Supporting gut health with medicinal cannabis in people with advanced cancer: potential benefits and challenges.

The side effects of cancer therapy continue to cause significant health and cost burden to the patient, their friends and family, and governments. A major barrier in the way in which these side effects are managed is the highly siloed mentality that results in a fragmented approach to symptom control. Increasingly, it is appreciated that many symptoms are manifestations of common underlying pathobiology, with changes in the gastrointestinal environment a key driver for many symptom sequelae. Breakdown of the mucosal barrier (mucositis) is a common and early side effect of many anti-cancer agents, known to contribute (in part) to a range of highly burdensome symptoms such as diarrhoea, nausea, vomiting, infection, malnutrition, fatigue, depression, and insomnia. Here, we outline a rationale for how, based on its already documented effects on the gastrointestinal microenvironment, medicinal cannabis could be used to control mucositis and prevent the constellation of symptoms with which it is associated. We will provide a brief update on the current state of evidence on medicinal cannabis in cancer care and outline the potential benefits (and challenges) of using medicinal cannabis during active cancer therapy.

Population pharmacokinetics of posaconazole in allogeneic haematopoietic stem cell transplant patients.

BACKGROUND: Invasive fungal disease (IFD) in the early post-allogeneic HSCT (alloHCT) period is associated with increased likelihood of catastrophic outcomes. The utility of oral modified release (MR) posaconazole tablets is limited by reduced drug absorption from gastrointestinal toxicity induced by cytotoxic chemotherapy, necessitating a switch to the IV posaconazole formulation. OBJECTIVES: To describe the population pharmacokinetics of posaconazole for oral MR and IV formulations in alloHCT patients and determine dosing regimens likely to achieve therapeutic exposures. METHODS: We performed a prospective observational pharmacokinetic study in adult patients in the early post-alloHCT period requiring a change in posaconazole formulation (oral to IV). Samples were analysed using a validated LC-MS/MS method. Population pharmacokinetic analysis and Monte Carlo simulations (n = 1000) were performed using Pmetrics for R. RESULTS: Twenty patients aged between 21 and 70 years were included in the study. A two-compartment model, incorporating mucositis/diarrhoea to modify the bioavailability for oral administration best described the data. To achieve ≥90% PTA, simulations showed that higher than currently recommended doses of oral MR posaconazole were required for prophylaxis Cmin targets (≥0.5 and ≥0.7 mg/L), while increased doses of both formulations were required for IFD treatment PK/PD targets, with patients experiencing oral mucositis/diarrhoea unlikely to achieve these. CONCLUSIONS: Increased doses of posaconazole should be considered for both prophylaxis and treatment of IFD to increase the proportion of alloHCT patients achieving therapeutic exposures, particularly the oral formulation in patients with mucositis and/or diarrhoea. Posaconazole therapeutic drug monitoring should be considered for all formulations in this setting.

Improving the performance of machine learning penicillin adverse drug reaction classification with synthetic data and transfer learning.

BACKGROUND: Machine learning may assist with the identification of potentially inappropriate penicillin allergy labels. Strategies to improve the performance of existing models for this task include the use of additional training data, synthetic data and transfer learning. AIMS: The aims of this study were to investigate the use of additional training data and novel machine learning strategies, namely synthetic data and transfer learning, to improve the performance of penicillin adverse drug reaction (ADR) machine learning classification. METHODS: Machine learning natural language processing was applied to free-text penicillin ADR data extracted from a public health system electronic health record (EHR). The models were developed by training on various labelled data sets. ADR entries were split into training and testing data sets and used to develop and test a variety of machine learning models. The effect of training on additional data and synthetic data versus the use of transfer learning was analysed. RESULTS: Following the application of these techniques, the area under the receiver operator curve of best-performing models for the classification of penicillin allergy (vs intolerance) and high-risk allergy (vs low-risk allergy) improved to 0.984 (using the artificial neural network model) and 0.995 (with the transfer learning approach) respectively. CONCLUSIONS: Machine learning models demonstrate high levels of accuracy in the classification and risk stratification of penicillin ADR labels using the reaction documented in the EHR. The model can be further optimised by incorporating additional training data and using transfer learning. Practical applications include automating case detection for penicillin allergy delabelling programmes.

