MedsScan Issue 2, 2023
These reviews provide updates on the international literature on therapeutics. Expert pharmacy practitioners — via SHPA’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.
- Clinical trials
- Critical care
- Education and educational visiting
- Geriatric medicine
- Oncology and haematology
- Palliative care
- Technicians and assistants
- Transitions of care and primary care
- Women's and newborn health
MedsScan Editor for #SHPAClinTrials: June Challen
The impact of extramural DAIT/NIAID pharmacy programs and pharmacist scientist oversight
This article presents results from a retrospective observational study conducted by the Division of Allergy, Immunology and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID), based in the United States.
The researchers observed that over the past two decades, the involvement of a pharmacist scientist (also referred to as research pharmacist, research pharmacist scientist, pharmacist specialist and pharmacist throughout this article) in clinical settings has improved patient safety, decreased medication errors and enabled successful conduct of clinical trials and faster product development. They note that many research institutions in the United States now have pharmacists as essential members of their clinical research enterprise, serving in a wide variety of roles such as principal investigator/sub-investigator, research coordinator, pharmaceutical sponsor, clinical trial manager, monitor, institutional review board (equivalent to Australian human research ethics committees) member and research institutional administrators. However, the impact of an oversight by a pharmacist scientist on clinical trial performance and execution in terms of pharmacy and Investigational Product (IP)-related deviations has been under-evaluated. Thus, the purpose of this study was to evaluate the association of DAIT/ NIAID pharmacy, pharmaceutical program services and pharmacist scientist oversight with specific metrics of study execution and performance.
The researchers evaluated monitoring data from 116 studies conducted between 2006–2020, assessing the association of the number of pharmacy and Investigational Product (IP)-related deviations with pharmacist oversight and use of DAIT pharmacy/pharmaceutical services in two groups: Intervention Group (IG) and the Control Group (CG). They found a statistically significant association between pharmacist scientist involvement and oversight from protocol development to study execution and a reduction in pharmacy and IP-related deviations.
The results from this study support having a trained research pharmacist as part of each study team from protocol development through study implementation and conduct. Hence, the researchers conclude that the most effective research whether hospital-based, industry-based or in public heath, should be done by a team that includes scientists that are pharmacists as well as physicians, nurses, statisticians and regulatory specialists.
Hamrah SD, Gallagher S, Ortega-Villa AM, Wheatley LM, Touré O. Impact of extramural DAIT/NIAID pharmacy programs, research pharmacist scientist oversight on study performance, and lessons learned. Contemp Clin Trials 2023; 124: 106938.
No animal testing for new drugs in the United States
In late December 2022, it was legislated that new medicines no longer require animal testing to be approved by the United States Food and Drug Administration (FDA). Animal welfare organisations have advocated for this change arguing that computer modelling, including organ chips, and other nonanimal methods can effectively replace animal testing. This news article in Science notes that “[i]n place of the 1938 stipulation that potential drugs be tested for safety and efficacy in animals, the law allows FDA to promote a drug or biologic — a larger molecule such as an antibody — to human trials after either animal or nonanimal tests”.
The author discusses alternative technologies, particularly organ chips and organoids, that can replace the need for animal testing for new medicines. Organ chips are made of hollow channels embedded in silicone-based polymers and are small in size. The hollow channels in organ chips are lined with living cells and tissues from organs such as the brain, and fluid is made to flow through the channels. This fluid aims to mimic blood moving through tiny vessels and fluid tracking through tissue. This replicates processes in living organs. The author explains that “[i]n the body, drug damage often shows up in the liver because it breaks down drugs for excretion. A human liver chip can warn of such toxicity when an experimental drug pumped through it damages the cells”. Organoids also mimic the properties of tissue. Derived from stem cells, they are hollow and comprised of 3D clusters of cells. Organoids have demonstrated positive results in predicting liver and cardiac toxicities.
The emergence of these technologies may provide alternative methods to test the safety of new medicines seeking FDA approval, providing drug companies non-animal testing pathways for approval.
Wadman M. FDA no longer has to require animal testing for new drugs. Science 2023; 379: 127–8.
Clinical trials must focus on people, not just systems and processes
The authors of this discussion paper, published in the Medical Journal of Australia, highlight that the more than 1000 new clinical trials starting each year makes Australia a leading destination for clinical trials and represents more than one billion dollars in direct expenditure, with estimated benefits related to improved patient outcomes and higher quality care worth $5.80 for every dollar invested. The paper discusses several reforms that the Australian Government has introduced to increase competitiveness for clinical trial activity including: embedding research as core to the health system; developing a standardised approach to ethics and governance systems; and; making clinical research easier to access (i.e. including conducting, participating and investing in clinical research).
While these improvements would be very valuable, they may not address the common challenge clinical trials face; that of patient recruitment, with only half of all trials achieving their target sample size. Low patient recruitment rates are attributed to low levels of public awareness of, and participation in, clinical trials in Australia. An estimated 95000 Australians participated in trials in 2019, representing 0.4% of the population.
The authors of this paper, from the University of Sydney, discuss the current strategies being employed to address participation rates. They argue that the “current Australian governments’ investments in improving systems and processes for clinical trial activity need to be matched by investment in coordinated and sustained engagement with the people who are essential to successful clinical trials: clinicians and patients”. Instead, they suggest that government funded education campaigns and increased marketing could improve public awareness of the importance of clinical trials and how people can participate in them. From a clinicians’ perspective, the authors suggest the need for accessible and easily understood information about clinical trials, facilitating easier and more informed discussions with their patients.
Todd AL, Nutbeam D. More and better clinical trials in health care: focusing on people, not just systems and processes. Med J Aust 2023; 218: 209–11.
MedsScan Editors for #SHPACritCare: Lucy Arno and Grainne Hughes
Andexanet alpha and reversal of acute major bleeds associated with Factor Xa Inhibitors
Special contributor: Kasey Schuler
The benefits of factor Xa (FXa) inhibitors in the reduction of thrombotic events in patients with nonvalvular atrial fibrillation and venous thromboembolism are undoubted. However, the risk of major bleeding, particularly intracranial haemorrhage, while on treatment with these agents carries significant morbidity and mortality with few options for successful reversal. Enter modified recombinant inactive factor Xa andexanet alpha, designed to reverse factor Xa activity. Milling Jnr et al., enrolled 479 adult patients with a mean age of 78 years who experienced acute major bleeding (intracranial 69%; gastrointestinal 23%) and presented to hospital within 18 hours while being treated with either apixaban (51%), rivaroxaban (37%), edobaxan (8%) or enoxaparin (5%), with a median time to last dose of 11.4 hours.
