PROTOCOL: Factors influencing the implementation of non-pharmacological interventions for behaviours and psychological symptoms of dementia in residential aged care homes: A systematic review and qualitative evidence synthesis.

This is a protocol for a Cochrane Review. The objectives are as follows. This paper aims to describe a protocol for a systematic review that will synthesise the qualitative evidence regarding factors influencing the implementation of non-pharmacological interventions (NPIs) for behavioural and psychological symptoms of dementia (BPSD) management in residential aged care homes (RACHs). The planned systematic review aims to answer the research question: 'What are the factors influencing the implementation of NPIs in the management of BPSD at RACHs?'. Additionally, the planned systematic review also aims to generate recommendations to guide stakeholders (e.g., clinicians and aged care staff) and policymakers in the implementation of NPIs for managing BPSD at RACHs.

Association Between Metabolically Different Adiposity Subtypes and Osteoarthritis: A Mendelian Randomization Study.

OBJECTIVE: In this Mendelian randomization (MR) study, the objective was to investigate the causal effect of metabolically different adiposity subtypes on osteoarthritis. METHODS: We performed 2-sample MR using summary-level data for osteoarthritis (10,083 cases and 40,425 controls) from a genome-wide association using the UK Biobank, and for site-specific osteoarthritis from the Arthritis Research UK Osteoarthritis Genetics consortium. We used 3 classes of genetic instruments, which all increase body mass index but are associated with different metabolic profiles (unfavorable, neutral, and favorable). Primary analysis was performed using inverse variance weight (IVW), with additional sensitivity analysis from different MR methods. We further applied a nonlinear MR using UK Biobank data to understand the nature of the adiposity-osteoarthritis relationship. RESULTS: Greater metabolically unfavorable and metabolically neutral adiposity were associated with higher odds of osteoarthritis (IVW odds ratio [OR] 1.56 [95% confidence interval (95% CI) 1.31, 1.85] and OR 1.60 [95% CI 1.15, 2.23], respectively). The estimate for the association between metabolically favorable adiposity and osteoarthritis was similar, although with notable imprecision (OR 1.55 [95% CI 0.70, 3.41]). Using site-specific osteoarthritis, metabolically unfavorable, neutral, and favorable adiposity were all associated with higher odds of knee osteoarthritis (OR 1.44 [95% CI 1.04, 1.98], OR 2.28 [95% CI 1.04, 4.99], and OR 6.80 [95% CI 2.08, 22.19], respectively). We found generally consistent estimates with a wider confidence interval crossing the null from other MR methods. The nonlinear MR analyses suggested a nonlinear relationship between metabolically unfavorable adiposity and osteoarthritis (Pnonlinear  = 0.003). CONCLUSION: Metabolic abnormalities did not explain the association between greater adiposity and the risk of osteoarthritis, which might suggest that the association is largely due to a mechanical effect on the joints.

Medicine-Induced Acute Kidney Injury Findings from Spontaneous Reporting Systems, Sequence Symmetry Analysis and a Case-Control Study with a Focus on Medicines Used in Primary Care.

INTRODUCTION: Primary care provides an opportunity to prevent community acquired, medicine or drug-induced acute kidney injury. One of the barriers to proactive prevention of medicine-induced kidney injury in primary care is the lack of a list of nephrotoxic medicines that are most problematic in primary care, particularly one that provides a comparison of risks across medicines. OBJECTIVE: The aim of this study was to consolidate evidence on the risks associated with medicines and acute kidney injury, with a focus on medicines used in primary care. METHOD: We searched the MEDLINE and EMBASE databases to identify published studies of all medicines associated with acute kidney injury identified from spontaneous report data. For each medicine positively associated with acute kidney injury, as identified from spontaneous reports, we implemented a sequence symmetry analysis (SSA) and a case-control design to determine the association between the medicine and hospital admission with a primary diagnosis of acute kidney injury (representing community-acquired acute kidney injury). Administrative claims data held by the Australian Government Department of Veterans' Affairs for the study period 2005-2019 were used. RESULTS: We identified 89 medicines suspected of causing acute kidney injury based on spontaneous report data and a reporting odds ratio above 2, from Japan, France and the US. Spironolactone had risk estimates of 3 or more based on spontaneous reports, SSA and case-control methods, while furosemide and trimethoprim with sulfamethoxazole had risk estimates of 1.5 or more. Positive association with SSA and spontaneous reports, but not case control, showed zoledronic acid had risk estimates above 2, while candesartan telmisartan, simvastatin, naproxen and ibuprofen all had risk estimates in SSA between 1.5 and 2. Positive associations with case-control and spontaneous reports, but not SSA, were found for amphotericin B, omeprazole, metformin, amlodipine, ramipril, olmesartan, ciprofloxacin, valaciclovir, mycophenolate and diclofenac. All with the exception of metformin and omeprazole had risk estimates above 2. CONCLUSION: This research highlights a number of medicines that may contribute to acute injury; however, we had an insufficient sample to confirm associations of some medicines. Spironolactone, furosemide, and trimethoprim with sulfamethoxazole are medicines that, in particular, need to be used carefully and monitored closely in patients in the community at risk of acute kidney injury.

