MedsScan Issue 3, 2025

These reviews provide updates on the international literature on therapeutics. Expert pharmacy practitioners — via AdPha’s Specialty Practice Groups — scan major peer-reviewed journals in areas relevant to Australian pharmacy practice and present precis on major clinical trials, important pharmacoepidemiology studies and pharmacoeconomic research, and other updates relevant to practice. Interested readers are encouraged to explore the original publications in greater detail.

ABORIGINAL AND TORRES STRAIT ISLANDER HEALTH

MedsScan Editors for Aboriginal and Torres Strait Islander health SPG: Susan Welch, Sanja Mirkov and Danny Tsai

Conducting culturally appropriate research with Aboriginal and/or Torres Strait Islander Peoples

Author: Sanja Mirkov

Little is known about culturally responsive clinical pharmacy services in the Australian hospital setting. Using the Connecting the Dots of Care study that aimed to optimise diabetes care for Aboriginal and/or Torres Strait Islander Peoples admitted to a metropolitan hospital,1 the authors of this article aim to outline the process of ethical research with First Peoples in the hospital pharmacy setting.

This qualitative study was an evaluation of the cultural appropriateness of the research process using the four discrete components: 1) timeline; 2) alignment with the Aboriginal Health & Medical Research Council of NSW (AHMRC) NSW Aboriginal health ethics guideline;2 3) the Australian Bicultural Model of Care;3 and 4) Community participation.

The study found that cultural appropriateness of the design and implementation of the research study was demonstrated across the four analyses:

  1. Timeline and key steps

Relationships take time to develop. The study was co-created in partnership with the local Aboriginal and Torres Strait Islander Health Unit and Aboriginal Health Committee to ensure community participation. The article provides the detailed steps and timeline of the cultural responsiveness learning of the research study team.

  1. Alignment with AHMRC Aboriginal health ethics guidelines 

The study ensured the benefits at individual and community level by empowering patients with knowledge about importance of diagnosis and management of diabetes and referral to Endocrinology team. The research study was co-designed with Aboriginal health professionals, research leaders and investigators and the local community.  

  1. Australian Bicultural Model of Care

Australian Bicultural Model of Care is guided by community and holistic care, includes cultural perspectives and healing traditions of Aboriginal and/or Torres Strait Islander Peoples.3  Treatment and healing (delivery of bicultural care) included yarning to improve health literacy and empower patients to make behaviour change on their own terms. Service strategies included respectful identification of Aboriginal and/or Torres Strait Islander Peoples in hospital (Aboriginal flag icon in eMR), easy communication built on strong partnerships to ensure referrals to linked care and reflexive social advocacy to enable referrals.  The article presents an artwork of the Australian Bicultural Care Model.

  1. Community participation in research process

Respectful, non-rushed, two-way communication and removing power imbalances by obtaining regular feedback is essential when working with community leaders, researchers and health professionals. Communication methods include respectful yarning, active listening, reflexivity, use of infographics and feedback using plain English.

The strengths demonstrated by this study are considerable, such as respect for community priorities, facilitating sufficient time to build relationships and strong partnerships and reciprocity. It provides an overview of the cultural and transformational journey towards a bicultural philosophy approach to improve health outcomes with, and for, Aboriginal and/or Torres Strait Islander Peoples. In addition, the research study used The CONSolIDated critERtia for strengthening the reporting of health research involving Indigenous Peoples (CONSIDER) statement as a checklist for the reporting of health research involving First Peoples to advance Indigenous outcomes.4

The limitations of the study include a lack of generalisability given the diversity of Aboriginal and/or Torres Strait Islander Peoples’ culture, however, it could inform future efforts in other hospital settings.    

Pharmacists wishing to contribute to the research for improving health outcomes for Aboriginal and/or Torres Strait Islander Peoples should start by building relationships with communities well before the study initiation. The Australian Bicultural Model of Care offers the research at the interface methodology, by combining the way of knowing, being and doing of the two worlds and working with Aboriginal and/or Torres Strait Islander Peoples to deliver the culturally responsive care to improve health outcomes.

References

  1. Welch S, Moles R, Viardot A, Deweerd P, Daly S, Lee K. Connecting the Dots of Care: a pilot study linking Aboriginal and/or Torres Strait Islander peoples with diabetes care in hospital, using hospital pharmacists. Exploratory Res Clin Soc Pharm 2023; 12: 100351.
  2. Aboriginal Health & Medical Research Council of NSW (AHMRC). NSW Aboriginal health ethics guidelines: key principles. Sydney: AHMRC; 2023.
  3. Purcell-Khodr G, Webster E, Harrison K, Dawson A, Lee KS, Conigrave K. The importance of culture in alcohol care: listening to First Nations staff in Australian Aboriginal Community Controlled Health Services. Int Indigenous Policy J 2022; 13:1–29.
  4. Huria T, Palmer SC, Pitama S, Beckert L, Lacey C, Ewen S, et al. Consolidated criteria for strengthening reporting of health research involving indigenous peoples: the CONSIDER statement. BMC Med Res Methodol 2019; 19: 173.

Welch S, Purcell-Khodr G, Deweerd P, Moles R, Viardot A, Daly S, et al. Working together to ensure research conducted with Aboriginal and/or Torres Strait Islander Peoples is culturally appropriate illustrated using a pharmacy-intervention study. J Pract Pharm Res 2025; [online ahead of print].

Extended-spectrum beta-lactamase producing Escherchia Coli infections are associated with prior antimicrobial use and poor prognosis in a remote Australian setting

Antimicrobial resistance has been shown to be significantly higher in rural and remote settings. This study aimed to study the epidemiology of extended spectrum beta-lactamase (ESBL, referred to as third-generation cephalosporin resistant [3GCR] in this article) Escherichia coli (E. coli) infections in remote Australia.

The authors utilised a case-control study design in their hospital, located in Central Australia. Using data including patient characteristics, antibiotic usage and clinical outcomes from 2018–2019, the authors compared adult hospital admissions of patients with ESBL and susceptible E. coli isolates and used Poisson regression to determine the incidence of ESBL admissions between Aboriginal and Torres Strait Islander patients and non-Indigenous patients.

A total of 889 E. coli isolates were identified and of these, 21% (n = 187) were ESBL. Using person-time — a unit determined by multiplying the number of participants by the length of time of the study — the incidence of ESBL E. coli infection was found to be 2.15 per 1000 person-years, with an incidence rate ratio of 6.8 (95% confidence interval [CI] 4.6–10.1) between Indigenous and non-Indigenous patient admissions. Aboriginal and Torres Strait Islander patients were more likely to present with a E. coli infection with 69.3% of the total 889 patients identifying as Aboriginal or Torres Strait Islander people. Upon comparison with the control group, ESBL E. coli infections were associated with a higher Charlson Comorbidity Index (CCI) (CCI ≥ 3 in 30.7% vs 15.0%, p < 0.001), which is used to predict mortality risk. After adjusting for comorbidity, a higher one-year mortality was observed in the ESBL group (odds ratio [OR] 4.43, p = 0.002), but not at 30 days (2.4% vs 0.0%, p = 0.2). In addition, the ESBL patient group used more antibiotics in the previous 3 (OR 5.75, p < 0.001) and 12 months (OR 3.65, p < 0.001).

The findings of this study indicate that ESBL E. coli infections in remote Australia disproportionally affect Aboriginal and Torres Strait Islander peoples and are associated with a higher burden of comorbidities and antibiotic use. From these findings, future research should focus on enhancing antimicrobial stewardship in remote Australian settings.

Camilleri S, Tsai D, Langham F, Ullah S, Chiong F. Epidemiology, clinical outcomes and risk factors of third-generation cephalosporin-resistant Escherichia coli hospitalized infections in remote Australia—a case–control study. JAC Antimicrob Resist 2023; 5: dlad138.

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COMPOUNDING SERVICES

MedsScan Editor for Compounding Service SPG: Rachel Berry

A review of surface contamination with cytotoxics in hospitals

Despite advances in personal protective equipment (PPE) and the cabinets used to handle cytotoxic drugs, concern regarding healthcare worker exposure to cytotoxic compounds persists. Despite this, there is no standard international methodology for reporting surface contamination, making direct comparison of available data difficult.

This review included 29 studies conducted from 2017–2022 with a focus on contamination in areas where healthcare workers may be exposed. Twenty-two studies collected samples from both the clinical area and pharmacy. The largest proportion of the studies were from Canada and Italy, accounting for 15 out of the 29 studies. Three of the studies were multinational cross-sectional studies involving up to 12 countries. The included studies covered more than 30 different cytotoxic tracers, with the most used and detected being cyclophosphamide, 5-fluorouracil, ifosfamide, methotrexate, gemcitabine, paclitaxel and platinum derivatives which are all commonly prepared cytotoxic agents in Australian facilities.

Studies with sample sizes below 500 were found to have higher positive rates of contamination with a higher degree of variability (59.1% + 28.1%, n = 10), whereas studies with sample sizes over 800 showed greater consistency in rates of contamination (41.7% + 6.8%, n = 8). A total of 6454 samples from a total of 16 196 samples across 20 studies were positive for cytotoxic contamination, a rate of 39.8%. Nine studies reported no positive samples.

Limitations of this study include exclusion of data due to variability in collection techniques. In addition, differences in sample size may have contributed to the consistency of the results, and limiting the number of tracers analysed possibly provided more accurate results. This study highlights that further work is required on standardising how residual cytotoxic contamination is tested for. Cytotoxic contamination remains a concern in both pharmacies and clinical areas and the importance of both monitoring and protecting staff with adequate PPE, equipment and cleaning methods is highlighted.

Favier B, Simonin C, Tokatian S, Guitton J, Darnis S, Basset M, et al. Cytotoxic surface contamination in hospitals: current practices, challenges and perspectives. J Oncol Pharm Pract 2025; 31: 305–314.

Extemporaneous compounding practices in Australian community pharmacies

This study explored extemporaneous compounding practices in Australian community pharmacies since the introduction of the Pharmacy Board compounding guidelines in 2015.1 A survey was sent to 3349 publicly available community pharmacy email addresses and completed by a range of staff. Two hundred and seventy responses were included in the results.

Pharmacies self-identified whether they were specialised compounding pharmacies. The data collected included the number of products compounded per week, record keeping and quality assurance processes, awareness of the Pharmacy Board guidelines, reference sources used and the training of staff.