Patients were administered a bolus, followed by a two-hour infusion of andexanet alpha in doses (high or low dose regimen) that were based on which FXa inhibitor they were taking and the dose and time since last dose. As a co-primary endpoint of the study, reduction of anti-FXa activity by a median of 93% (95% confidence interval [CI], 94–93) in apixaban patients, 94% (95% CI 95–93) in rivaroxaban patients, 71% (95% CI, 82–65) in edoxaban patients and 75% (95% CI, 79–67) in therapeutic enoxaparin (≥1 mg/kg) patients was observed following andexanet alpha administration. At 30 days, the incidence of patients with thrombotic events was 10.4% (n = 50).
Results from this final cohort of patients in the multicentre, phase-3b/4 study in the ANNEXA series showed that treatment with andexanet alpha achieved good to excellent haemostasis in 80% (95% CI, 75–84) of patients experiencing a major bleed associated with the use of factor Xa inhibitors, although with a lack of comparator group, these findings are all observational.
Milling Jnr TJ, Middeldorp S, Xu L, Koch B, Demchuk A, Eikelboom J, et al. Final study report of andexanet alfa for major bleeding with factor Xa inhibitors. Circulation 2023; 147: 1026–38.
Does hydrocortisone decrease mortality in patients with severe community acquired pneumonia?
Many aspects of the role of steroids in critical care remain uncertain, and numerous trials have been undertaken in recent years to gain further insight into various steroid indications. This paper looked specifically at the use of steroids for patients admitted with severe community acquired pneumonia (CAP) to 31 French intensive care units (ICUs). Patients with influenza or septic shock were excluded.
The study was a phase 3 multicentre, double blind, randomised controlled trial. In a population of patients admitted to ICU for severe CAP, hydrocortisone was administered continuously at a dose of 200 mg daily for 4 or 8 days, followed by tapering to a total duration of 8 or 14 days. The length of treatment was determined by pre-defined criteria relating to patient improvement. Treatment was discontinued at the time of ICU discharge. Hydrocortisone was compared to placebo. All patients received standard antibiotics and supportive care. Recruitment was ceased after 800 patients in March 2020 due to COVID-19.
The primary outcome was death at 28 days, and the authors concluded that hydrocortisone lowered the risk of death at 28 days by 5.6% (95% confidence interval [CI], -9.6–-1.7; P = 0.006). Secondary outcomes of note included significantly less intubation and vasopressor initiation in the intervention group.
It is worth noting that a very high proportion of the patients screened were excluded (5948 screened, 5148 excluded), indicating that the study looked at quite a specific sub-group of ICU patients, so these results have limited applicability to a general patient population. Of note, septic shock and aspiration pneumonia patients were excluded. The groups were well balanced (other steroid responsive respiratory pre-existing conditions [chronic obstructive pulmonary disease and asthma] were balanced across groups). The optimal tapering regime remains undetermined. REMAP-CAP, a larger adaptive platform trial with a similar question may further inform practice.
Dequin PF, Meziani F, Quenot JP, Kamel T, Ricard JD, Badie J, et al. Hydrocortisone in severe community-acquired pneumonia. N Engl J Med 2023 [preprint].
The impact of selective decontamination of the digestive tract in critically ill patients receiving mechanical ventilation
This study was conducted as a randomised, cluster, crossover trial in which 5982 adult mechanically ventilated patients from 19 Australian intensive care units were observed, and data collected from April 2018 to May 2021. The two arms of this trial consisted of selective decontamination of the digestive tract (SDD) versus standard care. SDD is the application of non-absorbable antibiotic and antifungal agents to the upper gastrointestinal tract combined with IV antibiotics to minimise the risk of ventilator acquired pneumonia (VAP). SDD intervention was an oral paste mixture of colistin, tobramycin and nystatin. This paste was applied 6-hourly to the buccal mucosa and oropharynx and patients were also given 10 ml of a gastric suspension consisting of the same ingredients, 6-hourly via gastric tube. The SDD group also received a four-day course of IV antibiotics.
The primary outcome, of in-hospital mortality within 90 days, showed no significant difference (27% vs 29.1%) (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.82–1.02; P = 0.12) between the groups. There was also no significance seen in secondary outcomes: in-ICU mortality; number of days alive; number of days free from mechanical ventilation; ICU admission; and hospital admission. The microbiological secondary outcomes did however show a statistically significant reduction in the SDD group versus the standard care group that cultured new antibiotic resistant organisms (23.1% vs 34.6%) and those who had new positive blood cultures (5.6% vs 8.1%). Notably there was no difference in diagnosis of new Clostridioides difficile infections between the two groups.
An ecological assessment was conducted to determine changes in microbiological flora in participating ICUs however it did not assess changes at a hospital level and was observed over a relatively short period of time. This leads one to wonder about the long-term exposure of SDD on the environment overall. The study was conducted on a large population with high acuity of illness and was assessed on a robust patient-centred outcome.
SuDDICU Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group, Myburgh JA, Seppelt IM, Goodman F, Billot L, Correa M, et al. Effect of selective decontamination of the digestive tract of hospital mortality in critically ill patients receiving mechanical ventilation: A randomized clinical trial. JAMA 2022; 328: 1911–21.
EDUCATION AND EDUCATIONAL VISITING
MedsScan Editor for #SHPAEdu&EduVisiting: Michelle Hansen
Pharmacy Residency Resiliency Program
Special Contributor: Diana Bortoletto
Resilience is relevant in pharmacists and residents who experience a high level of demand and potential for burnout. The American Society of Health-System Pharmacists (ASHP) recommends residency programs resilience education. This American study presents experiences from the Atrium Health’s Carolinas Medical Centre in creating and executing a formal, structured pharmacy residency resiliency program (PRRP).
The program comprised of eight curriculum-based sessions centred on skill development and new habit formation. The virtual program was run by an external facilitator with one hour sessions held every six weeks over 12 months and included facilitator check-ins three weeks post sessions. Participants completed a post-program electronic survey designed to evaluate their perceptions.
Nine residents underwent and evaluated the program. All participants “highly recommended” this program and thought the program “exceeded their expectations”. The two main benefit themes emerging were the longitudinal design to help with reflection and application; and conducting PRRPs separate to the residency program with external facilitators, which built trust and openness. All participants strongly agreed that the PRRP provided skills that helped alleviate stress/anxiety associated with residency training and that resilience is an important skill for residents.
While this PRRP was only implemented and evaluated at one hospital with few residents, it provides valuable insight into the benefits of such a program within a residency program. Program sustainability will be ensured through continuous involvement of external resources and assessing that other residency experiences are not compromised as a result of the PRRP. With current high attention to burnout in the Australian healthcare system, the availability and completion of external to workplace resilience programs should be considered.