Implementation and Evaluation of a Digitally Enabled Precision Public Health Intervention to Reduce Inappropriate Gabapentinoid Prescription: Cluster Randomized Controlled Trial.

BACKGROUND: Digital technologies can enable rapid targeted delivery of audit and feedback interventions at scale. Few studies have evaluated how mode of delivery affects clinical professional behavior change and none have assessed the feasibility of such an initiative at a national scale. OBJECTIVE: The aim of this study was to develop and evaluate the effect of audit and feedback by digital versus postal (letter) mode of delivery on primary care physician behavior. METHODS: This study was developed as part of the Veterans' Medicines Advice and Therapeutics Education Services (MATES) program, an intervention funded by the Australian Government Department of Veterans' Affairs that provides targeted education and patient-specific audit with feedback to Australian general practitioners, as well as educational material to veterans and other health professionals. We performed a cluster randomized controlled trial of a multifaceted intervention to reduce inappropriate gabapentinoid prescription, comparing digital and postal mode of delivery. All veteran patients targeted also received an educational intervention (postal delivery). Efficacy was measured using a linear mixed-effects model as the average number of gabapentinoid prescriptions standardized by defined daily dose (individual level), and number of veterans visiting a psychologist in the 6 and 12 months following the intervention. RESULTS: The trial involved 2552 general practitioners in Australia and took place in March 2020. Both intervention groups had a significant reduction in total gabapentinoid prescription by the end of the study period (digital: mean reduction of 11.2%, P=.004; postal: mean reduction of 11.2%, P=.001). We found no difference between digital and postal mode of delivery in reduction of gabapentinoid prescriptions at 12 months (digital: -0.058, postal: -0.058, P=.98). Digital delivery increased initiations to psychologists at 12 months (digital: 3.8%, postal: 2.0%, P=.02). CONCLUSIONS: Our digitally delivered professional behavior change intervention was feasible, had comparable effectiveness to the postal intervention with regard to changes in medicine use, and had increased effectiveness with regard to referrals to a psychologist. Given the logistical benefits of digital delivery in nationwide programs, the results encourage exploration of this mode in future interventions.

The Risk of Preoperative Central Nervous System-Acting Medications on Delirium Following Hip or Knee Surgery: A Matched Case-Control Study.

