Measuring and reporting treatment adherence:what can we learn by comparing two respiratory conditions?

Medication non-adherence, defined as any deviation from the regimen recommended by their healthcare provider, can increase morbidity, mortality and side effects, while reducing effectiveness. Through studying two respiratory conditions, asthma and tuberculosis (TB), we thoroughly review the current understanding of the measurement and reporting of medication adherence. In this paper, we identify major methodological issues in the standard ways that adherence has been conceptualised, defined and studied in asthma and TB. Between and within the two diseases there are substantial variations in adherence reporting, linked to differences in dosing intervals and treatment duration. Critically, the communicable nature of TB has resulted in dose-by-dose monitoring becoming a recommended treatment standard. Through the lens of these similarities and contrasts, we highlight contemporary shortcomings in the generalised conceptualisation of medication adherence. Furthermore, we outline elements in which knowledge could be directly transferred from one condition to the other, such as the application of large-scale cost-effective monitoring methods in TB to resource-poor settings in asthma. To develop a more robust evidence-based approach, we recommend the use of standard taxonomies detailed in the ABC taxonomy when measuring and discussing adherence. Regimen and intervention development and use should be based on sufficient evidence of the commonality and type of adherence behaviours displayed by patients with the relevant condition. A systematic approach to the measurement and reporting of adherence could improve the value and generalisability of research across all health conditions.status: publishe

Forgiveness Is the Attribute of the Strong:Nonadherence and Regimen-Shortening in Drug-Sensitive TB

RATIONALE: 'Forgiveness' charts the ability of a drug or regimen to withstand non-adherence without negative clinical consequences. OBJECTIVES: We aimed to determine the influence of regimen length, regimen drugs and dosing, and when during treatment non-adherence occurs on the forgiveness of anti-tuberculosis regimens. METHODS: Using data from three randomised controlled trials comparing experimental four-month regimens for drug-sensitive tuberculosis with the standard six-month regimen, we used generalised linear models to examine how the risk of a negative composite outcome changed as dose-taking decreased. The percentage of doses taken and absolute number of doses missed were calculated, during the intensive and continuation phases of treatment, and overall. A mediation analysis was undertaken to determine how much of the association between intensive phase dose-taking and the negative composite outcome was mediated through continuation phase dose-taking. MEASUREMENTS AND MAIN RESULTS: Forgiveness of the four-month and six-month regimens did not differ for any treatment period. Importantly, four-month regimens were no less forgiving of small numbers of absolute missed doses than the six-month regimen (e.g. for 3-7 missed doses versus no missed doses (baseline), six-month regimen adjusted risk ratio 1.65 (95% confidence interval 0.80-3.41) and four-month regimens 1.80 (1.33-2.45)). No four-month regimen was conclusively more forgiving than another. We found evidence of mediation by continuation phase dose-taking on the intensive phase dose-taking and negative composite outcome relationship. CONCLUSIONS: With the current appetite for, and progress towards, shorter drug-sensitive tuberculosis regimens worldwide, we offer reassurance that shorter regimens are not necessarily less forgiving of non-adherence. Given the importance of continuation phase adherence, patient support during this period should not be neglected

Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality

Funding: HRS and MF are supported by the Medical Research Council [MR/R008345/1]. CJ’s salary came through MRC core funding MC_UU_12023/26. SJS is funded by the Wellcome Trust [WT 209560/Z/17/Z]. CRS has received funding from the Medical Research Council [MR/R008345/1], the National Institute for Health Research [11/46/23] and the New Zealand Health Research Council [20/1018] and Ministry for Business, Innovation and Employment. EV is funded by the Medical Research Council [MR/R008345/1] through the EAVE II grant and supported by the Scottish Government. We also acknowledge the support of HDR UK. The views and opinions expressed here are those of the authors and do not necessarily reflect those of the Health Technology Assessment programme, NIHR, NHS, or the UK Department of Health.Background Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. Methods Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. Results One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. Conclusions The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected.Publisher PDFPeer reviewe