Kneuss TG, Wolff AS, Meadors PL, Reynolds DR, Hammer JM. Implementation of a pharmacy residency resiliency program for PGY1 and PGY2 residents: Program structure and resident perceptions. Am J Health Syst Pharm 2022; 79: 1290–5.
Clinical Reasoning in Pharmacy
Special Contributor: Caitlin Hardman
Pharmacists make clinical decisions daily that directly affect patient safety and quality of care outcomes. The thought processes associated with clinical decisions are known as clinical reasoning — the ability to gather, analyse and integrate relevant information to benefit patients. The two cornerstone approaches to clinical reasoning are intuitive reasoning and analytical reasoning. This scoping review provided an overview of primary studies that examined the use of cognitive processes in clinical reasoning in pharmacy practice. From 2252 identified articles, 13 studies were included for review.
Two main categories of study contexts for clinical reasoning by pharmacists emerged: diagnosis-forming (n = 9) and medication review (n = 4). Extracted data was categorised into operationalisation, conceptualisation of clinical reasoning, and key study findings on cognitive processes When determining medicine appropriateness, an analytical approach was reported predominantly to an intuitive approach. This study reported that clearly clarifying the concept of clinical reasoning by pharmacists is essential for effectively teaching these skills.
Pharmacy educators need to revise their teaching strategies to help learners acquire the necessary knowledge, skills and attitudes, which may vary depending on the context of clinical reasoning. While clinical reasoning is a professional expectation of pharmacists in practice, pharmacy educators may find it difficult to teach and assess the complexity and nuances of clinical reasoning. It is recommended that this competence be taught by explicating and reflecting on clinical reasoning as separate stages of the clinical decision-making process with transparent cognitive processes.
Mertens JF, Koster ES, Deneer VHM, Bouvy ML, van Gelder T. Clinical reasoning by pharmacists: A scoping review. Curr Pharm Teach Learn 2022; 14: 1326–36.
Gamification in Pharmacy Education
Gamification uses the elements of games and applies them to non-game contexts. The use of gamification in education is increasing, however further understanding of its use in health professional education is warranted. This systematic review aimed to identify trends and gaps on the use of gamification in pharmacy education as described in literature.
A literature search was conducted to identify relevant articles published between 2020 and February 2022. The 623 unique articles found were screened further, with 66 included for review. Two thirds of the articles were from authors from the United States of America and the majority focused on a unidisciplinary (pharmacy only) approach. Interventions included gamified simulations, computer games, board games, quizzes and most commonly, escape rooms (30%). Improving knowledge (58%), teamwork and collaboration (33%), and skills acquisition (23%) were the most common intended learning outcomes from the gamified activities. Pre and Post testing was used in 41% of studies and data collection was most frequently completed through student survey (79%). Gaps were highlighted in the quality of reporting in the articles, with only one article meeting all quality criteria assessed.
A diverse range of gamification applications have been demonstrated within pharmacy education with a recent increase in prevalence. Hope et al. find that the educational benefits of gamification but be balanced against its reported costs, including time and resources, and suggest “[e]ducators must align gamification with competency, outcomes and skills-based reporting”. This systematic review highlights the need for increased quality of reporting for gamified interventions in the literature. This will allow for further assessment and understanding of the impacts of this educational practice and ensure alignment with evidence-based practice.
Hope DL, Grant GD, Rogers GD, King MA. Gamification in pharmacy education: a systematic quantitative literature review. Int J Pharm Prac 2023; 31: 15–31.
MedsScan Editors for #SHPAGeri: Alex Ho Yin Chan and David Nguyen
CLARITY AD trial: Are we all clear for a new drug class in the treatment of Alzheimer’s disease?
Special contributor: Anna Jennings
New immunotherapies targeting the neurotoxin amyloid-beta (Ab) in brain tissues are being developed to slow Alzheimer’s Disease progression. Modest, yet promising results have been observed, albeit with safety concerns around the risk of amyloid-related imaging abnormalities (ARIA) (i.e. cerebral oedema and haemorrhage). This study aimed to determine the safety and efficacy of lecanemab, a monoclonal antibody that targets Aβ in patients with early Alzheimer’s Disease.
An 18-month, multi-centred, double blinded randomised controlled trial was conducted with 1795 patients receiving either placebo or lecanemab IV 10 mg/kg every two weeks. The primary outcome was the change in Clinical Dementia Rating Sum of Boxes (CDR-SB) after 18 months. Secondary outcomes included the change in three other cognitive tests and levels of Ab from baseline.
Patients who received lecanemab had a slower decline in cognition and significantly reduced physical levels of Ab in brain tissue compared to those receiving placebo. The decline in CDR-SB score was reduced by 27% (difference −0.45; 95% confidence interval [CI] -0.67–-0.23; P < 0.001). However, rates of ARIA were 17.3% (ARIA-H: haemorrhages) and 12.6% (ARIA-E: oedema/effusions), compared to 9.0% and 1.7% respectively with placebo.
Whilst these results are promising, clinicians should recognise that reduced decline in CDR-SB may not result in clinically meaningful patient outcomes. The potential benefit must be balanced against the risk of serious adverse effects, cost and the treatment burden associated with fortnightly infusions. Despite lecanemab not currently being available in Australia, clinicians should be aware of the emerging evidence and the potential for future advancements.
van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M et al. Lecanemab in Early Alzheimer's Disease. N Engl J Med 2023; 388: 9–21.
Improved psychological well-being with antidepressant augmentation in treatment-resistant depression
Special contributor: Elizabeth Manias
Treatment-resistant depression generally involves augmenting existing pharmacotherapy with either an antidepressant from a different class or an antipsychotic. However, there is limited evidence for this approach in older people, due to age exclusion in clinical trials. This two-step, open-label study initially investigated the effect of augmentation with either bupropion or aripiprazole, as compared with a switch to bupropion, among older people that did not have a good response to two previous courses of antidepressants. Participants who did not experience remission or who were ineligible in the initial bupropion/aripiprazole treatment, were randomised in the second phase to receive augmentation with lithium or switch to nortriptyline. The primary outcome was psychological well-being after ten weeks.
In total, 742 patients were enrolled (mean age of 69 years). Augmentation with aripiprazole improved psychological well-being significantly more than switching to bupropion. Bupropion augmentation produced similar psychological well-being but was associated with a higher rate of falls. Remission occurred in approximately 29% of older people in the aripiprazole augmentation group, 28% in the bupropion augmentation group and 19% in the switch-to bupropion group. Lithium augmentation or a switch to nortriptyline showed small and similar well-being improvement, with remission in 18.9% and 21.5% of patients respectively.
