MedsScan, Issue 1, 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.

• Compounding services
• Emergency medicine
• General medicine
• Infectious diseases
• Mental health
• Pain management
• Pharmacy informatics and technology
• Research
• Transitions of care and primary care

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COMPOUNDING SERVICES

MedsScan Editor for Compounding services SPG: Rachel Berry

Leachable compounds in product containers used in sterile compounding

Hospital pharmacy departments prepare products in a range of containers such as syringes, bags and vials. Awareness of the potential harm from plastics has also entered public consciousness in recent years and is an increasing area of concern.

This study looked at three products for paediatric and neonatal use prepared in hospital pharmacy departments in Switzerland. The first was vancomycin 5 mg/mL in a Becton, Dickson and Company (BD) Plastipak (polypropylene barrel, bromobutyl isoprene rubber [BIIR] plunger lubricated with silicone oil) syringe. The second product was a paediatric parenteral nutrition solution containing 7% amino acids, 9.8% glucose, 0.29% sodium chloride, 0.15% potassium chloride, 0.15% calcium gluconate and 0.4% magnesium sulfate in a single layer ethylene vinyl oxide (EVA) bag. The third was a solution of insulin 1 IU/mL of diluted NovoRapid 100 IU/mL in sodium chloride 0.9% in a cyclic olefin co-polymer (COC) vial with a thermoplastic elastomer (TPE) stopper. The period of storage prior to testing was based on the usual expiry of these products (12 months), noting that this exceeds usual practice in Australian hospital pharmacy departments. Vancomycin was tested after six months refrigerated storage, and the parenteral nutrition and insulin were tested after 12 months refrigerated storage.

Seventeen leachable compounds were identified in the vancomycin syringes, with two exceeding permissible daily exposure, although there were limitations to these calculations. 25 leachable compounds were identified in the parenteral nutrition bag, with none exceeding permissible daily exposure. Ten leachable compounds, all below permissible daily exposure, were identified in the insulin vial. Potential endocrine disruptors were also assessed. The number of potential endocrine disruptors in both the polypropylene syringes and EVA bags was significant but further study is required in this area to understand the potential impact on health in vulnerable patient groups.

This study highlights the importance of consideration of the effect of the container material used for storage of compounded products, in addition to the physical and chemical stability of the drug compound.

Bello W, Pezzatti J, Rudaz S, Sadeghipour F. Study of leachable compounds in hospital pharmacy-compounded prefilled syringes, infusion bags and vials. J Pharm Sci 2024; 113: 3227–3237.

Oral gels as an alternative base for paediatric oral formulations

Suitable oral preparations are often not commercially available for paediatric patients, requiring pharmacy prepared off-label preparations. Usual practice is to compound a liquid formulation, but there can be difficulties masking taste and ensuring full administration of the required volume. This study proposed oral gels prepared with cellulose derivatives or carbomers as an alternative to liquid preparations. The proposed advantages would be texture, palatability and reduced risk from sediment formation in a suspension formulation.

Hydrogels were prepared containing valsartan 4 mg/g and candesartan 1 mg/g. Tablets of both medicines were crushed and incorporated into the hydrogel base by trituration in a mortar. Carbomer, hydroxyethylcellulose and carmellose sodium were used as three bases. The resultant gels contained sweeteners including sorbitol 4% and preservatives including parabens and were stored in plastic containers. Preparations were stored at 25 ^°C and 4 ^°C for 35 days. Every seven days the gels were observed and analysed for physical and chemical stability.

Valsartan was chemically stable throughout the study at both storage temperatures whereas candestartan exhibited greater than 10% loss at both storage temperatures after 14 days. A limitation of this study is that the effect on bioavailability of crushing tablets and incorporating the crushed powder in a viscous medium was not studied. It was noted that this process would have a similar effect to crushing tablets and mixing with food, which is common practice in paediatrics. Notably, the preparations contained both parabens, preservatives and sorbitol. It was noted that the sorbitol concentration was lower than that often found in paediatric syrups but would need to be taken into consideration.

While the authors noted that the proposed gels cannot be extrapolated as universal bases due to the possibility for interactions between active substances, gel bases and other excipients, this study highlights possible future alternatives for other paediatric formulations and warrants further research.

Trofimiuk M, Sznitowska M, Winnicka K. Oral gels as an alternative to liquid pediatric suspensions compounded from commercial tablets. Pharmaceutics 2024; 16: 1229.

Hydroxycarbamide (hydroxyurea) oral solution formulation

Hydroxycarbamide (hydroxyurea) is only commercially available as oral capsules. A previously studied oral solution formulation was time consuming and difficult to compound. There is therefore, a need for a formulation that is simple to compound.

This study tested a 50 mg/mL solution prepared by emptying the contents of seven 500 mg hydroxycarbamide capsules into an amber glass bottle. Water of suitable quality (35 mL) was added, the cap replaced and the bottle shaken until the hydroxycarbamide dissolved. Once dissolved, 35 mL of Ora-Sweet was added and the resultant solution shaken to mix. Solutions were observed over 78 days stored at 4 ^°C, 26 ^°C and 40 ^°C. There was no change in appearance of the solutions stored at all temperatures over the study period, but the solution stored at 40 °C exhibited greater than 10% loss after 28 days.

Of note is this formulation is made up to volume with Ora-Sweet and not a 50:50 mix of Ora-Plus suspending agent and Ora-Sweet, which would be usual practice with this product. Caution must therefore be exercised when assigning an expiry date as the usual concentration of preservative has been halved. It would therefore be advisable to consider this solution unpreserved and assign a shorter expiry date accordingly. Caution must also be taken when opening the hydroxycarbamide capsules and appropriate personal protective equipment should be used when handling oral cytotoxic compounds.

This study detailed a formulation that can easily be prepared in a pharmacy environment, providing an alternative option for patients who are unable to tolerate capsules.

Hovey MT, Patel US, Servos MA, Hovey SW, Van Haandel L. Stability of extemporaneously prepared hydroxyurea solutions. Am J Health Syst Pharm 2024; 82: 74–78.

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EMERGENCY MEDICINE

MedsScan Editor for Emergency medicine SPG: Jill Upton

Intravenous thrombolysis, ischemic stroke and direct oral anticoagulation therapies

Special contributor: Nathan Kwok

Use of intravenous thrombolysis (IVT) for ischaemic stroke is an important component of recanalisation therapy, in conjunction with mechanical thrombectomy, as indicated. Direct oral anticoagulation therapies (DOACs) have become increasingly common as primary stroke prevention treatment as an alternative to vitamin K antagonists (VKA). It is estimated that roughly 1 in every 6 patients qualifying for IVT are taking DOACs. Current guidelines list DOAC use within 48 hours as a contraindication to IVT due to concerns regarding symptomatic intracranial haemorrhage (sICH). However, data supporting or refuting increased incidence of sICH and DOAC use within 48 hours prior to IVT is lacking.