Population Pharmacokinetics of Ganciclovir in Allogeneic Hematopoietic Stem Cell Transplant Patients.

Treatment of cytomegalovirus (CMV) infection in allogeneic hematopoietic stem cell transplantation (alloHCT) patients with ganciclovir is complicated by toxicity and resistance. This study aimed to develop an intravenous ganciclovir population pharmacokinetic model for post-alloHCT patients and to determine dosing regimens likely to achieve suggested therapeutic exposure targets. We performed a prospective observational single-center pharmacokinetic study in adult alloHCT patients requiring treatment with intravenous ganciclovir for CMV viremia or disease. Samples were analyzed using a validated ultraperformance liquid chromatography method. Population pharmacokinetic analysis and Monte Carlo simulations (n = 1000) were performed using Pmetrics for R. Twenty patients aged 18 to 69 years were included in the study. A 2-compartment model with linear elimination from the central compartment and between occasion variability best described the data. Incorporating creatinine clearance (CLCR) estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and presence of continuous renal replacement therapy as covariates for ganciclovir clearance improved the model. Compared to current dosing recommendations, simulations demonstrated loading doses were required to achieve a target AUC24 of 80 to 120 mg.h/L on day 1 of induction therapy. Increased individualization of post-loading induction and maintenance doses based on CLCR is required to achieve the suggested exposures for efficacy (AUC24 >80/>40 mg.h/L for induction/maintenance) while remaining below the exposure thresholds for toxicity (AUC24 <120/<60 mg.h/L for induction/maintenance). Intravenous ganciclovir dosing in alloHCT patients can be guided by CLCR estimated by CKD-EPI. Incorporation of loading doses into induction dosing regimens should be considered for timely achievement of currently suggested exposures.

Prevalence of Trimethoprim-Sulfamethoxazole Adverse Reaction Mislabelling in Australia.

INTRODUCTION: Trimethoprim-sulfamethoxazole (TMP-SMX) is an important antibiotic, with the most compelling indications for Pneumocystis jirovecii pneumonia prophylaxis and methicillin-resistant Staphylococcus aureus treatment. Previous adverse reactions (AR) to TMP-SMX may limit the usability of TMP-SMX. Electronic medical record (EMR) of AR for other antibiotics has previously been shown to be inaccurate; however, the extent to which this occurs for TMP-SMX is unknown. METHODS: A multi-centre retrospective observational study was conducted for consecutive inpatient admissions over a 2.5-year period commencing 2020. Adverse reactions to TMP-SMX recorded in the EMR were collected and reviewed by two independent medical officers using pre-defined expert criteria for the classification of allergies and intolerances. RESULTS: TMP-SMX AR were present in the EMR of 759 individuals (prevalence 0.6%). The majority were labelled as allergy (725, 95.5%) rather than intolerance (34, 4.5%). Most common AR were rash, vomiting, and swelling. When classified against the gold-standard expert criteria, there were 437 allergies (57.6%) and 159 intolerances (21.0%). Overall, the number of incorrect EMR AR labels was 133/759 (17.5%). Both medical and surgical specialties had significant numbers of patients with TMP-SMX AR labels and incorrectly classified EMR AR labels. CONCLUSION: TMP-SMX AR labels affect inpatients admitted under multiple specialty units. The user-entered categorization as allergy or intolerance labels in EMRs are frequently used incorrectly. These incorrect labels may inappropriately contraindicate the use of TMP-SMX, and formal evaluation of TMP-SMX ARs with immunological assessment and relabelling where appropriate may increase the use of this agent.

Machine learning models automate classification of penicillin adverse drug reaction labels.

There is a growing interest in the appropriate evaluation of penicillin adverse drug reaction (ADR) labels. We have developed machine learning models for classifying penicillin ADR labels using free-text reaction descriptions, and here report external and practical validation. The models performed comparably with expert criteria for the categorisation of allergy or intolerance and identification of high-risk allergies. These models have practical applications in detecting individuals suitable for penicillin ADR evaluation. Implementation studies are required.

Artificial intelligence-enabled penicillin allergy delabelling: an implementation study.

