Comparative Effectiveness Research (CER) ‒ A Case Study

Background: The Australian healthcare system is complex. Assessing the quality of the care provided in the management of acute coronary syndromes (ACS) is problematic because of disparate systems that constrain an integrated reporting approach. Registry data reported within a comparative effectiveness research (CER) framework establishes the case for clinical process indicators to measure and report hospital performance. Objectives: To aggregate data from The Global Registry of Acute Coronary Events (GRACE) and the Cooperative National Registry of Acute Coronary Care Guideline Adherence and Clinical Events (CONCORDANCE) to describe temporal trends in the management of ACS and associations with in-hospital events, hospital readmission and six month mortality; to develop a composite score of hospital performance quality; to determine associations between adherence to the quality composite score and in-hospital events, hospital readmission and six month mortality and develop a benchmarked stakeholder hospital performance report. Methods: A single case study embedding three units of analysis was used to explore and explain how data reported in a CER framework measures hospital performance in the management of ACS. Analysis: Descriptive analyses of prospectively collected data on the management and outcomes of over 7000 patients admitted to 46 hospitals from 1999 to 2016. Findings: The first Unit of Analysis reports temporal trends in the management of ACS across 11 hospitals in the GRACE registry from 2000 to 2007 which informed the design of the CONCORDANCE registry; The second Unit of Analysis combines both GRACE and CONCORDANCE registries and reports on the management of ST-elevation acute myocardial infarction (STEMI ) from 1999 to 2016 revealing gains in pre-hospital care and fewer in-hospital clinical events, and readmission for urgent revascularisation without a significant reduction in in-hospital or six month mortality. The third Unit of Analysis reports the observed and risk-adjusted association between adherence to the quality composite score and reduced in-hospital events, and increased survival at hospital discharge and at six months post discharge. Conclusion: Case-study analysis of CER in the context of ACS registries provides evidence on adherence to evidence-based care and a quality composite measure of hospital performance in the management of ACS

Optimising use of electronic health records to describe the presentation of rheumatoid arthritis in primary care: a strategy for developing code lists

Background Research using electronic health records (EHRs) relies heavily on coded clinical data. Due to variation in coding practices, it can be difficult to aggregate the codes for a condition in order to define cases. This paper describes a methodology to develop ‘indicator markers’ found in patients with early rheumatoid arthritis (RA); these are a broader range of codes which may allow a probabilistic case definition to use in cases where no diagnostic code is yet recorded. Methods We examined EHRs of 5,843 patients in the General Practice Research Database, aged ≥30y, with a first coded diagnosis of RA between 2005 and 2008. Lists of indicator markers for RA were developed initially by panels of clinicians drawing up code-lists and then modified based on scrutiny of available data. The prevalence of indicator markers, and their temporal relationship to RA codes, was examined in patients from 3y before to 14d after recorded RA diagnosis. Findings Indicator markers were common throughout EHRs of RA patients, with 83.5% having 2 or more markers. 34% of patients received a disease-specific prescription before RA was coded; 42% had a referral to rheumatology, and 63% had a test for rheumatoid factor. 65% had at least one joint symptom or sign recorded and in 44% this was at least 6-months before recorded RA diagnosis. Conclusion Indicator markers of RA may be valuable for case definition in cases which do not yet have a diagnostic code. The clinical diagnosis of RA is likely to occur some months before it is coded, shown by markers frequently occurring ≥6 months before recorded diagnosis. It is difficult to differentiate delay in diagnosis from delay in recording. Information concealed in free text may be required for the accurate identification of patients and to assess the quality of care in general practice

Northern Territory Heart Failure Initiative–Clinical Audit (NTHFI–CA)–a prospective database on the quality of care and outcomes for acute decompensated heart failure admission in the Northern Territory: study design and rationale

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/Introduction Congestive heart failure is a significant cause of morbidity and mortality in Australia. Accurate data for the Northern Territory and Indigenous Australians are not presently available. The economic burden of this chronic cardiovascular disease is felt by all funding bodies and it still remains unclear what impact current measures have on preventing the ongoing disease burden and how much of this filters down to more remote areas. Clear differentials also exist in rural areas including a larger Indigenous community, greater disease burden, differing aetiologies for heart failure as well as service and infrastructure discrepancies. It is becoming increasingly clear that urban solutions will not affect regional outcomes. To understand regional issues relevant to heart failure management, an understanding of the key performance indicators in that setting is critical. Methods and analysis The Northern Territory Heart Failure Initiative—Clinical Audit (NTHFI-CA) is a prospective registry of acute heart failure admissions over a 12-month period across the two main Northern Territory tertiary hospitals. The study collects information across six domains and five dimensions of healthcare. The study aims to set in place an evidenced and reproducible audit system for heart failure and inform the developing heart failure disease management programme. The findings, is believed, will assist the development of solutions to narrow the outcomes divide between remote and urban Australia and between Indigenous and Non-Indigenous Australians, in case they exist. A combination of descriptive statistics and mixed effects modelling will be used to analyse the data. Ethics and dissemination This study has been approved by respective ethics committees of both the admitting institutions. All participants will be provided a written informed consent which will be completed prior to enrolment in the study. The study results will be disseminated through local and international health conferences and peer reviewed manuscripts

Timing and impact of psychiatric, cognitive, and motor abnormalities in Huntington disease