This retrospective cohort study sought to investigate whether, for patients presenting with ischaemic stroke, DOAC use within 48 hours prior to IVT was associated with increased risk of sICH and whether selection strategies for patients with recent ingestion of DOACs impacted safety. These selection strategies included DOAC level measurement, reversal, clinical dismissal of level or reversal requirement and inadvertent IVT with DOAC use subsequently discovered.

The study was an international, multi-centre, retrospective analysis. 64 contributing centres were identified via systematic literature search of published studies. Studies were identified through PubMed/EMBASE using a predefined search strategy using keywords concepts of ischaemic stroke, DOAC and IVT. Publications between 2008 and 2021 were included.

Inclusion criteria included adult patients >18 years of age with confirmed ingestion of DOAC within the last 48 hours prior to stroke onset, according to local guidelines. There was no limit regarding time window to IVT. Patients were excluded if DOAC ingestion was >48 hours prior to stroke onset. The control group was patients with ischaemic stroke requiring IVT without any prior anticoagulation therapy. The primary outcome was sICH within 36 hours of IVT. Secondary outcomes included haemorrhagic transformation on follow-up imaging within 36 hours and functional independence within 90 days.

Thirty-three thousand, two hundred and seven patients were enrolled (n = 832 DOAC and n = 32375 control). There was a significant difference in the primary outcome of incidence of sICH in patients with recent ingestion of DOACs (2.5% of DOAC population) compared to patients without DOAC ingestion (4.1% of control population) with an adjusted odds ratio [OR] of 0.57 (95% confidence interval [CI] 0.36–0.92, p = 0.02). Secondary outcomes did not show any significant differences between groups.

The discussion proposes that DOAC use may not represent a contraindication to IVT. Given results appear to favour DOAC use and reduced incidence of sICH compared to control, justifications include selection bias for patients at lower risk of sICH post IVT, DOAC pretreatment leading to smaller infarcts with lower risk of haemorrhagic transformation and pathophysiological explanation describing protective effects of thrombin inhibition toward sICH. The paper concludes with a call for guidelines to reconsider DOAC ingestion as a contraindication to IVT.

The implications to current practice are that this would increase the number of patients eligible for IVT, however efficacy outcomes have yet to be investigated. Although an emerging area of practice, patients presenting with DOAC ingestion within 48 hours of ischaemic stroke eligible for IVT should still be cautiously managed until high quality studies using patient specific outcomes are published.

Meinel TR, Wilson D, Gensicke H, Scheitz JF, Ringleb P, Goganau I, et al. Intravenous thrombolysis in patients with ischemic stroke and recent ingestion of direct oral anticoagulants.  JAMA Neurol 2023; 80: 233–243.

Erratum: Error in byline, affiliations, and table 1. JAMA Neurol 2023; 80: 422.   

Comparing tenecteplase and alteplase for pulmonary embolism

Special contributor: Belinda Wilson

Pulmonary embolism (PE) is a leading cause of morbidity and mortality, with thrombolysis increasingly recommended for unstable massive PE. Limited studies exist comparing tenecteplase (TNK) and alteplase in PE, and this study provides further insight into their safety and efficacy. Additionally, there is insufficient information on the optimal TNK dose for massive PE, specifically whether to use the myocardial infarction (MI) dose of 30–50 mg or the stroke dose of 0.25 mg/kg. Pharmacists should pay close attention, as these findings could influence the management of unstable massive PE in the emergency department, where rapid administration and ease of use are key considerations.

This retrospective cohort study utilised data from the TriNetX Global Health Research Network, comparing patients with PE treated with TNK or alteplase. Patients aged 18 or older who received thrombolysis within 7 days of PE diagnosis were included. Cohorts were propensity-matched for demographics, anticoagulant use, comorbidities, laboratory results and vital signs. Dosage and timing of TNK or alteplase were not documented. The study primarily focused on 30-day outcomes, including mortality, major bleeding (frequency of blood transfusions), and intracranial haemorrhage.

A total of 283 matched PE patients were included in each cohort (TNK and alteplase). There was no significant difference in 30-day mortality between TNK and alteplase. Mortality rates were 19.4% for TNK and 19.8% for alteplase, with a risk ratio of 0.982 (95% CI 0.704–1.371, p-value not significant). Safety outcomes could not be analysed due to low rates of intracranial haemorrhage and blood transfusion at 30 days.

The study concluded that TNK had similar 30-day mortality rates compared to alteplase in treating PE with haemodynamic instability. However, the retrospective design, lack of dosing information, small TNK cohort, and limited bleeding-related safety outcomes make these conclusions less definitive. While the ease of administration and cost-effectiveness of TNK are promising, the infrequent occurrence of adverse events in this study limits the ability to conduct a comprehensive safety assessment and fully evaluate its risk profile, as well as to identify the ideal TNK dose for PE.

Murphy LR, Singer A, Okeke B, Paul K, Talbott M, Jehle D. Mortality outcomes with tenecteplase versus alteplase in the treatment of massive pulmonary embolism. J Emerg Med 2024; 67: e432–e441.

Pharmacists in trauma

Despite its importance to patient wellbeing, administration of appropriate analgesia in trauma is often delayed due to competing priorities. This unblinded randomised trial performed at an Australian level 1 trauma centre compared emergency medicine pharmacist involvement in trauma callouts to standard care.

The primary outcome was the proportion of patients who received their first dose of analgesia within 30 minutes of presentation to the emergency department. From 15 July 2021 to 31 January 2022, 119 patients were randomised. Thirty-seven patients were excluded because analgesia was not required. Of the remaining 82 patients included for analysis, 39 were in the control arm and 43 in the intervention arm. First dose analgesia was given within 30 minutes for 25 (64.1%) patients in the control arm and 36 (83.7%) patients in the pharmacist arm (risk ratio [RR] 1.31, 95% CI 1.0–1.71, p = 0.042). Time to analgesia was 28 (95% CI 22–35) minutes in the control arm and 20 (95% CI 15–26) minutes in the pharmacist arm; p = 0.025. The initial dose of analgesia was prescribed by the pharmacist for 88.4% of patients in the pharmacist arm.

This study supports inclusion of emergency medicine pharmacists in trauma response teams to reduce time to first analgesia and optimize medication management.  Allowing other clinicians to focus on competing demands may improve team efficiency.

Roman C, Dooley M, Fitzgerald M, Smit V, Cameron P, Mitra B. Pharmacists in trauma: a randomised controlled trial of emergency medicine pharmacists in trauma response teams.  Emerg Med J 2024; 41: 397–403.

