Exploring Adaptive Phenotypes for the Human Calcium-Sensing Receptor Polymorphism R990G.

Rainforest hunter-gatherers from Southeast Asia are characterized by specific morphological features including a particularly dark skin color (D), short stature (S), woolly hair (W), and the presence of steatopygia (S)-fat accumulation localized in the hips (DSWS phenotype). Based on previous evidence in the Andamanese population, we first characterized signatures of adaptive natural selection around the calcium-sensing receptor gene in Southeast Asian rainforest groups presenting the DSWS phenotype and identified the R990G substitution (rs1042636) as a putative adaptive variant for experimental follow-up. Although the calcium-sensing receptor has a critical role in calcium homeostasis by directly regulating the parathyroid hormone secretion, it is expressed in different tissues and has been described to be involved in many biological functions. Previous works have also characterized the R990G substitution as an activating polymorphism of the calcium-sensing receptor associated with hypocalcemia. Therefore, we generated a knock-in mouse for this substitution and investigated organismal phenotypes that could have become adaptive in rainforest hunter-gatherers from Southeast Asia. Interestingly, we found that mouse homozygous for the derived allele show not only lower serum calcium concentration but also greater body weight and fat accumulation, probably because of enhanced preadipocyte differentiation and lipolysis impairment resulting from the calcium-sensing receptor activation mediated by R990G. We speculate that such differential features in humans could have facilitated the survival of hunter-gatherer groups during periods of nutritional stress in the challenging conditions of the Southeast Asian tropical rainforests.

Decentralised clinical trials in rural Australia: Opportunities and challenges.

AIMS: To present opportunities and a model to redress the under-representation of rural communities and people in Australian clinical trials. CONTEXT: Clinical trials are essential for building and understanding the health evidence base. The lack of representation of rural people in clinical trials is evident in other countries. Examining the Australian New Zealand Clinical Trial Registry (ANZCTR) suggests this is also the case in Australia. APPROACH: We propose an approach that empowers rurally based academics and clinicians to co-design clinical trials and increase rural Australians' participation in clinical trials to address this inequality of access. A case study of a decentralised, co-designed clinical trial is presented to support this approach. CONCLUSION: Decentralising clinical trials could improve access to clinical trials, strengthen the social capital of rural communities and help address the health inequalities that exist between rural and metropolitan communities.

Supporting nursing and allied health student placements in rural and remote Australia: a narrative review of publications by university departments of rural health.

University departments of rural health are Commonwealth-funded to improve recruitment and retention of the rural allied health and nursing (including midwifery) workforce, primarily through student placements. We examined publications by university departments of rural health that were focused on allied health and nursing students undertaking placements in rural Australia, to understand the characteristics, main findings and implications of the research conducted. Interprofessional learning was a key feature of placements and placement education, although other activities such as community engagement added to placement experiences. Factors such as quality supervision and being involved in the community contributed to a positive placement experience and increased rural practice intention. Tracking studies showed a relationship between rural placements, rural practice intention and rural practice. Rural placements occurred across a variety of settings and in locations consistent with the policy framework. Embedding university departments of rural health in rural communities enabled staff to build relationships and increase placement capacity.

Do undertaking rural placements and place of origin inform where allied health graduates work in South Australia?

OBJECTIVE: To examine the principal place of practice after graduation of students who participated in the Rural Health Multidisciplinary Training (RHMT) program and allied health students' place of origin. DESIGN: Cross-sectional study. PARTICIPANTS: Graduates who completed their degree in podiatry, occupational therapy and physiotherapy in 2019. MAIN OUTCOME MEASURES: Principal place of practice at first and third years after graduation. RESULTS: In 2020, 40 allied health professionals (AHPs) who graduated from the University of South Australia in 2019 were practising in rural areas but only 26 of them remained in the rural practice in 2022. The retention rate for rural practice was 65% within 2 years. However, in 2022, 25 allied health professionals left their metropolitan employment location and transitioned to rural practice. Of the 25 allied health graduates who joined the rural practice in 2022, most of them (80%, 20/25) had either rural exposure through the RMHT program or were from rural origin. CONCLUSIONS: Rural exposure via the RHMT program and allied health students' rural place of origin have an important role for rural principal place of practice at first and third years after graduation.

Geographical distribution of 3 allied health professions in South Australia: A summary of access and disadvantage.