Inaccurate penicillin allergy labels may be delabelled following evaluation. The intervention in this study was an email-based notification system regarding the appropriateness for penicillin allergy evaluation, with a view to delabelling, as identified by a deep learning artificial intelligence algorithm. Of the intervention group (n = 59), three (5.1%) individuals had their penicillin allergies delabelled, which was significantly more than the control group (0%, P = 0.002). Further research to optimise such approaches is required.

Artificial intelligence and the potential for perioperative delabeling of penicillin allergies for neurosurgery inpatients.

PURPOSE OF THE ARTICLE: Patients with penicillin allergy labels are more likely to have postoperative wound infections. When penicillin allergy labels are interrogated, a significant number of individuals do not have penicillin allergies and may be delabeled. This study was conducted to gain preliminary evidence into the potential role of artificial intelligence in assisting with perioperative penicillin adverse reaction (AR) evaluation. MATERIAL AND METHODS: A single-centre retrospective cohort study of consecutive emergency and elective neurosurgery admissions was conducted over a two-year period. Previously derived artificial intelligence algorithms for the classification of penicillin AR were applied to the data. RESULTS: There were 2063 individual admissions included in the study. The number of individuals with penicillin allergy labels was 124; one patient had a penicillin intolerance label. Of these labels, 22.4% were not consistent with classifications using expert criteria. When the artificial intelligence algorithm was applied to the cohort, the algorithm maintained a high level of classification performance (classification accuracy 98.1% for allergy versus intolerance classification). CONCLUSIONS: Penicillin allergy labels are common among neurosurgery inpatients. Artificial intelligence can accurately classify penicillin AR in this cohort, and may assist in identifying patients suitable for delabeling.

Optimizing antifungal prophylaxis in allogeneic stem cell transplantation: A cohort study of two different approaches.

BACKGROUND: Limited consensus exists on the optimal use of antifungal agents to prevent invasive fungal infection in the early post allogeneic hematopoietic stem cell transplant (alloHCT) period, particularly when patients cannot tolerate oral medication administration. METHODS: We undertook a retrospective observational cohort study to assess the tolerability, efficacy, and cost of a new antifungal prophylaxis pathway at a major tertiary alloHCT centre. Patients aged ≥16 years who underwent alloHCT between February 2018 and October 2019 (cohort 1) or between April 2020 and November 2021 (cohort 2) were included. In both cohorts, first line prophylactic therapy was oral posaconazole. The second line drugs where oral therapy was unable to be administered were intravenous voriconazole (cohort 1) versus intravenous posaconazole (cohort 2). RESULTS: There were 142 patients enrolled in the study, 71 in each cohort. The proportion of patients remaining on first-line prophylaxis or progressing to second-, third-, and fourth-line options was 22.5%, 39.4%, 29.6%, and 8.5% in cohort 1 and 39.4%, 59.2%, 1.4%, and 0% in cohort 2, respectively. The frequency of neuropsychiatric adverse events was significantly higher in cohort 1 compared to cohort 2 (49.3% vs. 19.8%, p = .0004). Occurrence of proven and probable fungal infections was not significantly different between cohorts. Antifungal drug expenditure was $359 935 (AUD) more in cohort 1 ($830 486 AUD) compared to cohort 2 ($477 149 AUD). CONCLUSION: The antifungal prophylaxis pathway used in cohort 2 resulted in reduced antifungal-associated adverse effects, less patients requiring progression to 3rd and 4th line prophylaxis and reduced antifungal drug costs.

Appropriateness of inpatient dosing of direct oral anticoagulants for atrial fibrillation.