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GENERAL MEDICINE

MedsScan Editor for General medicine SPG: Christina Hanciu

Duration of antimicrobial treatment in conserving future benefit

Special Contributor: Shobana Mahendran

Given the rise in bacterial resistance, reducing antibiotic duration is seen as a fundamental strategy to prevent future resistance. Pharmacists have a role in preserving the current armamentarium of antimicrobials during everyday practice through judicious use of antimicrobials.

The duration of antimicrobial treatment for bloodstream infections caused by Enterobacterales (eBSIs) based on expert opinions varies between 7 and 14 days for catheter-related cases with no clear guidance for other infection sources. In this open-label, randomised controlled study, patients developing eBSI with appropriate source control were randomised and assigned to 7 days or 14 days of antibiotic treatment and followed for 28 days post-treatment to assess outcomes of clinical cure, relapse of eBSI and relapse of fever. Statistical margins were assigned, and efficacy and safety were assessed together with a DOOR/RADAR (desirability of outcome ranking and response adjusted for duration of antibiotic risk) analysis.

The DOOR/RADAR analysis indicated that patients receiving a 7-day antibiotic course had a 77.7% higher probability of achieving better overall outcomes compared to those on a 14-day course. This study strengthens the growing evidence favouring shorter antibiotic courses in certain infections and has significant implications for antimicrobial stewardship. This trial builds on previous research, confirming that shorter treatment durations do not negatively impact clinical outcomes.

Some individual patients may require longer treatment, but systematically extending antibiotic courses for all patients carries ecological risks, including increased antibiotic resistance and drug-related adverse events. Despite certain limitations, such as limited ability to assess rare outcomes like mortality, the study's findings reinforce the feasibility of implementing shorter antibiotic treatments in routine practice.

Molina J, Montero-Mateos E, Praena-Segovia J, León-Jiménez E, Natera C, López-Cortés LE, et al. Seven-versus 14-day course of antibiotics for the treatment of bloodstream infections by Enterobacterales: a randomized, controlled trial. Clin Microbiol Infect 2022; 28: 550–557.

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INFECTIOUS DISEASES

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

Rezafungin versus caspofungin: comparative efficacy and safety for invasive Candida infections

This industry-authored publication pooled data from two randomised controlled trials (RCTs) that compared the efficacy and safety of rezafungin to caspofungin for invasive Candida infections:

• The STRIVE phase 2 trial, published in 2021 and
• The ReSTORE multicentre, double-blind, phase 3 trial, published in 2023.

Two hundred and ninety-four patients were included in the pooled, microbiological intention-to-treat (mITT) analysis: 139 patients were included in the rezafungin group (46 from STRIVE and 93 from ReSTORE) and 155 patients were included in the caspofungin group. All were adults (≥ 18 years) with systemic signs and mycological confirmation of candidaemia or invasive candidiasis at baseline. Patients from the STRIVE trial that has been randomised to 400 mg rezafungin weekly were excluded from the pooled analysis.

Baseline demographics were similar in both groups; the proportion with an APACHE II score ≥ 20 (associated with an increased mortality risk) was 15% (21/137) for the rezafungin group and 17% (26/152) for those in the caspofungin group. The proportion of neutropenic patients (neutrophil count < 500 cells per µL at baseline) was 5% in the rezafungin group and 3% in the caspofungin group. The primary pooled efficacy endpoint was all-cause mortality at 30 days. Mycological eradication at day 5 and day 14 was a secondary efficacy endpoint, and was defined for patients with a positive culture at baseline, as a negative culture on or prior to the day of assessment with no subsequent positive culture.

Patients randomised to rezafungin received an initial dose of 400 mg on day 1, followed by 200 mg weekly. Caspofungin patients received 70 mg on day 1, then 50 mg daily for at least three days. Patients in both groups could switch to oral therapy if stable (placebo in rezafungin group, fluconazole in caspofungin group). Median study drug exposure (intravenous and oral combined) was similar: 14 days (interquartile range [IQR] 10–14) for rezafungin and 14 days (IQR 13–15) for caspofungin.

The pooled analysis showed no difference in overall mortality between the rezafungin and caspofungin groups at day 30 (19% in both groups). There was no significant difference between the groups in mycological eradication at day 5 and day 14. In the rezafungin group, 72% (100/139) of patients achieved mycological eradication at day 14, compared to 68% (106/155) in the caspofungin group. Subgroup analyses found no significant difference in day 30 mortality according to Candida species. There were no cases of Candida auris included in either treatment arm of the STRIVE or ReSTORE studies. Hypokalaemia and gastrointestinal adverse effects (vomiting, nausea and diarrhoea) were the most frequently reported adverse effects. Hypokalaemia was reported in 15% of patients in the rezafungin group compared to 10% of the caspofungin group.

Excluded from both trials were patients with fungal septic arthritis, osteomyelitis, endocarditis, myocarditis, meningitis, chorioretinitis, any central nervous system infection, chronic disseminated candidiasis or urinary candidiasis. Further evidence is required to assess the effectiveness of rezafungin for more difficult-to-treat invasive candidiasis requiring long-term treatment, including against multidrug-resistant Candida species such as Candida auris.

Thompson GR 3^rd, Soriano A, Honore PM, Bassetti M, Cornely OA, Kollef M, et al. Efficacy and safety of rezafungin and caspofungin in candidaemia and invasive candidiasis: pooled data from two prospective randomised controlled trials. Lancet Infect Dis 2024; 24: 319–328.

The BALANCE study: 7 versus 14 days antibiotic treatment for hospitalised patients with bloodstream infections

The BALANCE study (Bacteraemia Antibiotic Length Actually Needed for Clinical Effectiveness) was a multi-centre, non-inferiority randomised controlled trial that compared the efficacy and safety of 7 days versus 14 days antibiotic treatment for hospitalised patients with bacteraemia. Three thousand, six hundred and thirty-one patients across seven countries were randomised between 2014 and 2023: 3608 patients were included in the intention-to-treat analysis with 1824 in the 7-day group and 1807 in the 14-day group.

The list of exclusion criteria was extensive. Patients were excluded from the study if they had previously been enrolled in the study (i.e. only one instance of participation per patient), were severely immunocompromised (neutropenia or on immunosuppressive therapy following solid-organ or stem-cell transplantation), had prosthetic heart valves or endovascular grafts, or had documented or suspected infectious endocarditis, osteomyelitis, septic arthritis, undrained abscess or unremoved prosthetic-associated infection. Patients with a positive blood culture for Staphylococcus aureus, Staphylococcus lugdunensis, Candida species or other fungal species were also excluded.