INTRODUCTION: Medicines acting on the central nervous system can increase the risk of postoperative delirium, but the specific medicines associated with greatest risk remain unclear. OBJECTIVES: We aimed to examine the risk of individual central nervous system-acting medicines used preoperatively on delirium after hip or knee surgery. METHODS: A matched case-control study was conducted using data from the Australian Government Department of Veterans' Affairs. We included people aged 65 years or older who had knee or hip surgery between 2000 and 2019. People with hip or knee surgery who developed postoperative delirium were cases and controls were people with hip or knee surgery but who did not develop postoperative delirium. Use of medicines including anxiolytics, sedatives, and hypnotics, opioid analgesics and antidepressants prior to surgery was compared between cases and controls. RESULTS: A total of 2614 patient cases with postoperative delirium were matched by same sex, age (±2 years), and year of admission (±2 years) with 7842 controls without postoperative delirium. Cases were more likely to be exposed to nitrazepam (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.24-2.64), sertraline (OR = 1.50, 95% CI 1.20-1.87), mirtazapine (OR = 1.38, 95% CI 1.11-1.74), venlafaxine (OR = 1.42, 95% CI 1.02-1.98), citalopram (OR = 1.54, 95% CI 1.19-1.99), escitalopram (OR = 1.42, 95% CI 1.06-1.89) or fluvoxamine (OR = 5.01, 95% CI 2.15-11.68) prior to surgery than controls. At the class level, exposure to benzodiazepines (OR = 1.20, 95% CI 1.05-1.37) and antidepressants (OR = 1.64, 95% CI 1.47-1.83) prior to surgery was significantly higher in cases than in controls. The numbers needed to treat to harm for one additional delirium case were 43 for sertraline, 40 for citalopram, 57 for mirtazapine and 26 for nitrazepam. Whereas, the numbers needed to treat to harm were found to be 20 for sertraline, 17 for citalopram, 19 for mirtazapine and 10 for nitrazepam in the 85 years or older age group, indicating that the harmful effect of these medicines is pronounced as age advances. CONCLUSIONS: People who developed delirium following hip or knee surgery were more likely to be exposed to nitrazepam, sertraline, mirtazapine, venlafaxine, citalopram, escitalopram or fluvoxamine at the time of admission for surgery. Planning to reduce use of these medicines well prior to surgery may decrease the risk of postoperative delirium.

Evaluation of Renal Function Testing in Older Australian Veterans Dispensed Medicines that Require Renal Function Monitoring.

INTRODUCTION: Renal function testing should be performed prior to initiating medicines that require dose adjustment in renal impairment, with ongoing monitoring in continued use, particularly in older people. There is little evidence regarding the extent to which renal function monitoring is performed in older Australians dispensed medicines requiring renal function monitoring. OBJECTIVE: The aim of this study was to determine the extent of renal function testing in older people dispensed medicines requiring renal function monitoring. METHODS: A retrospective analysis of administrative claims data from the Australian Government Department of Veterans' Affairs was conducted for people aged 65 years or older who were dispensed one or more medicines requiring renal function monitoring, from 1 June 2019 to 30 September 2019, to investigate the proportion of people with a claim for a pathology test that included creatinine levels in the 6-12 months before or after dispensing of a medicine requiring renal function monitoring. RESULTS: There were 100,113 people who were dispensed at least one medicine requiring renal function monitoring during the study period, of whom 15% had a history of renal impairment and 16% had diabetes mellitus. Sixty-one percent had a claim for a test in the prior 6 months; this increased to 80% of participants with a claim for a test in the prior 12 months. The rate of claims for testing was lower in aged care facility residents compared with people living in the community (54% vs 62% in the previous 6 months; p < 0.001), and was higher in people with diabetes (75% vs 58%; p < 0.001), history of renal impairment (91% vs 59%; p < 0.001) or heart failure (77% vs 60%; p < 0.001) compared with those without these conditions. CONCLUSION: Medicines that require renal function monitoring are commonly used in older Australians, and while the majority have claims for tests that include renal function, some are missing out.

Medication-related hospital admissions in aged care residents.

OBJECTIVE: To determine the prevalence of medication-related hospitalisations preceded by potentially suboptimal processes of care in aged care residents. METHOD: We conducted a retrospective analysis of administrative claims data from the Australian Government Department of Veterans' Affairs (DVA). We identified all hospital admissions for aged care residents between 1 July 2014 and 30 June 2019. The proportion of hospital admissions preceded by potentially suboptimal medication-related processes of care was determined. RESULTS: A total of 18 874 hospitalisations were included, and 46% were preceded by potentially suboptimal medication-related care. One-quarter of fracture admissions occurred in residents at risk of fracture who were not using a medicine to prevent fracture, and 87% occurred in residents using falls-risk medicines. Thirty per cent of heart failure admissions occurred in patients who were not using an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. CONCLUSION: Nearly half of hospital admissions were preceded by potentially suboptimal medication-related processes of care. Interventions to improve use of medicines for aged care residents in these areas are warranted.

