Gabapentin for Pain in Pediatric Palliative Care.

OBJECTIVE: Gabapentin is commonly used to treat pain in children receiving pediatric palliative care. This study describes the real-world use of gabapentin and the associated benefits and adverse effects/events (AEs). METHODS: A prospective, multicenter cohort of standardized data collection after a clinical decision was made to use gabapentin for managing neuropathic or nociplastic pain in children attended on by a pediatric palliative care service. It was conducted across 11 sites in seven countries including hospital, inpatient, and outpatient services. Clinical outcomes were graded using pain scales validated for age and cognitive ability and the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE) at baseline, 14 days, 28 days, six weeks and 12 weeks after initiation of gabapentin. Ad-hoc safety reporting continued throughout the study. RESULTS: Data were collected from 127 children with a median age of 4.7 years (IQR 0.1-17.9); 61% had a neurological disorder, 21% advanced cancer and the cohort had a high level of disability (Lansky/Karnofsky performance score 37.1). Gabapentin was prescribed at standard pediatric doses. On average, 76% of children had a reduction in pain and 42% experienced a potential AE. The mean pain score decreased from 6.0 (SD 2.6) at baseline to 3.3 (SD 2.4) at 14 days and 1.8 (SD 1.8) after 12-weeks of gabapentin therapy. Ten percent had increased pain at each time point. AEs did not increase when individual changes over time were accounted for except for somnolence (7%). Serious AEs attributable to gabapentin were possible or probable in 3% of children. CONCLUSIONS: Gabapentin prescribed at standard doses for advanced cancer and severe neurological injury in children under a pediatric palliative care service was associated with generally improved pain intensity at previously described levels of adverse effects.

Lidocaine for Neuropathic Cancer Pain (LiCPain): study protocol for a mixed-methods pilot study.

INTRODUCTION: Many patients experience unrelieved neuropathic cancer-related pain. Most current analgesic therapies have psychoactive side effects, lack efficacy data for this indication and have potential medication-related harms. The local anaesthetic lidocaine (lignocaine) has the potential to help manage neuropathic cancer-related pain when administered as an extended, continuous subcutaneous infusion. Data support lidocaine as a promising, safe agent in this setting, warranting further evaluation in robust, randomised controlled trials. This protocol describes the design of a pilot study to evaluate this intervention and explains the pharmacokinetic, efficacy and adverse effects evidence informing the design. METHODS AND ANALYSIS: A mixed-methods pilot study will determine the feasibility of an international first, definitive phase III trial to evaluate the efficacy and safety of an extended continuous subcutaneous infusion of lidocaine for neuropathic cancer-related pain. This study will comprise: a phase II double-blind randomised controlled parallel-group pilot of subcutaneous infusion of lidocaine hydrochloride 10% w/v (3000 mg/30 mL) or placebo (sodium chloride 0.9%) over 72 hours for neuropathic cancer-related pain, a pharmacokinetic substudy and a qualitative substudy of patients' and carers' experiences. The pilot study will provide important safety data and help inform the methodology of a definitive trial, including testing proposed recruitment strategy, randomisation, outcome measures and patients' acceptability of the methodology, as well as providing a signal of whether this area should be further investigated. ETHICS AND DISSEMINATION: Participant safety is paramount and standardised assessments for adverse effects are built into the trial protocol. Findings will be published in a peer-reviewed journal and presented at conferences. This study will be considered suitable to progress to a phase III study if there is a completion rate where the CI includes 80% and excludes 60%. The protocol and Patient Information and Consent Form have been approved by Sydney Local Health District (Concord) Human Research Ethics Committee 2019/ETH07984 and University of Technology Sydney ETH17-1820. TRIAL REGISTRATION NUMBER: ANZCTR ACTRN12617000747325.

Cyclizine pharmacovigilance in hospice/palliative care: net effects for nausea or vomiting.

