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Introduction: Workforce development is a key strategy for building the capacity and capability of a workforce. Accordingly, rural and remote practising allied health professionals require relevant and accessible continuing professional development to enhance their knowledge and skills and improve consumer health outcomes. This study explored the impact of an online postgraduate allied health rural generalist education program, from the perspective of allied health professionals participating in the program and their supervisors and managers. Methods: A qualitative, exploratory descriptive study design was employed using semistructured interviews. This study formed the qualitative component of a larger convergent mixed-methods evaluation study aimed at evaluating the reach, quality and impact of an online rural generalist education program for allied health professionals in Australia. Allied health professionals from seven professions enrolled in an online postgraduate rural generalist education program, the rural generalist program (RGP). Their designated work-based supervisors and their managers who were responsible for the operational management of the study sites were invited to participate in the study. All participants were employed in rural and remote health services in 10 sites across four Australian states. Study participants' experience and perceptions of the impact of the RGP on themselves, the healthcare service and the broader community were explored using semistructured interviews. Data were thematically analysed site by site, then across sites using Braun and Clarke's (2012) systematic six-phase approach. Provisional codes were generated and iteratively compared, contrasted and collapsed into secondary, more advanced codes until final themes and subthemes were developed. Results: Semistructured interviews were conducted with 23 allied health professionals enrolled in the RGP and their 27 work-based supervisors and managers across the 10 study sites. Three final themes were identified that describe the impact of the RGP: building capability as rural generalist allied health professionals; recruiting and building a rural workforce; enhancing healthcare services and consumer outcomes. Conclusion: Allied health professionals working in rural and remote locations valued the RGP because it provided accessible postgraduate education that aligned with their professional and clinical needs. Integrated into a supportive, well-structured development pathway, the experience potentiated learning and facilitated safe clinical practice that met the needs of consumers and organisations. The findings demonstrate that effective work-integrated learning strategies can enhance the development of essential capabilities for rural practice and support early-career allied health professionals' transition to rural and remote practice. These experiences can engage allied health professionals in a way that engenders a desire to remain working in rural and remote contexts.

IntroductionA high burden of unintentional fatal drowning has been reported in low- and middle-income countries. However, little is known about unintentional drowning in Indonesia.MethodsThis population-based retrospective cohort study analysed unintentional drowning data for Indonesia sourced from The Global Burden of Disease Study 2019. Estimates of trends, mortality rates, incidence rates, years lived with disability (YLDs) and disability adjusted life years were generated.ResultsA decline in unintentional drowning mortality rates was observed, with an average annual mortality rate of 2.58/100 000. Males were 1.81 (95% CI 1.79 to 1.84) times more likely than females to unintentionally drown. Average annual mortality rates were highest among the under-5 age group (9.67/100 000) and 70 and over (5.71/100 000 for males; 5.14/100 000 for females). Distributions of drowning deaths vary depending on region, with mortality rates higher in Papua, Kalimantan, Sulawesi, Maluku, Sumatra and Nusa Tenggara regions.DiscussionWhile a decline in drowning mortality rates in Indonesia was identified between 2005 and 2019, mortality rates for unintentional drowning remained high among children under 5 years, the elderly population and those residing in Papua, Kalimantan, Sulawesi, Maluku, Sumatra and Nusa Tenggara, warranting further focused attention.ConclusionA downward trend in the rate of unintentional drowning deaths in Indonesia is observed from 2005 onwards, with risk variation based on age, gender and region. The findings highlight the importance of addressing drowning as a cause of premature mortality and health system burden in Indonesia, including through enhancing drowning data collection systems and identifying drowning risk factors.