Specialised pharmacies prepared a median of 50 products per week. The Australian Pharmaceutical Formulary and Handbook (APF) was used to support compounding practices in 73.1% of specialised compounding pharmacies and 81.5% of non-specialised pharmacies, however the proportion of formulations guided by the APF was lower in specialised compounding pharmacies. Standard operating procedures were more likely to be found in specialised compounding pharmacies, but quality assurance processes were reported by most respondents including expiry date checks, equipment calibration, visual product checks and product testing. All pharmacists working in specialised pharmacies had undergone further training but 31.5% of all pharmacists surveyed were unaware of the changes implemented in the 2015 Pharmacy Board guidelines. For non-specialised pharmacies, 10.7% were performing complex compounding, highlighting a gap in knowledge of the Pharmacy Board requirements.

A limitation of this study is the low response rate. Only 301 responses were received (9.4% response rate) and a further 31 responses were omitted due to being partially complete. Eleven pharmacies did not undertake any compounding. Therefore, this sample is not necessarily representative of all pharmacies. Responses are from 2018 which predates the revised Pharmacy Board guidelines in 2024 and publicity from recent events including the compounding of unapproved semaglutide in community pharmacies.

This data gives a snapshot of compounding practices in Australian community pharmacies, highlighting gaps in knowledge and training of pharmacists compounding in the community. Opportunity exists for improved training and oversight and further evaluation of practices from a larger proportion of community pharmacies.

References

  1. Pharmacy Board of Australia (PBA). Guidelines on compounding of medicines [updated August 2017]. Melbourne: PBA; 2015.

Cooper N, Hoyle DJ, Holmes SE, Bereznicki LR. Extemporaneous compounding in Australian community pharmacies: extent, nature, and opinions. Int J Pharm Pract 2025; 33:180–187.

Stability of antibiotic dilutions for allergy testing

Dilutions of antibiotics used for intradermal and skin prick allergy testing are either prepared by clinicians at the point of testing, or by hospital pharmacy departments by dilution of antibiotic vials or commercially available kits. Protocols require a significant number of dilutions for each patient, making preparation in advance of testing a desirable option. A limiting factor in preparing dilutions ahead of testing is the lack of stability data for low concentration dilutions.

This study investigated the chemical and physical stability of 16 antibiotics commonly used in allergy testing. Dilutions were prepared under vertical laminar flow by an aseptically trained pharmacist. Chemical and physical stability were assessed across a 7-day period. Commercially available antibiotic vials were reconstituted as per the Australian injectable drugs handbook1 instructions to provide a stock solution, then further diluted to prepare a maximum non irritating concentration (NIC). Samples were prepared in both water for injection and phenolated saline and stored in both plastic syringes and glass vials.

Dilutions prepared in water for injection and stored in Terumo plastic syringes are of particular interest as this is commonly seen in clinical practice. Most antibiotics demonstrated chemical and physical stability for up to two days when diluted in water for injection to the NIC in water apart from amoxicillin/clavulanic acid and ampicillin.

In clinical practice, further dilution can occur, making this data useful, but not necessarily allowing the preparation of all required dilutions ahead of testing. This data may allow consideration of preparing the stock solution and the NIC ahead of time, and further dilutions to be prepared at the time of testing.

This data supports the preparation of stock solutions and NIC of amoxicillin, aztreonam, benzylpenicillin, cefazolin, cefepime, cefotaxime, ceftazidime, ceftriaxone, ciprofloxacin, flucloxacillin, meropenem, piperacillin/tazobactam and vancomycin ahead of testing, when prepared in an appropriate pharmacy facility. According to this study, amoxicillin/clavulanic acid, ampicillin and sulfamethoxazole/trimethoprim dilutions are not stable and therefore should not be prepared ahead of time.

References

  1. Symons K, Wong E, eds. Australian injectable drugs handbook. 9th edition. Collingwood: Society of Hospital Pharmacists of Australia (trading as Advanced Pharmacy Australia); 2023.

Wanandy T, Handley SA, Le TTA, Lau WY, Turner ME, Wiese MD. Stability of antibiotics for use in the testing of immediate drug allergy reactions. J Allergy Clin Immunol Pract 2025; 13: 343–352.

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EMERGENCY MEDICINE

MedsScan Editor for Emergency medicine SPG: Jill Upton

Olanzapine vs Haloperidol in the emergency department: which is better for acute agitation?

Special contributor: Grace Lucas

Acute agitation is a common presentation in the emergency department (ED) which can be managed with different pharmacological agents. Choice can depend on the cause and severity of agitation, patient comorbidities, drug cost and adverse effects.

This open label, randomised controlled trial at a tertiary care hospital in India, aimed to compare the efficacy and safety of olanzapine versus haloperidol for acute agitation in ED. Patients in Group A received olanzapine 10 mg intramuscular (IM), while Group B received haloperidol 5 mg IM. The primary outcome measure was adequate sedation at 15 minutes classified as an altered mental status score of 0 or less. Secondary outcome measures included adequate sedation at 30 minutes (min), need for rescue medications and reported adverse events.

There were 94 patients included in the trial, with an even split of 47 receiving each medicine. At 15 min, 31.9% of patients were sedated in the olanzapine group and compared with 25.5% in the haloperidol group (relative risk [RR] 1.25, 95% confidence interval [CI] 0.65–2.37, p = 0.494). The respective proportions were 61.7% and 48.9% at 30 min (p = 0.213). Rescue medications were needed in 12.7% of the olanzapine group and 25.5% of the haloperidol group (RR 0.5, 95% CI 0.2–1.22, p = 0.116). Adverse effects were reported in 4.2% of the olanzapine group and 10.6% of the haloperidol group (RR 0.4, 95% CI 0.08–1.96; p = 0.238).

Agitated patients in the ED endanger both staff and workflow requiring prompt management. Second generation antipsychotics may be preferred over first-generation agents, given similar efficacy profiles but lower risk of extrapyramidal adverse effects. In this study looking at undifferentiated agitation, both agents were found to be effective for agitation. Olanzapine may  be an alternative option in the ED however, further research should directly compare first line therapies with established efficacy in this cohort of patients such as droperidol as part of a multi-centre trial.

Choudhary Y, Jamshed N, Mathew R, Rout SP, Patra GP, Sahu AK, et all. Olanzapine vs haloperidol for management of acute agitation in emergency department: an open label randomized controlled trial. J Emerg Med 2025; 73: 42–51.

Naloxone: does adding an intramuscular dose to intravenous titration improve outcomes?

Special contributor: Gary Ward

Naloxone is an effective antidote to opioid toxicity; however it has a short half-life and repeated doses and infusions are often required. This single-centre, double-blinded randomised placebo-controlled trial studied the addition of intramuscular naloxone 1600 microgram to titrated intravenous naloxone 100 microgram in opioid poisoning to prevent recurrence of respiratory depression. The study enrolled 136 adult patients with suspected opioid intoxication, and all received titrated naloxone 100 microgram intravenous [IV], plus either naloxone 1600 microgram or normal saline intramuscular [IM].

The primary outcome measure was the proportion of patients with a recurrence of respiratory depression within 4 hours of IM injection. Secondary outcomes included the proportion of patients receiving naloxone infusion, total number of naloxone IV doses, proportion with effective reversal of respiratory depression at 10 minutes, and the occurrence of withdrawal symptoms.

Respiratory depression recurred within 4 h in fewer patients receiving IM naloxone (41% vs 72%, 95% CI 13%–46%, p < 0.001). There were also fewer naloxone infusions and bolus IV doses in the IM recipients. Similar effectiveness in reversal of respiratory depression at 10 min was seen between the groups, whilst opioid withdrawal was more often seen in the IM group (51% vs 42%, 9% difference, 95% CI -8%–27%, p = 0.308). An increase in the development of agitation was observed, however the authors note that the study was likely underpowered to detect this.

Study limitations include the single centre, and heroin being the predominant opioid. These results may not be generalisable to settings involving the use of longer acting opioids. This trial supports the early use of intramuscular naloxone 1600 microgram in the ED setting in addition to titrated IV naloxone boluses, with improved reversal of respiratory depression and reduced need for rescue therapy.

Isoardi KZ, Harris K, Currey E, Buckley NA, Isbister GK. Effectiveness of intramuscular naloxone 1,600 μg in addition to titrated intravenous naloxone 100 μg for opioid poisoning: a randomised controlled trial. Clin Toxicol (Phila) 2024; 62: 643–650.

Opioid-sparing analgesia in chest trauma 

Special contributor: Jasmine Walker

Adequate analgesia is imperative in chest trauma management to reduce the risk of complications, including pneumonia and respiratory failure. This was a double-blind, randomised trial across three sites that compared the analgesic effect of ketamine 0.25 mg/kg IV to ketorolac 30 mg IV administered over 5 minutes in patients with blunt or penetrating chest trauma involving at least two rib fractures or chest tube insertion in the Emergency Department (ED). Forty-five patients were assigned to the ketamine group and 45 patients were assigned to the ketorolac group.

The primary outcome measure was median pain score using a numeric rating scale (NRS) from 0–10 at 30 min and 60 min after medication administration. Secondary outcome measures included the proportion of patients requiring morphine as rescue analgesia and the proportion of patients experiencing adverse effects. Ketamine resulted in greater analgesic effect compared to ketorolac (at 30 min, median NRS = 3.0, interquartile range [IQR] 1.0, 95% confidence interval [CI] 2.8–3.5 versus median NRS = 5.0, IQR 4.5, 95% CI 4.2–5.8, p = 0.006, respectively; and 60 min median NRS = 3.0, IQR 2.0, 95% CI 2.7–3.7 versus median NRS = 5.6, IQR 1.7, 95% CI 4.7–6.4, p < 0.001 respectively). Of the 45 patients in the ketamine group, 28.9% (n = 13) required rescue analgesia, compared to 60% (n = 27) of the 45 patients in the ketorolac group. Participants were more likely to experience transient nystagmus and severe nausea in the ketamine group.

Existing literature supports a multimodal pain regime.1 This study adds to the literature on use of ketamine IV bolus as an analgesic agent for chest trauma, particularly for patients requiring chest tube insertion. Ketamine reduces opioid requirements and potentially opioid related respiratory depression which traditionally causes complications in chest trauma. Ketorolac may be effective in patients with rib fractures. Pharmacists involved in early analgesic decision making for patients presenting with chest trauma should consider ketamine as part of routine treatment.  