Objective To assess the prevalence, timing and functional impact of psychiatric, cognitive and motor abnormalities in Huntington’s disease (HD) gene carriers, we analysed retrospective clinical data from individuals with manifest HD. Methods Clinical features of HD patients were analysed for 6316 individuals in the European REGISTRY study from 161 sites across 17 countries. Data came from clinical history and the patient-completed Clinical Characteristics Questionnaire that assessed eight symptoms: motor, cognitive, apathy, depression, perseverative/obsessive behavior, irritability, violent/aggressive behavior, and psychosis. Multiple logistic regression was used to analyse relationships between symptoms and functional outcomes. Results The initial manifestation of HD is increasingly likely to be motor, and less likely to be psychiatric, as age at presentation increases, and is independent of pathogenic CAG repeat length. The Clinical Characteristics Questionnaire captures data on non-motor symptom prevalence that correlate specifically with validated clinical measures. Psychiatric and cognitive symptoms are common in HD gene carriers, with earlier onsets associated with longer CAG repeats. 42.4% of HD patients reported at least one psychiatric or cognitive symptom before motor symptoms, with depression most common. Each non-motor symptom was associated with significantly reduced total functional capacity scores. Conclusions Psychiatric and cognitive symptoms are common and functionally debilitating in HD gene carriers. They require recognition and targeting with clinical outcome measures and treatments. However, as it is impossible to distinguish confidently between non-motor symptoms arising from HD and primary psychiatric disorders, particularly in younger pre-manifest patients, non-motor symptoms should not be used to make a clinical diagnosis of HD

Do clinically relevant differences in outcomes exist between women and men undergoing treatment for cardiovascular disease?

IntroductionThroughout my own clinical practice, I became aware that differences may exist between men and women in the decisions for treatment and the outcomes after intervention for cardiovascular disease. Clinical trials have corroborated this with women typically presenting at an older age and studies have suggested there are innate differences between the sexes with women believed to have worse outcomes than men. However, historically women have been poorly represented in clinical trials, which has led to biased result interpretation, despite cardiovascular disease remaining the leading cause of death in women. Therefore, extrapolation of results to women may lead to differences in expected outcomes.The aim of this thesis was to explore the question: ‘Do outcomes differ between women and men in the treatment of cardiovascular disease?’MethodsThe over-arching research question was addressed by integrating results from 5 individual datasets. Following the literature review, the areas identified for investigation were: 1) The role of female sex in the treatment of the left main coronary artery; 2) Bleeding risk in women undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction; 3) Does sex play a role in the activated clotting time during angioplasty; 4) The role of sex on outcomes following transcatheter aortic valve implantation; and 5) Sex differences in the perceived intensity of symptoms in patients with aortic stenosis.Each of these studies involved observational data from real world patients and allowed for assessment of matched populations to allow for a comparison when appropriate. The datasets were then analysed utilising the constructivist paradigm to identify themes that contribute to robust and generalisable new knowledge in this field.ResultsThe treatment of the complex left main coronary artery is first addressed and demonstrates no differences between the sexes in those undergoing percutaneous coronary intervention, however there was an advantage in women undergoing coronary artery bypass grafting. In patients presenting with ST-elevation myocardial infarction, women have more episodes of bleeding, however despite this have the same good outcome as men in hospital and therefore require the same access to treatment. The anti-coagulation regime during percutaneous coronary intervention is then considered and demonstrates that for a similar dose of unfractionated heparin, women are more likely to have a very high activated clotting time which may explain the increased risk of bleeding in the prior chapter.In the assessment of aortic stenosis, in symptomatic patients undergoing transcatheter aortic valve implantation, women again appear to have an advantage over men, with male sex a predictor of mortality at long-term follow-up. However, finally addressing the symptomatology of aortic stenosis, there were no differences between sexes in the symptoms of breathlessness or in NT-pro-BNP levels.ConclusionsThe analysis demonstrated that despite an older presentation in women who underwent treatment, women can do as well as men (in coronary artery disease) or even fare better (for transcatheter aortic valve implantation) despite more bleeding and vascular complications. This may impact significantly regarding the multi-disciplinary discussion regarding intervention for these patients and needs to be considered by the clinicians involved in the treatment of cardiovascular disease.The limitations of the studies are that the data are non-randomised and in 2 of the data sets there are small sample sizes. Additionally, there are the difficulties associated with the analysis of mixed methods research in analysing quantitative data qualitatively.In summary, when determining if patient sex should be a factor when deciding upon the management of acquired cardiovascular disease, the triangulation of data from across a number of data sets in this thesis suggests that sex should not be the primary consideration. Further research is needed to refine clinical understanding of which factors should be taken into account

The onset and prevalence of motor and psychiatric symptoms in Huntington’s disease

Background Huntington’s disease is characterised by a range of motor, psychiatric and cognitive symptoms. These present in different combinations through the disease course and impact on daily life and functioning. Huntington’s disease is caused by a dominant CAG repeat expansion in the HTT gene, and longer repeats are associated with earlier onset of motor symptoms. Objectives To investigate the onset, prevalence and functional impact of motor and psychiatric symptoms of Huntington’s disease. Methods We analysed clinical phenotype data from the European REGISTRY study for 6316 individuals with manifest Huntington’s disease. Onset and prevalence data for motor and psychiatric symptoms were extracted from the clinical history part of REGISTRY and the detailed Clinical Characteristics Questionnaire. Generalised linear models were constructed to assess relationships between symptoms and functional outcomes. Results As age at first presentation of Huntington’s disease increases, the likelihood that the initial presenting symptom is motor also increases. This is not associated with pathogenic CAG repeat length. At a population level there were conserved relationships between symptoms across different repeat lengths, with depression often occurring early followed by motor and then cognitive symptoms. There were significant relationships between all individual psychiatric and cognitive symptoms and reduced functional capacity. Conclusions There are conserved patterns of symptoms in HD that can be quantified. Psychiatric and behavioural symptoms significantly impair daily functioning and should be considered part of the disease trajectory at any age