OBJECTIVE: To describe the distribution of 3 allied health professionals-occupational therapists, physiotherapists and podiatrists-in South Australia stratified by the Modified Monash Model and the Index of Relative Socio-Economic Disadvantage. DESIGN: A descriptive data linkage cross-sectional study. SETTING: The state of South Australia, Australia. PARTICIPANTS AND MAIN OUTCOME MEASURES: Distribution of the 3 registered allied health professional groups stratified by Modified Monash Model and Index of Relative Socio-Economic Disadvantage. RESULTS: The largest proportion of the 3 allied health professional groups (occupational therapists, physiotherapists and podiatrists) were found in areas classified as Modified Monash 1 and Modified Monash 2 (86.5%). The lowest proportion of allied health professionals were found in Modified Monash 7. The largest number of allied health professionals per 10 000 population was found in areas classified as Modified Monash 1 and Modified Monash 2. The lowest number of allied health professionals per 10 000 population was found in Modified Monash 7 areas. The largest number of allied health professionals per 10 000 population was found in areas with Index of Relative Socio-Economic Disadvantage quintile 2, while the lowest number of allied health professionals per 10 000 population was found in areas with Index of Relative Socio-Economic Disadvantage quintile 1. CONCLUSIONS: The distribution of allied health professionals according to geographical remoteness, socio-economic disadvantage and per 10 000 population varies widely in South Australia. The number of allied health professionals per 10 000 population was lowest in rural and remote/very remote areas, explaining the typically poor access to allied health services for communities in these areas. The number of allied health professionals per 10 000 population according to Index of Relative Socio-Economic Disadvantage was variable within the context of both urban and rural areas.

Positive selection in admixed populations from Ethiopia.

BACKGROUND: In the process of adaptation of humans to their environment, positive or adaptive selection has played a main role. Positive selection has, however, been under-studied in African populations, despite their diversity and importance for understanding human history. RESULTS: Here, we have used 119 available whole-genome sequences from five Ethiopian populations (Amhara, Oromo, Somali, Wolayta and Gumuz) to investigate the modes and targets of positive selection in this part of the world. The site frequency spectrum-based test SFselect was applied to idfentify a wide range of events of selection (old and recent), and the haplotype-based statistic integrated haplotype score to detect more recent events, in each case with evaluation of the significance of candidate signals by extensive simulations. Additional insights were provided by considering admixture proportions and functional categories of genes. We identified both individual loci that are likely targets of classic sweeps and groups of genes that may have experienced polygenic adaptation. We found population-specific as well as shared signals of selection, with folate metabolism and the related ultraviolet response and skin pigmentation standing out as a shared pathway, perhaps as a response to the high levels of ultraviolet irradiation, and in addition strong signals in genes such as IFNA, MRC1, immunoglobulins and T-cell receptors which contribute to defend against pathogens. CONCLUSIONS: Signals of positive selection were detected in Ethiopian populations revealing novel adaptations in East Africa, and abundant targets for functional follow-up.

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.

Teleconsultation Between Patients and Health Care Professionals in the Catalan Primary Care Service: Message Annotation Analysis in a Retrospective Cross-Sectional Study.