References

  1. Witt CE, Bulger EM. Comprehensive approach to the management of the patient with multiple rib fractures: a review and introduction of a bundled rib fracture management protocol. Trauma Surg Acute Care Open 2017; 2: e000064.

Mahmoodabadi HZ, Javadein ZS, Moosaie F, Faegh A, Bahreini M. Comparison of the analgesia dose of intravenous ketamine versus ketorolac in patients with chest trauma: a randomized double-blind clinic trial. Acad Emerg Med 2025; 32: 426–433.

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GENERAL MEDICINE

MedsScan Editor for General medicine SPG: Christina Hanciu

The use of mirtazapine for the management of chronic insomnia in older adults

Special contributor: Sylvia Andrew

Mirtazapine, an antidepressant with sedative properties, is frequently prescribed off-label for insomnia management, particularly in older adult populations, owing to its perceived favourable safety profile. However, conclusive clinical evidence validating its efficacy for this indication remains insufficient. The MIRAGE study was designed to assess whether low-dose mirtazapine (7.5 mg/day) alleviates insomnia in older patients without comorbid severe depression.

A randomised, double-blind, placebo-controlled trial was conducted involving participants aged >65 years diagnosed with chronic insomnia. Exclusion criteria comprised current use of hypnotic agents or participation in cognitive behavioural therapy for insomnia.

Treatment with mirtazapine resulted in a statistically significant reduction in Insomnia Severity Index (ISI) scores compared to placebo (−6.5, 95% confidence interval [CI] −8.3 to −4.8) versus (−2.9, 95% CI −4.4 to −1.4), p = 0.003, though the clinical significance of this improvement remained uncertain due to broad confidence intervals. While 50% of mirtazapine-treated participants achieved a clinically meaningful response (defined as ≥6-point reduction in ISI score), no between-group differences were observed in objective sleep metrics. Adverse effects that were reported, including daytime drowsiness, dizziness and abnormal dreams, occurred more frequently in the mirtazapine group, contributing to higher treatment discontinuation rates, however no severe adverse events (death or hospitalisation) were reported.

The study findings suggest potential therapeutic benefits of low-dose mirtazapine for insomnia management in older adults; however, its clinical utility may be limited by tolerability issues. Additional constraints include the brief 28-day evaluation period and modest sample size, which may compromise the generalisability of results. Currently, mirtazapine may be considered for management of insomnia refractory to non-pharmacological intervention. Further investigation through large-scale, extended follow-up clinical trials is warranted to establish definitive efficacy and safety profiles of mirtazapine.

Nguyen PV, Dang-Vu TT, Forest G, Desjardins S, Forget MF, Vu TT, et al. Mirtazapine for chronic insomnia in older adults: a randomised double-blind placebo-controlled trial-the MIRAGE study. Age Ageing 2025; 54: afaf050.

The effects of tirzepatide in heart failure with preserved ejection fraction

Special Contributor: Wei Mann Chew

Current therapy in patients with heart failure with preserved ejection fraction (HFpEF) has not demonstrated a reduction in mortality. In this study, tirzepatide, a glucagon-like peptide-1 GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, has been studied in patients with HFpEF to measure improvement of cardiovascular outcomes in addition to its weight loss benefits.

In this double-blind, randomised, placebo-controlled trial, patients with a left ventricular ejection fraction above 50% and body mass index of above 30 were randomised to receive weekly subcutaneous tirzepatide or placebo, and were followed for 52 weeks. Subjects receiving tirzepatide started with a weekly dose of 2.5 mg, with 2.5 mg increments every 4 weeks up to the dose of 15 mg or the maximum tolerable dose.

Adjudicated death from cardiovascular causes or a worsening heart-failure event occurred in 9.9% in the tirzepatide group and in 15.3% in the placebo group (hazard ratio [HZ] 0.62, 95% confidence interval [CI] 0.41 to 0.95, P = 0.026). Worsening heart-failure events occurred in 8.0% in the tirzepatide group and in 14.2% in the placebo group (HZ 0.54, 95% CI 0.34 to 0.85). A small number of patients in the treatment arm discontinued due to gastrointestinal side effects.

The study concluded that there are beneficial effects of tirzepatide on composite death from cardiovascular causes and a reduction in worsening heart failure events, however the study was not sufficiently powered. Also of note was the exclusion of participants with a decompensated heart failure event within 12 months before baseline, which could have impacted study results. More robust studies with larger sample sizes are required to investigate the therapeutic benefits of tirzepatide in HFpEF.

At the time of writing, tirzepatide is not listed on the Pharmaceutical Benefits Scheme and clinicians should weigh up the costs versus benefits of treatment.

Packer M, Zile MR, Kramer CM, Baum SJ, Litwin SE, Menon V, et al. Tirzepatide for heart failure with preserved ejection fraction and obesity. N Engl J Med 2025; 392: 427–437.

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INFECTIOUS DISEASES

MedsScan Editors for Infectious diseases SPG: Nadine Hillock and Minyon Avent

The REVISIT trial: aztreonam-avibactam versus meropenem for serious Gram-negative infections

REVISIT was a prospective, randomised, open-label, industry-funded phase III trial to evaluate the efficacy and safety of aztreonam-avibactam (± metronidazole) compared with meropenem (± colistin) for the treatment of serious Gram-negative infections, including complicated intra-abdominal infections (cIAI) or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HAP/VAP).

Four hundred and twenty-two adult patients (312 with cIAI and 110 with HAP/VAP) were randomised 2:1, with 282 patients allocated to aztreonam-avibactam ± metronidazole and 140 to meropenem ± colistin. For patients with creatinine clearance (CrCl) > 50 mL/min the loading dose of aztreonam-avibactam was 500 mg/167 mg followed by 1500 mg/500 mg every 6 hours (administered by slow intravenous infusion over 3 hours). Doses were adjusted according to renal function for aztronam-avibactam, meropenem and colistin. Treatment duration was 5–14 days for cIAI and 7–14 days for HAP/VAP. The primary endpoint was clinical cure at the test-of-cure visit in the intent-to-treat (ITT) population.

The mean age of patients was 55.2 years in the aztreonam-avibactam group and 54.0 years in the meropenem group. More than two thirds (68%) of participants were male. Two hundred and seventy-one patients had at least one Gram-negative pathogen identified at baseline. For patients with cIAI, Escherichia coli was the most predominant pathogen identified, followed by Klebsiella pneumoniae. For patients with HAP/VAP, Klebsiella pneumoniae was the predominant pathogen followed by Pseudomonas aeruginosa (P. aeruginosa). Twenty-six patients (19%) in the meropenem group received concomitant colistin and 1% of the aztreonam-avibactam group received a concomitant aminoglycoside. Metronidazole was co-administered with aztreonam-avibactam in all but nine patients with cIAI.

In the ITT cohort, the overall clinical cure rate at the test-of-cure visit (day 28) was 68.4% in the aztreonam-avibactam group and 65.-7% in the meropenem group (treatment difference 2.7%, 95% confidence interval [CI] 6.6%–12.4%]). For patients with cIAI, the clinical cure rate in the aztreonam-avibactam group was 76.4% compared with 74.0% in the meropenem group (treatment difference 2.4%, 95% CI -7.4%– 13.0%). Cure rates in patients with HAP/VAP were 45.9% for aztreonam-avibactam and 41.7% for meropenem. Of the 282 patients, the 28-day all-cause mortality rate for patients in the aztreonam-avibactam arm was 4.3% (n = 12), with four patients with cIAI and eight with HAP/VAP. Thall-cause mortality rate was 7.1% (n = 10) of the 140 patients in the meropenem group, with 3 patients with cIAI and seven with HAP/VAP.

The rate of Clostridiodes difficile infections in the aztrenonam-avibactam group was 8%, compared with 4 % in the meropenem group. Mild-to-moderate hepatic adverse events were common in both groups (18% in the aztreonam-avibactam group versus 15% in the meropenem group).

It is noteworthy that patients with monomicrobial P. aeruginosa or Acinetobacter spp. infection or polymicrobial infections including P. aeruginosa were excluded from the clinically evaluable group, as aztreonam-avibactam has poor in-vitro activity against these pathogens. P. aeruginosa was identified in 23% of HAP/VAP patients in the micro-ITT dataset.

In summary, treatment differences between the aztreonam-avibactam group and the meropenem group were not significant, however aztreonam-avibactam may offer an alternative option against carbapenem-resistant Enterobacterales. Due to small numbers of infections with metallo-β-lactamases in this study, no conclusion can be drawn regarding the efficacy of aztreonam-avibactam for treatment of infections with these pathogens.

Carmeli Y, Cisneros JM, Paul M, Daikos GL, Wang M, Torre-Cisneros, et al. Aztreonam-avibactam versus meropenem for the treatment of serious infections caused by Gram-negative bacteria (REVISIT): a descriptive, multinational, open-label, phase 3, randomised trial. Lancet Infect Dis 2025; 25: 218–230.

Effect of hydrocortisone on mortality in severe community-acquired pneumonia

The REMAP-CAP trial is an ongoing adaptive randomised platform trial, managed by a blinded International Trial Steering Committee, which aimed to evaluate multiple interventions for adult patients hospitalised with severe community acquired pneumonia (CAP). This study, published in Intensive Care Medicine by the REMAP-CAP Investigators, provides the analysis of the effectiveness of intravenous hydrocortisone (50 mg every 6 h for 7 days) as an adjunct to CAP treatment.

Adult patients who presented with CAP and were admitted to the intensive care unit (ICU) within 48 h of hospital presentation for respiratory or cardiovascular support were eligible for enrolment. Exclusion criteria included known hypersensitivity to corticosteroids, chronic systemic corticosteroid use and >24 h since ICU admission. Additionally, for this analysis (but not the wider trial), patients with COVID-19 infection were excluded. The primary outcome was all-cause mortality at 90 days post-randomisation.

Of 656 patients included, 536 were randomised to the hydrocortisone arm and 122 to the placebo control. In the hydrocortisone arm 213/526 (39.7%) required invasive mechanical ventilation compared to 46/122 (37.7%) in the placebo arm. The median age in the intervention arm was 62.5 years (interquartile range [IQR] 52–73 years) and 58.5 years (IQR 48–68 years) in the control arm.

