Pharmacovigilance in hospice/palliative care: rapid report of net clinical effect of metoclopramide

Background: Understanding the performance of prescribed medications in day-to-day practice is important to minimize harm, maximize clinical benefits, and, eventually, better target the people who are most likely to benefit, especially in hospice/palliative care where there may be limited time to optimize prescribing. Metoclopramide, a benzamide prokinetic antiemetic, is widely used for a number of indications including nausea, vomiting, hiccups, and reflux. It has recently had a new ‘‘black box’’ warning issued by the Food and Drug Administration in relation to tardive dyskinesia to limit use to 12 weeks. Methods: A consecutive cohort of patients from 12 participating centers in two countries who were having metoclopramide initiated had data collected at three time points—baseline, 2 days (clinical benefit), and day 7 (clinical harm). Additionally, harms could be recorded at any time. Results: Of the 53 people included in the cohort, 23 (43%) reported benefit at 48 hours, but only 18 (34%) of these people were still using it one week after commencing it. For the other 5, the medication was ceased due to harms. The most frequent harms were akathisia (n = 4), headache (n = 4), and abdominal pain (n = 4). Nine people (17%) had no clinical benefit and experienced harms. Conclusion: Overall, one in three people gained net clinical benefit at one week. Limiting effects include sideeffects that need to be sought actively in clinical care

Electrochemical Benzylic C(sp3)−H Acyloxylation

[Image: see text] The development of sustainable C(sp(3))–H functionalization methods is of great interest to the pharmaceutical and agrochemical industries. Anodic oxidation is an efficient means of producing benzylic cations that can undergo subsequent in situ nucleophilic attack to afford functionalized benzylic products. Herein, we demonstrate the suitability of carboxylic acids as nucleophiles to yield benzylic esters. This method employs a series of secondary benzylic substrates and functionalized carboxylic acids and is demonstrated on a gram scale in flow

Pharmacovigilance in hospice/palliative care: Net effect of haloperidol for delirium

Introduction: Prescribing practice in hospice/palliative care is largely extrapolated from other areas of clinical practice, with few studies of net medication effects (benefits and harms) in hospice/palliative care to guide prescribing decisions. Hospice/palliative care patients differ in multiple ways from better studied participant groups, hence the applicability of studies in other participant groups is uncertain. Haloperidol, a butyrophenone derivative and dopamine antagonist, is commonly prescribed for nausea, vomiting, and delirium in hospice/palliative care. Its frequent use in delirium occurs despite little evidence of the effect of antipsychotics on the untreated course of delirium. The aim of this study was to examine the immediate and short-term clinical benefits and harms of haloperidol for delirium in hospice/palliative care patients. Method: A consecutive cohort of participants from 14 centers across four countries who had haloperidol commenced for delirium were recruited. Data were collected at three time points: baseline, 48 hours (clinical benefits), and day 10 (clinical harms). Investigators were also able to report clinical harms at any time up to 14 days after it was commenced. Results: Of the 119 participants included, the average dose was 2.1 mg per 24 hours; 42 of 106 (35.2%) reported benefit at 48 hours. Harm was reported in 14 of 119 (12%) at 10 days, the most frequent being somnolence (n=11) and urinary retention (n=6). Seven participants had their medication ceased due to harms (2 for somnolence and 2 for rigidity). Approximately half (55/119) were still being treated with haloperidol after 10 days. Conclusion: Overall, 1 in 3 participants gained net clinical benefit at 10 days. © Copyright 2013, Mary Ann Liebert, Inc. 2013

Characterisation of dust emissions from machined engineered stones to understand the hazard for accelerated silicosis

Engineered stones are novel construction materials associated with a recent upsurge in silicosis cases among workers in the stonemason industry. In order to understand the hazard for the short latency of lung disease among stonemasons, we simulated real-time dust exposure scenario by dry-machining engineered stones in controlled conditions, capturing and analysing the respirable dust generated for physical and chemical characteristics. Natural granite and marble were included for comparison. Cutting engineered stones generated high concentrations of very fine particles ( 80% respirable crystalline silica content, in the form of quartz and cristobalite. Engineered stones also contained 8–20% resin and 1–8% by weight metal elements. In comparison, natural stones had far lower respirable crystalline silica (4- 30%) and much higher metal content, 29–37%. Natural stone dust emissions also had a smaller surface area than engineered stone, as well as lower surface charge. This study highlighted the physical and chemical variability within engineered stone types as well as between engineered and natural stones. This information will ultimately help understand the unique hazard posed by engineered stone fabrication work and help guide the development of specific engineering control measures targeting lower exposure to respirable crystalline silica.Chandnee Ramkissoon, Sharyn Gaskin, Leigh Thredgold, Tony Hall, Shelley Rowett, Richard Gu

Pharmacovigilance in hospice/palliative care: Net effect of gabapentin for neuropathic pain

