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Rationale & Objective: Little is known about hospital admissions in nondialysis patients with chronic kidney disease (CKD) before death or starting kidney replacement therapy (KRT). Study Design: Retrospective observational cohort study Setting & Participants: Hospitalizations among 7,201 patients with CKD from 10 public renal clinics in Queensland (QLD), enrolled in the CKD.QLD registry starting in May 2011, were followed for 25,496.34 person-years until they started receiving KRT or died, or until June 30, 2018. Predictors: Demographic and clinical characteristics of patients with CKD. Outcomes: Hospital admissions. Analytical Approach: We evaluated the association of demographic and clinical features with hospitalizations, length of hospital stay, and cost. Results: Approximately 81.5% of the patients were admitted at least once, with 42,283 admissions, costing Australian dollars (AUD) 231 million. The average number of admissions per person-year was 1.7, and the cost was AUD 9,060, 10 times and 2 times their Australian averages, respectively. Single (1-day) admissions constituted 59.2% of all the hospital episodes, led by neoplasms (largely chemotherapy), anemia, CKD-related conditions and eye conditions (largely cataract extractions), but only 14.8% of the total costs. Approximately 41% of admissions were >1-day admissions, constituting 85.2% of the total costs, with cardiovascular conditions, respiratory conditions, CKD-related conditions, and injuries, fractures, or poisoning being the dominant causes. Readmission within 30 days of discharge constituted >42% of the admissions and 46.8% costs. Admissions not directly related to CKD constituted 90% of the admissions and costs. More than 40% of the admissions and costs were through the emergency department. Approximately 19% of the hospitalized patients and 27% of the admissions did not have kidney disease mentioned as either principal or associate causes. Limitations: Variable follow-up times because of different dates of consent. Conclusions: The hospital burden of patients with CKD is mainly driven by complex multiday admissions and readmissions involving comorbid conditions, which may not be directly related to their CKD. Strategies to prevent these complex admissions and readmissions should minimize hospital costs and outcomes. Plain-Language Summary: We analyzed primary causes, types, and costs of hospitalizations among 7,201 patients with chronic kidney disease (CKD) from renal speciality clinics across Queensland, Australia, over an average follow-up of 3.54 years. The average annual cost per person was $9,060, and was the highest in those with more advanced CKD, higher age, and with diabetes. More than 85% of costs were driven by more complex hospitalizations with longer length of stay. Cardiovascular disease was the single largest contributor for hospitalizations, length of hospital stay, and total costs. Readmission within 30 days of discharge, particularly for the same disorder, and multiday admissions should be the main targets for mitigation of hospital costs in this population.

In Australia, there has been a sustained investment in widening participation activities by the federal government through the Higher Education Participation and Partnership Program (HEPPP) and a sustained effort by universities and their partner schools to create high-quality widening participation programs. However, there is limited longitudinal evidence on if and how these widening participation activities influence the application rates to university by school leavers from low socio-economic status (SES) backgrounds. This article draws on a large mixed-methods study which aimed to investigate differences in university application rates between students from low SES backgrounds in urban versus rural, regional and remote (RRR) schools in Queensland. The research found that widening participation programs had a positive and statistically significant influence on application rates to university in highly engaged schools. We propose the concept of a virtuous circle of sustained widening participation activity to explain the positive results in highly engaged schools.

Synovial sarcoma (SS) is a rare cancer that disproportionately affects children and young adults. Cancer testis antigens (CTAs) are proteins that are expressed early in embryonic development, but generally not expressed in normal tissue. They are aberrantly expressed in many different cancer types and are an attractive therapeutic target for immunotherapies. CTAs are expressed at high levels in SS. This high level of CTA expression makes SS an ideal cancer for treatment strategies aimed at harnessing the immune system to recognize aberrant CTA expression and fight against the cancer. Pivotal clinical trials are now underway, with the potential to dramatically alter the landscape of SS management and treatment from current standards of care. In this review, we describe the rationale for targeting CTAs in SS with a focus on NY-ESO-1 and MAGE-A4, the current state of vaccine and T-cell receptor-based therapies, and consider emerging opportunities for future development.