By day 90, 78 (14.6%) of 521 patients assigned to hydrocortisone and 12 (9.8%) of 122 patients in the control arm had passed away. Fifteen patients in the intervention arm were lost to follow up. The trial platform ceased randomisation to the 7-day hydrocortisone arm in December 2023 due to a pre-specified stopping rule for futility compared to control. The median adjusted odds ratio for death at day 90 with hydrocortisone was 1.56 (95% CI 0.80–3.31), giving a 10% probability of superiority, a 3.4% probability of >20% reduction in the odds of death and a 90% probability of harm.

In summary, for patients admitted to ICU with severe CAP and either cardiovascular or respiratory failure, the addition of a 7-day course of intravenous hydrocortisone to usual care was unlikely to reduce mortality.

REMAP-CAP Investigators, Angus DC. Effect of hydrocortisone on mortality in patients with severe community-acquired pneumonia. Intensive Care Med 2025; 51: 665–680.

Efficacy and safety of faecal microbiota transplants for prevention of recurrent Clostridioides difficile infection

While most published trials investigating the efficacy of faecal microbiota transplant (FMT) as a treatment for Clostridioides difficile (C. difficile) infection (CDI) have been open label, this study was a randomised, placebo-controlled, double-blind study. The aim was to test the efficacy and safety of capsule-delivered FMT versus placebo, administered after successful initial antibiotic treatment of recurrent CDI, for the prevention of subsequent diarrhoea and C. difficile recurrence.

A CDI episode was defined as laboratory confirmation of C. difficile and either >3 loose/watery stools/24 h for two consecutive days or ileus or toxic megacolon. Patients with documented CDI recurrence within 90 days of a prior CDI episode were eligible if they reported resolution of symptoms for at least 48 h following antibiotic treatment for their most recent episode.

One hundred and fifty-three patients were randomised, 76 to FMT and 77 to placebo. The average time ± standard deviation (SD) between end of antibiotic treatment and enrolment was 6.6 ± 4 days. Most participants received oral vancomycin for the previous CDI episode. The mean age ± SD of participants in the FMT cohort (69.2 years ± 12.3) was slightly higher than the placebo group (63.9 years ± 14.6). Participants in the study were predominantly white (94.8%) and male (86.3%). Participants, the care provider and the investigator were all blinded to treatment arm. The FMT capsules were prepared from lyophilised faecal material from four standardised donors; capsules (both FMT and placebo) were administered orally. The primary outcome was CDI recurrence (as per the episode definition) or death within 56 days of randomisation.

There was no loss to follow up at 56 days. Of the 76 patients in the FMT arm and 77 patients in the placebo arm, 32.9% (n = 25) and 29.9% (n = 23) experienced possible or definite CDI recurrence or death within 56 days of capsule administration, respectively (absolute difference 3.0%, 95% CI -11.7% to 17.7%). One patient passed away in each group. There was no clinical or statistical difference in the rate of possible or definite CDI recurrence (odds ratio 1.18, 95% CI 0.59 to 2.35). In a subgroup analysis, there was an observed decrease in recurrence with FMT among participants with ≥two previous episodes but this reduction was not statistically significant.

This study showed no reduction in recurrence of CDI with oral FMT however the authors acknowledged there is no ‘standard’ for composition and dose of oral FMT and further comparative trials are needed.

Drekonja DM, Shaukat A, Hunag Y, Zhang JH, Reinink AR, Nugent S, et al. A randomized controlled trial of efficacy and safety of fecal microbiota transplant for preventing recurrent Clostridioides difficile infection. Clin Infect Dis 2025; 80: 52–60.

Erratum: Correction to: A randomized controlled trial of efficacy and safety of fecal microbiota transplant for preventing recurrent Clostridioides difficile infection. Clin Infect Dis 2025; 80: 242–243.

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MEDICINES INFORMATION

MedScan Editor for Medicines information SPG: Helen Trenerry

Knowledge gaps identified in queries to a Swedish drug information centre

Medicine (drug) Information Centres (MICs) are increasingly being consulted regarding complex patient cases, for support and advice in the decision-making process. However, knowledge gaps exist in the literature limiting the advice provided.

An analysis of queries received by a Swedish MIC during 2022 identified those with knowledge gaps where no advice could be provided. The authors analysed 209 queries that required a comprehensive response and included key signalling phrases (e.g. lack of available studies or evidence) to identify queries with a gap in knowledge. They then classed these queries into types and classes of drugs and reviewed responses to enquirers that provided advice.

Among the 209 responses, there were 49 (23.4%) with knowledge gaps, and 38 (18.2%) of all queries received no advice from the MIC. Most of the queries (94.7%) were initiated by doctors and 78.5% of queries were related to a specific patient. Queries with knowledge gaps (36.7%) and responses with no advice (39.5%) were most commonly about adverse effects and nervous system or antineoplastic and immunomodulating medications.

MICs offer a link between the evidence-based literature and its interpretation and application to clinical practice. However, knowledge gaps are still apparent, often due to exclusion of specific patient groups in clinical trials and can limit the advice provided for optimisation of patient care. MICs have an opportunity to identify areas where there are knowledge gaps and primary research is required.

Nilsson J, Kindblom JM, Izsak J. Analysis of queries to a Swedish drug information centre identifies scientific knowledge gaps. Sci Rep 2024; 14: 30412.

Erratum: Nilsson J, Kindblom JM, Izsak J. Author correction: analysis of queries to a Swedish drug information centre identifies scientific knowledge gaps. Sci Rep 2025; 15: 10629.

Can ChatGPT answer clinical pharmacy questions?

Artificial intelligence (AI) has increasing applications in healthcare and the role of ChatGPT (OpenAI, San Francisco, CA, USA) is being explored to assist pharmacists in their daily practice.

ChatGPT was assessed as a tool for answering pharmacy-based clinical questions. ChatGPT was asked 32 questions and the responses analysed. Question types included six standard drug information questions, six enhanced prompt drug information questions, five patient case questions, five calculations questions and 10 drug knowledge (from the top 200 drugs) questions to reflect pharmacy practice. The standard and enhanced drug information questions also asked ChatGPT to include citations. The responses were then assessed for appropriateness.

ChatGPT had an overall score of 21/44 (47.7%) points. ChatGPT scored high in questions that did not require interpretation, such as pharmacy calculation (100%), drug information (83%) and drug knowledge (80%) but low in drug information prompt (33%) and patient case (20%) categories. The two questions answered incorrectly in the drug knowledge section were both contraindication questions. ChatGPT scored 0 (0%) points when assessed for identifying drug information sources in both the standard and enhanced categories.

ChatGPT scored highly in drug calculation, medication-related multiple choice (top 200 drugs) and short-answer drug information questions where a high degree of interpretation is not required. ChatGPT performed poorly with patient case questions where there are multiple factors and comorbidities that need to be considered and interpreted before providing a response. The authors indicate that ChatGPT may have a role in aiding pharmacists to carry out routine tasks but is inappropriate for the medicines management of complex patients.

Munir F, Gehres A, Wai D, Song L. Evaluation of ChatGPT as a tool for answering clinical questions in pharmacy practice. J Pharm Pract 2024; 37: 1303–1310.

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MENTAL HEALTH

MedsScan Editors for Mental health SPG: Judy Longworth and Amy Sieff

Valbenazine for tardive dyskinesia

Tardive dyskinesia (TD) refers to a range of chronic, abnormal movements associated with ongoing use of antipsychotic medications.1 TD often causes distress and significantly diminishes quality of life.2 There are few effective or tolerable options available to manage TD beyond early detection and reducing the dose of, or ceasing, the causative agent. If the drug is ceased, TD sometimes persists.3

The aim of this study was to assess safety, efficacy and tolerability of valbenazine for TD. This was a randomized, double-blind, placebo-controlled, parallel-group, fixed-dose trial completed over six weeks. Participants were included based on psychiatric diagnosis, mental state, and the presence of moderate to severe TD induced by medication for at least three months. The Abnormal Involuntary Movement Scale (AIMS) was used to assess efficacy.

TD improvement was observed in the valbenazine 40 mg and 80 mg daily groups compared with placebo. The 80 mg group improvement was statistically significant. The most common adverse effect was somnolence, reported in 5.3% of patients in the valbenazine groups and in 3.9% of patients in the placebo group. Seven participants withdrew due to adverse effects, including two from the placebo group. One withdrawal due to hepatitis was deemed possibly related to the study. Psychiatric stability and suicidality were largely unchanged.

Participants over the age of 65 are often excluded from clinical trials.4 Given older people are more likely to experience TD, a notable advantage of this study was that 205 participants were aged 18–85 years in this study. Another benefit was that AIMS assessments were centralised, performed via video analysis and blinded. Disadvantages include the relatively short time period for the study, and that the 40 mg and 80 mg valbenazine groups were not directly compared to one another. This trial supported the approval of valbenazine for TD by the United States Food and Drug Administration. Valbenazine is not currently available for the management of TD in Australia and neither is deutetrabenazine. The only vesicular monoamine transporter type 2 inhibitor (VMAT2) option in Australia is tetrabenazine.

References

  1. Kanodia S, Guha S. Tardive dyskinesia responsive to deep brain stimulation. Aust N Z J Psychiatry 2018; 52: 717.
  2. English T, Castle D. Treating schizophrenia: should we emphasise ‘first do no harm’? Aust N Z J Psychiatry  2022; 56: 8–10.
  3. Ismail O, Albdour K, Jaber Y, Jaber K, Alsaras A. Efficacy and safety of different pharmacological interventions in the treatment of tardive dyskinesia: a systematic review and network analysis. Eur J Clin Pharmacol 2024; 80: 1471–1482.
  4. Schwartz JB. Representative enrolment of older adults in clinical trials: the time is now. Lancet Healthy Longev 2023; 4: e301–e303.

Hauser RA, Factor SA, Marder SR, Knesevich MA, Ramirez PM, Jiminez R, et al. KINECT 3: A phase 3 randomized, double-blind, placebo-controlled trial of Valbenazine for tardive dyskinesia. Am J Psychiatry 2017; 174: 476–484.

Deprescribing or switching?

This is a comprehensive review paper of child and adolescent antidepressant randomised controlled trials, concentrating on the withdrawal and switching aspects of therapy. Although there are adult guidelines there is a paucity of guidelines for child and adolescent antidepressant use and this paper helps provide needed guidance.

This review included 28 studies, including 13 randomised, double-blind, placebo-controlled trials, with a total of 3026 patients. Ultimately, the authors found that deprescribing antidepressant medicines requires careful consideration of the following: clinical status, treatment response, and often, the pharmacokinetics and pharmacodynamics of both the medicine being ceased and the medicine being initiated.