While full antidepressant effects may take about 6–8 weeks, older people may respond more slowly to antidepressant treatment. Since the trial lasted only ten weeks, a longer period may have produced different effectiveness or falls results. Remission remained low in treatment-resistant depression, underscoring the need for more effective treatment to help older people.
Lenze EJ, Mulsant BH, Roose SP, Lavretsky H, Reynolds III CF, Blumberger DM, et al. Antidepressant augmentation versus switch in treatment-resistant geriatric depression. New Eng J Med 2023; 388: 1067–79.
Time to ‘shed some meds’ among older people at hospital discharge and post-acute care
Special contributor: Samantha Fraser
Although the evidence is robust, most deprescribing studies target specific drug classes and/or medical conditions. Few studies have initiated comprehensive deprescribing interventions among hospitalised older patients transitioning to post-acute care (PAC).
The Shed-MEDS trial aimed to evaluate the efficacy of a patient-centred deprescribing protocol, Shed-MEDS (Best Possible Medication History, Evaluation, Deprescribing Recommendations, and Synthesis) among hospitalised older adults with polypharmacy who were transitioning to a PAC facility. The Shed-MEDS intervention consisted of a pharmacist-or nurse practitioner-led medication review, patient or surrogate-approved deprescribing recommendations and deprescribing actions that were commenced in the hospital and continued through to the PAC facility stay.
The trial included 284 participants (mean age of 76.7 years). Overall, patients in the intervention group were taking significantly fewer medicines at PAC facility discharge (mean ratio, 0.86; 95% confidence interval [CI] 0.80–0.93; P<0.001), and fewer medicines at the 90-day follow-up (mean ratio 0.85; 95% CI 0.78–0.92; P<0.001), compared with the control group. The intervention also resulted in significantly fewer potentially inappropriate medications and lower Drug Burden Index at discharge from PAC and at 90-day follow-up.
Deprescribing plays an important role in reducing inappropriate medications and ensuring safer transitions across the care continuum. This trial reiterates that deprescribing for hospitalised older people is safe, achievable and effective — albeit resource and time-intensive. It also demonstrates that follow-up of deprescribing actions can sustain reduced medication burden up to 90 days post discharge. Post-acute care settings, such as aged care facilities and rehabilitation centres, may present opportunities for pharmacists to facilitate safe deprescribing practices.
Vasilevskis EE, Shah AS, Hollingsworth EK, Shotwell MS, Kripalani S, Mixon AS, et al. Deprescribing medications among older adults from end of hospitalization through postacute care: A Shed-MEDS randomized clinical trial. JAMA Intern Med 2023; 183: 223–31.
ONCOLOGY AND HAEMATOLOGY
MedsScan Editor for #SHPAOncHaem: Hayley Vasileff
A new edition of the ISOPP Standards for the Safe Handling of Cytotoxics
Special Contributor: Shaun O’Connor
The International Society of Oncology Pharmacy Practitioners (ISOPP) have released the second revision of their ‘Standards for the Safe Handling of Cytotoxics’. This revision updates the initial version from 2007, with significant changes to recommendations for the use of closed systems and contamination monitoring, as well as adding additional chapters for monoclonal antibodies, automation, oral anti-cancer therapy, investigational drugs, medical surveillance, electronic prescribing systems, dose banding and safe handling of hazardous drugs in research facilities.
The ISOPP Standards have provided an extensive source of information for best practice of oncology pharmacy practice, detailing recommendations for handling and required precautions, education and training, environmental and personnel monitoring, spill management, containment infrastructure including Containment Primary Engineering Controls (cabinets and isolators) and Containment Secondary Engineering Controls (cleanrooms), waste handling and risk management.
SHPA members at the time of writing played a prominent role in reviewing and developing the updated ISOPP Standards. Suzanne Staude, Marliese Alexander, Antoine Sedrak and Sarah Glewis are listed as contributors.
The standards initial version has been a benchmark for practice standards worldwide, having been translated into multiple languages and having featured prominently as a source for local guidelines, as shown by being cited 142 times. This shows the breadth of impact worldwide, and this updated version will continue to lift practice standards for the next decade.
ISOPP Standards for the Safe Handling of Cytotoxics. J Oncol Pharm Pract 2022; 28: S1–S126.
Potential new treatment option in chronic lymphocytic leukaemia
Special Contributor: Aisling McGowan
Patients with chronic lymphocytic leukaemia (CLL) and 17p deletion have an unfavourable prognosis and respond poorly to standard therapies. The SEQUOIA trial was an open-label, multi-centre, randomised phase 3 study of treatment naïve (TN) patients with CLL. Patients with centrally confirmed 17p deletion were not randomised during SEQUOIA screening but were later assigned to single agent zanubrutinib in a separate cohort (Arm C). Arm C investigated the use of Zanubrutinib, a bruton tyrosine kinase inhibitor (TKI) in patients with confirmed del(17p). The aim of this arm was to determine the overall response rate (ORR), progression-free survival (PFS), duration of response (DOR), and safety in this patient group.
Zanubrutinib was dosed at 160 mg twice a day until intolerance or progressive disease (PD). Median DOR, PFS and event-free survival rates were estimated using Kaplan-Meier methodology with corresponding 95% confidence interval (CI). One hundred and nine patients were enrolled in Arm C. ORR was 94.5%, which included three patients (2.8%) with complete response and 95 patients (87.2%) with partial response. DOR ≥ 12 months was 92.8%. Estimated 18-month overall survival (OS) was 95.1%. Patients experiencing a ≥ Grade 3 adverse event was 48.6% and four patients discontinued treatment. Zanubrutinib showed similar safety and efficacy to current treatments. However, Arm C did not directly compare zanubrutinib to placebo/another targeted therapy. Duration of follow-up was relatively short and median PFS, OS and DOR were not reached. Zanubrutinib is currently TGA approved in Australia for Waldenstrom macroglobulinaemia and mantle call lymphoma (also PBS approved for this indication).
This study demonstrates the safety and efficacy of zanubrutinib in this patient cohort and this study will be of relevance if the TGA also approves zanubrutinib for CLL in the future.
Tam C, Robak T, Ghia P, Kahl BS, Walker P, Janowski W, et al. Zanubrutinib monotherapy for patients with treatment-naïve chronic lymphocytic leukaemia and 17p deletion. Haematologica 2021; 106: 2354–63.
Triple negative breast cancer: a new treatment paradigm?
