Evidence-based policy to end rheumatic heart disease in Australia

Rheumatic heart disease (RHD) stems from an abnormal immune response to Streptococcus pyogenes infection. The disease affects 40 million people globally, overwhelmingly in settings where resource constraints and equity gradients are large. In Australia, more than 5000 people live with RHD or its precursor acute rheumatic fever (ARF), the vast majority of whom are Aboriginal or Torres Strait Islander people. In this thesis, I outline a framework for reducing the burden of RHD among Aboriginal and Torres Strait Islander people in Australia. I use this framework to outline the international evidence for disease control strategies, synthesise approaches to eliminate RHD in Australia, and present empiric findings for selected approaches in primary care prevention. Section 1 introduces the issue of RHD and the scope of this thesis. Section 2 contextualises RHD control in Australia and internationally, beginning with Chapter 1 outlining RHD control programs and registers. Chapter 2 provides an overview of awareness of RHD and advocacy initiatives worldwide. Chapter 3 addresses the direct and indirect drivers of the disproportionate burden of RHD experienced by Indigenous people living in high-income countries. Section 3 addresses the opportunities for RHD control in Australia, first in Chapter 4 by synthesising evidence for strategies to achieve RHD elimination in Australia. Chapter 5 explores mathematical modelling of these strategies. Section 4 examines primary care interventions for prevention of ARF in more detail, beginning with review of current guidelines in Chapter 6. Chapter 7 outlines recommendations for Australian primary care providers for primary prevention of ARF and uses an eDelphi prioritisation method to understand primary care provider preferences for improving care delivery. Finally, Chapter 8 outlines the evaluation of a community-based intervention addressing environmental health and support for households affected by RHD. In Section 5, I discuss how, collectively, these studies provide a consolidated approach to addressing RHD in Australia at community, provider, health system and policy levels. This thesis offers new evidence for effective environmental health and primary prevention strategies to reduce rheumatic fever incidence and provides a comprehensive foundation for action to eliminate RHD in the next decade in Australia

Making mapping matter: a case study for short project international partnerships by global public health students

Background: A large number of global public health students seek international experience as part of their academic curriculum. These placements are often short, given the constraints of cost and time available within the academic calendar. In contrast to international electives for clinical students there are few published guidelines on practical, ethical or feasible projects. This paper describes a ten-day sanitation mapping project in Mumbai, India and explores the broader implications for global public health student electives. Methods: Three graduate public health students conducted a geographic review of sanitation facilities in Cheeta Camp informal settlement, Mumbai. Forty-six toilet blocks with 701 individual seats were identified. The project was reviewed ethically, educationally and logistically as a possible model for other short-term international projects. Conclusions: Clearer guidelines are needed to support non-clinical placements by global public health students. Projects that are feasible, relevant and meaningful should be foster maximise benefit for learners and host communities

Modes of transmission and attack rates of group A Streptococcal infection: a protocol for a systematic review and meta-analysis

Background Group A Streptococcus (Strep A) is an important cause of mortality and morbidity globally. This bacterium is responsible for a range of different infections and post-infectious sequelae. Summarising the current knowledge of Strep A transmission to humans will address gaps in the evidence and inform prevention and control strategies. The objective of this study is to evaluate the modes of transmission and attack rates of group A streptococcal infection in human populations. Methods This systematic review protocol was prepared according to the Preferred Reporting Items for Systematic reviews and Meta-analysis Protocols (PRISMA-P) 2015 Statement. Using a comprehensive search strategy to identify any transmission studies that have been published in English since 1980, full-text articles will be identified and considered for inclusion against predefined criteria. We will include all studies reporting on Strep A transmission, who have identified a mode of transmission, and who reported attack rates. Risk of bias will be appraised using an appropriate tool. Our results will be described narratively and where feasible and appropriate, a meta-analysis utilizing the random-effects model will be used to aggregate the incidence proportions (attack rates) for each mode of transmission. In addition, we will also evaluate the emm genotype variants of the M protein causing Strep A infection and the association with transmission routes and attack rates, if any, by setting, socioeconomic background and geographical regions. Discussion We anticipate that this review will contribute to elucidating Strep A modes of transmission which in turn, will serve to inform evidence-based strategies including environmental health activities to reduce the transmission of Strep A in populations at risk of severe disease. Trial registration Systematic review registration: PROSPERO ( CRD42019138472 )

Surgery for rheumatic heart disease in the Northern Territory, Australia, 1997-2016: what have we gained?