Abstract Background Giving up driving is a pivotal life event and universal challenge for people living with dementia and their families, and a complex area of clinical practice for health professionals who monitor driving cessation. The best outcomes are for individuals to plan for and eventually cease driving, however with insufficient support programs in place, many avoid the issue until it is reaches a crisis point. This program of research investigates a comprehensive support- and education-based intervention targeted at people living with dementia and their care partners who are managing driving cessation. The primary aim of this research is to determine the effectiveness of the program through a cluster randomized controlled trial. Methods/design The intervention (CarFreeMe) is an intensive program delivered by a trained health professional that addresses practical and emotional needs relevant to driving cessation. The seven module program is person-centred, covering awareness raising, adjustment, and practical support that is individualized according to geographic location and the particular goals and preferences of participants. A cluster randomized controlled trial will evaluate the effectiveness of the program. Evaluation will take place pre-intervention, immediately following, and three months post-intervention. Clusters are randomized to either intervention or usual treatment. Participants within clusters will be recruited via primary and secondary care clinics, community agencies, service providers, local media, social media, support groups, and word of mouth. The primary outcome measure for persons with dementia and their care partners is lifespace, collected via (i) smartphone GPS technology and (ii) self-reported number of episodes away from home (during the past week). Secondary outcomes include safe alternative transport status, wellbeing, depression, anxiety, and self-efficacy, which will be collected from dyads. Caregiving strain will be collected from care partner/family member only. A process evaluation of the intervention will also be undertaken. Discussion There is an urgent need for therapeutic approaches to supporting people living with dementia and their families to negotiate the complex decision making involved in deciding to change their approach to driving. The driving cessation intervention may fill an important gap in service delivery to people living with dementia who are adjusting to life without driving. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12618000388213, 15 March 2018.

Objectives: To evaluate the efficacy of a brief tailored non-pharmacological intervention comprising breathing retraining and psychosocial support for managing dyspnea in cancer patients.Design: Multicenter, single blinded, parallel group, randomized controlled trial.Setting: Four major public hospitals, Brisbane, Australia.Participants: One hundred and forty four cancer patients, including 81 who received an 8-week tailored intervention and 63 who received standard care.Inclusion Criteria: Diagnosis of small or non-small cell lung cancer, mesothelioma or lung metastases; completed first line therapy for the disease; average dyspnea rating >2 on (0–10) rating scale in past week; anticipated life expectancy ≥3 months.Outcomes: The primary outcome measure was change in “worst” dyspnea at 8 weeks compared to baseline. Secondary outcomes were change in: dyspnea “at best” and “on average”; distress; perceived control over dyspnea; functional status, psychological distress; and use of non-pharmacological interventions to manage dyspnea at 8 weeks relative to baseline.Results: The mean age of participants was 67.9 (SD = 9.6) years. Compared to the control group, the intervention group demonstrated a statistically significant: (i) improvement in average dyspnea from T1(M = 4.5, SE = 0.22) to T3 (M = 3.6, SE = 0.24) vs. (M = 3.8, SE = 0.24) to (M = 4.1, SE = 0.26); (ii) greater control over dyspnea from T1 (M = 5.7, SE = 0.28) to T3 (M = 7.5, SE = 0.31) vs. (M = 6.8, SE = 0.32) to (M = 6.6, SE = 0.33); and (iii) greater reduction in anxiety from T1 (M = 5.4, SE = 0.43) to T3 (M = 4.5, SE = 0.45) vs. (M = 4.2, SE = 0.49) to (M = 4.6, SE = 0.50). This study found no intervention effect for best and worst dyspnea, distress from breathlessness, functional status, and depression over time.Conclusions: This study demonstrates efficacy of tailored non-pharmacological interventions in improving dyspnea on average, control over dyspnea, and anxiety for cancer patients.Clinical Trial Registration: The trial is registered at the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au). The registration number is ACTRN12607000087459.