The demographics of patients in both treatment arms were well-balanced. At enrolment, 55% of patients were in an intensive care unit and the remaining 45% on hospital wards. The majority (71%) of enrolled patients had a monomicrobial, Gram-negative bacteraemia. Escherichia coli was the most commonly isolated pathogen (44.4% in the 7-day group, 43.3% in the 14-day group), followed by Klebsiella species (15.0% in the 7-day group, 15.6% in the 14-day group). Seventeen percent of patients (17.3%) had a monomicrobial Gram-positive bacteraemia and 11.7% had a polymicrobial bloodstream infection. The source of bacteraemia was urinary in 42.2% of cases, followed by intraabdominal/hepatobiliary (18.8%) and lung (13.0%).     

Patients were randomly assigned to either 7-days or 14-days of ‘adequate’ antibiotic treatment, defined as antibiotic therapy to which the organism was susceptible. Antibiotic choice was at the discretion of clinicians. Ceftriaxone was the most frequently prescribed antibiotic (59.8% of all patients), followed by piperacillin-tazobactam (52%), vancomycin (29.2%), ciprofloxacin (25.7%) and meropenem (24%).  Allocation remained concealed until day 7.

The primary outcome, death from any cause at 90 days, occurred in 14.5% (261/1802) of patients in the 7-day group and 16.1% of patients in the 14-day group (286/1779). Based on the pre-specified non-inferiority margin of 4%, the investigators concluded that 7-days of antibiotics was non-inferior to 14-days (difference -1.6%, 95% confidence interval [CI] -4.0 to 0.8). Rates of nonadherence to the protocol (receipt of longer or shorter duration than assigned ±2 days) were 23.9% and 16.5% in the 7-day and 14-day groups respectively. The per-protocol analysis showed 7-days of antibiotics remained non-inferior to 14 days (difference -2.0%, 95% CI -4.5 to 0.6).

The implications for clinical practice suggest that an initial treatment plan for uncomplicated bacteraemia should be limited to 7days with review for consideration of extending treatment if required, rather than committing all patients to 14 days of treatment for bacteraemia. These results are not applicable to patients with Staphylococcus aureus bacteraemia or patients with other conditions listed in the study exclusion criteria.

Daneman N, Rishu A, Pinto R, Rogers BA, Shehabi Y, Parke R, et al. Antibiotic treatment for 7 versus 14 days in patients with bloodstream infections.  N Engl J Med 2024; [online ahead of print]. doi:10.1056/NEJMoa2404991.

The Trep-AB Study: Oral linezolid compared with benzathine penicillin G for early syphilis in adults

Special contributor: Tanja Gustafsson

This multicentre, prospective, open-label, non-inferiority randomised controlled trial assessed the efficacy of oral linezolid compared with the standard of care, benzathine penicillin G (BPG), for the treatment of early syphilis. Adult patients, aged 18 years or older, with serological or molecular confirmation of primary, secondary or early latent syphilis were eligible for participation in the trial.

Patients were randomly allocated (allocation concealed) to one of two treatment groups using a computer-generated block randomisation list, with allocation revealed after the study investigator had decided to enrol a patient. Patients were assigned to either the intervention group, receiving linezolid administered orally at a dose of 600 mg once daily for 5 days, or the control group, receiving BPG administered intramuscularly as a single dose of 2.4 million international units. The primary outcome was treatment response, that included clinical cure (defined as the healing of primary and secondary syphilis lesions, assessed at 2 weeks for primary syphilis and 6 weeks for secondary syphilis following treatment initiation), serological cure (defined as a four-fold decline in rapid plasma reagin titre or seroconversion at the prespecified timepoints of 12 weeks, 24 weeks, or 48 weeks) and absence of relapse (defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis, i.e., reinfection). Patients were followed for 48 weeks (study end) to assess treatment response. Monitoring for relapse was extended to 96 weeks. The prespecified non-inferiority margin was set at 10% based on an expected enrolment of 150 patients.

There were no significant differences in patient demographics, including age, gender and past medical history. Amongst the patients in the linezolid group, 31% had primary syphilis, 31% had secondary syphilis and 38% had early latent syphilis. In the BPG group, 30% of the patients had primary syphilis, 33% had secondary syphilis and 37% had early latent syphilis.

The trial was terminated prematurely at 24 weeks due to the futility of linezolid. At the time of termination 59 patients had been enrolled, 55 of whom were included in the per-protocol analysis. Seventy percent (19/27) of the patients in the linezolid intervention group achieved clinical and serological cure compared to 100% (28/28) of patients in the BPG control group (treatment difference -29.6%, 95% CI -50.5 to -8.8). Reported adverse events were all mild or moderate in both groups, with 17% of patients in both groups reporting an adverse event.

The investigators concluded that given the inferior efficacy of oral linezolid at a dose of 600 mg once daily compared to intramuscular BPG given as a single dose of 2.4 million international units, linezolid should not be used for the treatment of early syphilis. However, there may be scope for further investigation of the efficacy of linezolid at higher doses and longer dosing regimens.

Ubals M, Nadal-Baron P, Arando M, Rivero A, Mendoza A, Jorro VD, et al. Oral linezolid compared with benzathine penicillin G for treatment of early syphilis in adults (Trep-AB Study) in Spain: a prospective, open-label, non-inferiority, randomised controlled trial. Lancet Infect Dis 2024; 24: 404–416.

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MENTAL HEALTH

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

Hot weather and child and young person emergency department presentations

This paper explores the link between youth suicide and suicidal ideation emergency department (ED) presentations and ambient temperature. In the years since 2020 there has been an increase in ED presentations in New South Wales of 8.4% annually, as well as a corresponding increase in suicide mortality. Although there are known risk factors such as bullying, mental illness and COVID-19; direct exposure to increased temperatures is proposed as one of multiple other potential risk factors. This paper examines ED presentations of young people aged 12–24 years from 2012 to 2019 across five different climatic zones in New South Wales, as defined by the World Meteorological Organization. It specifically focuses on daily mean temperature (DMT) during the hotter months, from November to March.

Across the state, with modelling, there was a positive association between daily mean temperature (DMT) and suicidality presentations in ED. At an average DMT for the state of 21.9 ⁰C there was an average of 45.7 youth suicidality presentations per day. For every 1 ⁰C increase in DMT, presentations rose by 1.3% relative risk. The increased risk with higher DMT was replicated across four of the five climatic zones. Heatwaves showed no significant effect above that of ambient temperature. The positive linear association between ambient temperature and ED suicidality presentations mirrors that of adults previously studied.

Girls and young women showed linear association between DMT and suicidality in all climatic zones except the hot dry. In contrast the males showed a clear relationship in the hot dry climate, but greater uncertainty in the other four climate zones. There are clear implications for public health flowing from this study and the need to address both heatwaves and also single hot days when presenting warnings, including the need for monitoring of mental health in these warnings.