Children and adolescents are not simply small adults and as such have their own pharmacokinetic and pharmacodynamic idiosyncrasies which need to be considered when ceasing an antidepressant or switching to another. The paucity of clinical trials and recognition that children and adolescents are not small adults impedes the evaluation and analysis of the potential for withdrawal effects of any given antidepressant utilised in children and adolescents.

This paper reflects on each antidepressant studied and gives suggestions for management of adverse effects when children or adolescents are withdrawing from them, as well as recommendations for switching between antidepressants. There is also a very useful figure that shows switching suggestions pictorially, which may be helpful for all

Stimpfl JN, Walkup JT, Robb AS, Alford AE, Stahl SM, et al. Deprescribing antidepressants in children and adolescents: a systematic review of discontinuation approaches, cross-titration, and withdrawal symptoms. J Child Adolesc Psychopharmacol 2025; 35: 3–22.

New hypothesis for schizophrenia treatment

Since Avrid Carlsson postulated the dopamine hypothesis for schizophrenia in the 1960’s, treatment for schizophrenia has concentrated on the blockade of dopamine receptors, focusing mainly on the dopamine D2 receptor, but this does not account for the unique way clozapine works in treatment-resistant schizophrenia. These two papers highlight the unique way that acetylcholine and muscarinic receptor blockade also has an effect for the treatment of schizophrenia.

Morrison et al. aimed to explain the unique efficacy of clozapine, when compared to other antipsychotic medicines, arguing that previously offered explanations have been found to be inadequate. The authors examined previous accounts of the efficacy of clozapine arising from its low affinity for D2 and high affinity for D4 receptors respectively, arguing however that the unique clinical pharmacology of clozapine is explained by a partial agonism at muscarinic acetylcholine receptors M4, and potentially, at M1 receptors. To support this conclusion, the authors draw on the Phase III clinical trials of the of the pharmaceutical KarXT (xanomeline–trospium) study.

Kaul et al. present the results of the EMERGENT–2 study. EMERGENT–2 was a randomised, double-blind, placebo-controlled phase III trial for patients with schizophrenia, which aimed to assess the safety and efficacy of KarXT, a combination of xanomeline and trospium chloride. Xanomeline is a muscarinic receptor agonist that acts on M1 and M4 but does not block D2 receptors. Included participants were adults with schizophrenia, between 18 and 65 years old who had experienced recent hospitalisation and these patients were assigned (1:1) to either placebo or the KarXT group (50 mg xanomeline, 20 mg trospium twice per day for 2 days, and then 100 mg xanomeline and 20 mg trospium twice per day from day 3–7).

Two hundred and fifty-two participants were included, with 127 patients assigned to each group. The study found a statistically significant reduction in the Positive and Negative Syndrome Scale in the KarXT group compared to the placebo group. The authors demonstrated that KarXT is effective in blocking muscarinic receptors (mainly M1 and M4) in predominantly male adult patients with schizophrenia. Constipation, dyspepsia and headache were reported as significant adverse effects in the KarXT group when compared with the placebo group, but nil extrapyramidal motor symptoms were identified. This Emergent-2 trial is part of a longer study to further illustrate the efficacy and safety of KarXT in schizophrenia.

These articles present interesting developments in the treatment of schizophrenia, and we await further reports that look at future treatment options for those with severe mental illness and the emerging hypotheses associated with the actions of these medicines.

Morrison PD, Jauhar S, Young AH. The mechanism of action for clozapine. J Psychopharmacol 2025; 39: 297–300.

Kaul I, Sawchak S, Correll CU, Kakar R, Breier A, Zhu H, et al. Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline–trospium) in schizophrenia (EMERGENT–2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial. Lancet 2024; 403: 160–170.

Erratum: Corrected: Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline–trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial. Lancet 2024; 403: 2380.

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NEPHROLOGY

MedsScan Editor for Nephrology SPG: Laura Johnstone

Direct oral anticoagulants for atrial fibrillation and end-stage renal disease: to give or not to give?

Special contributor: Siev Hong Lor

Atrial fibrillation (AF) is commonly observed in patients with end-stage renal disease (ESRD). The decision to initiate anticoagulation, and the selection of an appropriate oral anticoagulant, remains complex and nuanced. This network meta-analysis of 42 studies aimed to review the efficacy and safety profiles of warfarin, apixaban, rivaroxaban, dabigatran and no anticoagulation in patients with AF and on dialysis (predominately haemodialysis). Among the patients, 4.81% received direct oral anticoagulants (DOACs) predominately apixaban, 38.04% received warfarin, and 57.15% were not anticoagulated. 

Reviewed outcomes included major bleeding, embolism and all-cause mortality. For major major bleeding, warfarin has higher risk compared to apixaban (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.61–0.86), dabigatran (HR 0.70, 95% CI 0.53–0.93) and no anticoagulation (HR 1.47, 95% CI 1.34–1.61). All DOACs showed no significant difference from warfarin or no anticoagulant in terms of embolism and all-cause mortality.

However, are we really comparing apples to apples? Time spent outside the therapeutic international normalised ratio (INR) range was unclear. Maintaining a therapeutic INR is notoriously difficult in dialysis patients due to uraemia, altered warfarin metabolism and changes in protein binding. Anticoagulation use during dialysis may further confound INR control. Additionally, whilst 185 864 patients were included from 42 studies only 4.81% (n = 8861) of patients received DOACs compared with 38.04% (n = 70 047) on warfarin and 57.15% (n = 105 228) on no anticoagulation. This review supports current thinking that the decision to anticoagulate for AF in the ESRD population is difficult to prognosticate due to the inherent increased risk both of bleeding and mortality these patients have. Would the results have been different if apixaban, rivaroxaban, dabigatran and warfarin were equally represented? A multi-arm randomised control trial may clarify these unanswered questions.

Kao TW, Chen ZW, Lin YH. Anticoagulation for patients with concomitant atrial fibrillation and end-stage renal disease: a systematic review and network meta-analysis. J Am Heart Assoc 2024; 13: e034176.

Is the reign of obinutuzumab for the treatment of lupus nephritis beginning? Results of the REGENCY trial

Special Contributor: Claudia Jahnigen

Background: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), characterized by immune complex deposition in the kidneys, leading to inflammation and progressive renal damage. Despite the availability of immunosuppressive therapies, including mycophenolate mofetil (MMF), glucocorticoids (prednisone/prednisolone), and newer agents like belimumab and voclosporin, many patients fail to achieve sustained remission or experience long-term renal decline.1 B cells play a central role in LN pathogenesis through autoantibody production, antigen presentation, and cytokine secretion.2

Obinutuzumab, a glycoengineered type II anti-CD20 monoclonal antibody, has demonstrated superior and potentially longer lasting peripheral B-cell depletion compared with rituximab, prompting clinical trials to evaluate its efficacy and safety in treating LN.  In the exploratory phase 2 NOBILITY trial, obinutuzumab showed a higher rate of complete renal response compared with that of placebo, as well as no increase in adverse effects.3 These findings set the stage for the subsequent phase 3 REGENCY trial.

Aim: To evaluate the efficacy and safety of obinutuzumab, in addition to standard therapy, in improving renal response in adults with active proliferative LN.

Method: REGENCY was a multicentre, randomised, double-blind placebo-controlled phase 3 trial conducted across 15 countries. Eligible participants were adults aged 18–75 years with biopsy-confirmed active class III or IV LN (with or without class V), a urinary protein-to-creatinine ratio (UPCR) ≥ 1, and positive antinuclear antibodies.

Patients were excluded if they had an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m², end-stage kidney disease, recent use of anti-CD20 therapy or active infections. Participants (N = 271) were randomised 1:1 to receive either obinutuzumab (n = 135) or placebo (n = 136), both in combination with standard therapy (MMF and oral prednisone). Obinutuzumab was administered intravenously at 1000 mg on day 1 and weeks 2, 24, 26 and 52, with an optional dose at week 50. Prednisone was tapered to 7.5 mg/day by week 12 and 5 mg/day by week 24.

The primary endpoint was the proportion of patients achieving a complete renal response at week 76, defined as UPCR < 0.5, eGFR ≥ 85% of baseline and no intercurrent event (e.g., treatment failure, rescue therapy, death or early trial withdrawal). Key secondary endpoints included complete renal response with prednisone ≤7.5 mg/day between weeks 64–76, UPCR < 0.8 without intercurrent event, change in eGFR, death or renal-related events, overall renal response at week 50 and change in fatigue (Functional Assessment of Chronic Illness Therapy – Fatigue [FACIT-F] score).

Results: Baseline characteristics were reasonably balanced between groups. Participants’ mean age was 33 years and 84% of the participants were female. Ethnically, 58% of participants identified as Hispanic or Latino and 15% as Black or African American. All enrolled patients had biopsy-proven active proliferative LN in the form of either Class III or IV LN. Baseline eGFR values were comparable between groups (102.8 mL/min/1.73 m2 for obinutuzumab versus 101.9 mL/min/1.73 m2 for placebo), while the obinutuzumab group had a slightly lower UPCR (2.13 versus 2.76 g/24 h).

At week 76, complete renal response was achieved in 46.4% in the obinutuzumab group versus 33.1% in the placebo group (adjusted difference 13.4%, 95% confidence interval [CI] 2.0–24.8, P = 0.02). This met the primary endpoint and confirmed the superiority of obinutuzumab over placebo when added to standard therapy.

Key secondary outcomes also included the following:

  • Complete renal response with prednisone ≤ 7.5 mg/day (tapered between week 64 to 76) was achieved in 42.7% (obinutuzumab) versus 30.9% (placebo) (P = 0.04).
  • UPCR < 0.8 without intercurrent event occurred in 55.5% versus 41.9% (P = 0.02).
  • Death or renal-related events occurred in 18.9% versus 35.6% (adjusted difference −16.8 percentage points, 95% CI, −27.4 to −6.2).
  • eGFR change was not statistically significant between groups.
  • FACIT-F scores improved modestly in both groups, with no significant difference.

Subgroup analyses showed consistent benefits across patients with high-risk features, including class IV nephritis, high baseline proteinuria and serologic activity (low C3 or C4 complement or high antibodies against double-stranded DNA). Notably, the placebo group had a higher complete response rate among men, though this subgroup was small.