Guest Contributor: Kimberley-Ann Kerr
Triple negative breast cancer is typically associated with a shorter overall survival compared with other subtypes of breast cancer. The current standard of care for patients with early disease is neoadjuvant chemotherapy. The KEYNOTE-522 study was a double-blind, randomised, phase 3 trial evaluating the addition of pembrolizumab to neoadjuvant chemotherapy and as an adjuvant treatment. Pathological complete response was previously reported, whereas this paper reports event-free survival.
Patients were randomised in a 2:1 ratio to either pembrolizumab-chemotherapy or placebo-chemotherapy. In the neoadjuvant phase, patients received either pembrolizumab 200 mg or placebo every three weeks, plus paclitaxel (once weekly) and carboplatin (weekly or every three weeks) for 12 weeks, and then either doxorubicin or epirubicin, as well as cyclophosphamide every three weeks for an additional 12 weeks. After surgery, patients received adjuvant pembrolizumab 200 mg or placebo every three weeks for up to nine cycles.
At 36 months, 15.7% of the pembrolizumab-chemotherapy group and 23.8% of the placebo-chemotherapy group had an event or died, showing a 37% lower risk of disease progression in the pembrolizumab-chemotherapy group (hazard ratio 0.63; 95% confidence interval 0.48–0.82; p < 0.001). Median event-free survival has not been reached in either group.
This study shows promising results for a cohort of patients who typically do not respond as well as other cohorts of breast cancer patients. The addition of pembrolizumab to standard treatment could be considered for high-risk patients, pending funding approvals.
Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kümmel S, et al. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. N Engl J Med 2022; 386: 556–67.
MedsScan Editors for #SHPAPalliative: Vicki Poulier, Jane Lewis and Pascale Dettwiller
Documenting palliative care patient or family involvement in medicines decisions at discharge
When a palliative approach to care is taken, multiple changes to a patient’s medicines often occur prior to hospital discharge. Documenting the changes and reasons for these allows continued care by other clinicians.
This retrospective study reviewed discharge summaries of 348 adult patients discharged from a single United States (US) hospital into hospice care over a seven-year period. It focused on documented medication changes — initiating, continuing or discontinuing medicines — which were discussed with patients or their families.
Of the 348 reviewed discharge patient summaries, 22% (n = 77) documented shared decisions about medicines with patients (15%) and/or their families (11%). Overall, almost half of the patients had cancer (49.1%), with a median Charlson Comorbidity Index (CCI) of 4. Significantly, documentation of discussions occurred in almost twice as many patients with cancer (adjusted odds ratio [OR] 1.99) compared to non-cancer patients. Increased documentation also occurred with increased CCI (adjusted OR 1.09). Specialist palliative care (SPC) was involved with 79.1% of patients, however this had no effect on documentation rate.
While the study found a low rate of patient/family participation in medicines decisions, a major limitation is reliance on documentation within the discharge summary, excluding conversations that occurred but were not documented or were documented elsewhere. However, the authors’ concern that poor clinical handover effects prescribing decisions after discharge is valid, particularly in the US setting where, unlike Australia, barriers to deprescribing may impact eligibility for hospice care. Pharmacists providing care to patients with a palliative diagnosis should consider interventions to improve documentation of shared medicines decisions on discharge to enable optimal prescribing by community clinicians.
Noble BN, Izumi S, Tjia J, Ku IY, Kadoyama KL, McPherson ML, et al. Patient and family participation in medication decisions on discharge to hospice care. J Pall Med 2022; 25: 1790–4.
Are antibiotics effective in treating pneumonia in cancer patients at end of life?
Evidence-based results to support decisions to prescribe antibiotic therapy in terminally ill cancer patients is scarce, with reported antibiotic response for various infections between 33 and 65%.
This prospective cohort study, conducted in 23 Japanese palliative care units/inpatient hospices, investigated antibiotic response at 72 hours when treating pneumonia at end of life, and patient factors that affected response. Good, moderate and no response were determined by recording improvement in respiratory symptoms of dyspnoea, cough and sputum production from day 1 to day 3.
Of 1896 admitted adult patients, 137 were included, with median Palliative Performance Scale of 20, and the majority of these patients had lung cancer (28.5%). The most frequent antibiotics administered were penicillins (41%), cephalosporins (40%) and carbapenems (11%). Overall, 65 (47.4%) patients had a good or moderate response, with lower Palliative Prognostic Index (PPI) ≤6 and respiratory rate (RR) <20 significantly associated with improvement. Severity of pneumonia determined by patient observations (e.g. temperature or pulse) or laboratory tests (e.g. white blood cells) did not affect response.
Almost 50% of patients given antibiotics for pneumonia had symptom relief, improving their quality of life. PPI and RR were associated with improvements that may assist in deciding whether to treat cancer patients at end of life with antibiotics. However, several limitations can be noted. Firstly, the enrolment of suitable patients in the palliative care setting is challenging. Secondly, more consistency in the diagnosis of pneumonia in this category of patients is needed, and finally, the antibiotics prescribed were not controlled, with antibiotic choice resting with the treating clinician. Side effects of the treatment were also not recorded, which may have affected the observed outcomes. The authors are calling for more formal clinical trials.
Odagiri T, Maeda I, Mori M, Morita T, Kaneishi K, Nozato J, et al. Effects of antibiotics on respiratory symptoms in terminally ill cancer patients with pneumonia: A multicenter cohort study. Am J Hosp Palliat Care 2022; 39: 1082–9.
Deprescribing interventions by palliative care pharmacists
There are few published studies on goals-of-care (GOC) related deprescribing recommendations by inpatient palliative care pharmacists. Cook et al., conducted a prospective, non-randomised interventional pilot study at three hospital sites in the United States. Deprescribing recommendations were reported using descriptive statistics, with success of the recommendation determined by inclusion in the discharge medication plan. The recommendation was given a rating by the authors based on perceived benefits and harms then categorised as either high or low priority for discontinuation.
The study was conducted in adult patients over three months in 2019 and included both hospice and non-hospice inpatient settings. The patient and/or carer took part in a GOC discussion and was subsequently seen by the palliative care pharmacist. Forty-five inpatient consultations were selected by sample of convenience method. Mean age was 75.9 years, the majority of patients were female (69%) and estimated to have less than six months to live (91%).
The study reported 82% of recommendations were successful and suggests the outcome was consistent with geriatric deprescribing studies. However, it is not clear from the discussion what protocols the comparison studies used, and recommendations in this study were based on the pharmacists’ experience and training. Each patient had a mean of 3.3 medicines ceased, the most common reason being to reduce pill burden (60%). Some discrepancies were noted in the results presented but they do not appear to significantly alter the interpretation.