BACKGROUND: Over the last decade, telemedicine services have been introduced in the public health care systems of several industrialized countries. In Catalonia, the use of eConsulta, an asynchronous teleconsultation service between primary care professionals and citizens in the public health care system, has already reached 1 million cases. Before the COVID-19 pandemic, the use of eConsulta was growing at a monthly rate of 7%, and the growth has been exponential from March 15, 2020 to the present day. Despite its widespread usage, there is little qualitative evidence describing how this tool is used. OBJECTIVE: The aim of this study was to annotate a random sample of teleconsultations from eConsulta, and to evaluate the level of agreement between health care professionals with respect to the annotation. METHODS: Twenty general practitioners retrospectively annotated a random sample of 5382 cases managed by eConsulta according to three aspects: the type of interaction according to 6 author-proposed categories, whether the practitioners believed a face-to-face visit was avoided, and whether they believed the patient would have requested a face-to-face visit had eConsulta not been available. A total of 1217 cases were classified three times by three different professionals to assess the degree of consensus among them. RESULTS: The general practitioners considered that 79.60% (4284/5382) of the teleconsultations resulted in avoiding a face-to-face visit, and considered that 64.96% (3496/5382) of the time, the patient would have made a face-to-face visit in the absence of a service like eConsulta. The most frequent uses were for management of test results (26.77%, 1433/5354), management of repeat prescriptions (24.30%, 1301/5354), and medical enquiries (14.23%, 762/5354). The degree of agreement among professionals as to the annotations was mixed, with the highest consensus demonstrated for the question "Has the online consultation avoided a face-to-face visit?" (3/3 professionals agreed 67.95% of the time, 827/1217), and the lowest consensus for the type of use of the teleconsultation (3/3 professionals agreed 57.60% of the time, 701/1217). CONCLUSIONS: This study shows the ability of eConsulta to reduce the number of face-to-face visits for 55% (79% × 65%) to 79% of cases. In comparison to previous research, these results are slightly more pessimistic, although the rates are still high and in line with administrative data proxies, showing that 84% of patients using teleconsultations do not make an in-person appointment in the following 3 months. With respect to the type of consultation performed, our results are similar to the existing literature, thus providing robust support for eConsulta's usage. The mixed degree of consensus among professionals implies that results derived from artificial intelligence tools such as message classification algorithms should be interpreted in light of these shortcomings.

Is there adaptation in the human genome for taste perception and phase I biotransformation?

BACKGROUND: During the modern human expansion, new environmental pressures may have driven adaptation, especially in genes related to the perception of ingested substances and their detoxification. Consequently, positive (adaptive) selection may have occurred in genes related to taste, and in those related to the CYP450 system due to its role in biotransformation of potentially toxic compounds. A total of 91 genes (taste receptors and CYP450 superfamily) have been studied using Hierarchical Boosting, a powerful combination of different selection tests, to detect signatures of recent positive selection in three continental human populations: Northern Europeans (CEU), East Asians (CHB) and Africans (YRI). Analyses have been refined with selection analyses of the 26 populations of 1000 Genomes Project Phase 3. RESULTS: Genes related to taste perception have not been positively selected in the three continental human populations. This finding suggests that, contrary to results of previous studies, different allele frequencies among populations in genes such as TAS2R38 and TAS2R16 are not due to positive selection but to genetic drift. CYP1 and CYP2 genes, also previously considered to be under positive selection, did not show signatures of selective sweeps. However, three genes belonging to the CYP450 system have been identified by the Hierarchical Boosting as positively selected: CYP3A4 and CYP3A43 in CEU, and CYP27A1 in CHB. CONCLUSIONS: No main adaptive differences are found in known taste receptor genes among the three continental human populations studied. However, there are important genetic adaptations in the cytochrome P450 system related to the Out of Africa expansion of modern humans. We confirmed that CYP3A4 and CYP3A43 are under selection in CEU, and we report for the first time CYP27A1 to be under positive selection in CHB.

Effect of Behavioral Activation for Women with Postnatal Depression: A Systematic Review and Meta-Analysis.

Evidence shows that behavioral activation (BA), a simple form of psychological therapy, is as effective as the more complex psychological therapy-cognitive behavioral therapy (CBT)-in treating general depression. However, it remains unclear whether BA when compared with treatment-as-usual (TAU) has greater contributions in reducing postnatal depression. This systematic review compared the effect of BA versus TAU in reducing depression symptoms among postnatal women. Five databases (MEDLINE, Embase, Emcare, Cochrane Library, and PsycINFO) were searched. Risk of bias was assessed using the Cochrane Collaboration's 'risk-of-bias 2 tool'. A random-effects meta-analysis was conducted to examine the effect of BA on postnatal depression. Of 2844 initial studies, only two randomized control trials (RCTs) met the inclusion criteria. The overall quality of evidence of these two RCTs was low. When compared to TAU, meta-analysis showed that BA was associated with reduced depression symptoms in postnatal women (standard mean difference -0.56; 95% confidence interval -0.76 to -0.37). This review suggests that BA might be more effective than TAU for alleviating postnatal depression. However, due to concerns about evidence quality, these findings should be interpreted cautiously.

Australian trial of behavioural activation for people with schizophrenia experiencing negative symptoms: a feasibility randomised controlled trial protocol.