In terms of safety, adverse events occurred in 92.6% of obinutuzumab-treated patients and 88.6% of placebo recipients. Serious adverse events were more frequent with obinutuzumab (32.4% versus 18.2%), primarily due to infection, including COVID-19-related pneumonia. Four deaths occurred during the trial (3 patients taking obinutuzumab and one patient taking placebo), most of these patients passed away early in the pandemic. Infusion-related reactions and neutropenia were more common in the obinutuzumab group, but no new safety signals emerged.

Key limitations: The trial occurred during the COVID-19 pandemic, which may have influenced infection rates and mortality, particularly early in the study before widespread vaccination. The follow up period was limited to 76 weeks; longer-term renal outcomes and durability of response remain unknown. The study did not stratify by disease duration or prior treatment history, which may influence response heterogeneity. The REGENCY trial was a large trial conducted across 15 nations however Australians, and First Nations peoples, were not included. This lack of representation limits the direct applicability of the trial’s findings to the Australian renal population. Furthermore, the trial evaluated obinutuzumab as an adjunct to standard therapy rather than a head-to-head study making it difficult to ascertain its place in clinical practice.

Impact on practice: The REGENCY trial provides robust phase 3 evidence that obinutuzumab, when added to standard therapy, significantly improves renal outcomes in patients with active LN. The findings support the role of deep B-cell depletion as a therapeutic strategy in LN, particularly for patients with high disease activity or poor prognostic features. While safety concerns, especially infection risk, must be considered, the overall risk-benefit profile is favourable. The higher cost of obinutuzumab compared to other available agents is a limiting factor and while the trial results could shape upcoming treatment recommendations and facilitate regulatory approval of obinutuzumab in lupus nephritis, head-to-head trials with existing therapies would provide more definitive guidance for its clinical use.

References

  1. Furie R, Rovin BH, Houssiau F, Malvar A, Tenng YKO, Contreras G, et al. Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med 2020; 383: 1117-–1128.
  2. Mohan C, Zhang T, Putterman C. Pathogenic cellular and molecular mediators in lupus nephritis. Nat Rev Nephrol 2023; 19: 491–508.
  3. Furie RA, Aroca G, Cascino MD, Garg JP, Rovin BH, Alvarez A, et al. B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis 2022; 81: 100–107

Furie RA, Rovin BH, Garg JP, Santiago MB, Aroca-Martínez G, Zuta Santillán AE, et al. Efficacy and safety of obinutuzumab in active lupus nephritis. New Engl J Med 2025; 392: 1471–1483.

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Oncology and haematology

MedsScan Editor for Oncology and haematology SPG: Alborz Soroush

Frontline use of ponatinib plus blinatumomab for Philadelphia positive acute lymphoblastic leukemia adult patients: intermediate analysis of GIMEMA ALL2820

Special contributor: Lily Rush

The GIMEMA ALL2820 study found that giving newly diagnosed adult Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL) patient’s ponatinib (tyrosine kinase inhibitor [TKI]) in induction and blinatumomab (bispecific T-cell engager) in consolidation shows promising beneficial survival outcomes. Ponatinib is a potent pan-TKI that is thought to overcome resistance associated with the T315I mutation.

The phase III multicentre, open-label study involved 200 newly diagnosed adult Ph+ ALL patients with no prior to current central nervous system disease who were randomly assigned in a 2:1 ratio to either receive ponatinib induction followed by blinatumomab (+ ponatinib) consolidation, or chemotherapy and imatinib induction followed by imatinib monotherapy consolidation. The experimental arm involved steroid pre-phase followed by a 70-day induction with ponatinib at 45 mg or 30 mg daily according to the patient’s age (less or more than 65 years), followed by at least 2 cycles (maximum 5) of blinatumomab at 28 mcg/day for 28 days.

The median age of the study arm was 57 years, without statistically significant differences in   male and female participants. The primary endpoint was event-free survival, and secondary endpoints included haematological and molecular response, overall survival, disease free survival and safety. Of the 200 participants randomised, 133 patients received the experimental arm of ponatinib and blinatumomab. By the end of induction, 110 patients (95%) achieved a complete haematological remission in the experimental arm, including four patients that passed away and two discontinuations (the remaining cases were still receiving induction). An overall molecular response was recorded in 45% of cases following induction. At the end of the second cycle of blinatumomab 98% of evaluable patients were in complete haematological remission, with one patient withdrawing consent and another experiencing haematologic relapse. The overall molecular response increased to 73%. The treatment combination was well tolerated overall, with few treatment discontinuations and severe adverse events. Allogenic stem cell transplantation (alloSCT) allocation via biomarkers was associated with reduced allograft rates, with only 12% of patient’s undergoing alloSCT.

The previous GIMEMA LAL2116 trial showed the effectiveness of a chemotherapy-free approach with dasatinib followed by blinatumomab. Based on the current interim analysis the ponatinib-based regimen in GIMEMA ALL2820 demonstrates a lower relapse rate and reduced need for alloSCT.

In summary, ponatinib and blinatumomab treatment demonstrated improved survival outcomes (overall survival 95.5% and disease-free survival 95.7% at 24 months) among adult patients with Ph+ ALL, through providing a more targeted and less toxic treatment, hence potentially reducing the need for allogenic stem cell transplantation in certain patients.

Although blinatumomab is currently PBS approved for relapsed or refractory B-cell precursor ALL and MRD disease, emerging data, particularly from recent trials, suggest its evolving role in frontline therapy. Notably, studies combining blinatumomab with TKIs in Ph+ ALL are demonstrating promising efficacy, potentially redefining standard first-line treatment strategies. Currently, ponatinib can only be accessed through the PBS as part of combination treatment for ALL if a patient has been refractory to, or intolerant of Dasatinib.

Chiaretti S, Leoncin M, Elia L, Soddu S, Piciocchi A, Matarazzo M, et al. Efficacy and Toxicity of Frontline Ponatinib Plus Blinatumomab for Adult Ph+ ALL Patients of All Ages. Intermediate Analysis of the Gimema ALL2820. Blood 2024; 144 (Supplement 1): 835.

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PAIN MANAGEMENT

MedsScan Editor for Pain management SPG: Jeremy Szmerling

Consensus on a core outcome set of patient reporting outcome measures (PROMs) in postoperative pain management

Special Contributor: Ryanne Coe

The use of heterogeneous or inadequate outcomes in postoperative pain management studies complicates evidence synthesis and may fail to accurately capture individual patient experiences. The Innovative Medicines Initiative PainCare Providing Standardised Consented PROMs for Improving Pain Treatment (IMI-PainCare PROMPT) project, aimed to establish a core outcome set of patient-reported outcome measures (PROMs) for the assessment of acute postoperative pain in adults.

The process involved systematic identification and evaluation of PROMs and a Delphi-based consensus with international stakeholders, including people with lived experience. PROMs were selected to assess four previously agreed-upon domains: pain intensity, physical function, self-efficacy and adverse events. For pain intensity, a numerical rating scale was selected to assess average pain, worst pain, pain at rest and procedure-specific pain during activity. Physical function was assessed using both a generic item (pain interference with doing activities in bed such as turning, sitting up and changing position) and procedure-specific items (e.g. bending knee post-knee surgery). The IMI-PainCare PROMPT adaptation of the Arthritis Self-Efficacy Scale (ASES) was selected for self-efficacy, and the Opioid-Related Symptom Distress Scale (OR-SDS) adaptation was selected for adverse events.

Pharmacists involved in clinical research or quality improvement can use these PROMs to ensure consistency in outcome reporting, which strengthens the validity and comparability of their findings across studies and settings. Moving beyond simple pain intensity scores to include domains such as physical function, self-efficacy and opioid-related adverse events supports a more nuanced understanding of patient experiences and treatment impact. Incorporating these PROMs into routine practice or research can also help pharmacists demonstrate the value of their clinical services and guide future practice improvements.

Pogatzki-Zahn EM, De Lucia S, Weinmann C, Heitkamp H, Hummelshoj L, Liedgens H, et al. A core outcome set of measurement instruments for assessing effectiveness and efficacy of perioperative pain management: results of the international IMI-PainCare PROMPT Delphi consensus process. Br J Anaesth 2025; 134: 1460–1473.

Pain and complexity: navigating analgesic risks in the multimorbid maze

Half of people with multimorbidity live with chronic pain, yet optimal analgesic strategies remain unclear. This systematic review aimed to quantify the risk of adverse outcomes from opioids, non-steroidal anti-inflammatory drugs (NSAIDs) and gabapentinoids in adults with multimorbidity.

Observational and interventional studies from MEDLINE, CINAHL, Web of Science, Embase and CENTRAL examining harms from these analgesics in adults with multimorbidity were included. Risk of bias was assessed using the Newcastle-Ottawa Scale and the Risk of Bias In Non-randomised studies – of Interventions (ROBINS-I) tool. After exclusions, 27 studies (n = 2 671 958) were reviewed.

Of 16 opioid studies, 12 reported harms, with multimorbidity associated with more severe outcomes including: increased rates of complications, overdose, hip fracture and up to seven-fold higher mortality, particularly with long-term use. Of the 11 NSAID studies, six reported harms, including increased risks of transfusion, acute kidney injury, gastrointestinal bleeding and cardiovascular events. One study on gabapentinoids found no increased mortality with gabapentin, but higher risks of delirium and pneumonia. Study quality varied, with 11 studies showing high risk of bias.

This review highlights that, while polypharmacy-related harms in multimorbidity are well documented, evidence specific to analgesic risks remains limited. Opioid-related harms are notable, but data on NSAIDs and gabapentinoids are scarce. In Australia, where chronic pain and multimorbidity are highly prevalent, this gap underscores the role of hospital pharmacists in incorporating multimorbidity into safety monitoring and deprescribing strategies. Greater inclusion of multimorbid patients in clinical trials and the development of tailored, evidence-based guidelines are urgently needed to support safer, more effective pain management.

Grant CH, Walker H, Barnett KN, Mark PB, Colvin LA, Bell S. Multimorbidity and analgesic-related harms: a systematic review. Br J Anaesth 2025; 134: 1717–1745.

Opioid prescribing following work-related neck and back injuries

Special Contributor: Finn Roser

This retrospective cohort study aimed to investigate the prevalence and predictors of early high-risk and persistent opioid prescribing in Australian workers with workers compensation claims for back and neck-related musculoskeletal disorders.