Direct oral anticoagulant (DOAC) use for stroke prevention in atrial fibrillation (AF) has dose reduction criteria including age, weight, serum creatinine, and creatinine clearance. There is a paucity of data for rates of inappropriate inpatient DOAC dosing in Australia. The objective was to determine the rates of inappropriate inpatient DOAC dosing in AF and identifying its associated underlying factors. We conducted a retrospective cross-sectional study from December 2013 to November 2019 across six South Australian public hospitals utilising a centralised electronic health record. Multivariate analysis was used to identify factors associated with underdosing of patients prescribed apixaban. Of 1882 inpatients, 544 (28.9 %) were inappropriately dosed. Underdosing was the most common form of inappropriate dosing with rates of 22.9 % (n = 295), 7.1 % (n = 7), and 25.1 % (n = 124) for apixaban, dabigatran, and rivaroxaban, respectively. Independent factors predictive of apixaban underdosing included higher age (adjusted odds ratio (aOR) 1.63 [95 % Confidence Interval (CI): 1.47-1.81]), higher serum creatinine (aOR 1.13 [95 % CI: 1.08-1.19]), higher total number of drugs on discharge (aOR 1.08 [95 % CI: 1.04-1.11]), and being already prescribed a DOAC on admission (aOR 1.63 [95 % CI: 1.12-2.38]). Nearly one quarter of all apixaban prescribing was inappropriately underdosed. Older patients with multimorbidity, frailty and polypharmacy present a challenge for clinicians in balancing risks of thromboembolism and bleeding. It is likely prescribers are more conservative in their apixaban dosing in this population. Clinicians should consider alternative drug regimens to avoid DOAC use at inappropriate doses at unknown safety and efficacy.

Prevalence of drug allergy in South Australia.

BACKGROUND: Drug allergy is commonly reported in patient notes and electronic health records. The prevalence of self-reported drug allergy in the general Australian population has not previously been studied. AIMS: To investigate the prevalence of self-reported drug allergy in the general adult population in South Australia. METHODS: We surveyed a representative sample of the South Australian adult population regarding their own perception of drug allergy, including drug type and severity, as well as the use of medical alert devices. Data were weighted to correspond to age and sex of the South Australian population. RESULTS: Twenty-two percent of adults in South Australia consider themselves allergic to one or more drugs: 9.3% declared themselves to be allergic to penicillin, 5% to an antibiotic other than penicillin and 13% to one or more antibiotics. Drug allergy and penicillin allergy was significantly more prevalent in females and increased with age. Thirteen percent of those with an antibiotic allergy reported a severe reaction, of whom 27% wore a medical notification device. Of those allergic to penicillin, 75% had their index reaction more than 10 years ago and did not report severe features. CONCLUSION: Self-reported drug allergy is common in the general population, as it is in medical clinic and hospital populations. The majority of those reporting penicillin allergy would be considered low-risk and suitable for de-labelling procedures.

Cardiac Implantable Electronic Devices: Reoperations and the Competing Risk of Death.

BACKGROUND: The use of cardiac implantable electronic devices (CIED), which includes pacemakers, implantable cardioverter-defibrillators (ICD), cardiac resynchronisation therapy pacemakers (CRT-P) and cardiac resynchronisation therapy defibrillators (CRT-D) has increased over the past 20 years, but there is a lack of real world evidence on the longevity of these devices in the older population which is essential to inform health care delivery and support clinical decisions. METHODS AND RESULTS: We conducted a retrospective cohort study using data from the Australian Government Department of Veterans' Affairs database. The cohort consisted of people who had a CIED procedure between 2005 and 2015. The cumulative risk of generator replacement/reoperations was estimated accounting for the competing risk of death. A total of 16,662 patients were included. In pacemaker recipients with an average age of 85 years, the 5-year risk of reoperation ranged from 2.8% in single chamber, 3.6% in dual chamber to 7.6% in CRT-P recipients, while the 5-year risk of dying with the index pacemaker in situ was 63% in single chamber, 46% in dual chamber and 56% in CRT-P recipients. In defibrillator recipients with an average age of 80 years, the 5-year risk of reoperation ranged from 11% in single chamber, 13% in dual chamber to 24% in CRT-D recipients, while the 5-year risk of dying with the index defibrillator in situ was 46% in single chamber, 40% in dual chamber and 41% in CRT-D recipients. CONCLUSION: In this cohort of older patients the 5-year risk of generator reoperation was low in pacemaker recipients whereas up to one in four CRT-D recipients would have a reoperation within 5 years.

Evaluation of the prescribing practice of guideline-directed medical therapy among ambulatory chronic heart failure patients.