INTRODUCTION: Negative symptoms are frequently experienced by people with schizophrenia. People with negative symptoms often have impaired social functioning and reduced quality of life. There is some evidence that cognitive-behavioural therapy results in a modest reduction in negative symptoms. Behavioural activation may be an effective alternative treatment for negative symptoms.The study aims to examine the feasibility and acceptability of implementing a behavioural activation trial delivered in three community mental health services in South Australia to support adult consumers experiencing negative symptoms of schizophrenia. METHOD AND ANALYSIS: This randomised controlled study will recruit a total of 60 consumers aged 18 years or above with mild-moderate negative symptoms of schizophrenia. The consumers will be randomly allocated to receive behavioural activation plus usual mental healthcare or usual mental healthcare alone. The intervention group will receive twelve 30 min sessions of behavioural activation, which will be delivered twice weekly over 6 weeks. In addition, we aim to recruit nine mental health workers from the three rural mental health services who will complete a 10-week online training programme in behavioural activation. Changes in negative symptoms of schizophrenia and depressive symptoms will be assessed at three time points: (a) at baseline, at 6 weeks and 3 month follow-ups. Changes in health-related quality of life (Short Form F36; secondary outcome) will be assessed at two time points: (a) at baseline and (b) immediately at postintervention after 6 weeks. At the end of the trial, interviews will be conducted with purposively selected mental health workers and consumers. Descriptive statistics and thematic analysis will be used to assess feasibility and acceptability. ETHICS AND DISSEMINATION: The findings from our feasibility study will inform the design of a fully powered randomised controlled trial to test the effectiveness of behavioural activation as a treatment for negative symptoms in schizophrenia. The study protocol was approved by the Central Adelaide Local Health Network Human Research Ethics Committee. The findings from this study will be disseminated through peer-reviewed scientific journals and conferences. TRIAL REGISTRATION NUMBER: ACTRN12623000348651p.

Behavioural activation for people in custody with depression: A protocol for a feasibility randomised controlled study.

People in custody are at high risk of developing depression. Accessing psychological treatments in a prison setting is a particular challenge, in part, due to difficulties accessing specialist mental health workers. Behavioural Activation (BA) may be helpful in improving health outcomes for people in custody experiencing depressive symptoms. The aim of this study is to establish the feasibility and acceptability of custodial health nurses delivering BA to improve depressive symptoms of people in custody. We will conduct a pilot randomised controlled trial with process observation examining the feasibility and acceptability of BA in treating people in custody with depressive symptoms. 60 people in custody presenting with depressive symptoms will be randomised to receive BA plus treatment as usual (TAU) or TAU provided by custodial health nurses. Eight custodial health nurses will be recruited, trained, and deliver BA. BA will be delivered twice a week for six weeks, with sessions lasting up to 30 minutes. Changes in depression and quality of life (QoL) will be assessed at baseline, 6 weeks, and 3 months post-intervention. Participants will be interviewed to understand feasibility and acceptability of BA in prison settings. The findings will inform the design of a randomised controlled trial to test the efficacy of BA for people in custody with depression. Findings will help determine whether BA for depression is suited to prison health care system and services. Improving depressive symptoms in people in custody has benefits beyond prison settings. The Central Adelaide Local Health Network Human Research Ethics Committee and University of South Australia Human Research Ethics Committee have approved the study. The trial results will be disseminated through peer-reviewed journals and scientific conferences and reported to local stakeholders and policy makers. If feasibility and acceptability is demonstrated, we will seek to progress to an effectiveness study. A potential strength of the trial model proposed, is in its scalability, with potential to increase the trial sites and locations. This trial has been prospectively registered with the Australian New Zealand Clinical Trials Registry (reference number: ACTRN12623000346673p). Trial registration ACTRN12623000346673p.

Optimising intravenous salbutamol in children: a phase 2 study.