Dey C, Wu J, Uesi J, Sara G, Dudley M, Knight K, et al. Youth suicidality risk relative to ambient temperatures and heatwaves across climate zones: a time series analysis of emergency department presentations in New Soth Wales, Australia. Aust N Z J Psychiatry 2025; 59: 18–28.

Burnout, depression and diminished well-being among physicians

This review is a timely reminder about the consequences of the well-known phenomenon of burnout and all its ramifications. Although specifically mentioning physicians, this is also applicable to mental health pharmacists as they too are working to improve lives but are often hampered by bureaucracy.

The authors advocate for clearer definitions of burnout and other related conditions, as well as improved psychometric measurements. When compared to the Diagnostic and statistical manual of mental disorders¹ (DSM-5) major depression diagnosis, there are numerous overlapping characteristics, raising the question of whether individuals are experiencing depression or burnout. If it is depression, there must also be removal of the stigma surrounding treatment for major depression, and the legal ramifications of doing so in a legalistic world where stigma for mental illness is prevalent and pervasive.

Studies of depression and burnout, the causes and interventions, particularly in junior physicians, have led to improvements in work-life balance. However, as individuals progress through the system, these improvements and studies are often not carried forward. When improvements do occur, they are typically targeted at specific groups, rather than being system wide. Although mindfulness intervention studies within physician groups have shown promise for enhancing wellbeing, other interventions such as professional coaching, gratitude journaling, exercise, yoga and building social connections have not been thoroughly studied. Additionally, many studies lack representation from women and diverse racial and ethnic groups, which is crucial when extrapolating findings and making recommendations.

As pharmacists, we should also be mindful of the consequences of burnout, both for ourselves and for the individuals we care for. This issue was highlighted again this year in a survey from the United Kingdom, which revealed that the vast majority of hospital pharmacists are at risk of burnout.² Further research is needed across all aspects, both for physicians and pharmacists, as their roles continue to expand to cover responsibilities traditionally handled by medical staff.

References

1. American Psychiatric Association (APA). Diagnostic and statistical manual of mental disorders. 5^th edition. Arlington, VA: APA; 2013.
2. Janković S. Vast majority of hospital pharmacists at risk of burnout, new RPS wellbeing survey shows. Hospital Pharmacy Europe. 29 February 2024. London: Cogora; 2024. Available from https://hospitalpharmacyeurope.com/news/vast-majority-of-hospital-pharmacists-at-risk-of-burnout-new-rps-wellbeing-survey-shows/. Accessed 4 March 2025.

Guille C, Sen S. Burnout, depression, and diminished well-being among physicians. New Engl J Med 2024; 391: 1519–1527.

Blinding anxiety and randomised controlled trials

Participant and assessor blinding in randomised controlled trials (RCTs) reduces observer and response biases.¹ Successful blinding minimises impacts of placebo effects, experimenter effects, demand characteristics and self-report or rater biases.² Blinding integrity in psychiatric RCTs is rarely assessed or reported on by authors, even though it may significantly affect study outcomes.³

This systematic review and meta-analysis explores the relationship between medication efficacy and blinding integrity in anxiety disorder RCTs. Eight databases were searched for RCTs involving adults with anxiety disorders, and medication and placebo interventions from 1980 to 2023. The authors calculated the frequency of blinding integrity assessment across the 247 RCTs which met inclusion criteria. Six included published assessments. Three further assessments were obtained by contacting authors. Blinding failed in 5 of the 9 assessed RCTs as per Bang’s blinding index.⁴ Associations were found between reduced assessor and consumer blinding integrity and increased treatment effect.

Ultimately a very small amount of data could be analysed in relation to the research question; therefore, the statistical significance and practical utility of the results are extremely limited. The key conclusion is that the impact of blinding integrity on study outcomes cannot be adequately evaluated unless the success of blinding is quantified; and this is rarely done.

References

1. Schulz KF, Grimes DA. Blinding in randomized trials: hiding who got what. Lancet 2002; 359: 696–700.
2. Scott AJ, Sharpe L, Colagiuri B. A systematic review and meta-analysis of the success of blinding in antidepressant RCTs. Psychiatry Res 2022; 307: 114297.
3. Freed B, Assall OP, Panagiotakis G, Bang H, Park JJ, Moroz A, et al. Assessing blinding in trials of psychiatric disorders: a meta-analysis based on blinding index. Psychiatry Res 2014; 219: 241–247.
4. Bang H, Ni L, Davis CE. Assessment of blinding in clinical trials. Control Clin Trials 2004; 25: 143–156.

Haq R, Molteni L, Huneke NTM. The relationship between blinding integrity and medication efficacy in randomized-controlled trials in patients with anxiety disorders: a systematic review and meta-analysis. Acta Psychiatr Scand 2024; 150: 187–197.

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PAIN MANAGEMENT

MedsScan Editor for Pain management SPG: Jeremy Szmerling

Opioid reduction before surgery: a step toward safer arthroplasty

Special contributor: Mary Zhang

Opioids are used in 20–54% of patients before hip and knee arthroplasty. Opioids offer limited benefits for osteoarthritic pain and increase the risk of adverse effects such as sedation and respiratory depression.

This pilot randomised clinical trial included patients aged 18 years and older, who used opioids on four or more days each week. The intervention group received pharmacist-partnered opioid tapering which commenced three months prior to surgery and continued until surgery. The second group received usual care. The study aimed to determine the feasibility and effectiveness of the intervention, which was defined as a decrease in baseline opioid dose of > 50% before surgery.

A total of 60 patients were included (n = 30 in each group). Ninety percent of patients in the intervention group (n = 27) successfully decreased their baseline daily opioid usage by > 50% before surgery, compared to 16.7% (n = 5) in the control group (P < 0.001). Patients in the intervention group reported improved physical function and social activities compared to the usual care group.

This study highlights the potential of pharmacist-partnered opioid tapering before surgery to reduce opioid use and improve patient outcomes. In Australia, where preoperative opioid use is common, implementing personalised tapering plans with pharmacist support throughout tapering may significantly decrease opioid consumption, reducing risks like sedation and respiratory depression. The results suggest that pharmacists can play a key role in improving both safety and quality of life for patients awaiting surgery. By integrating such interventions into standard care, Australian pharmacists can contribute to opioid stewardship and support more effective pain management strategies in the preoperative setting.

Liu S, Patanwala AE, Stevens J, Penm J, Naylor J, OpioidHALT Study Investigators and Coordinators. A pilot multicentre randomised clinical trial to determine the effect of a pharmacist-partnered opioid tapering intervention before total hip or knee arthroplasty. Anaesthesia 2024; 79: 1180–1190.