Workers with compensation claims for back and neck conditions received from 1 January 2010–31 December 2019, who filled at least one opioid prescription within the three months before, or after, the claim were included. Early high-risk opioid prescribing was defined as >350 mg oral morphine equivalent (OME) on initial dispensing or any of the following within the first 90 days: >50 mg OME daily, supply of long-acting formulations or co-prescription with other psychotropics. Persistent opioid use was defined as continued opioid prescriptions up to 1 year after the claim date or first prescription.

Persistent opioid use at one year affected nearly one in four injured workers. Early high-risk opioid prescribing occurred in 67.1% (n = 6278) and doubled the risk of persistent use (odds ratio [OR] 2.19, 95% confidence interval [CI] 1.89–2.53). Predictors of persistent use included living in disadvantaged areas, with not returning to work by three months increasing the odds nearly eightfold. Early high-risk prescribing was more likely in workers aged 35–44 years, those living in regional areas, and claims lodged between 2015–2019. Sex, socioeconomic status and injury type were not linked to early high-risk prescribing.

This study highlights the important role pharmacists can play in identifying early high-risk opioid prescribing, including the review of initial opioid prescriptions and monitoring of patients returning with subsequent opioid prescriptions, to help prevent persistent opioid use. Pharmacists are encouraged to ask about injury progress, support early return to work and review medical plans for ongoing pain management to prevent opioid harm.

Tefera YG, Gray S, Nielsen S, Di Donato M, Collie A. Early high-risk opioid prescribing and persistent opioid use in Australian workers with workers’ compensation claims for back and neck musculoskeletal disorders or injuries: a retrospective cohort study. CNS Drugs 2025; 39: 499–512.

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PALLIATIVE CARE

MedsScan Editors for Palliative Care SPG: Vicki Poulier, Gauri Godbole and Annette Bush

Establishing consensus on off-label drug use in palliative care

The use of medicines for unapproved indications is common in palliative care for numerous reasons, including a scarcity of high-level evidence. The lack of robust evidence, safety data and regulatory clarity can leave clinicians without clear, accessible guidance to support treatment decisions.

This Delphi study aimed to create consensus-based, evidence-informed recommendations for off-label drug use in adult palliative care. Two rounds of online surveys were conducted with clinicians in Germany, Austria and Switzerland, and included palliative care physicians, pharmacists and nurses. Participants rated 68 recommendations for 21 medicines across 14 indications, developed through structured review of literature and clinical guidelines.

Consensus was reached when a minimum of 80% of participating experts agreed very strongly or somewhat strongly with the recommendation. This occurred for 64 out of 68 recommendations. Finalised recommendations, along with supporting evidence and clinical guidance, are published in German and available free of charge at https://pall-OLU.de. Statements lacking consensus were not published on the website but may be revisited in a future Delphi study if new evidence is available.

This project provides a collaborative framework to improve transparency, safety and consistency in off-label prescribing in palliative care. While created for German-speaking countries, the methodology and findings are broadly applicable and could help inform similar efforts in Australia. This model offers a valuable framework for supporting clinical decision-making in areas where high-quality trial data are unlikely to emerge.

Pügge S, Dukic-Ott A, Baumgärtel J, Jünger S, Bausewein C, Rémi C, et al. Off-label drug use in palliative medicine: delphi study for the consensus of evidence-based treatment recommendations. Palliat Med 2025; 39: 530–542.

Understanding the patient and family experience of deprescribing in palliative care

This study aimed to explore the decision-making processes involved in deprescribing medications for individuals receiving palliative care, alongside their family members. With polypharmacy being common in people with palliative care needs, the study sought to identify the challenges and preferences related to deprescribing decisions.

The researchers conducted semi-structured interviews with 25 patients in palliative care settings, with 12 interviews conducted as dyads (i.e. where the patient and a family member were interviewed together). Participants were recruited from various settings including hospice outpatient and inpatient units, care facilities and patients’ homes. The interviews were evaluated using reflexive thematic analysis, which allowed for themes to emerge from participant responses regarding their experiences and views on deprescribing.

The analysis revealed two main themes. The first, “Laying the foundations of deprescribing decision-making” emphasised the importance of understanding patient needs and backgrounds to facilitate informed discussions about medication dose reduction. The second, “Having a voice in deprescribing decision-making”, highlighted patients’ and families’ desires to actively participate in discussions regarding their medications. This informed approach supports shared decision-making, aligning treatment with patient values and goals.

While this study provides valuable insight, it is limited by its sample size and diversity, which may not completely represent broader populations in palliative care. Consideration could also be given, in future research, to include participants aged outside of the age-range of this study. Inclusion of factors such as health literacy, independence, perceptions of medications and the impact on lifestyle could capture a more comprehensive view of deprescribing practices in this context.

Robinson-Barella A, Richardson CL, Bayley Z, Husband A, Bojke R, Bojke A, et al. 'Do I actually even need all these tablets?' A qualitative study exploring deprescribing decision-making for people in receipt of palliative care and their family members. Palliat Med 2025; 39: 543–552.

Exploring pharmacist-led deprescribing in palliative care clinical practice

Assessment of medicine appropriateness is important in advanced disease, but in clinical practice, patients often remain on preventative medicines. It is not always clear when poor tolerance and increased adverse effects begin to outweigh benefits, or if patients will accept deprescribing suggestions.

This study evaluated the impact of pharmacist deprescribing recommendations in 48 adult cancer patients admitted to specialist inpatient settings within a single organisation in Ireland over a 2-month period. Reasons for admission included end-of-life (EOL), symptom control and respite. Potentially inappropriate medicines (PIMs) were identified by four pharmacists during medication reconciliation using the OncPal guideline1 and clinical judgement. Recommendations for deprescribing included reducing doses or discontinuing, with advice on dose tapering provided where needed.

Of 449 medicines prescribed, one quarter were recorded as PIMs with 99 recommended for discontinuation and 14 for dose reduction. OncPal identified 86.7% PIMs. Deprescribing was implemented for 71.7%, with no difference between PIMs defined by OncPal or clinical judgement. Reflux medicines were significantly less likely to be deprescribed than other medicine groups (26.7% versus 78.6%, p < 0.0001). The most common reason for physicians not deprescribing was patient preference to continue.

While limited by its small sample size, this study highlights that pharmacist clinical judgement provides valued nuance to deprescribing alongside guidelines. It also examines some of the reasons that deprescribing recommendations are declined. Future research should include patients with non-malignant diseases and further explore clinical outcomes of deprescribing on ongoing symptom control, possible withdrawal effects and quality of life, particularly in the context of prognosis.

References

  1. Lindsay J, Dooley M, Martin J, Fay M, Kearney A, Khatun M, et al. The development and evaluation of an oncological palliative care deprescribing guideline: the ‘OncPal deprescribing guideline’. Support Care Cancer 2015; 23: 71–78.

McAdam C, O’Dwyer E, Dalton K. Pharmacist-led deprescribing interventions for cancer patients in a specialist palliative care setting. Support Care Cancer 2025; 33: 321.

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PHARMACY INFORMATICS AND TECHNOLOGY

MedsScan Editors for Pharmacy informatics and technology: James Grant and Sarah Dinh

Adoption of clinical decision support systems over time 

This systematic review aims to explore how clinicians’ acceptance and use of Clinical Decision Support (CDS) systems evolve over time in hospital settings. The review emphasises the temporal dynamics of CDS uptake, —examining early, mid-term and long-term use — and included in 67 studies published between 2007–January 2024. Factors influencing CDS use were mapped to the Consolidated Framework for Implementation Research (CFIR).The review identified 132 unique factors influencing clinician engagement with CDS systems, mapped across six CFIR domains, with intervention characteristics (e.g. complexity, adaptability, cost) and inner setting (e.g. organisational context including culture, leadership and communication) factors being most frequently reported, highlighting the importance of system design quality and compatibility with existing workflows. The review revealed clear temporal patterns: in the early phase (0–6 months) clinicians focused on perceived outcomes and system utility; by the mid-term (6–12 months) individual attitudes and beliefs became increasingly influential; and in the long term (1+ years), workarounds were often developed to manage system limitations. Most of the CDS systems evaluated were knowledge-based, relying on rule-based alerts, though a subset incorporated artificial intelligence (AI) or machine learning elements. Interruptive alerts for medication management were the most common feature across studies.

There are several strengths and limitations of the study to consider. Key strengths include its comprehensive scope covering a wide range of systems, settings and methodologies and the use of a framework-based approach. In addition, the use of a temporal lens offered insights into how CDS adoption evolves over time. Limitations include the heterogeneity of included studies and the low level of studies that used longitudinal data. The most significant limitation of the study is the exclusion of 196 papers that failed to report the timing of evaluation in relation to CDS implementation, despite their relevance. This omission hindered a more comprehensive analysis of how clinician acceptance and use of CDS systems evolve over time. The authors advocate for future studies to clearly report the time of data collection relative to implementation and recommend updating research reporting guidelines to make this a standardised requirement.

CDS systems must be treated as evolving tools; open to iterative redesign shaped by real-world use. Actively involving pharmacists in evaluating CDS effectiveness reinforces the importance of engaging clinicians not only during initial development but continuously over time in feedback loops to identify and resolve both anticipated and unforeseen issues that emerge throughout the life of the system.

Newton N, Bamgboje-Ayodele A, Forsyth R, Tariq A, Baysari MT. A systematic review of clinicians’ acceptance and use of clinical decision support systems over time. NPJ Digit Med 2025; 8: 309.

Using international standards to merge medication formularies: lessons from abroad

This publication outlines the efforts of a large German hospital to standardise medication formularies across its systems, including those used for dispensing, intensive care units (ICUs), and the general-purpose electronic health record. In alignment with international best practices, the authors modelled a ‘master’ formulary structure using the Health Level Seven Fast Healthcare Interoperability Resources (HL7 FHIR) standard,1 incorporating local guideline requirements. Although the work remained largely conceptual, and the modelled formulary has yet to be fully populated or integrated with local systems, the authors highlight challenges and opportunities highly relevant to Australian pharmacy and informatics services. 

The authors identified several advantages during the standardisation. These included: a reduction of medication errors because standardised data was shared across systems, the likelihood of unintended discrepancies and adverse drug events was lowered; enabling a practical implementation of closed-loop medication administration (CLMA) and medication reconciliation. This led to a reduction in errors during prescribing, administration and transitions of care; and improved integration across European health data, supporting public health outcomes and clinical research. While the benefits were substantial, the authors encountered challenges such as difficulties integrating different medication software platforms and local processes and datasets (i.e. ICU, pharmacy department),the existing medication formularies contained inconsistent naming conventions, incomplete data and free-text entries, limiting structured data use without manual cleaning, and finally, the limited availability of sustained IT support and funding to maintain progress over time remains an issue.