BACKGROUND: Studies have demonstrated that heart failure (HF) patients who receive direct pharmacist input as part of multidisciplinary care have better clinical outcomes. This study evaluated/compared the difference in prescribing practices of guideline-directed medical therapy (GDMT) for chronic HF patients between two multidisciplinary clinics-with and without the direct involvement of a pharmacist. METHODS: A retrospective audit of chronic HF patients, presenting to two multidisciplinary outpatient clinics between March 2005 and January 2017, was performed; a Multidisciplinary Ambulatory Consulting Service (MACS) with an integrated pharmacist model of care and a General Cardiology Heart Failure Service (GCHFS) clinic, without the active involvement of a pharmacist. RESULTS: MACS clinic patients were significantly older (80 vs. 73 years, p < .001), more likely to be female (p < .001), and had significantly higher systolic (123 vs. 112 mmHg, p < .001) and diastolic (67 vs. 60 mmHg, p < .05) blood pressures compared to the GCHF clinic patients. Moreover, the MACS clinic patients showed more polypharmacy and higher prevalence of multiple comorbidities. Both clinics had similar prescribing rates of GDMT and achieved maximal tolerated doses of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in HFrEF. However, HFpEF patients in the MACS clinic were significantly more likely to be prescribed ACEIs/ARBs (70.5% vs. 56.2%, p = 0.0314) than the GCHFS patients. Patients with both HFrEF and HFpEF (MACS clinic) were significantly less likely to be prescribed ß-blockers and mineralocorticoid receptor antagonists. Use of digoxin in chronic atrial fibrillation (AF) in MACS clinic was significantly higher in HFrEF patients (82.5% vs. 58.5%, p = 0.004), but the number of people anticoagulated in presence of AF (27.1% vs. 48.0%, p = 0.002) and prescribed diuretics (84.0% vs. 94.5%, p = 0.022) were significantly lower in HFpEF patients attending the MACS clinic. Age, heart rate, systolic blood pressure (SBP), anemia, chronic renal failure, and other comorbidities were the main significant predictors of utilization of GDMT in a multivariate binary logistic regression. CONCLUSIONS: Lower prescription rates of some medications in the pharmacist-involved multidisciplinary team were found. Careful consideration of demographic and clinical characteristics, contraindications for use of medications, polypharmacy, and underlying comorbidities is necessary to achieve best practice.

Documentation of adverse drug reactions to opioids in an electronic health record.

BACKGROUND: Allergy to opioids is the second most common drug allergy label in electronic health records (EHR). Adverse drug reactions (ADR) to opioids cause significant morbidity and contribute to healthcare costs, while incorrect opioid allergy labels may unnecessarily complicate patient management. AIMS: To examine the documentation of opioid ADR in a large-scale hospital-based EHR. METHODS: A cross-sectional retrospective review of EHR documentation of opioid ADR at four public hospitals in South Australia was conducted. Data were extracted from all ADR entries including the reported allergen, ADR category (allergy or intolerance) and reaction details. Expert criteria were used to determine consistency of ADR categorisation as allergy or intolerance. RESULTS: Of 86 727 unique ADR reports, there were 13 781 ADR to opioids with most being entered as allergy (n = 8913, 64.7%) rather than intolerance (n = 4868, 35.3%). The most commonly documented reactions were nausea/vomiting (n = 3912, 28%), rash (n = 647, 5%), itch (n = 642, 5%) and hallucinations (n = 527, 4%). There were 362 (3%) ADR labels of anaphylaxis. Of those ADR containing a reaction description (n = 11 868), 89% of reports entered as allergy had a reaction description that was consistent with intolerance and 8% of the entered intolerances had descriptions consistent with allergy when assessed using predefined criteria. CONCLUSIONS: This large EHR-based study demonstrates the high rate of opioid ADR labels in EHR. The majority of these labels were for symptoms suggestive of pharmacological intolerance. Reactions consistent with true allergy were uncommon. Systematic review of ADR by a dedicated clinical service would improve the accuracy of documentation.