Painful choices: comparing modified versus immediate release opioids after surgery

Special contributor: Lana Jamil

Modified release (MR) opioids now account for 30% of all opioids prescribed post-surgery. The intent behind this prescribing is most likely to achieve sustained pain relief, reduce the number of tablets taken to avoid harm and decrease nursing workload. To assess the safety and efficacy of MR opioids prescribed post-surgery, a systematic review and meta-analysis was conducted, focusing on original studies including adults aged ≥ 18 years who underwent surgery and were prescribed opioids as part of their pain regimen.

A total of eight papers were identified and included in this study. The analysis found that those who received MR opioids following surgery experienced worse pain during the first 24 hours post-surgery compared to those who received only immediate-release (IR) opioids. The absolute standardised mean difference in pain scores was 0.2 (95% confidence interval [CI] 0.04–0.37, p = 0.02) higher in the MR opioid group during this period. MR opioid users were also 2.76 times more likely to experience opioid-related adverse events.

Despite the low overall quality of evidence, this study raises concerns about the widespread use of MR opioids in post-surgical pain management. The findings suggest that MR opioids may not offer the intended benefits of sustained pain relief and could increase the risk of adverse events compared to IR opioids only. For Australian pharmacists, these results emphasise the need to critically evaluate MR opioid prescriptions in postoperative care and prioritise safer, more effective analgesic options to reduce opioid-related harms and improve patient recovery outcomes.

Liu S, Athar A, Quach D, Patanwala AE, Naylor JM, Stevens JA, et al. Risks and benefits of oral modified-release compared with oral immediate-release opioid use after surgery: a systematic review and meta-analysis. Anaesthesia 2023; 78: 1225–1236.

The pain gap: sex bias in emergency pain management

This study investigates sex bias in pain management, analysing emergency department (ED) practices across Israel and the United States of America. It highlights disparities in analgesic prescribing and patient care based on sex.

Researchers analysed discharge records of 21 851 ED patients and conducted a controlled experiment with health care providers. Data included pain scores, demographic details and prescribed medications. The primary focus was differences in analgesic prescriptions for male and female patients, accounting for pain severity and other factors. A clinical vignette experiment assessed bias in pain perception among nurses and physicians.

Female patients were consistently less likely to receive analgesics than male patients (38% versus 47%, p < 0.001), regardless of pain levels and medication type. Their pain scores were less frequently recorded, and they spent longer in the ED. The experimental component revealed that providers rated pain as less intense for female patients in otherwise identical scenarios.

Sex disparities in healthcare, as highlighted in this study, are also a focus in Australia, which has a National Strategy to Achieve Gender Equality.¹ This strategy aims to address systemic inequities in healthcare that often result in women being less likely than men to receive timely or appropriate pain management, leading to poorer health outcomes. This aligns with the study’s findings of systemic bias against female patients, where their pain is underestimated and undertreated. Addressing such disparities requires clinician education to promote gender-sensitive care, including raising awareness of implicit biases, developing tools to reduce psychological bias in decision-making and fostering cultural shifts to ensure equitable and effective pain management for all patients.

References

1. Department of the Prime Minister and Cabinet. Working for women: a strategy for gender equality. Canberra: Commonwealth of Australia; 2024.

Guzikevits M, Gordon-Hecker T, Rekhtman D, Salameh S, Israel S, Shayo M, et al. Sex bias in pain management decisions. PNAS 2024; 121 (33): e2401331121.

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PHARMACY INFORMATICS AND TECHNOLOGY

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

Hybrid machine learning and rules based decision support for patients on medications

Medication review by pharmacists is considered the gold standard for preventing medication errors and adverse drug events. However, given the increasing complexity of prescribing — particularlyfor patients with polypharmacy, renal impairment and advanced age — there is growing interest in using artificial intelligence (AI) to enhance medication safety. A recent study evaluated Lumio Medication, a machine learning-based clinical decision support system (CDS), which aims to identify prescriptions at high risk of medication errors. The system combines rule-based alerts (which use predefined criteria, such as incorrect dosage or frequency) with machine learning algorithms, which adapt over time based on data patterns.

The study was conducted in a 592-bed hospital in Paris, using 18 months of electronic health record (EHR) data from over 94 000 hospitalisations. The AI system was trained to answer the question: ‘Does this patient’s medications require pharmacist review?’ and analysed data including demographics, lab results, medical history and physiological data to assess medication risks. System alerts were categorised into issues such as suboptimal dosing and formulary noncompliance.

The Lumio Medication algorithm demonstrated 74% sensitivity (recall) — correctly identifying 74% of prescriptions needing pharmacist intervention — and 74% precision (positive predictive value), meaning 74% of flagged cases were valid. This represented a 15.6% improvement over standard multi-criteria query techniques and 21% improvement over a traditional CDS alert system.

This study demonstrated the potential usefulness of AI tools to improve accuracy, reduce false alerts and potentially reduce pharmacist workload and alert fatigue. The combination of rule-based and machine learning methods likely enhances detection of rare but clinically significant errors. It is important to note that none of the false negatives (missed cases) were life-threatening, suggesting the system’s risk of overlooking critical errors was low.

There were several limitations to the study. Most significantly, the use of a single site limits generalisability and the AI algorithm was trained using historical data which may not reflect current prescribing patterns or new medications. AI models also possess the potential for bias. In this case, the machine learning component learns from past prescribing data, meaning any systemic biases in historical prescribing practices may be reinforced. If pharmacists historically focused on certain high-risk patients (e.g., elderly, renal impairment), the system may over-prioritise these cases while missing risks in younger or lower-risk groups. In addition, findings regarding real world usability were not reported. Despite these limitations, the Lumio Medication AI approach shows promise as an augmented decision-support tool, potentially improving efficiency and enhancing medication safety. However, further studies are needed to evaluate its generalisability, real-world usability, and potential biases. For pharmacists, AI-driven tools like Lumio should be viewed as complementary rather than replacements for clinical judgment. While machine learning can improve risk stratification, the pharmacist’s expertise remains essential in evaluating context-specific factors that AI may not fully capture. As AI-driven medication safety tools evolve, ongoing pharmacist involvement in their development, validation and implementation will be crucial to ensuring their reliability and effectiveness in clinical practice.

Corny J, Rajkumar A, Martin O, Dode X, Lajonchère J-P, Billuart O,  et al. A machine learning-based clinical decision support system to identify prescriptions with a high risk of medication error. J Am Med Inform Assoc 2020; 27: 1688–1694.

SNOMED CT upsides in the real world still mostly theoretical

Standardised clinical terminology plays a crucial role in modern healthcare by ensuring consistency in how patient information is recorded, shared and analysed. SNOMED CT (Systematised Nomenclature of Medicine — Clinical Terms) is one of the most comprehensive structured medical terminologies, designed to enhance clinical documentation, decision support and research applications. Despite being widely used across over 50 countries, relatively little research has examined its real-world clinical effectiveness.