OBJECTIVES: To describe the contemporary real-world use of cyclizine for nausea or vomiting, and the associated benefits and harms. METHODS: This was a prospective, consecutive case series of routine clinical use of cyclizine for nausea or vomiting in palliative care conducted across 19 sites in Australia, Aotearoa/New Zealand and the UK. Clinical outcomes were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events at baseline and 72 hours after initiation of cyclizine. Ad hoc safety reporting continued for 2 weeks. RESULTS: Data were collected from 101 patients between May 2018 and December 2020. Cyclizine was mostly used in combination with another antiemetic. Overall, 79 patients benefited and 32 experienced harm (56 had benefit without harm; 9 had harm without benefit). The most common harms were constipation (13%), somnolence (9%) and confusion (7%), adding to the already high rates of these symptoms at baseline. For the four patients with serious harms (grade ≥3), these were exacerbations of existing symptoms. Nine patients stopped cyclizine at 72 hours and a further 20 patients within 2 weeks. The most common reasons for stopping were lack of benefit and symptom resolution; none stopped because of harms. CONCLUSIONS: When used as described in a palliative care setting, cyclizine benefits about three-quarters of patients, with about one-third experiencing tolerable harms.

The frequency of urinary tract infections and the value of antiseptics in community-dwelling people who undertake intermittent urinary catheterization: A systematic review.

BACKGROUND: This systematic review had 2 aims. First to identify the incidence of urinary tract infection (UTI) and bacteriuria in people undertaking intermittent catheterization (IC), second to determine the effectiveness of antiseptic cleaning of the meatal area prior to IC in reducing the incidence of UTI and bacteriuria. METHODS: A systematic review was conducted. Medline and the Cumulative Index to Nursing and Allied Health Literature electronic databases were systematically searched between January 1, 1990 and January 31, 2020, to identify studies that reported either the incidence of UTI or bacteriuria or the impact of using antiseptics for meatal cleaning prior to IC on incidence of these same outcomes. RESULTS: Twenty-five articles were identified for the first aim, 2 articles for the second. The proportion of participants experiencing ≥1 UTIs per year ranged from 15.4% to 86.6%. Synthesis of these studies suggest a combined incidence of 44.2% (95%CI 40.2%-48.5%) of participants having ≥1 UTIs per year. One of the 2 studies exploring the benefit of antiseptics in reducing UTI suggest some potential benefit of using chlorhexidine in reducing UTIs. Both studies have significant limitations, making interpretation difficult. CONCLUSIONS: A large proportion of people undertaking IC in the community have UTIs each year. Evidence on the role of antiseptics in the prevention of UTI for people who undertake IC remains unclear.

Beyond the black stump: rapid reviews of health research issues affecting regional, rural and remote Australia.