Effectiveness of the Pharmacist-Involved Multidisciplinary Management of Heart Failure to Improve Hospitalizations and Mortality Rates in 4630 Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: There is evidence that heart failure (HF) patients who receive pharmacist care have better clinical outcomes. METHODS AND RESULTS: English-language peer-reviewed randomized controlled trials comparing the pharmacist-involved multidisciplinary intervention with usual care were included. We searched PubMed, MEDLINE, EMBASE, CINAHL, Web of Science, Scopus, and the Cochrane Library from inception through March 2017. Cochrane method for risk of bias was used to assess within and between studies. 18 RCTs (n = 4630) were included for systematic review, and 16 (n = 4447) for meta-analysis. Meta-analysis showed a significant reduction in HF hospitalizations {odds ratio (OR) 0.72 [95% confidence interval (CI) 0.55-0.93], P = .01, I2  =  39%} but no effect on HF mortality. Similarly, a significant reduction in all-cause hospitalizations [OR 0.76, 95% CI (0.60-0.96), P = .02, I2  =  52%] but no effect on all-cause mortality was revealed. The overall trend was an improvement in medication adherence. There were significant improvements in HF knowledge (P<.05), but no significant improvements were found on health care costs and self-care. CONCLUSIONS: The pharmacist is a vital member of a multidisciplinary team in HF management to improve clinical outcomes. There was a great deal of variability about which specific intervention is most effective in improving clinical outcomes.

Comprehension and recall from the informed consent process by phase I healthy volunteers before dose administration.

AIMS/BACKGROUND: A fundamental part of all clinical trials is informed consent, reflecting the respect for the volunteer's autonomy. Research participation is voluntary; therefore, certain aspects of the proposed study must be disclosed so that volunteers can make an informed decision. In this study, we aimed to examine the level of comprehension and recall of healthy volunteers from the informed consent process. METHODS: The study was carried out at a single phase I clinical trials unit. A questionnaire was administered to each volunteer to assess recall of important aspects of the study at the day-1 visit following the informed consent process. The questionnaire contained seven questions regarding study objectives, route, frequency and type of drug administration, adverse effects, number of subjects previously exposed and remuneration. One point was awarded for each correct answer. RESULTS: A total of 266 volunteers were administered the questionnaire. The mean total score (±standard deviation) for all volunteers was 4.5 ± 1.1 points out of 7, with a range of 0.8-6.7. For all 10 studies, 91% of volunteers responded correctly when answering about the route of administration, and 90% were able to accurately state the correct payment amount. Only 7% were able to repeat the aims of the study correctly. CONCLUSION: The poor performance of our study volunteers raises concerns about recall of information prior to study drug administration. This has implications for the volunteer's safety and ability to provide true informed consent. Interventions to improve recall prior to dosing should be undertaken.

Magnetic Resonance Imaging in People With Cardiac Implantable Electronic Devices: A Population Based Cohort Study.

Magnetic resonance imaging (MRI) is a widely used diagnostic tool with great benefits but has been considered contraindicated in people with cardiac implantable electronic devices (CIED). We investigated the occurrence of MRI in people with CIEDs and associated adverse events in a national cohort. Of 17,848 people included, 56 (0.3%) had at least one MRI; 16 of 16,102 (0.1%) with MRI non-compatible CIEDs and 40 of 1746 (2%) with MRI compatible CIEDs. Following MRI exposure, hospitalisations for potential serious adverse events were rare.

Understanding 30-day re-admission after hospitalisation of older patients for diabetes: identifying those at greatest risk.

OBJECTIVE: To identify factors that contribute to older Australians admitted to hospital with diabetes being re-hospitalised within 30 days of discharge. DESIGN, SETTING AND PARTICIPANTS: A retrospective cohort study of Department of Veterans' Affairs administrative data for all patients hospitalised for diabetes and discharged alive during the period 1 January - 31 December 2012. MAIN OUTCOME MEASURES: Causes of re-hospitalisation and prevalence of clinical factors associated with re-hospitalisation within 30 days of discharge. METHODS: Multivariate logistic regression analysis (backward stepwise) was used to identify characteristics predictive of 30-day re-hospitalisation. RESULTS: 848 people were hospitalised for diabetes; their median age was 87 years (interquartile range, 77-89 years) and 60% were men. 209 patients (24.6%) were re-hospitalised within 30 days of discharge, of whom 77.5% were re-admitted within 14 days of discharge. 51 re-hospitalisations (24%) were for diabetes-related conditions; 41% of those re-admitted within 14 days had not seen their general practitioner between discharge and re-admission. Factors predictive of re-hospitalisation included comorbid heart failure (adjusted odds ratio [aOR], 1.49; 95% confidence interval [CI], 1.03-2.17; P = 0.036), numbers of prescribers in previous year (aOR [for each additional prescriber], 1.06; 95% CI, 1.01-1.08; P = 0.031), and two or more hospitalisations in the 6 months before the index admission (aOR, 1.79; 95% CI 1.15-2.78; P = 0.009). CONCLUSION: Older people hospitalised for diabetes who have comorbid heart failure, multiple recent hospitalisations, and multiple prescribers involved in their care are at greatest risk of being re-admitted to hospital within 30 days. Targeted follow-up during the initial 14 days after discharge may facilitate appropriate interventions that avert re-admission of these at-risk patients.