Objective Hospice/palliative care patients may differ from better studied populations, and data from other populations cannot necessarily be extrapolated into hospice/palliative care clinical practice. Pharmacovigilance studies provide opportunities to understand the harms and benefits of medications in routine practice. Gabapentin, a γ-amino butyric acid analogue antiepileptic drug, is commonly prescribed for neuropathic pain in hospice/palliative care. Most of the evidence however relates to nonmalignant, chronic pain syndromes (diabetic neuropathy, postherpetic neuralgia, central pain syndromes, fibromyalgia). The aim of this study was to quantify the immediate and short-term clinical benefits and harms of gabapentin in routine hospice/palliative care practice. Design Multisite, prospective, consecutive cohort. Population 127 patients, 114 of whom had cancer, who started gabapentin for neuropathic pain as part of routine clinical care. Settings 42 centres from seven countries. Data were collected at three time points-at baseline, at day 7 (and at any time; immediate and shortterm harms) and at day 21 (clinical benefits). Results At day 21, the average dose of gabapentin for those still using it (n=68) was 653mg/24h (range 0-1800mg) and 54 (42%) reported benefits, of whom 7 (6%) experienced complete pain resolution. Harms were reported in 39/127 (30%) patients at day 7, the most frequent of which were cognitive disturbance, somnolence, nausea and dizziness. Ten patients had their medication ceased due to harms. The presence of significant comorbidities, higher dose and increasing age increased the likelihood of harm. Conclusions Overall, 42% of people experienced benefit at a level that resulted in continued use at 21 days

A before and after study of the impact of academic detailing on the use of diagnostic imaging for shoulder complaints in general practice

Background: The aim of this study was to assess the impact that Academic Detailing (AD) had on General Practitioners' use of diagnostic imaging for shoulder complaints in general practice and their knowledge and confidence to manage shoulder pain. Methods: One-to-one Academic Detailing (AD) for management of shoulder pain was delivered to 87 General Practitioners (GPs) in metropolitan Adelaide, South Australia, together with locally developed clinical guidelines and a video/DVD on how to examine the shoulder. Three months after the initial AD a further small group or an individual follow up session was offered. A 10-item questionnaire to assess knowledge about the shoulders was administered before, immediately after, and 3 months after AD, together with questions to assess confidence to manage shoulder complaints. The number of requests for plain film (X-ray) and ultrasound (US) imaging of the shoulder was obtained for the intervention group as well as a random comparison group of 90 GP's from the same two Divisions. The change in the rate of requests was assessed using a log Poisson GEE with adjustment for clustering at the practice level. A linear mixed effects model was used to analyse changes in knowledge. Results: In an average week 54% of GPs reported seeing fewer than 6 patients with shoulder problems. Mean (SD) GP knowledge score before, immediately after and 3-months after AD, was 6.2/10 (1.5); 8.6/10 (0.96) and; 7.2/10 (1.5) respectively (p < 0.0001). Three months after AD, GPs reported feeling able to take a more meaningful history, more confident managing shoulder pain, and felt their management of shoulder pain had improved. Requests for ultrasound imaging were approximately 43.8% higher in the period 2 years before detailing compared to six months after detailing (p < 0.0001), but an upward trend toward baseline was observed in the period 6 months to 1 year after AD. There was no statistically significant change in the rate of requests from before to after AD for plain-radiographs (p = 0.11). No significant changes in the rate of requests over time were observed in the control groups. Conclusion: These results provide evidence that AD together with education materials and guidelines can improve GPs' knowledge and confidence to manage shoulder problems and reduce the use of imaging, at least in the short term.Norm A Broadhurst, Christopher A Barton, Debra Rowett, Lisa Yelland, David K Matin, Angela Gialamas, and Justin J Beilb

Clinicians\u27 delirium treatment practice, practice change, and influences: A national online survey

Background: Recent studies cast doubt on the net effect of antipsychotics for delirium. Aim: To investigate the influence of these studies and other factors on clinicians’ delirium treatment practice and practice change in palliative care and other specialties using the Theoretical Domains Framework. Design: Australia-wide online survey of relevant clinicians. Setting/participants: Registered nurses (72%), doctors (16%), nurse practitioners (6%) and pharmacists (5%) who cared for patients with delirium in diverse settings, recruited through health professionals’ organisations. Results: Most of the sample (n=475): worked in geriatrics/aged (31%) or palliative care (30%); in hospitals (64%); and saw a new patient with delirium at least weekly (61%). More (59%) reported delirium practice change since 2016, mostly by increased non-pharmacological interventions (53%). Fifty-five percent reported current antipsychotic use for delirium, primarily for patient distress (79%) and unsafe behaviour (67%). Common Theoretical Domains Framework categories of influences on respondents’ delirium practice were: emotion (54%); knowledge (53%) and physical (43%) and social (21%) opportunities. Palliative care respondents more often reported: awareness of any named key study of antipsychotics for delirium (73% vs 39%, p\u3c0.001); decreased pharmacological interventions (60% vs 15%, p\u3c0.001); off-label medication use (86% vs 51%, p\u3c0.001); antipsychotics 79% vs 44%, p\u3c0.001); benzodiazepines 61% vs 26%, p\u3c0.001); and emotion as an influence (82% vs 39%, p\u3c0.001). Conclusion: Clinicians’ use of antipsychotic during delirium remains common and is primarily motivated by distress and safety concerns for the patient and others nearby. Supporting clinicians to achieve evidence-based delirium practice requires further work