A recent systematic literature review set out to evaluate the implementation and benefits of SNOMED CT for clinical use cases. The researchers analysed 17 studies published between 2017–2022, covering studies from the United Kingdom (n = 5), United States of America (n = 3), Australia (n = 2) and Spain (n = 2), among others.

The review identified several key use cases. Of the 17 included studies, the integration of SNOMED CT into existing electronic health records (EHRs) was the most common use case (n = 8), often seeking to improve communication between hospital areas, inpatient and outpatient settings and the continuity of care. Decision support and data retrieval was the second most common reason, (n = 4) with a focus on enabling more detailed documentation of clinical events in a standardised way. Clinical research and data sharing was also identified in two studies, as the availability of standard SNOMED CT terms enabled more efficient and comprehensive retrieval of patients for studies and the summarisation of relevant data. Automating clinical coding (billing and mandatory reporting requirements) was also identified, whereby automated systems scanning EHRs could achieve higher reliability by seeking SNOMED CT terms or support standardisation by mapping their findings back to SNOMED CT. Overall, the review demonstrated thatSNOMED CT did support better information exchange, particularly for clinical researchers (and their academic brethren) and health systems with many individual facilities. It also had a positive impact on improving the completeness and consistency of problem lists and clinical pathways utilised for patient care, as well as demonstrated some benefit to clinical decision support (CDS) using the standardised terms and meanings of SNOMED CT.

There were some limitations that should be noted. Specifics on how health systems and sites precisely implement and interact with SNOMED CT were not mentioned in the studies, leading to no concrete views on workflow and workload impacts. The studies did not consistently identify which user groups (e.g., pharmacists, nurses, medical informaticians) were the target of their work and so whether the above benefits are generalisable to the broader healthcare workforce cannot be concluded. At least one study noted that even 20 years after SNOMED CT implementation its adoption was not as high as it could be given demands on time and ongoing training availability. The review was also unable to draw direct patient outcome impacts from SNOMED CT such as helping improve medication safety (which could perhaps be inferred from standardisation, however, is not a robust or evidence-based point). Despite these limitations, the authors’ findings offer insight into how SNOMED CT is used in EHRs, its impact on healthcare workflows and challenges in adoption. For pharmacists, SNOMED CT presents both opportunities and challenges. It has the potential to enhance medication safety, standardise documentation and support clinical decision-making. However, the real-world impact on pharmacist workflows remains unclear, and successful adoption depends on structured training and integration into user-friendly EHRs. Further research should focus on real-world implementation outcomes, particularly how SNOMED CT affects prescribing, medication review and patient safety in pharmacy practice. While promising, SNOMED CT's full potential will only be realised if clinicians and pharmacists are actively involved in shaping its use.

Vuokko R, Vakkuri A, Palojoki S. Systematized nomenclature of Medicine-Clinical Terminology (SNOMED CT) clinical use cases in the context of electronic health record systems: systematic literature review. JMIR Med Inform 2023; 11: e43750.

3D printed medications: a novel way forward for customisation of paediatric doses?

Special contributor: Jillian Campbell

There is significant variability in paediatric compounding practices across Europe and the United Kingdom. For example, all custom dose preparation in Sweden is managed by a single facility, and it takes an average of 5 days for patients to receive their medication. This study explored the use of Semisolid Extrusion (SSE) additive manufacturing, a form of 3D printing, for producing customised paediatric doses of metoprolol tartrate within the hospital setting. SSE allows for rapid, in-house preparation of customised medicines, addressing limitations of commercial availability of suitable paediatric doses and the challenges of traditional compounding, including risks associated with manual dose manipulation (e.g. cross contamination, uneven dose distribution in split tablets). Originally designed for printing biological materials such as cells, SSE printers are optimised for sterile environments and ease of cleaning. The technology extrudes a semi-solid formulation from a syringe through a nozzle under constant pressure, allowing for precise, layer-by-layer tablet fabrication. SSE enables flexible customisation of tablet shape, formulation (e.g. chewable tablets), size, and drug release profile, supporting improved acceptability and compliance in paediatric patients.

The study aimed to determine the suitability of SSE in the hospital setting and assess pharmacists' perceptions of SSE to determine if SSE is a viable alternative to traditional paediatric dose compounding. SSE additive manufacturing was used to produce 5 mg doses of metoprolol tartrate. These SSE tablets were made from commercial metoprolol tartrate ground in a mortar, mixed with excipients to form a gel, loaded into syringes, printed and dried at 40 °C overnight in a small vacuum oven. The tablets were assessed for size, weight, drug content, release profile, disintegration properties, microbial contamination and preparation time and then compared to compounded capsules from an external compounding facility. In addition to this, another batch of SSE tablets were made start to finish by a hospital pharmacist and were evaluated against the same parameters, made under supervision of the study’s authors. Five participants, from a range of educational backgrounds and clinical experience, assessed SSE usability, benefits, risks, quality, safety and adoption potential. The authors reported there was no significant variability observed between SSE batches prepared by different individuals, confirming the process is sufficiently consistent to be suitable for hospital use. The SSE tablets were smaller than externally compounded capsules, with more uniform drug content (± 6% deviation from 5 mg). One compounded capsule contained double the expected dose, likely due to drug clumping, suggesting SSE tablets are potentially safer, and more acceptable for patients. The SSE tablets exhibited prolonged-release properties similar to commercial metoprolol tablets, while the compounded capsules showed immediate release properties. Microbial assays confirmed the safety of SSE tablets produced within standard hospital workflows, demonstrating feasibility for in-house manufacturing. Interview data revealed a preference for using pre-loaded syringes over making medicated gels in-house in terms of efficiency, as well as the importance of clear labelling to prevent mix-ups and adequate staff training. Despite these concerns, the interview participants also demonstrated an appreciation for SSE's customisability for non-standard dosages, especially for paediatric and dysphagia patients, its capacity to reduce waste (e.g. discarding unused half of split tablets), improved ergonomics and enhanced workflow efficiency. There was strong interest in incorporating SSE technology into hospital pharmacy workflows.

The main limitation of this study is that only one commercially available medication and  one custom dose (5 mg) was studied. There is scope for many more medications to be assessed to develop a comprehensive and reliable formulary for producing SSE tablets in range of doses. Trial and error was used to determine the best formulation and printer parameters for use in the study and being able to standardise these parameters would be essential before SSE tablets can be reliably useful in the hospital pharmacy environment.