Use of analgesics following rescheduling of codeine in Australia: An interrupted time series analysis in the veteran population.

BACKGROUND: The Australian medicines regulator, the Therapeutic Goods Administration (TGA), rescheduled all codeine-containing medicines to be available only on prescription on 1 February 2018. This study was conducted to determine whether use of analgesics changed following codeine re-scheduling to prescription only status, and whether there was a change in the use of codeine preparations and a therapeutic shift to stronger opioids or other analgesics in the Australian veteran population following the change. METHODS: Interrupted time series analysis using Repatriation Pharmaceutical Benefits Scheme (RPBS) claims data from the Australian Government Department of Veterans' Affairs (DVA) for clients with dispensing of opioid and non-opioid analgesics between January 2015 and April 2019. Trends in the monthly rate of analgesic dispensings (opioid and non-opioid) were compared for the period between January 2015 and January 2018 with the period February 2018 to April 2019. RESULTS: Paracetamol with codeine 8mg was the only analgesic with an increased rate of dispensing following the February 2018 codeine scheduling changes. Prior to codeine re-scheduling, the rate of dispensing of paracetamol with codeine 8mg was decreasing by 0.9% each month. Immediately after the scheduling changes, dispensing of paracetamol with codeine 8mg increased by 45% (95%CI=1.282-1.676, p<0.001) and in the fifteen month period thereafter (February 2018 to April 2019), the rate of dispensing increased by 4% each month (95%CI=1.027-1.054, p<0.001). Therapeutic shift from over-the-counter codeine products to other opioids was not observed, with no increase in the rate of dispensing of any of the other opioid (or non-opioid) analgesics following the codeine scheduling changes. CONCLUSION: A significant increase in prescription use of paracetamol with codeine 8mg was observed after the February 2018 codeine re-scheduling. Therapeutic shift to stronger opioid analgesics was not observed in the study population.

Prevalence and Duration of Use of Medicines Recommended for Short-Term Use in Aged Care Facility Residents.

BACKGROUND: Multiple studies have assessed the appropriateness of the use of medicines for nursing home residents; however, few have included duration of use in their assessment. The aim of this study was to assess the level and duration of use of medications recommended for short-term use in residents of aged care facilities in Australia. METHODS: Australian Government Department of Veterans' Affairs (DVA) administrative claims data were used for this study. Veterans eligible for all health services subsidised by DVA were followed for one year from 1 July 2015 to 30 June 2016. The number of days covered for each medicine was calculated by multiplying the number of prescriptions dispensed during the year by the pack duration for the medicine. The pack duration was calculated by dividing the quantity supplied at each dispensing by the usual number of doses per day in older people according to Australian prescribing guidelines. The proportion of patients using each medicine and the number of days covered during the study period were determined. RESULTS: 14, 237 residents met the inclusion criteria. One in five participants were dispensed antipsychotics, and the median duration of use was 180 days in the one-year period. More than one-third were dispensed a benzodiazepine, and the median duration of use was 240 days in the year. Half were dispensed an opioid analgesic with a median duration of use of 225 days in the year. Fifty-two percent were dispensed proton pump inhibitors with a median duration of use of 360 days in the year. A quarter received an antibiotic recommended for the management of urinary tract infection, with a median duration of use of 14 days in the year. CONCLUSION: Long-term use of antipsychotics, benzodiazepines, opioid analgesics and proton pump inhibitors is common in aged care residents. Ensuring appropriate duration of use for these medicines is necessary to reduce risk of harm.

Use of medicines that may precipitate delirium prior to hospitalisation in older Australians with delirium: An observational study.

OBJECTIVE: To assess the use of medicines associated with delirium prior to hospital admission in older Australian patients with a recorded diagnosis of delirium. METHODS: A retrospective observational study was conducted using de-identified data from the Australian Government Department of Veterans' Affairs Health Care Claims Database. The prevalence of use of medicines associated with delirium was determined in people 65 years or older with a delirium diagnosis. RESULTS: Three-quarters of the total 22 923 older patients included were taking at least one medicine associated with delirium, the median number of medications per patient was two (interquartile range, 1-3). The most frequently used medicines known to be associated with delirium were psycholeptics, opioids and tricyclic antidepressants. CONCLUSION: A substantial proportion of older hospitalised patients with a delirium diagnosis were taking medicines known or suspected to precipitate delirium prior to admission. There may be an opportunity to decrease medication-associated delirium by reducing use of risky medication.