Background: Children with ADHD and sleep problems have more caregiver deficits and decreased school attendance than children with ADHD but without a sleep problem. We conducted an N-of-1 trial of melatonin for children with ADHD on stimulants. As a follow-up study, we aim to conduct a cost effectiveness analysis (CEA) of melatonin therapy by comparing costs of this condition (of using melatonin) to costs of the baseline condition (usual care with no N-of-1 trial). Methods: The CEA will compare participants who remained on melatonin vs those who chose to cease melatonin. Costs will be determined by medication cost to the caregiver(s), school/work absences, other sleep remedy costs, and health service utilization costs, including incidentals like parking. These costs will be determined at baseline, end of 6-week trial, and 6 months post-trial. We will also calculate Quality-Adjusted Life-Years (QALY) based on responses to PedsQL or SF-12v2 for patients and caregiver(s) and assess differences between remaining on melatonin or not; and assess the intermediate-term effectiveness and adverse effects of melatonin at 6 months. Discussion: We hypothesize that shorter sleep-onset-latency will be associated with improved QALYs for patients and caregivers. We also expect that targeting melatonin to positive responders will be cost effective both for individuals and society. Cost per QALY for positive responders to melatonin is useful for doctors when creating treatment plans since melatonin is not an over-the-counter pharmaceutical in Australia. Trial registration number: ACTRN12614000542695. Keywords: N-of-1, Melatonin, QALY, ADHD, Children, Insomnia, Cost effective

Abstract Background Nausea/vomiting (N/V) not related to anti-cancer treatment is common in patients with advanced cancer. The standard approach to management is to define a dominant cause, and treat with an antiemetic selected through pathophysiologic knowledge of emetic pathways. High rates of N/V control have been reported using both etiology-based guideline-driven antiemetic regimens and an empiric approach using single agents in uncontrolled studies. These different approaches had never been formally compared. Methods This randomized, prospective, open label, dose-escalating study used readily available antiemetics in accordance with etiology-based guidelines or single agent therapy with haloperidol. Participants had a baseline average nausea score of ≥3/10. Response was defined as a ≥ 2/10 point reduction on a numerical rating scale of average nausea score with a final score

Abstract Background Chronic kidney disease (CKD) is a growing global problem affecting around 10% of many countries’ populations. Providing appropriate palliative care services (PCS) to those with advanced kidney disease is becoming paramount. Palliative/supportive care alongside usual CKD clinical treatment is gaining acceptance in nephrology services although the collaboration with and use of PCS is not consistent. Methods The goal of this study was to track and quantify the health service utilisation of people with CKD stages 3-5 over the last 12 months of life. Patients were recruited from a kidney health service (Queensland, Australia) for this prospective, longitudinal study. Data were collected for 12 months (or until death, whichever was sooner) during 2015-17 from administrative health sources. Emergency department presentations (EDP) and inpatient admissions (IPA) (collectively referred to as critical events) were reviewed by two Nephrologists to gauge if the events were avoidable. Results Participants (n = 19) with a median age of 78 years (range 42-90), were mostly male (63%), 79% had CKD stage 5, and were heavy users of health services during the study period. Fifteen patients (79%) collectively recorded 44 EDP; 61% occurred after-hours, 91% were triaged as imminently and potentially life-threatening and 73% were admitted. Seventy-four IPA were collectively recorded across 16 patients (84%); 14% occurred on weekends or public holidays. Median length of stay was 3 days (range 1-29). The median number of EDP and IPA per patient was 1 and 2 (range 0-12 and 0-20) respectively. The most common trigger to both EDP (30%) and IPA (15%) was respiratory distress. By study end 37% of patients died, 63% were known to PCS and 11% rejected a referral to a PCS. All critical events were deemed unavoidable. Conclusions Few patients avoided using acute health care services in a 12 month period, highlighting the high service needs of this cohort throughout the long, slow decline of CKD. Proactive end-of-life care earlier in the disease trajectory through integrating renal and palliative care teams may avoid acute presentations to hospital through better symptom management and planned care pathways.

