets in their suite of formats and health professionals need to support consumers guiding them to trusted websites.

Extracellular vesicles as the next-generation modulators of pharmacokinetics and pharmacodynamics of medications and their potential as adjuvant therapeutics.

BACKGROUND AND MAIN BODY: Pharmacokinetics (PK) and pharmacodynamics (PD) are central concepts to guide the dosage and administration of drug therapies and are essential to consider for both healthcare professionals and researchers in therapeutic planning and drug discovery. PK/PD properties of a drug significantly influence variability in response to treatment, including therapeutic failure or excessive medication-related harm. Furthermore, suboptimal PK properties constitute a significant barrier to further development for some candidate treatments in drug discovery. This article describes how extracellular vesicles (EVs) affect different aspects of PK and PD of medications and their potential to modulate PK and PD properties to address problematic PK/PD profiles of drugs. We reviewed EVs' intrinsic effects on cell behaviours and medication responses. We also described how surface and cargo modifications can enhance EV functionalities and enable them as adjuvants to optimise the PK/PD profile of conventional medications. Furthermore, we demonstrated that various bioengineering strategies can be used to modify the properties of EVs, hence enhancing their potential to modulate PK and PD profile of medications. CONCLUSION: This review uncovers the critical role of EVs in PK and PD modulation and motivates further research and the development of assays to unfold EVs' full potential in solving PK and PD-related problems. However, while we have shown that EVs play a vital role in modulating PK and PD properties of medications, we postulated that it is essential to define the context of use when designing and utilising EVs in pharmaceutical and medical applications. HIGHLIGHTS: Existing solutions for pharmacokinetics and pharmacodynamics modulation are limited. Extracellular vesicles can optimise pharmacokinetics as a drug delivery vehicle. Biogenesis and administration of extracellular vesicles can signal cell response. The pharmaceutical potential of extracellular vesicles can be enhanced by surface and cargo bioengineering. When using extracellular vesicles as modulators of pharmacokinetics and pharmacodynamics, the 'context of use' must be considered.

Policies and cost analyses of voluntary assisted dying (VAD) laws - a mapping review & analysis.

OBJECTIVES: To investigate the current literature on healthcare policies and cost analyses around international Voluntary Assisted Dying (VAD) laws. The study design is a mapping literature review following Preferred-Reporting-Items-for-Systematic-Reviews-and-Meta-Analyses (PRISMA) guidelines. METHODS: Original research articles published between January 1990 to March 2023, investigating the financial cost and healthcare budget effect of VAD laws internationally. Citations were screened for relevance and eligibility, and any non-full-text research that did not explore cost analysis was excluded. The following data sources were screened: MEDLINE, PubMed, EMBASE, CINAHL and any relevant international health authority annual reports were also reviewed. RESULTS: Of the 2790 screened articles, eight studies met the inclusion criteria and three were included in the mapping review. The reviewed studies included prospective studies, two Canadian and one US. Only one of the Canadian studies provided a cost analysis using data from current VAD laws. All three studies showed VAD laws would reduce healthcare spending, with the US approximating $627million in 1995. Canada approximating $17.1 to $77.1million in 2017 and $86.9 to $149.0million in 2021, overall, leading to an average percentage reduction in costs of approximately 87% compared to original costs of end-of-life care. CONCLUSION: This review identifies a scarcity in cost-analysis literature and provides a summary of the latest international VAD laws, from which a potential cost reduction is apparent. The absence of retrospectively collated financial VAD data highlights a need for future research to inform policymakers of the economic factors affecting current policies with a need for annual fiscal reports and to optimise future legislative frameworks internationally.

Paracetamol Combination Therapy for Back Pain and Osteoarthritis: A Systematic Review and Meta-Analyses.