As a pilot study, the authors failed to connect the significant barriers, bias and limitations discussed with improvement of their study design. As a result of the study the authors report implementation of a standard deprescribing form on the pilot site electronic medical record software which will support future deprescribing research.
Cook H, Walker KA, Felton Lowry M. Deprescribing interventions by palliative care clinical pharmacists surrounding goals of care discussions. J Palliat Med 2022; 25: 1818–23.
MedsScan Editor for #SHPAResearch: Jacinta Johnson
The evolution of the RE-AIM framework
The RE-AIM framework is a widely used framework in implementation science that provides a systematic approach for evaluating the adoption, implementation and sustainability of interventions or programs. RE-AIM guides research to evaluate the Reach, Effectiveness, Adoption, Implementation and Maintenance of a new initiative, intervention or service. This article discusses the evolution of the RE-AIM framework.
The paper addresses 13 areas where misconceptions have been noted concerning the use of RE-AIM and summarises current guidance on these issues. Some important points highlighted were that RE-AIM is a quantitative framework and is not useful for understanding the context or process of implementation. It focuses only on the evaluation of the intervention, not the development or planning stages and primarily applies to interventions that are being scaled up or widely disseminated.
The article also provides resources to guide application of the framework. Hospital pharmacists and pharmacy technicians could benefit from understanding the correct use of the RE-AIM framework, as it can be a useful tool for research evaluating the implementation of new interventions or programs within the healthcare setting. By using the framework appropriately, hospital pharmacists and pharmacy technicians can ensure that interventions are effectively reaching the intended population, are being adopted and implemented properly, and are sustainable over time.
Holtrop JS, Estabrooks PA, Gaglio B, Harden SM, Kessler RS, King DK, et al. Understanding and applying the RE-AIM framework: Clarifications and resources. J Clin Transl Sci 2021; 5: e126.
Academic engagement: a review of predictors and consequences
This article provides a systematic review of the recent literature exploring predictors and consequences of academic engagement with external organisations, including those which relate to research. Academic engagement refers to knowledge-related interactions between academic scientists and external organisations, including collaborative research with industry, contract research, consulting and informal ties. Academic engagement can involve collaborative research with those practicing within the healthcare sector and hospital pharmacists and technicians may be potential collaborators with academic researchers in this context.
The review found that individual characteristics associated with academic engagement include being scientifically productive, senior, male, locally trained and commercially experienced, and that peer effects and disciplinary characteristics also influence academic engagement. Importantly, academic engagement was positively associated with subsequent scientific productivity. Hospital pharmacists and pharmacy technicians may be able to leverage this to promote and advocate for collaboration with academics within the University sector. Collaboration with academic researchers may also enhance hospital pharmacists’ and pharmacy technicians’ research skills and knowledge, and ultimately, can have positive impacts on patient care and health outcomes.
Perkmann M, Salandra R, Tartari V, McKelvey M, Hughes A. Academic engagement: A review of literature 2011–2019. Res Policy 2021; 50: 104384.
Co-design with Aboriginal and Torres Strait Islander communities requires authentic partnerships
The co-design method is an approach often used in research to create solutions that meet the needs, preferences and values of the stakeholders, ensuring that the product is effective in meeting the intended goals. This paper explores the principles of co-design with Aboriginal and Torres Strait Islander communities. Co-design in this context refers to a collaborative approach to designing healthcare services or interventions with Aboriginal and Torres Strait Islander communities that values different knowledge systems, promotes inclusive involvement and requires authentic partnerships. Research focused upon development and implementation of new hospital pharmacy services could involve co-design processes. The paper has been authored by a working group from Services for Rural and Remote Allied Health (SARRAH), a member-based organisation working to improve health outcomes for rural and remote Australians.
The approach taken involved a review of available literature, seeking member perspectives and sharing experiences and understandings of co-design. The paper proposes that successful co-design with Aboriginal and Torres Strait Islander communities places legitimate value on different knowledge systems, is built on strong and trusting relationships, promotes inclusive involvement and requires authentic partnerships. The principles of co-design could be utilised by hospital pharmacists and pharmacy technicians planning to implement and evaluate new services for Aboriginal and Torres Strait Islander people to promote meaningful improvements in hospital pharmacy practice.
Tamwoy N, Rosas S, Davis S, Farthing A, Houghton C, Johnston H, et al. Co-design with Aboriginal and Torres Strait Islander communities: A journey. Aust J Rural Health 2022; 30: 816–22.
TECHNICIANS AND ASSISTANTS
MedsScan Editors for #SHPATechnicians: Tara Clayson-Fisher, Bryan Walker and Debbie Parker
Factors that positively influence pharmacy technicians and their acceptance of new roles
Australian and overseas pharmacy technician roles are expanding beyond their historical scope. An online survey was disseminated to a randomised sample of 3000 certified pharmacy technicians in the United States to solicit data on their willingness to participate in emerging roles and also on a number of environmental, organisational and personal resilience factors.
Of the disseminated surveys, 745 completed responses were received with respondents being predominantly female, Caucasian/white and from a variety of service settings including hospitals and community pharmacies. The emerging tasks most relevant to Australian settings that pharmacy technicians were most willing to participate in were medication history data collection, supervision of other technicians and tech-check-tech roles.
It was identified that pharmacy technicians working in metropolitan, hospital and specialist settings were more likely to be interested in emerging roles, with this attributed to potential exposure to these activities. Surprisingly there was no similar correlation for salary, though future uncertainty and age did have a statistically significant, but comparatively minor impact. What did have a statistically significant and high degree of correlation with technician willingness scores was transformative leadership behaviours performed by supervising pharmacists, co-worker support and individual resilience.
This piece of work indicates that our hospital organisations and the behaviours of pharmacists who supervise technicians are key contributors to technician willingness to participate in emerging roles. This highlights the importance of creating pharmacy workplace cultures that articulate a clear vision for pharmacy technicians so that they can then commit to expanded roles.
Desselle SP, Wasem V, Woodyard A, Hosseini S, Hohmeier KC, McKeirnan KC. Cultures of support and resilience are associated with certified pharmacy technicians embracing new roles. Res Social Adm Pharm 2023; 19: 316–21.
The long game pays off: investment in pharmacy technician structure improves organisations
This descriptive report details the process and progress that the West Virginia University Health System undertook to transform their pharmacy technician workforce. The West Virginia University Health System provides services to 18 hospital precincts across three states and routine employee engagement measures found that pharmacy technicians were consistently ranked as one of the least engaged groups in the entire organisation. Additionally, pharmacy technicians had an annual turnover rate of 42.3% in 2018 while conversely, pharmacists scored well in both measures.