Introduction: Health promotion is a key component of comprehensive primary health care. Health promotion approaches complement healthcare management by enabling individuals to increase control over their health. Many primary healthcare staff have a role to play in health promotion practice, but their ability to integrate health promotion into practice is influenced by their previous training and experience. For primary healthcare staff working in rural and remote locations, access to professional development can be limited by what is locally available and prohibitive in terms of cost for travel and accommodation. This study provides insight into how staff at a large north Queensland Aboriginal community controlled health service access skill development and health promotion expertise to support their work. Methods: A qualitative exploratory study was conducted. Small group and individual semi-structured interviews were conducted with staff at Apunipima Cape York Health Council ('n'=9). A purposive sampling method was used to recruit participants from a number of primary healthcare teams that were more likely to be involved in health promotion work. Both on-the-ground staff and managers were interviewed. All participants were asked how they access skill development and expertise in health promotion practice and what approaches they prefer for ongoing health promotion support. The interviews were transcribed verbatim and analysed thematically. Results: All participants valued access to skill development, advice and support that would assist their health promotion practice. Skill development and expertise in health promotion was accessed from a variety of sources: conferences, workshops, mentoring or shared learning from internal and external colleagues, and access to online information and resources. With limited funds and limited access to professional development locally, participants fostered external and internal organisational relationships to seek in-kind advice and support. Irrespective of where the advice came from, it needed to be applicable to work with Aboriginal and Torres Strait Islander remote communities. Conclusions: To improve health outcomes in rural and remote communities, the focus on health promotion and prevention approaches must be strengthened. Primary healthcare staff require ongoing access to health promotion skill development and expertise to increase their capacity to deliver comprehensive primary health care. Practice-based evidence from staff working in the field provides a greater understanding of how skill development and advice are accessed. Many of these strategies can be formalised through organisational plans and systems, which would ensure that a skilled health promotion workforce is sustained.

A phase II clinical trial with single-agent decitabine was conducted in older patients (≥60 years) with previously untreated acute myeloid leukemia (AML) who were not candidates for or who refused intensive chemotherapy. Subjects received low-dose decitabine at 20 mg/m² i.v. over 1 h on days 1 to 10. Fifty-three subjects enrolled with a median age of 74 years (range, 60-85). Nineteen (36%) had antecedent hematologic disorder or therapy-related AML; 16 had complex karyotypes (≥3 abnormalities). The complete remission rate was 47% (n = 25), achieved after a median of three cycles of therapy. Nine additional subjects had no morphologic evidence of disease with incomplete count recovery, for an overall response rate of 64% (n = 34). Complete remission was achieved in 52% of subjects presenting with normal karyotype and in 50% of those with complex karyotypes. Median overall and disease-free survival durations were 55 and 46 weeks, respectively. Death within 30 days of initiation of treatment occurred in one subject (2%), death within 8 weeks in 15% of subjects. Given the DNA hypomethylating effect of decitabine, we examined the relationship of clinical response and pretreatment level of miR-29b, previously shown to target DNA methyltransferases. Higher levels of miR-29b were associated with clinical response (P = 0.02). In conclusion, this schedule of decitabine was highly active and well tolerated in this poor-risk cohort of older AML patients. Levels of miR-29b should be validated as a predictive factor for stratification of older AML patients to decitabine treatment.

Age is the dominant risk factor for most chronic human diseases, but the mechanisms through which ageing confers this risk are largely unknown 1 . The age-related acquisition of somatic mutations that lead to clonal expansion in regenerating haematopoietic stem cell populations has recently been associated with both haematological cancer 2 – 4 and coronary heart disease 5 —this phenomenon is termed clonal haematopoiesis of indeterminate potential (CHIP) 6 . Simultaneous analyses of germline and somatic whole-genome sequences provide the opportunity to identify root causes of CHIP. Here we analyse high-coverage whole-genome sequences from 97,691 participants of diverse ancestries in the National Heart, Lung, and Blood Institute Trans-omics for Precision Medicine (TOPMed) programme, and identify 4,229 individuals with CHIP. We identify associations with blood cell, lipid and inflammatory traits that are specific to different CHIP driver genes. Association of a genome-wide set of germline genetic variants enabled the identification of three genetic loci associated with CHIP status, including one locus at TET2 that was specific to individuals of African ancestry. In silico-informed in vitro evaluation of the TET2 germline locus enabled the identification of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. Overall, we observe that germline genetic variation shapes haematopoietic stem cell function, leading to CHIP through mechanisms that are specific to clonal haematopoiesis as well as shared mechanisms that lead to somatic mutations across tissues. Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes) 1 . In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%. The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Background Malaria remains a significant public health burden, necessitating evidence-based strategies to reduce prevalence and associated morbidity. This study explores the potential of integrated healthcare, encompassing both modern and traditional herbal medicine (THM), for malaria control in Ghana. Methods Employing a qualitative approach, semi-structured interviews were conducted with medical doctors, pharmacists, and THM providers. Thematic analysis approach was utilized to inductively analyse interview data and integrate participants’ lived experiences and suggestions. Results Six themes emerged: Standardization of THM practice; Training on THM broadened; Research on THM expanded; Increasing awareness of THM integration hospitals and inclusion of THM in national health insurance scheme; Constant supply of certified herbal medications; and Tax relief provision. These recommendations form the ‘STRICT’ framework for developing functional health system for promoting an effective malaria control through integrated healthcare in Ghana. Conclusion It was evident that the ‘STRICT’ framework can potentially transform healthcare delivery and improve service quality for malaria patients. Policymakers, healthcare providers, and managers can utilize these insights to advocate for and implement integrated healthcare strategies, ultimately enhancing service delivery for all Ghanaians, particularly those suffering from malaria.