Abstract Background N-of-1 trials have a potential role in promoting patient-centered medicine in developing countries. However, there is limited academic literature regarding the use of N-of-1 trials in the clinical care of patients in resource-poor settings. Objective To assess the extent of use, purpose and treatment outcome of N-of-1 trials in developing countries. Method A systematic review of clinical N-of-1 trials was conducted between 1985 and September 2015 using PubMed, Embase, CINAHL, Web of Science and the Cochrane Central Register of Controlled Trials. Grey literature databases and clinical trial registers were also searched. This review included randomized, multi-cycle, crossover within individual patient trials involving drug intervention. Quality assessment and data extraction were conducted by two independent reviewers. Result Out of 131 N-of-1 trials identified, only 6 (4.5%) were conducted in developing countries. The major reason that N-of-1 trials were used was to provide evidence on feasibility, effectiveness and safety of therapies. A total of 72 participants were involved in these trials. Five of the studies were conducted in China and all evaluated Chinese traditional medicine. The remaining study was conducted in Brazil. The completion rate was 93%. More than half, 46 (69%) of subjects made medication changes consistent with trial results after trial completion. A number of threats to the validity of the included evidence limited the validity of the evidence. In particular, the estimated overall effect in four of the included studies could have been affected by the “carry over” of the previous treatment effect as no adequate pharmacokinetic evidence regarding traditional medicines was presented. Conclusion The prevalence and scope of N-of-1 trials in developing countries is low. A coordinated effort among government, clinicians, researchers and sponsor organizations is needed to increase their uptake and quality in developing countries. Systematic review registration PROSPERO CRD42015026841.

Abstract Background Clinical trials for identification of efficient and effective new diagnostic and treatment modalities are needed to address disproportionately high burden of communicable (e.g., HIV/AIDS, tuberculosis, and malaria) and non-communicable diseases (e.g., diabetes) in developing countries. However, gross under-representation in global clinical trial platforms contributes to sustained health inequity in these countries. We reviewed the literature on barriers facing clinical researchers in developing countries for conducting clinical trials in their countries. Methods Literature indexed in PubMed, Embase, CINAHL and Web of Science, WHO Global Health Library were searched. Grey literature was also searched. Search key words included barriers, challenges, clinical trials and developing countries. Articles within the scope of this review were appraised by two reviewers. Results Ten studies, which are reported in 15 papers, were included in this review. Following critical review we identified five unifying themes for barriers. Barriers for conducting clinical trials included lack of financial and human capacity, ethical and regulatory system obstacles, lack of research environment, operational barriers and competing demands. Conclusion and recommendation There were substantial barriers at system, organization and individual level. We propose that to address this problem, instituting a system for wider implementation of local investigator-initiated trials is warranted. These trials are more applicable to local populations because they build on local healthcare knowledge. They are more demand-led, influence policy and responsive to a country’s needs because they are driven by a local or national agenda.

Abstract Background Hypertension is one of the leading causes of morbidity and mortality in Ethiopia. Treatment usually involves lifelong medication use. Enalapril is a common drug for the treatment of hypertension in Ethiopia. However, the drug is expensive and, therefore, there is limited capacity for people to afford the treatment. Locally produced Enalapril is a cost-effective solution to treat the disease. However, as local medicines regulation does not include bioequivalence tests on locally produced drugs, physicians and patients need assurance about the effectiveness and safety of local generics. Evidence on therapeutic equivalence is needed on these untested local drugs. Methods This is a hospital-based, randomized, partially blinded, three-cycle crossover trial in single patients, comparing a locally produced version of enalapril with enalapril imported from Europe. Patients involved in this trial are not blinded, as there is no local facility to produce relatively small numbers of placebos or encapsulated drugs. To ensure blinding of study investigators and data analysts, study medications are prepared by an independent pharmacy unit using opaque medication packaging. The importance of maintaining blinding is also part of patient pre-trial education. Each N-of-1 trial will consist of three successive 14-day treatment pairs, each pair comprising 7 days of 5–20 mg local and 7 days of 5–20 mg imported enalapril taken once daily in the morning. The primary outcome will be the average difference in systolic blood pressure as measured by home blood pressure measurements. Discussion The number of locally produced products, such as enalapril, being approved without proof of bioequivalence is dramatically increasing. By bridging the information gap on bioequivalence, the trial will give rigorous evidence on therapeutic equivalence of locally produced enalapril in the treatment of hypertension. If there is no difference, the hypothesized result, then patients can take the local medicine with confidence. This trial will also will determine whether aggregated N-of-1 studies are feasible to evaluate untested generic drugs in resource-limited countries where bioequivalence testing centers are unavailable. Trial registration number Australian and New Zealand Clinical Trial Registry, ID: ACTRN12616001088437p . Registered on 12 August 2016.