All non-adherence is equal, but is some more equal than others? TB in the digital era

Karina Kielmann - ORCID 0000-0001-5519-1658 https://orcid.org/0000-0001-5519-1658Aaron S. Karat - ORCID 0000-0001-9643-664X https://orcid.org/0000-0001-9643-664XReplaced AM with VoR 2020-11-06Adherence to treatment for tuberculosis (TB) has been a concern for many decades, resulting in the World Health Organization’s recommendation of the direct observation of treatment in the 1990s. Recent advances in digital adherence technologies (DATs) have renewed discussion on how to best address non-adherence, as well as offering important information on dose-by-dose adherence patterns and their variability between countries and settings. Previous studies have largely focussed on percentage thresholds to delineate sufficient adherence, but this is misleading and limited, given the complex and dynamic nature of adherence over the treatment course. Instead, we apply a standardised taxonomy- as adopted by the international adherence community- to dose-by-dose medication-taking data, which divides missed doses into a) late/non-initiation (starting treatment later than expected/not starting), b) discontinuation (ending treatment early), and c) suboptimal implementation (intermittent missed doses). Using this taxonomy, we can consider the implications of different forms of non-adherence for intervention and regimen design. For example, can treatment regimens be adapted to increase the ‘forgiveness’ of common patterns of suboptimal implementation to protect against treatment failure and the development of drug resistance? Is it reasonable to treat all missed doses of treatment as equally problematic and equally common when deploying DATs? Can DAT data be used to indicate the patients that need enhanced levels of support during their treatment course? Critically, we pinpoint key areas where knowledge regarding treatment adherence is sparse and impeding scientific progress.https://doi.org/10.1183/23120541.00315-20206pubpub

2017 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1004/thumbnail.jp

Epidemiological studies of Johne’s Disease in cattle from Scottish farms, with a focus on slaughterhouse investigations

The PARABAN project has been a Scotland-wide initiative to develop and deliver farm-specific ‘best practice’ for the control of Mycobacterium avium ssp. paratuberculosis (MAP) in cattle using ‘Knowledge Exchange’. A range of partners have been involved, including nine ‘Champion Farms’. With input from the farmer, his/her vet and PARABAN advisors, a tailored monitoring and control programme was devised for each ‘Champion Farm’, taking into account the history of the disease on the farm, the physical facilities available and farmer objectives. Culling decisions based on live animal test results were incorporated into each farm-specific programme to complement the management programme already in place to maintain each herd. Results were analysed and discussed with all the partners throughout the project and then offered for wider scrutiny at farm open days. Feedback and questions from these open days have been used to complete the ‘Knowledge Exchange’ cycle. As a major component of the PARABAN project the author collected samples from all adult animals culled from ‘Champion Farms’ at slaughter or as fallen stock, irrespective of in-life MAP test status. These were then subjected to histopathological examination by experienced veterinary pathologists and the results compared with the results from in-life MAP testing. This was intended to evaluate the contribution slaughterhouse sampling could make towards decision making for disease control on farm and formed the main aim of this thesis. In total, samples of terminal ileum and draining lymph node were collected from three-hundred and fifty-two animals. A positive result on histopathology was defined as the presence of lesions typical of MAP and also the presence of acid-fast bacteria within the sections. There was found to be fair agreement between the overall results from histopathology and serum ELISA (Kappa = 0.33), though there appeared to be some variation in agreement between the tests on the individual ‘Champion Farms’. The presence of MAP was confirmed in seven of the eight farms which contributed animals to this study, despite sometimes prolonged efforts at controlling the disease. A separate study was undertaken to make use of the archives of the Scottish Centre for Production Animal Health and Food Safety at the Veterinary School, University of Glasgow. The archive contained records of cases from across southern Scotland and northern England. Analysis of the data generated from examination of these records suggested that MAP is widespread within the Scottish cattle herd and may well be increasin