In patients who had undergone stem-cell transplantation, lenalidomide maintenance therapy improved progression-free and overall survival, though at the expense of some increased hematologic toxicity and second malignant tumors. A goal of therapy for multiple myeloma, to induce complete remission and prolong survival, is usually accomplished with combination therapy. 1 , 2 Autologous hematopoietic stem-cell transplantation is often used after induction chemotherapy to improve the response or to consolidate complete remission. 1 , 2 However, since most patients with multiple myeloma have disease recurrence or progression after transplantation, maintenance therapies have been used to prolong complete remission and prevent relapse or progressive disease. Low-dose melphalan, interferon alfa, and glucocorticoids have been used for maintenance after primary therapy, but their long-term use is limited by toxicity and modest efficacy. 3 – 6 Five studies involving patients who . . .

Analyses of data from genome-wide association studies on unrelated individuals have shown that, for human traits and diseases, approximately one-third to two-thirds of heritability is captured by common SNPs. However, it is not known whether the remaining heritability is due to the imperfect tagging of causal variants by common SNPs, in particular whether the causal variants are rare, or whether it is overestimated due to bias in inference from pedigree data. Here we estimated heritability for height and body mass index (BMI) from whole-genome sequence data on 25,465 unrelated individuals of European ancestry. The estimated heritability was 0.68 (standard error 0.10) for height and 0.30 (standard error 0.10) for body mass index. Low minor allele frequency variants in low linkage disequilibrium (LD) with neighboring variants were enriched for heritability, to a greater extent for protein-altering variants, consistent with negative selection. Our results imply that rare variants, in particular those in regions of low linkage disequilibrium, are a major source of the still missing heritability of complex traits and disease. Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

Background The integration of herbal and orthodox medicines has gained momentum in global health, ensuring improved management of infectious diseases like malaria. This study explored the experiences of medical herbalists working in Ghana’s diverse ecological zones to understand the contributions of integrated healthcare to malaria control. Methods A phenomenological design was employed to conduct in-depth interviews with 19 purposively sampled medical herbalists. Framework analytical approach and Donabedian’s conceptual framework for quality of care were utilised in analysing the data. Results Findings revealed high awareness of integrated healthcare practices among participants. Medical herbalists perceived integrated care as instrumental in enhancing malaria management through factors such as improved quality assurance, increased accessibility to integrated health facilities, patient-centred care, follow-up practices, and opportunities for continuous professional development. However, structural and process-related challenges were identified, including inadequate healthcare personnel, medicines, and equipment. Additionally, limited promotional activities, non-comprehensive National Health Insurance Scheme (NHIS), and ineffective referral systems were recognised as barriers hindering the effectiveness of the integrated system and its potential contribution to malaria control. Conclusion Although national and health system-based challenges have thwarted the importance of integration on malaria control, medical herbalists feel optimistic about the intervention. To optimise the effectiveness of integrated healthcare in controlling malaria in Ghana would require policy modification and implementation. Future research could focus on developing healthcare frameworks, particularly for malaria, that prioritise quality service delivery within an integrated system.