CHAPTER 1: RETAIL INITIATIVES TO IMPROVE THE HEALTHINESS OF FOOD ENVIRONMENTS IN RURAL, REGIONAL AND REMOTE COMMUNITIES: Objective: To synthesise the evidence for effectiveness of initiatives aimed at improving food retail environments and consumer dietary behaviour in rural, regional and remote populations in Australia and comparable countries, and to discuss the implications for future food environment initiatives for rural, regional and remote areas of Australia. STUDY DESIGN: Rapid review of articles published between January 2000 and May 2020. DATA SOURCES: We searched MEDLINE (EBSCOhost), Health and Society Database (Informit) and Rural and Remote Health Database (Informit), and included studies undertaken in rural food environment settings in Australia and other countries. DATA SYNTHESIS: Twenty-one articles met the inclusion criteria, including five conducted in Australia. Four of the Australian studies were conducted in very remote populations and in grocery stores, and one was conducted in regional Australia. All of the overseas studies were conducted in rural North America. All of them revealed a positive influence on food environment or consumer behaviour, and all were conducted in disadvantaged, rural communities. Positive outcomes were consistently revealed by studies of initiatives that focused on promotion and awareness of healthy foods and included co-design to generate community ownership and branding. CONCLUSION: Initiatives aimed at improving rural food retail environments were effective and, when implemented in different rural settings, may encourage improvements in population diets. The paucity of studies over the past 20 years in Australia shows a need for more research into effective food retail environment initiatives, modelled on examples from overseas, with studies needed across all levels of remoteness in Australia. Several retail initiatives that were undertaken in rural North America could be replicated in rural Australia and could underpin future research. CHAPTER 2: WHICH INTERVENTIONS BEST SUPPORT THE HEALTH AND WELLBEING NEEDS OF RURAL POPULATIONS EXPERIENCING NATURAL DISASTERS?: Objective: To explore and evaluate health and social care interventions delivered to rural and remote communities experiencing natural disasters in Australia and other high income countries. STUDY DESIGN: We used systematic rapid review methods. First we identified a test set of citations and generated a frequency table of Medical Subject Headings (MeSH) to index articles. Then we used combinations of MeSH terms and keywords to search the MEDLINE (Ovid) database, and screened the titles and abstracts of the retrieved references. DATA SOURCES: We identified 1438 articles via database searches, and a further 62 articles via hand searching of key journals and reference lists. We also found four relevant grey literature resources. After removing duplicates and undertaking two stages of screening, we included 28 studies in a synthesis of qualitative evidence. DATA SYNTHESIS: Four of us read and assessed the full text articles. We then conducted a thematic analysis using the three phases of the natural disaster response cycle. CONCLUSION: There is a lack of robust evaluation of programs and interventions supporting the health and wellbeing of people in rural communities affected by natural disasters. To address the cumulative and long term impacts, evidence suggests that continuous support of people's health and wellbeing is needed. By using a lens of rural adversity, the complexity of the lived experience of natural disasters by rural residents can be better understood and can inform development of new models of community-based and integrated care services. CHAPTER 3: THE IMPACT OF BUSHFIRE ON THE WELLBEING OF CHILDREN LIVING IN RURAL AND REMOTE AUSTRALIA: Objective: To investigate the impact of bushfire events on the wellbeing of children living in rural and remote Australia. STUDY DESIGN: Literature review completed using rapid realist review methods, and taking into consideration the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement for systematic reviews. DATA SOURCES: We sourced data from six databases: EBSCOhost (Education), EBSCOhost (Health), EBSCOhost (Psychology), Informit, MEDLINE and PsycINFO. We developed search terms to identify articles that could address the research question based on the inclusion criteria of peer reviewed full text journal articles published in English between 1983 and 2020. We initially identified 60 studies and, following closer review, extracted data from eight studies that met the inclusion criteria. DATA SYNTHESIS: Children exposed to bushfires may be at increased risk of poorer wellbeing outcomes. Findings suggest that the impact of bushfire exposure may not be apparent in the short term but may become more pronounced later in life. Children particularly at risk are those from more vulnerable backgrounds who may have compounding factors that limit their ability to overcome bushfire trauma. CONCLUSION: We identified the short, medium and long term impacts of bushfire exposure on the wellbeing of children in Australia. We did not identify any evidence-based interventions for supporting outcomes for this population. Given the likely increase in bushfire events in Australia, research into effective interventions should be a priority. CHAPTER 4: THE ROLE OF NATIONAL POLICIES TO ADDRESS RURAL ALLIED HEALTH, NURSING AND DENTISTRY WORKFORCE MALDISTRIBUTION: Objective: Maldistribution of the health workforce between rural, remote and metropolitan communities contributes to longstanding health inequalities. Many developed countries have implemented policies to encourage health care professionals to work in rural and remote communities. This scoping review is an