Multicomponent Interventions Reduce High-Risk Medications for Delirium in Hospitalized Older Adults.

Delirium threatens the functional independence and cognitive capacity of patients. Medications, especially those with strong anticholinergic effects, have been implicated as a preventable cause of delirium. We evaluated the effect of multicomponent interventions aimed at reducing the use of 9 target medications in hospitalized older adults at risk of delirium. This continuous quality improvement program was undertaken at a tertiary care facility and 4 community hospitals in a hospital system. We included 21, 541 hospital admissions with patients aged 70 and older on acute care medical or surgical units from the preintervention (2012) period, and 27,764 from the postintervention (2015) period. Implemented interventions include formulary and policy changes, technology-assisted medication review, age-conditional order set modifications, best practice alerts, and education. The proportion of hospital admissions with individual's receiving at least 1 target medication declined from 45.6% to 31.3% (relative reduction (RR)=31.4%) from before to after the intervention, meaning that target medication exposure was avoided in approximately 4,000 older adults. The greatest effect was observed for zolpidem (11.2% to 5.3%, RR=52.6%) and diphenhydramine (12.9% to 7.1%, RR=45%). Furthermore, the mean number of doses administered during all hospital admissions was reduced for 7 of 9 medications. Multicomponent interventions implemented in our hospital system were effective at reducing exposure to target medications in hospitalized older adults at risk of delirium. These systematic changes applied throughout the medication use process are sustained today.

Do Risk Prediction Models for Postoperative Delirium Consider Patients' Preoperative Medication Use?

BACKGROUND: Medicines are potentially modifiable risk factors for postoperative delirium. However, the extent to which preoperative medicines are included in risk prediction models (RPMs) is unknown. OBJECTIVE: This systematic review aimed to assess the extent of inclusion of preoperative medications in RPMs for postoperative delirium. METHODS: Articles were systematically searched from MEDLINE, EMBASE and CINAHL using Medical Subject Headings (MeSH) where possible and keywords for postoperative delirium and prediction model. Studies published until May 2017 with a primary outcome of postoperative delirium that developed an RPM containing preoperative patient information were considered. Where a study had two cohorts, a derivation and a validation cohort, findings from the derivation cohort were extracted and reported. RESULTS: Eighteen prospective and one retrospective cohort studies were included for review. Of the 19 studies, only nine considered preoperative medication data, with medications appearing as predictor variables in five models. There was wide variability in the factors included in the final models, with the most frequent predictors being age and cognitive impairment, appearing in 13 (68%) and 11 (58%) RPMs, respectively. CONCLUSION: While medications are commonly cited risk factors for delirium, they are not adequately considered when developing RPMs. Future studies aiming to develop an RPM for postoperative delirium should include preoperative medication data as a potential predictor variable because of the modifiable nature of medication use and its impact on other factors commonly in models, such as cognition.

Preoperative medication use and postoperative delirium: a systematic review.