OBJECTIVE: The ß2-agonists such as salbutamol are the mainstay of asthma management. Pharmacokinetic-pharmacodynamic (PKPD) models to guide paediatric dosing are lacking. We explored the relationship between salbutamol dose, serum concentration, effectiveness and adverse effects in children by developing a PKPD model. DESIGN: A prospective cohort study of children admitted to hospital with acute asthma, who received intravenous salbutamol. SETTING: Children were recruited in two cohorts: the emergency departments of two London hospitals or those retrieved by the Children's Acute Transport Service to three London paediatric intensive care units. PATIENTS: Patients were eligible if aged 1-15 years, admitted for acute asthma and about to receive or receiving intravenous salbutamol. INTERVENTIONS: Treatment was according to local policy. Serial salbutamol plasma levels were taken. Effectiveness measurements were recorded using the Paediatric Asthma Severity Score (PASS). Toxicity measurements included lactate, pH, glucose, heart rate, blood pressure and arrhythmias. PKPD modelling was performed with non-linear mixed-effect models. MAIN OUTCOMES: Fifty-eight children were recruited with 221 salbutamol concentration measurements from 54 children. Median (range) age was 2.9 (1.1-15.2) years, and weight was 13.6 (8-57.3) kg. Ninety-five PASS measurements and 2078 toxicity measurements were obtained. RESULTS: A two-compartment PK model adequately described the time course of salbutamol-plasma concentrations. An EMAX (maximum drug effect) concentration-effect relationship described PASS and toxicity measures. PKPD simulations showed an infusion of 0.5 µg/kg/min (maximum 20 µg/min) for 4 hours after bolus achieves >90% maximal bronchodilation for 12 hours. CONCLUSIONS: A paediatric PKPD model for salbutamol is described. An infusion of 0.5 µg/kg/min after bolus achieves effective bronchodilation. Higher rates are associated with greater tachycardia and hyperglycaemia.

Efficacy of behavioural activation in the treatment of negative symptoms in people with schizophrenia spectrum disorders: A systematic review.

Background: Negative symptoms, frequently experienced by people with schizophrenia, can impair functional outcomes and quality of life. Negative symptoms typically affect motivation, communication, and the ability to live independently and are difficult to treat. Several meta-analyses suggest that cognitive behavioural therapy results in a modest reduction in negative symptoms. It is unclear if similar effects can be achieved using behavioural activation. Behavioural activation is a derivative of cognitive behavioural therapy that helps to improve social and emotional functioning by encouraging patients to engage in activities that they value whilst modifying the avoidance responses. Behavioural activation can be a standalone treatment for depressive symptoms that is equally as efficacious as cognitive behavioural therapy. Objective: This systematic review aimed to identify and summarise the evidence about the efficacy of behavioural activation in treating negative symptoms. Design: Systematic review. Setting/Participants: Two published studies conducted in South Korea and the United Kingdom recruited 55 patients. Method: We searched five databases and four trial registries for clinical treatment trials of behavioural activation involving adults diagnosed with negative symptoms of schizophrenia. Studies were screened according to the inclusion criteria and assessed for quality. Results: We identified 5023 published studies. After removing duplicates and conducting screening, two studies were included in this review. One study used a parallel non-randomised trial design whilst the other adopted a single group test-re-test design. Fifty-five participants were recruited from hospital and community settings. Both studies delivered 10 face-to-face sessions of behavioural activation; these were individual in one study and group sessions in the other. One study involved behavioural activation as the treatment whilst the other delivered behavioural activation with motivational interviewing. Neither study reported harms or adverse events. Conclusions: Based on the included studies, there is low-quality evidence that behavioural activation may be helpful in the treatment of negative symptoms. Key limitations of the studies include small sample sizes and overall low study quality. Study registration: The protocol covering this review was registered with Open Science on 18 February 2022 (Registration DOI 10.17605/OSF.IO/57QSW; Weblink: https://osf.io/57qsw). Tweetable abstract: Behavioural activation holds promise in supporting patients experiencing negative symptoms of schizophrenia.

The distribution of registered occupational therapists, physiotherapists, and podiatrists in Australia.