Objective: To present the process of identification of palliative care patients in a Family Health Strategy´s team in Brazil. Methods: The identification process ocurred 1) using the system of work of a Family Health Strategy Team and the principles of primary care and 2) by applying the SPICT, a tool to help identify patients who might benefit with palliative care. Results: Twenty-three patients were enrolled in the palliative care program at the beginning of the project. By the end of the 12 month period, we had identified 38 patients. Six patients died during the time period. Thus during 2015, 38 people were identified with palliative needs from a total population of 3,000 (1.2% of the practice population). Of these 58% (n=22) were women, 63% (n=24) over 65 years, 74.7% (n=28) reported white ethnicity. The most frequent major diagnoses were cancer (39.5%), psychiatric disease (18.4%), cardiovascular disease (15.8%), frailty (10.5%), dementia (10.5%), and respiratory disease (7.9%). Multimorbity was higher in patients over 65 years (t-test, p=0.009) with a median of four diseases. The most prevalent conditions among those suffering multimorbidity were cardiovascular disease (73.7%), psychiatric disease (65.8%), cancer (50%), frailty (39.5%), diabetes mellitus (31.6%), and respiratory diseases (23.7%). Conclusion: We applied a tool for identifying patients who would benefit from palliative care in primary care in a community of Rio Grande. It was practical and feasible. Its further refinement, implementation and evaluation in Brazil is indicated at community centres of Family Health Strategy, specifically taking account of social and economic factors.

Palliative care planning for nursing home residents with advanced dementia is often suboptimal. This study compared effects of facilitated case conferencing (FCC) with usual care (UC) on end-of-life care.A two arm parallel cluster randomised controlled trial was conducted. The sample included people with advanced dementia from 20 Australian nursing homes and their families and professional caregivers. In each intervention nursing home (n = 10), Palliative Care Planning Coordinators (PCPCs) facilitated family case conferences and trained staff in person-centred palliative care for 16 hours per week over 18 months. The primary outcome was family-rated quality of end-of-life care (End-of-Life Dementia [EOLD] Scales). Secondary outcomes included nurse-rated EOLD scales, resident quality of life (Quality of Life in Late-stage Dementia [QUALID]) and quality of care over the last month of life (pharmacological/non-pharmacological palliative strategies, hospitalization or inappropriate interventions).Two-hundred-eighty-six people with advanced dementia took part but only 131 died (64 in UC and 67 in FCC which was fewer than anticipated), rendering the primary analysis under-powered with no group effect seen in EOLD scales. Significant differences in pharmacological (P < 0.01) and non-pharmacological (P < 0.05) palliative management in last month of life were seen. Intercurrent illness was associated with lower family-rated EOLD Satisfaction with Care (coefficient 2.97, P < 0.05) and lower staff-rated EOLD Comfort Assessment with Dying (coefficient 4.37, P < 0.01). Per protocol analyses showed positive relationships between EOLD and staff hours to bed ratios, proportion of residents with dementia and staff attitudes.FCC facilitates a palliative approach to care. Future trials of case conferencing should consider outcomes and processes regarding decision making and planning for anticipated events and acute illness.Australian New Zealand Clinical Trial Registry ACTRN12612001164886.

Abstract Current trends in population ageing show that, in the near future, while more people will live longer, more will also die at any one time. Health systems, as well as individual practitioners, are only just becoming aware of the extent of this problem. Health systems will have to rapidly change practice to manage the number of people dying in the coming years, many with complex multimorbid conditions. The changes involved should include a personal recognition by all health professionals of their role in caring for the dying, and healthcare education must include end-of-life care management as part of the core curriculum. Further, health systems must improve integration between primary care and specialist clinicians to ensure the burden is shared efficiently across the system. Finally, it should be recognised that end-of-life care is not terminal care, but should be anticipated months or sometimes years ahead through advance care planning for known future complications by the patient’s clinical team, as well as by patients and their main carers, to manage crises as they ariserather than react to them once they arise. Please see related article: https://bmcmedicine.biomedcentral.com/articles/ 10.1186/s12916-017-0860-2 .