BACKGROUND: Medications are frequently reported as both predisposing factors and inducers of delirium. This review evaluated the available evidence and determined the magnitude of risk of postoperative delirium associated with preoperative medication use. METHODS: A systematic search in Medline and EMBASE was conducted using MeSH terms and keywords for postoperative delirium and medication. Studies which included patients 18 years and older who underwent major surgery were included. The methodological quality of included studies was assessed independently by two authors using the Newcastle-Ottawa quality assessment scale for cohort studies. RESULTS: Twenty-nine studies; 25 prospective cohort, three retrospective cohort and one post hoc analysis of RCT data were included. Only four specifically aimed to assess medicines as an independent predictor of delirium, all other studies included medicines among a number of potential predictors of delirium. Of the studies specifically testing the association with a medication class, preoperative use of beta-blockers (OR = 2.06[1.18-3.60]) in vascular surgery and benzodiazepines RR 2.10 (1.23-3.59) prior to orthopedic surgery were significant. However, evidence is from single studies only. Where medicines were included as one possible factor among many, hypnotics had a similar risk estimate to the benzodiazepine study, with one significant and one non-significant result. Nifedipine use prior to cardiac surgery was found to be significantly associated with delirium. The non-specific grouping of psychoactive medication use preoperatively was generally higher with an associated two-to-seven-fold higher risk of postoperative delirium, while only two studies included narcotics without other agents, with one significant and one non-significant result. CONCLUSIONS: There was a limited number of high quality studies in the literature quantifying the direct association between preoperative medication use and postsurgical delirium. More studies are required to evaluate the association of specific preoperative medications on the risk of postoperative delirium so that comprehensive guidelines for medicine use prior to surgery can be developed to aid delirium prevention. TRIAL REGISTRATION: This systematic review has been registered on PROSPERO International prospective register of systematic reviews (Registration number: CRD42016051245 ).

Current practice and opinions of hospital pharmacists regarding their role in the screening, prevention and treatment of delirium.

Background An interdisciplinary approach is fundamental for effective prevention and treatment of delirium. Pharmacists could play a role in identifying and resolving medication-related delirium. However, little is known about their role in delirium care. Objective The main purpose of this survey was to assess the current practice and opinions of pharmacists concerning their involvement in screening, prevention and treatment of delirium. Setting Pharmacists in public and private hospitals in Australia. Method A cross-sectional survey was conducted using a pilot tested web-based questionnaire which was distributed primarily via a link in the electronic newsletter of the Society of Hospital Pharmacists of Australia. Main outcome measure Number and proportion of respondents answering questions related to the practice and perceptions of pharmacists in delirium management. Results Responses from 106 pharmacists were included in the analysis. Most respondents believed that pharmacists could play a role in prevention (92%) and screening (62%) of patients for delirium. However, in practice only 8% of pharmacists reported that they had ever screened a patient for delirium using a validated tool and 79% indicated that pharmacists were never or rarely involved in delirium treatment. When pharmacists did make recommendations half of the respondents said that pharmacists' recommendations were frequently or always accepted by the delirium treating teams. Conclusion Hospital pharmacists are underutilised in the prevention and management of delirium. Strategies to increase their involvement in the prevention and management of delirium should be implemented.

Maternal outcomes of magnesium sulphate and diazepam use in women with severe pre-eclampsia and eclampsia in Ethiopia.

BACKGROUND: Preferred anticonvulsant used to treat and prevent fits in eclampsia currently is magnesium sulphate. Clinical monitoring of tendon reflexes, respiration rate and measuring hourly urine output should be done to ensures safe administration of magnesium sulphate. OBJECTIVE: This study was conducted to evaluate maternal outcomes of magnesium sulphate and diazepam use in the management of severe pre-eclampsia and eclampsia in Jimma University Specialized Hospital. METHODS: A retrospective hospital based cross-sectional comparative study was conducted using data collection format. Data was collected from the hospital delivery care register and patient chart records of all pregnant women who presented with the diagnosis of severe pre-eclampsia and eclampsia in two years and three months period from January, 2010 to April, 2012. Data analysis was done by SPSS version 16.0. A P-value of <0.05 was considered statistically significant in all tests. RESULTS: A total of 357 patient charts, 217 from magnesium sulphate and 140 from diazepam treated pregnant women group, were reviewed and analyzed. Three pregnant women from the magnesium sulphate treated group and eleven pregnant women from diazepam treated group had at least one convulsion after taking the drug. Greater proportion of patients in the magnesium sulphate treated group had less than four days postpartum stay as compared to the diazepam treated patients (82.3% versus 66.2%). Seizure occurrence, duration of postpartum hospital stays and birth outcome had a statistically significant association with the type of anticonvulsant used. CONCLUSIONS: Magnesium sulphate is more effective than diazepam in the management of severe pre-eclamptic and eclamptic pregnant women in terms of seizure prevention, shortening postpartum hospital stay and reducing maternal morbidities.