Documentation of penicillin adverse drug reactions in electronic health records: inconsistent use of allergy and intolerance labels.

BACKGROUND: The majority of patients with penicillin allergy labels tolerate penicillins. Inappropriate avoidance of penicillin is associated with increased hospitalisation, infections and healthcare costs. AIMS: To examine the documentation of penicillin adverse drug reactions (ADR) in a large-scale hospital-based electronic health record. METHODS: Penicillin ADR were extracted from 96 708 patient records in the Enterprise Patient Administration System in South Australia. Expert criteria were used to determine consistency of ADR entry and suitability for further evaluation. RESULTS: Of 43 011 unique ADR reports, there were 5023 ADR to penicillins with most being entered as allergy (n = 4773, 95.0%) rather than intolerance (n = 250, 5.0%). A significant proportion did not include a reaction description (n = 1052, 20.9%). Using pre-set criteria, 10.1% of reports entered as allergy had a reaction description that was consistent with intolerance and 31.0% of the entered intolerances had descriptions consistent with allergy. Virtually all ADR (n = 4979, 99.1%) were appropriate for further evaluation by history taking or immunological testing and half (50.7%, n = 2549) had documented reactions suggesting low-risk of penicillin allergy. CONCLUSION: The frequency of penicillin allergy label in this data set is consistent with the known overdiagnosis of penicillin allergy in the hospital population. ADR documentation was poor with incomplete entries and inconsistent categorisation. The concepts of allergy and intolerance for ADR classification, whilst mechanistically valid, may not be useful at the point of ADR entry by generalist clinicians. Systematic evaluation of reported ADR is needed to improve the quality of information for future prescribers.

What is polypharmacy? A systematic review of definitions.

BACKGROUND: Multimorbidity and the associated use of multiple medicines (polypharmacy), is common in the older population. Despite this, there is no consensus definition for polypharmacy. A systematic review was conducted to identify and summarise polypharmacy definitions in existing literature. METHODS: The reporting of this systematic review conforms to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist. MEDLINE (Ovid), EMBASE and Cochrane were systematically searched, as well as grey literature, to identify articles which defined the term polypharmacy (without any limits on the types of definitions) and were in English, published between 1st January 2000 and 30th May 2016. Definitions were categorised as i. numerical only (using the number of medications to define polypharmacy), ii. numerical with an associated duration of therapy or healthcare setting (such as during hospital stay) or iii. Descriptive (using a brief description to define polypharmacy). RESULTS: A total of 1156 articles were identified and 110 articles met the inclusion criteria. Articles not only defined polypharmacy but associated terms such as minor and major polypharmacy. As a result, a total of 138 definitions of polypharmacy and associated terms were obtained. There were 111 numerical only definitions (80.4% of all definitions), 15 numerical definitions which incorporated a duration of therapy or healthcare setting (10.9%) and 12 descriptive definitions (8.7%). The most commonly reported definition of polypharmacy was the numerical definition of five or more medications daily (n = 51, 46.4% of articles), with definitions ranging from two or more to 11 or more medicines. Only 6.4% of articles classified the distinction between appropriate and inappropriate polypharmacy, using descriptive definitions to make this distinction. CONCLUSIONS: Polypharmacy definitions were variable. Numerical definitions of polypharmacy did not account for specific comorbidities present and make it difficult to assess safety and appropriateness of therapy in the clinical setting.