Pharmacy leadership partnered with the human resources department to commence a career restructure process, initially at the West Virginia University Hospitals campus. This 800-bed multi-site service includes an academic site and numerous community and ‘critical access’ (regional) hospitals. The combined pharmacy departments were made up of approximately 390 full-time equivalents (FTE), with pharmacy technicians representing 50% of their workforce.
The pharmacy technician career structure had only two non-supervisory roles connected to national certifications. Previous attempts to modernise the technician structure had been made, these efforts were inconsistent between sites and had been identified as workarounds of certification requirements; and ultimately, these efforts were not successful.
In consultation with technicians, three non-supervisory specialised career tracks were established, each with three tiers of progression. Additionally, two technician leadership positions were created and identified as roles that would participate in teaching and training. In December 2018, current employees went through a human resources process to identify which new work level their current work aligned with, their salary grades were adjusted and the career pathway was officially established.
In the three years since implementation there has been a significant change in the employee engagement scores, turnover and retention. Due to increased dispensing activity enabled by the career structure changes, the department has seen improved financial performance and the aim is for the changes to be cost neutral. Annual turnover rate has improved significantly and has consistently scored between 17–18% (the organisational target is 15%), with employee engagement shifting from a Tier 3 ranking (the lowest possible) to a high-Tier 2 level. It isn’t possible to singularly attribute these changes to the technician career restructure, but it is evident improving the career structure has positively contributed to these changes.
The West Virginia University Health System has since committed to rolling out this career structure at all other member hospitals within their organisation, with the initial staffing reviews underway in late 2021.The initial implementation through their diverse multi-site service demonstrated that the structure would be viable in multiple settings and the authors are hopeful that this will be mirrored by other organisations around the country.
While there are differences in certification of hospital pharmacy technicians between our two nations, there are similar desires to increase the minimum education requirements while also experiencing relatable workforce supply issues for already qualified candidates. The authors propose that neither of these things are likely to change until organisations ensure pharmacy technicians have fulfilling careers with appropriate salaries.
Australian pharmacy departments also grapple with the question of which comes first, changes to formal training programs or better career pathways and expanded scope roles. This successful transformation process shows us that pharmacy departments must invest in proactive support for their technician workforce — not doing so risks disengagement and negatively impacts long-term recruitment, attraction, and retention of staff.
O’Neil DP, Henderson JM, Gifford HR, Karpinski TA, Kaminsky L. Building a pharmacy technician structure for the future: a lesson from a multihospital academic health system. Am J Health Sys Pharm 2023; 80: 304–11.
TRANSITIONS OF CARE AND PRIMARY CARE
MedsScan Editors for #SHPATransitionCare: Margaret Jordan, Ahmed Zeidan and Deirdre Criddle
Older patients continue to experience paternalistic decision-making about medicines changes: an OPERAM trial
Special contributor: Elizabeth Manias
A patient-centred approach is important for shared decision-making with the goal of improving quality of care and patient safety. The aim of this mixed-methods study was to explore the experiences of older patients with multimorbidity about medicines changes in hospital. Semi-structured interviews were conducted in teaching hospitals situated in Belgium, Ireland, Switzerland and The Netherlands, in the local languages of each country. Older patients also completed the Beliefs about Medicines Questionnaire,1 while the Shared Decision-Making Questionnaire2 was completed by clinicians comprising doctors and pharmacists.
In all, 48 patients participated in the study from the intervention or control arms of the trial. The Beliefs about Medicines Questionnaire showed patients had low concern beliefs about their medicines. While participating clinicians (N = 17) reported high levels of shared decision-making, many patients indicated they received little information about medicines changes, particularly in relation to reasons for the medicines and anticipated side effects. Medicines decisions were largely made by clinicians, and patients were informed after these decisions were made. Barriers to participation included patients’ beliefs about their lack of competence in decision-making, a dismissive approach from clinicians, and lack of time in obtaining reassurance and understanding.
Paternalistic practices were very common across diverse settings, which is a major concern considering the study was conducted after the OPERAM trial had been running for 12 months. These results indicate the need for significant behavioural changes, better preparation for enhanced partnerships between patients and clinicians across transitions of care, and enhanced understandings of complex contextual issues influencing patients’ experiences.
Thevelin S, Pétein C, Metry B, Adam L, van Herksen A, Murphy K, et al. Experience of hospital-initiated medication changes in older people with multimorbidity: a multicentre mixed-methods study embedded in the Optimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people (OPERAM) trial. BMJ Qual Saf 2022; 31: 888–98.
- Horne R, Weinman J, Hankins M. The beliefs about medicines questionnaire: The development and evaluation of a new method for assessing the cognitive representation of medication. Psychol Health 1999; 14: 1–24.
- Scholl I, Kriston L, Dirmaier J, Buchholz A, Härter M. Development and psychometric properties of the Shared Decision Making Questionnaire – physician version (SDM-Q-Doc). Patient Educ Couns 2012; 88: 284–90.
National survey insights: Approaches and processes of clinical pharmacists in Home Medicines Review
Home Medicines Review (HMR) services in Australia play a crucial role in improving medicines management, preventing adverse drug events and enhancing patient outcomes. Lee et al., conducted a study highlighting the importance of understanding the approaches and processes used by pharmacists in HMRs. The survey investigated pharmacists’ strategies and techniques when performing HMRs.
The study found that the most common information in HMR referrals was a medication list (97%). Before consumer consultation, participants primarily collected community pharmacy details and history (71%). During the consultation, approximately a quarter of pharmacists collected anthropometric data, blood pressure and performed formal assessments of medication adherence and anticholinergic burden. All participants included recommendations in their written reports, and 80% reported consumer preferences and therapy goals.
The authors identified that inconsistencies in methods and procedures could impact HMR quality and effectiveness. They acknowledged the study’s limitations, such as potential response bias and cross-sectional design. Nevertheless, the study emphasises the extensive information needs of consultant pharmacists, leading to holistic and comprehensive HMR reports. It also reveals the variable utilisation of clinical tools in HMR service delivery and highlights person-centred HMR reports.
The findings provide valuable insights for hospital pharmacists and those involved in HMR services, identifying current practices and areas for improvement. Future research should focus on expanding the information provided in HMR referrals and examining the potential benefits of standardisation.
Lee K, Kouladjian O'Donnell LK, Cross AJ, Hawthorne D, Page AT. Clinical pharmacists’ reported approaches and processes for undertaking Home Medicines Review services: A national survey. Arch Gerontol Geriatr 2023; 109: 104965.
On-site aged care pharmacists: are we ready for this new scope of practice?
To improve medication management in Australian residential aged care facilities, one recommendation from the Royal Commission into Aged Care Quality and Safety was to engage on-site pharmacists.1 Enabled by a federal funding commitment, the pharmacy workforce is preparing for this emerging role.