The introduction of SSE technology into hospital pharmacy workflows has the potential to significantly enhance efficiency and safety for paediatric patient populations requiring tailored medicine doses. However, the currently available technology needs to be developed further to support easier user interfaces for pharmacists and technicians to interact with, and incorporate medication safety practices such as closed loop principles and safe labelling to ensure production of SSE tablets can be done consistently and safely outside of the research lab environment. Training staff on the technology will be essential for effective use and adoption. Overall, SSE is likely to be a promising solution to reduce waste, improve ergonomics associated with compounding custom doses and optimise pharmacy workflows.

Levine VR, Paulsson M, Strømme M, Quodbach J, Lindh J. Off-the-shelf medication transformed: Custom-dosed metoprolol tartrate tablets via semisolid extrusion additive manufacturing and the perception of this technique in a hospital context. Int J Pharm X 2024; 8: 100277.

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RESEARCH

MedsScan Editors for Research SPG: Jacinta Johnson and Sid Patanwala

A framework to assess causal claims in observational research

Differentiating between causation and association is fundamental in research. Traditionally, medical journals have limited causal language to results confirmed via randomised clinical trials. This article discusses how advancements in observational study methodologies now allow for causal interpretations under certain conditions. The authors argue a structured approach to using causal language in observational studies would improve communication of research goals, aid in assessing assumptions and design choices, and ensure clearer, more accurate result interpretation and propose a new structured framework to determine when the use of causal language is appropriate in observational research.

The proposed framework involves six key questions:

1. What is the causal question?
2. What quantity would, if known, answer the causal question?
3. What is the study design?
4. What causal assumptions are being made?
5. How can the observed data be used to answer the causal question in principle and in practice?
6. Is a causal interpretation of the analyses tenable?

According to Dahabreh and Bibbins-Domingo, by systematically addressing these questions, researchers can determine when causal interpretation is appropriate in observational studies. This approach acknowledges that while randomised clinical trials are the gold standard for causal inference, well-conducted observational studies can also provide valuable causal insights, especially when randomised clinical trials are impractical or unethical. By emphasising transparency in assumptions and rigor in design, this approach enhances the reliability of causal claims.

For pharmacists and pharmacy technicians and assistants, the framework is especially relevant given the prevalence of observational studies relevant to pharmacy practice. Pharmacists can apply the guidance in this paper to critically assess the validity and reliability of causal claims in studies they encounter. When conducting their own research, pharmacists, technicians and assistants can also consider the questions within the framework when developing their study design to enhance the rigor and transparency of their observational studies.

Dahabreh IJ, Bibbins-Domingo K. Causal inference about the effects of interventions from observational studies in medical journals. JAMA 2024; 331: 1845–1853.

Improving the reporting of citation searching: The TARCiS Framework

Literature reviews are essential in the fields of medicine and pharmacy for synthesising existing research and guiding practice. While keyword searching is a standard method for identifying relevant studies, citation searching enhances this process by including backward citation searching (examining references cited by a study) and forward citation searching (identifying studies that cite the article) and other co-citing approaches. Citation searching methodology and terminology has not yet been standardised, which can make it difficult to assess the completeness, reliability, and reproducibility of literature reviews.

To address this, a scoping review and Delphi study of international methodological experts were conducted to reach consensus on citation searching best practice. Findings were used to develop the Terminology, Application and Reporting of Citation Searching (TARCiS) statement, comprising 10 specific recommendations, on when and how to conduct and report citation searching in the context of systematic literature searches. In brief TARCiS states:

1. Specific terminology (provided) should be used to describe citation searching
2. Supplementary citation searching should be seriously considered for topics that are difficult to search for
3. While not critical for topics that are easier to search for, reference list checking can be used to confirm search strategy sensitivity
4. Supplementary backward and forward citation searching generally should be based on all included records of the primary search
5. Backward citation searching should ideally include screening titles and abstracts of the references cited
6. If available, using two citation indexes for citation searching can enhance coverage
7. Results of citation screening should be de-duplicated before screening
8. If citation searching identifies new papers, consider another iteration of citation searching
9. Citation searching alone should not be used for comprehensive literature searches
10. Guidelines (provided) should be followed for completeness of reporting.

The development of the TARCiS recommendations is a significant step in improving the rigor and usefulness of literature searches. Moving forward, pharmacists, technicians and assistants interested in developing their research skills should use the TARCiS statement to standardise and improve citation searching practices when conducting systematic literature reviews.

Hirt J, Nordhausen T, Fuerst T, Ewald H, Appenzeller-Herzog C on behalf of the TARCiS study group. Guidance on terminology, application, and reporting of citation searching: the TARCiS statement. BMJ 2024; 385: e078384.

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TRANSITIONS OF CARE AND PRIMARY CARE

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

A promising app to systemise deprescribing? More evidence required

Polypharmacy in older people is well-recognised. Evidence exists that reducing their medication burdens can be safely achieved. An integrated, systemised team-based approach is proposed to counter barriers to translating deprescribing evidence into practice.

This article describes such a strategy — the Team Approach to Polypharmacy Evaluation and Reduction (AusTAPER) — a web-based software application (app), which utilises a structured, clinical pathway to share patients’ information between pharmacists, hospital teams and their usual general practitioners (GPs). The app performs medicines reviews, considering interactions, appropriateness, anticholinergic and serotonergic loads, deprescribing resources and patient preferences. The described randomised controlled trial evaluated AusTAPER’s effectiveness in reducing the number of medicines in older Australian inpatients (aged ≥70 years) taking five or more regular medicines, discharged for GP follow up. Following pharmacist consultations, medicines plans were created with team and GP input for 49 inpatients, emphasising ‘pausing and monitoring’ medicines and criteria for restarting, if necessary. The primary outcome was the change in regular medicines at 12 months, compared to 49 control patients who received routine hospital clinical pharmacy services. Quality-adjusted life years (QALYs), healthcare and medicines costs were evaluated.

Both groups had significant reductions in medicines, including inappropriate medicines, without significant between-group differences. Health outcomes, QALYs, healthcare utilisation and medicine costs were similar. These findings were attributed to the study unfortunately coinciding with COVID-19: recruitment was low, and planned research follow up was restricted to telephone contact. Although implemented across three Perth hospitals, participants were mostly discharged from the subacute hospital, from which previous evidence suggests greater medicine reductions are achieved, compared to acute hospitals. Pragmatically, the research pharmacists provided care across both intervention and control patients.

Post-discharge HMRs were referenced, although it is not clear if or how these were utilised. From the perspective of possible widespread adoption, discussion of this aspect and the feasibility of AusTAPER as a clinical tool in Australian practice would have been welcome.

Etherton‐Beer C, Page A, Criddle D, Somers G, Parkinson L, Clifford R, et al. The Australian team approach to polypharmacy evaluation and reduction (AusTAPER) hospital study: effect of a collaborative medication review on the number of current regular medicines for older hospital inpatients. Intern Med J 2024; 54: 1719–1732.

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