BACKGROUND AND OBJECTIVE: Although paracetamol (acetaminophen) combined with other analgesics can reduce pain intensity in some pain conditions, its effectiveness in managing low back pain and osteoarthritis is unclear. This systematic review investigated whether paracetamol combination therapy is more effective and safer than monotherapy or placebo in low back pain and osteoarthritis. METHODS: Online database searches were conducted for randomised trials that evaluated paracetamol combined with another analgesic compared to a placebo or the non-paracetamol ingredient in the combination (monotherapy) in low back pain and osteoarthritis. The primary outcome was a change in pain. Secondary outcomes were (serious) adverse events, changes in disability and quality of life. Follow-up was immediate (≤ 2 weeks), short (> 2 weeks but ≤ 3 months), intermediate (> 3 months but < 12 months) or long term (≥ 12 months). A random-effects meta-analysis was conducted. Risk of bias was assessed using the original Cochrane tool, and quality of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Twenty-two studies were included. Pain was reduced with oral paracetamol plus a non-steroidal anti-inflammatory drug (NSAID) at immediate term in low back pain (paracetamol plus ibuprofen vs ibuprofen [mean difference (MD) - 6.2, 95% confidence interval (CI) -10.4 to -2.0, moderate evidence]) and in osteoarthritis (paracetamol plus aceclofenac vs aceclofenac [MD - 4.7, 95% CI - 8.3 to - 1.2, moderate certainty evidence] and paracetamol plus etodolac vs etodolac [MD - 15.1, 95% CI - 18.5 to - 11.8; moderate certainty evidence]). Paracetamol plus oral tramadol reduced pain compared with placebo at intermediate term for low back pain (MD - 11.7, 95% CI - 19.2 to - 4.3; very low certainty evidence) and osteoarthritis (MD - 6.8, 95% CI - 12.7 to -0.9; moderate certainty evidence). Disability scores improved in half the comparisons. Quality of life was infrequently measured. All paracetamol plus NSAID combinations did not increase the risk of adverse events compared to NSAID monotherapy. CONCLUSIONS: Low-to-moderate quality evidence supports the oral use of some paracetamol plus NSAID combinations for short-term pain relief with no increased risk of harm for low back pain and osteoarthritis compared to its non-paracetamol monotherapy comparator.

Prescription and dispensing duration of medicines for hypertension and other chronic conditions: a review of international policies and evidence to inform the Australian setting.

The duration of treatment for which a physician may prescribe a medicine, 'prescription duration', is often dispensed at the pharmacy on multiple occasions of shorter time periods, 'dispensing duration'. These durations vary significantly between and within countries. In Australia, the quantity of medication supplied at each dispensing has recently been extended from 30 to 60 days for a selection of medicines used for chronic health conditions, such as diabetes and hypertension. Dispensing durations vary between countries, with 30, 60 or 90 days being the most common-with 90 days aligning with the recommendation of the 2023 Global Report on Hypertension from the World Health Organization. The full impact of shorter vs longer prescription durations on health costs and outcomes is unknown, but current evidence suggests that 90-day dispensing could reduce costs and improve patient convenience and adherence. More rigorous research is needed.

How is postoperative pain after hip and knee replacement managed? An analysis of two large hospitals in Australia.

BACKGROUND: Multimodal analgesia regimens are recommended for the postoperative period after hip and knee replacement surgeries. However, there are no data on practice patterns for analgesic use in the immediate postoperative period after hip and knee replacements in Australia. OBJECTIVES: To describe analgesic prescribing patterns in the inpatient postoperative phase for patients undergoing hip and knee replacement. METHODS: Retrospective study of electronic medical record data from two major hospitals in Sydney, Australia. We identified analgesic medication prescriptions for all patients aged 18 years and older who underwent hip or knee replacement surgery in 2019. We extracted data on pain medications prescribed while in the ward up until discharge. These were grouped into distinct categories based on the Anatomical Therapeutic Chemical classification. We described the frequency (%) of pain medications used by category and computed the average oral morphine equivalent daily dose (OMEDD) during hospitalisation. RESULTS: We identified 1282 surgeries in 1225 patients. Patients had a mean (SD) age of 69 (11.8) years; most (57.1%) were female. Over 99% of patients were prescribed opioid analgesics and paracetamol during their hospital stay. Most patients (61.4%) were managed with paracetamol and opioids only. The most common prescribed opioid was oxycodone (87.3% of patients). Only 19% of patients were prescribed nonsteroidal anti-inflammatories (NSAIDs). The median (IQR) average daily OMEDD was 50.2 mg (30.3-77.9). CONCLUSION: We identified high use of opioids analgesics as the main strategies for pain control after hip and knee replacement in hospital. Other analgesics were much less frequently used, such as NSAIDs, and always in combination with opioids and paracetamol.

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.

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.

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.

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.

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.