BACKGROUND: In Australia, the distribution of occupational therapists, physiotherapists, and podiatrists density (per 10,000 population) by measure of location/rurality, usual resident population, and area-level socioeconomic status has not been described. OBJECTIVE: To describe the national as well as states-and territories-wide distribution of registered allied health workforce-occupational therapists, physiotherapists, and podiatrists-by measures of rurality and area-level socioeconomic position in Australia. METHODS: A linked data study that brings together (1) the location of health practitioners' principal place of practice from the Australian Health Practitioner Regulation Agency, (2) a measure of location/rurality-Modified Monash Model (MMM), and (3) an area-level measure of socioeconomic status-Index of Relative Socio-Economic Advantage and Disadvantage (IRSAD). The provider-to-population ratio (i.e., density) of three Australia's allied health workforce (occupational therapists, physiotherapists, and podiatrists) was calculated according to the MMM classifications (i.e., Modified Monash 1-7) and IRSAD quintiles at state and national level. RESULTS: Nationwide, the density of occupational therapists and physiotherapists was highest in metropolitan areas (Modified Monash 1) and decreased with the increasing levels of the MMM categories. The national density of podiatrists was highest in Modified Monash 3 areas. The density of occupational therapists, physiotherapists, and podiatrists was highest in areas with IRSAD quintile 5 (i.e., the highest socioeconomic position) and decreased with the declining levels of the IRSAD quintiles nationwide. Moreover, there were notable disparities in the density of occupational therapists, physiotherapists, and podiatrists across each state and territory in Australia when stratified by the MMM classifications and IRSAD quintiles. CONCLUSIONS: There was uneven distribution of registered occupational therapists, physiotherapists, and podiatrists when stratified by measures of location/rurality and area-level socioeconomic status across Australian jurisdictions. The density of these three groups of allied health workforce tended to be more concentrated in metropolitan and most advantaged areas while remote and most disadvantaged areas exhibited less allied health workforce distribution across each state and territory.

Promoting Comfort: A Clinician Guide and Evidence-Based Skin Care Plan in the Prevention and Management of Radiation Dermatitis for Patients with Breast Cancer.

Patients with breast cancer may be offered adjuvant radiation therapy (RT) after surgery. Up to 95% of these patients develop radiation dermatitis (RD) during or following RT. Randomized clinical trials and other literature provide evidence that RD can be prevented or reduced. The aim of this article is to propose a Clinician Guide and Evidence-based Skin Care Plan to prevent and/or reduce radiation dermatitis and promote the comfort of breast cancer patients receiving RT. As an integrative review, the databases searched were CINAHL and Medline, using the key terms: breast cancer, skin care, radiation, radiation therapy, radiotherapy, radiation dermatitis, and radiation skin reaction, prevention, and management. Search criteria included English language, full text, published between 2012 through 2020, and peer-reviewed. The search yielded 320 articles. Relevant articles were evaluated using the Quality Assessment Tool (QAT), and highly rated articles were selected to be included in the review of literature. The outcomes were the development of a Clinician Guide to offer holistic, patient-centered care and an Evidence-based Skin Care Plan. The research literature supports a standard skin care regimen, along with use of an emollient cream to the treatment area, use of deodorants depending on patient preferences, and application of a topical steroid cream daily throughout treatment and two weeks post RT. Clinician's weekly assessments of patients offers therapeutic support and ensures optimal skin care during and post-RT. The comfort of breast cancer patients receiving RT requires the best level of evidence regarding the efficacy of interventions, coupled with clinician's judgement, and patient's preferences and wishes. The clinician-patient relationship is essential in addressing the physical, emotional, social, spiritual, and functional challenges associated with a cancer diagnosis and adjunctive radiation therapy to improve long-term survival.

Use of behavioural activation to manage pain: a systematic scoping review.

BACKGROUND: Behavioural activation (BA) is an effective treatment for depression; however, it is unclear if it can be used to manage pain. OBJECTIVES: To conduct a scoping review of primary research that reported using BA to support people living with chronic pain to understand how BA had been used in relation to pain. In addition, we wanted to understand whether there were any reported changes in that pain, and how and who delivered BA. ELIGIBILITY CRITERIA: Primary research published in English. SOURCES OF EVIDENCE: We searched seven databases MEDLINE, Ovid Embase, Ovid Emcare, PsycINFO, CINAHL, Scopus and Web of Science, for primary research. No initial date limit was used with the date the searches were conducted used as the end date limit (1 July 2021). CHARTING METHODS: A customised data extraction table was developed, piloted and used. RESULTS: 551 papers were screened for inclusion, with 15 papers included in our review. Studies were conducted in North America and in Canada. These included three case studies, nine uncontrolled trials and three randomised controlled trials. Only two studies reported pain as the primary outcome. BA was applied across a range of pain related conditions. The dose of BA ranged from 3 to 16 sessions. Duration of treatment was 3 weeks to 12 months. Most studies reported reductions in pain following exposure to BA. CONCLUSION: BA has the potential to reduce pain. Caution needs to be exercised in the interpretation of these findings as a high risk of bias was observed in most studies. High-quality research is required to test if BA is an effective intervention for chronic pain.