This article also included some interesting images of some of the FHIR resources they created, particularly those to suit ICU, where they have blended standard ‘generic / strength / form / brand / pack’ information with dosing, infusion rate and combination of infusion fluid in Medication and Medication Request types. 

For those adopting the FHIR standard or pursuing greater standardisation, barriers such as data silos and poor data quality can be addressed with sustained effort. However, securing ongoing financial and IT support, along with strong stakeholder buy-in, is likely to be more critical — and more challenging. This paper offers a valuable preview of what Australian health services may encounter as national efforts toward interoperability, medication safety, and improved transitions of care continue to advance.

References

  1. Health Level Seven (HL7) Fast Healthcare Interoperability Resources (FHIR). FHIR: release 5. Ann Arbor: HL7 International; 2023. Available from <https://www.hl7.org/fhir/overview.html>.

Salgado-Baez E, Heidepriem R, Delucchi Danhier R, Rinaldi E, Ravi V, Poncette A-S, et al. Toward interoperable digital medication records on Fast Healthcare Interoperability Resources: development and technical validation of a minimal core dataset. JMIR Med Inform 2025; 13: e64099.

Impact on medication dispensing errors by closing the gaps in medication management systems with technology

This study set out to evaluate how the implementation of three medication-related technologies — Automated Dispensing Cabinets (ADC), Barcode Medication Administration (BCMA) and Smart Dispensing Counters (SDC) — impacts dispensing error rates and pharmacy workflow. A before-and-after study was conducted at a 2202-bed medical centre in Taiwan. 

Data was collected from 2017–2023 and completed across four stages: Stage 0: Pre-intervention; Stage 1: Post-ADC; Stage 2: Post-BCMA; and Stage 3: Post-SDC.

The authors found that dispensing error rates dropped significantly, with each stage revealing improvements: Stage 0: 0.0063%; Stage 1: 0.0038%; Stage 2: 0.0035%; and Stage 3: 0.0014%. The study demonstrated that staged implementation of medication-related technologies led to a marked and sustained reduction in dispensing errors over seven years in a large academic hospital. Wrong drug errors, the most prevalent issue, decreased by over 80% by the final implementation stage. These improvements were statistically significant, and most errors caused no harm, underscoring the clinical benefit and safety potential of such systems. 

Despite these findings, there were some limitations that require consideration. These included being a single-site study, limiting generalisability, the workflow analysis was primarily quantitative whereas qualitative insights from pharmacists were not explored, limited insight was given into staff training and adoption challenges, and finally, no cost-benefit analysis of technology implementation was conducted.

Over recent years, hospitals have increasingly adopted medication-related technologies within pharmacy operations, yet real-world data on their impact, particularly on prescription dispensing error rates, has been scarce. This study contributes important evidence that demonstrates how such technologies can significantly reduce errors over time, offering valuable guidance for other institutions considering similar implementations. It strengthens the case for investing in technology-enabled safety systems and highlights specific error types that may be significantly reduced.

Yu W-N, Cheng Y-D, Hou Y-C, Hsieh Y-W. Implementation of medication-related technology and its impact on pharmacy workflow: real-world evidence usability study. J Med Internet Res 2025; 27: e59220.

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TRANSITIONS OF CARE AND PRIMARY CARE

MedsScan Editors for Transitions of care and primary care: Ahmed Zeidan and Margaret Jordan

Optimising medicines following critical illness: concerns at transitions of care

Patients transitioning through healthcare are vulnerable to medication-related problems due to unintended discrepancies, errors, adverse events, changing clinical conditions and poor communication. This systematic review of 47 studies from 10 countries sought to understand the nature and risk factors for medication-related problems for people who survive critical care, identified through medication review at, or soon after, hospital discharge.

Although the definitions varied, up to 80% of patients reviewed were found to have experienced at least one ‘medication-related problem’. The review identified medicines of concern (gastro-protection, psychotropic, analgesic and cardiac), risk factors, and the appropriateness of persistence of these medicines post-discharge.

For gastro-protective and psychotropic medicines, persistence was determined to be inappropriate in up to 100% of patients. Documented indications were often absent for psychotropics, with one study determining that one-fifth of critical care survivors remained on psychotropics at discharge, despite having a normal mental status recorded. Opioids were similarly identified as newly prescribed and inappropriately continued, although one study conversely found a reduction in opioid doses on discharge compared to pre-hospital doses. Midodrine was continued in approximately one-third of patients, with half deemed as inappropriate. Other long-term cardiac medicines (including statins and antiplatelets) discontinued in hospital were not recommenced on discharge. A sepsis diagnosis, mechanical ventilation, length-of-stay, illness severity, discharge from a surgical unit or to a long-term care facility were all identified as risk factors for increased medication-related issues.

Medication reconciliation for patients transitioning between care is an accepted role for all pharmacists. However, bed availability pressures, exacerbated by frequent changes in patient conditions and prescribed medicines may hamper this task being performed by highly-trained specialist critical care pharmacists. Although this review included two Australian studies, further local research is needed to determine our current performance in this important area.

Short A, McPeake J, Andonovic M, McFee S, Quasim T, Leyland A, et al. Medication-related problems in critical care survivors: a systematic review. Eur J Hosp Pharm 2023; 30: 250–256.

From jargon to clarity: using artifical intelligence to bridge the discharge gap

Many patients struggle to understand their hospital discharge summaries due to complex medical language. This study evaluated the use of artificial intelligence (AI) to simplify discharge summaries into patient-friendly formats.

This cross-sectional study used GPT-4 (via Azure OpenAI [OpenAI, San Francisco, CA USA]) to convert 50 hospital discharge summaries into simplified versions. The revised, patient-friendly summaries were evaluated using the Flesch-Kincaid Grade Level (a readability test measuring school-grade reading level) and the Patient Education Materials Assessment Tool (PEMAT), which assesses understandability. Physician reviewers also evaluated each summary’s accuracy and completeness. Results from AI-generated summaries were compared to the original clinical notes.

AI-generated summaries had significantly improved readability and higher PEMAT understandability scores (81% versus 13%, P < 0.001). However, only 54% were rated as fully accurate, and 18% raised safety concerns, largely due to omissions or ‘hallucinations’: a term used to describe when the AI confidently states factually incorrect content. Completeness was variable, especially for procedures and history of present illness. The study was conducted in a single health system in New York, USA, so the study’s generalisability is limited and requires local adaptation for broader use.

This study highlights the potential for AI to support patient-centred discharge communication, an area of critical importance for pharmacists at transitions-of-care. Improved readability could enhance medication understanding and reduce preventable readmissions. However, risks linked to incomplete or inaccurate summaries, particularly around medication details, underscore the continued need for pharmacist oversight. In Australia, where discharge summaries guide post-discharge medication reviews and Home Medicines Reviews (HMRs), any tool used must ensure clinical accuracy. Locally co-designed prompts and integration with My Health Record could support safer adoption in community settings.

Zaretsky J, Kim JM, Baskharoun S, Zhao Y, Austrian J, Aphinyanaphongs Y, et al. Generative artificial intelligence to transform inpatient discharge summaries to patient-friendly language and format. JAMA Network Open 2024; 7: e240357..

New hormonal contraceptive PBS listings a step towards improving chronic disease management and reducing avoidable harm for Australians

Approximately 1 in 10 and 1 in 7 Australians live with polycystic ovarian syndrome (PCOS) and endometriosis respectively.1 The 2023 Australian Institute of Health and Welfare (AIHW) and most recent Australian PCOS and Endometriosis guidelines all echo how individuals with these conditions experience higher rates of hospitalisation, emergency department (ED) presentation and poorer quality of life.1–3 Hormonal contraception remains a first-line treatment in both conditions, yet affordable options have been limited, as no new oral contraceptives have been listed on the Pharmaceutical Benefits Scheme (PBS) in over 30 years.

This changed with the PBS listing of Yaz and Yasmin on 1 March 2025, followed by Slinda and Ryeqo on 1 May 2025. These additions will improve treatment access for over 150 000 Australians and save individuals between AUD $120–$2700 a year, depending on the medicine.4,5 However, the impact of these new PBS listings will extend beyond cost savings; increased access to a broader range of hormonal contraceptives allows for more individualised treatment, which is critical in PCOS and endometriosis management as no single contraceptive has demonstrated clinical superiority in either condition.

In practice, increased uptake of these newly subsidised contraceptives may also reduce preventable ED presentations and the invasive anaemia-related interventions (e.g. iron infusions and blood transfusions) commonly seen by ED and Transitions of Care (ToC) pharmacists. For example, a hospital avoidance service in South Australia administers AUD ~$75 000 of intravenous iron annually. These new contraceptive listings have the potential to reduce the cost of treating PCOS and endometriosis associated complications to both the individual and the service providers. Furthermore, the risks of medication-related harm associated with these transitions of care may also be reduced.

All pharmacists across primary care, transitions of care, and hospital sectors will play a key role in identifying, recommending and educating appropriate consumers on these newly subsidised medicines, and ensuring continuity of treatment. This significant update represents a long-overdue step toward healthcare equity and improved chronic disease management for thousands of Australians.

References

  1. Australian Institute of Health and Welfare (AIHW). Endometriosis in Australia 2023. Canberra: AIHW, 2023. https://www.aihw.gov.au/getmedia/3e95587a-4bbe-4248-a960-56da9956f174/endometriosis-in-australia-2023.pdf.aspx.
  2. Teede H, Misso M, Costello M, Moran L, Joham A, Gibson-Helm M, et al. International evidence-based guideline for the assessment and management of polycystic ovary syndrome. Melbourne: Monash University; 2023.
  3. Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG). Australian living evidence guidelines: endometriosis [updated April 2025]. Melbourne: RANZCOG, 2021.
  4. Department of Health, Disability and Ageing. More choice, lower costs and better health care for women [7 February 2025]. Canberra: Commonwealth of Australia; 2025.
  5. Hon Mark Butler, Minister for Health and Ageing, Minister for Disability and the national Disability Insurance Scheme [media release]. . Government delivering even more choice for women’s contraception, endometriosis and IVF journeys [16 March 2025]. Canberra: Commonwealth of Australia; 2025.

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