A national survey of 643, mainly consultant pharmacists, investigated factors influencing pharmacist interest and preparedness and those factors considered important for the success of the role. Responses to free-text survey questions were thematically analysed. Demographics and experience details were also collected.
Factors influencing interest included details of the role: the employment model, autonomy, opportunities to use clinical skills and to engage and be accepted into interprofessional and facility teams. Interest was influenced by circumstances of the pharmacist, with driving factors being a consultant pharmacist or having aged care experience. Familiarity with the aged care setting, communication skills and experience with systems-level quality use of medicines activities influenced preparedness. The success of the model was perceived as dependent upon the attributes of the pharmacist, the pharmacy workforce, support for the role and engagement of facilities.
Government, medical and pharmacy organisations are united in agreement that to improve medication safety in Australian aged care facilities, investment and expertise are required. Many are eager to understand the optimal model for implementation. The survey responses did not indicate doubt of clinical ability, but that pharmacists’ attributes, skills and experience were key to the uptake of the role. Although this research found that the model matters, it also suggested that an iterative and flexible process will be the key to success, rather than it being prescriptive at the outset.
Cross AJ, Hawthorne D, Lee K, O'Donnell LK, Page AT. Factors influencing pharmacist interest and preparedness to work as on-site aged care pharmacists: insights from qualitative analysis of free-text survey responses. Arch Gerontol Geriatr 2023; 110: 104971.
- Royal Commission Into Aged Care Quality and Safety. Final Report: Care, Dignity and Respect. Canberra: Commonwealth of Australia; 2021.
WOMEN'S AND NEWBORN HEALTH
MedsScan Editor for #SHPAWomenNewborn: Kate Luttrell
Psychiatric Manifestations of Domperidone Withdrawal When Used as a Galactagogue
Domperidone is commonly used off-label to increase breast milk production. While there is evidence of its efficacy, there have been significant safety concerns, particularly relating to potential QT-interval prolongation and the subsequent risk of ventricular arrhythmias. Neuropsychiatric effects have also been reported.
This article describes three subjects taking domperidone as a galactagogue who reported significant neuropsychiatric adverse effects during treatment withdrawal. All subjects were from the United States and consumed 90–150 mg/day of domperidone for five weeks to eight months before attempts were made to stop treatment and withdrawal symptoms developed. Withdrawal symptoms involved insomnia, severe anxiety, depression and intrusive thoughts (including suicidality). Symptoms only improved once domperidone therapy was reinstated or the dose was increased to its previous level, with little benefit noted from prescribing of psychotropics.
This report provides further supporting evidence to limit treatment to the lowest effective dose for the shortest possible duration. Users of domperidone are advised to taper their dose when stopping treatment, however, there remains no consensus on best approaches to dose tapering. A common regimen suggests reducing the dose by 10 mg/day each week, but a slower approach may be necessary in some cases.
Importantly, Majdinasab et al., showed early dismissal of symptoms thought to be related to postpartum anxiety or depression (rather than domperidone) and hesitancy of individuals to divulge domperidone use to treating healthcare professionals. This raises relevant points for practitioners working in this setting.
Majdinasab E, Haque S, Stark A, Krutsch K, Hale TW. Psychiatric manifestations of withdrawal following domperidone used as a galactagogue. Breastfeed Med 2022; 17: 1018–24.
Reducing the pain of opioid consumption post-caesarean section
Opioid analgesics are commonly prescribed for pain relief following caesarean section (CS). Despite their known risks to mother and baby, many developed countries have seen dramatic rises in opioid prescribing rates in recent years, including Australia. This highlights the need for continued efforts to address excessive opioid supply.
A retrospective cohort study was conducted in a United States hospital in women (over the age of 18 years) undergoing CS. A multi-pronged quality improvement activity was implemented with the aim of minimising post-caesarean opioid usage. This initiative involved development of an electronic postpartum prescribing order set, education of physicians and nursing staff and data-driven performance feedback. Prescribing habits and opioid consumption were compared, six months before and after implementation.
Following implementation, median inpatient opioid use decreased from 75 mg to 30 mg morphine (or equivalent), a reduction of over 60%. Additionally, there were less opioids prescribed on discharge, and more patients discharged without an opioid prescription. Importantly, despite this reduction in opioid use, patient-reported pain scores slightly decreased post-intervention. This data shows it is possible to reduce opioid consumption post caesarean section without adversely affecting patients’ pain control.
Many Australian hospitals have developed innovative strategies to minimise opioid use, from guideline development, formulary restrictions and education campaigns, to formalised opioid stewardship programs. However, there is a noticeable lack of evidence within an obstetric setting. This study addresses this research gap and provides potential strategies that could be successfully implemented in an Australian obstetric unit.
Llarena NC, Krivanek K, Yao M, Kim DD, Devarajan J, Ayad S, et al. A multimodal approach to reducing post-caesarean opioid use: a quality improvement initiative. BJOG2022; 129: 1583–90.
Guideline to manage neonatal pain for minor surgeries
Opioids are effective for the management of neonatal postoperative pain and are frequently prescribed despite their potential risks. Given the limited availability of published evidence-based guidelines, practices vary significantly between providers and institutions.
An interdisciplinary pain and sedation work group (including a pharmacist) developed an evidence-based pain management guideline (PMG) for neonates undergoing minor surgical procedures in a large level IV neonatal intensive care unit. The overarching goal of the project was to reduce opioid use without compromising pain control, by using principles of opioid stewardship. Specifically: promoting the use of nonopioids; using clinical decision support; educating clinicians; involving an interdisciplinary team; and incorporating information technology.
The PMG was used for 32 neonates, and overall showed a reduction in opioid use by 88%. Fifty-six percent of neonates received only paracetamol and no opioids, 32% required <0.15 mg/kg dose equivalent of morphine, and only 9% required >0.15 mg/kg dose equivalent of morphine. This is compared to pre-implementation rates of 100% opioid use and 0% non-opioid analgesic use post-operatively. It is difficult to generalise the results of this project due to the relatively small number of neonates and the short duration of the project. However, it provides a useful example of a systematic approach to standardising practice.
This quality improvement activity highlights how pharmacists can be involved in similar initiatives, and reiterates the use of electronic prescribing sets, interdisciplinary teamwork, regular review and adjustment of clinical processes in implementing any practice change. Discussion of using appropriate age-specific tools for assessing and managing neonatal patients is also relevant to practitioners in this setting.
David L, Forrest S. Development and implementation of a neonatal pain management guideline for minor surgeries. Adv Neonat Care 2022; 22: 391–9.