Background: Between 1964 and 1996, the 10-year survival of patients having valve replacement surgery for rheumatic heart disease (RHD) in the Northern Territory, Australia, was 68%. As medical care has evolved since then, this study aimed to determine whether there has been a corresponding improvement in survival. Methods: A retrospective study of Aboriginal patients with RHD in the Northern Territory, Australia, having their first valve surgery between 1997 and 2016. Survival was examined using Kaplan-Meier and Cox regression analysis. Findings: The cohort included 281 adults and 61 children. The median (IQR) age at first surgery was 31 (18-42) years; 173/342 (51%) had a valve replacement, 113/342 (33%) had a valve repair and 56/342 (16%) had a commissurotomy. There were 93/342 (27%) deaths during a median (IQR) follow-up of 8 (4-12) years. The overall 10-year survival was 70% (95% CI: 64% to 76%). It was 62% (95% CI: 53% to 70%) in those having valve replacement. There were 204/281 (73%) adults with at least 1 preoperative comorbidity. Preoperative comorbidity was associated with earlier death, the risk of death increasing with each comorbidity (HR: 1.3 (95% CI: 1.2 to 1.5), p50 mm Hg before surgery (HR 1.9 (95% CI: 1.2 to 3.1) p=0.007) were independently associated with death. Interpretation: Survival after valve replacement for RHD in this region of Australia has not improved. Although the patients were young, many had multiple comorbidities, which influenced long-term outcomes. The increasing prevalence of complex comorbidity in the region is a barrier to achieving optimal health outcomes

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Functional and quality of life outcomes of localised prostate cancer treatments (prostate testing for cancer and treatment [ProtecT] study)

Objective To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and Methods Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes

Evolution, evidence and effect of secondary prophylaxis against rheumatic fever

The association between group A streptococcal infection and rheumatic fever (RF) was established in the early 20 th century. At the time, RF and subsequent rheumatic heart disease (RHD) were an untreatable scourge of young people in developed and developing countries. Resultingly, research efforts to understand, treat and prevent the disease were widepread. The development of antibiotics in the 1930s offered therapeutic promise, although antibotic treatment of acute RF had little impact. Improved understanding of the post-infectious nature of RF prompted attempts to use antibiotics prophylactically. Regular doses of sulphonamide antibiotics following RF appeared to reduce disease progression to RHD. Development of penicillin and later, benzathine penicillin G, was a further thereputic advance in the 1950s. No new prophylactic options against RF have emerged in the intervening 60 years, and delivery of regularly scheduled BPG injections remains a world wide challenge

Modalities of group A streptococcal prevention and treatment and their economic justification

Abstract Infection by group A Streptococcus (Strep A) results in a diverse range of clinical conditions, including pharyngitis, impetigo, cellulitis, necrotising fasciitis, and rheumatic heart disease. In this article, we outline the recommended strategies for Strep A treatment and prevention and review the literature for economic evaluations of competing treatment and prevention strategies. We find that most economic evaluations focus on reducing the duration of illness or risk of rheumatic fever among people presenting with sore throat through diagnostic and/or treatment strategies. Few studies have evaluated strategies to reduce the burden of Strep A infection among the general population, nor have they considered the local capacity to finance and implement strategies. Evaluation of validated costs and consequences for a more diverse range of Strep A interventions are needed to ensure policies maximise patient outcomes under budget constraints. This should include attention to basic public health strategies and emerging strategies such as vaccination