international synthesis of those policies, examining their effectiveness at recruiting and retaining nursing, dental and allied health professionals in rural communities. STUDY DESIGN: Using scoping review methods, we included primary research - published between 1 September 2009 and 30 June 2020 - that reported an evaluation of existing policy initiatives to address workforce maldistribution in high income countries with a land mass greater than 100 000 km2 . DATA SOURCES: We searched MEDLINE, Ovid Embase, Ovid Emcare, Informit, Scopus, and Web of Science. We screened 5169 articles for inclusion by title and abstract, of which we included 297 for full text screening. We then extracted data on 51 studies that had been conducted in Australia, the United States, Canada, United Kingdom and Norway. DATA SYNTHESIS: We grouped the studies based on World Health Organization recommendations on recruitment and retention of health care workers: education strategies (n = 27), regulatory change (n = 11), financial incentives (n = 6), personal and professional support (n = 4), and approaches with multiple components (n = 3). CONCLUSION: Considerable work has occurred to address workforce maldistribution at a local level, underpinned by good practice guidelines, but rarely at scale or with explicit links to coherent overarching policy. To achieve policy aspirations, multiple synergistic evidence-based initiatives are needed, and implementation must be accompanied by well designed longitudinal evaluations that assess the effectiveness of policy objectives. CHAPTER 5: AVAILABILITY AND CHARACTERISTICS OF PUBLICLY AVAILABLE HEALTH WORKFORCE DATA SOURCES IN AUSTRALIA: Objective: Many data sources are used in Australia to inform health workforce planning, but their characteristics in terms of relevance, accessibility and accuracy are uncertain. We aimed to identify and appraise publicly available data sources used to describe the Australian health workforce. STUDY DESIGN: We conducted a scoping review in which we searched bibliographic databases, websites and grey literature. Two reviewers independently undertook title and abstract screening and full text screening using Covidence software. We then assessed the relevance, accessibility and accuracy of data sources using a customised appraisal tool. DATA SOURCES: We searched for potential workforce data sources in nine databases (MEDLINE, Embase, Ovid Emcare, Scopus, Web of Science, Informit, the JBI Evidence-based Practice Database, PsycINFO and the Cochrane Library) and the grey literature, and examined several pre-defined websites. DATA SYNTHESIS: During the screening process we identified 6955 abstracts and examined 48 websites, from which we identified 12 publicly available data sources - eight primary and four secondary data sources. The primary data sources were generally of modest quality, with low scores in terms of reference period, accessibility and missing data. No single primary data source scored well across all domains of the appraisal tool. CONCLUSION: We identified several limitations of data sources used to describe the Australian health workforce. Establishment of a high quality, longitudinal, linked database that can inform all aspects of health workforce development is urgently needed, particularly for rural health workforce and services planning. CHAPTER 6: RAPID REALIST REVIEW OF OPIOID TAPERING IN THE CONTEXT OF LONG TERM OPIOID USE FOR NON-CANCER PAIN IN RURAL AREAS: Objective: To describe interventions, barriers and enablers associated with opioid tapering for patients with chronic non-cancer pain in rural primary care settings. STUDY DESIGN: Rapid realist review registered on the international register of systematic reviews (PROSPERO) and conducted in accordance with RAMESES standards. DATA SOURCES: English language, peer-reviewed articles reporting qualitative, quantitative and mixed method studies, published between January 2016 and July 2020, and accessed via MEDLINE, Embase, CINAHL Complete, PsycINFO, Informit or the Cochrane Library during June and July 2020. Grey literature relating to prescribing,deprescribing or tapering of opioids in chronic non-cancer pain, published between January 2016 and July 2020, was identified by searching national and international government, health service and peek organisation websites using Google Scholar. DATA SYNTHESIS: Our analysis of reported approaches to tapering conducted across rural and non-rural contexts showed that tapering opioids is complex and challenging, and identified several barriers and enablers. Successful outcomes in rural areas appear likely through therapeutic relationships, coordination and support, by using modalities and models of care that are appropriate in rural settings and by paying attention to harm minimisation. CONCLUSION: Rural primary care providers do not have access to resources available in metropolitan centres for dealing with patients who have chronic non-cancer pain and are taking opioid medications. They often operate alone or in small group practices, without peer support and access to multidisciplinary and specialist teams. Opioid tapering approaches described in the literature include regulation, multimodal and multidisciplinary approaches, primary care provider support, guidelines, and patient-centred strategies. There is little research to inform tapering in rural contexts. Our review provides a synthesis of the current evidence in the form of a conceptual model. This preliminary model could inform the development of a model of care for use in implementation research, which could test a variety of mechanisms for supporting decision making, reducing primary care providers' concerns about potential harms arising from opioid tapering, and improving patient outcomes.