Evaluating the effect of inequalities in oral anti-coagulant prescribing on outcomes in people with atrial fibrillation.

Aims: Whilst anti-coagulation is typically recommended for thromboprophylaxis in atrial fibrillation (AF), it is often never prescribed or prematurely discontinued. The aim of this study was to evaluate the effect of inequalities in anti-coagulant prescribing by assessing stroke/systemic embolism (SSE) and bleeding risk in people with AF who continue anti-coagulation compared with those who stop transiently, permanently, or never start. Methods and results: This retrospective cohort study utilized linked Scottish healthcare data to identify adults diagnosed with AF between January 2010 and April 2016, with a CHA2DS2-VASC score of ≥2. They were sub-categorized based on anti-coagulant exposure: never started, continuous, discontinuous, and cessation. Inverse probability of treatment weighting-adjusted Cox regression and competing risk regression was utilized to compare SSE and bleeding risks between cohorts during 5-year follow-up. Of an overall cohort of 47 427 people, 26 277 (55.41%) were never anti-coagulated, 7934 (16.72%) received continuous anti-coagulation, 9107 (19.2%) temporarily discontinued, and 4109 (8.66%) permanently discontinued. Lower socio-economic status, elevated frailty score, and age ≥ 75 were associated with a reduced likelihood of initiation and continuation of anti-coagulation. Stroke/systemic embolism risk was significantly greater in those with discontinuous anti-coagulation, compared with continuous [subhazard ratio (SHR): 2.65; 2.39-2.94]. In the context of a major bleeding event, there was no significant difference in bleeding risk between the cessation and continuous cohorts (SHR 0.94; 0.42-2.14). Conclusion: Our data suggest significant inequalities in anti-coagulation prescribing, with substantial opportunity to improve initiation and continuation. Decision-making should be patient-centred and must recognize that discontinuation or cessation is associated with considerable thromboembolic risk not offset by mitigated bleeding risk.

How Least Developed to Lower-Middle Income Countries Use Health Technology Assessment: A Scoping Review.

Health Technology Assessment (HTA) is a multidisciplinary tool to inform healthcare decision-making. HTA has been implemented in high-income countries (HIC) for several decades but has only recently seen a growing investment in low- and middle-income countries. A scoping review was undertaken to define and compare the role of HTA in least developed and lower middle-income countries (LLMIC). MEDLINE and EMBASE databases were searched from January 2015 to August 2021. A matrix comprising categories on HTA objectives, methods, geographies, and partnerships was used for data extraction and synthesis to present our findings. The review identified 50 relevant articles. The matrix was populated and sub-divided into further categories as appropriate. We highlight topical aspects of HTA, including initiatives to overcome well-documented challenges around data and capacity development, and identify gaps in the research for consideration. Those areas we found to be under-studied or under-utilized included disinvestment, early HTA/implementation, system-level interventions, and cross-sectoral partnerships. We consider broad practical implications for decision-makers and researchers aiming to achieve greater interconnectedness between HTA and health systems and generate recommendations that LLMIC can use for HTA implementation. Whilst HIC may have led the way, LLMIC are increasingly beginning to develop HTA processes to assist in their healthcare decision-making. This review provides a forward-looking model that LLMIC can point to as a reference for their own implementation. We hope this can be seen as timely and useful contributions to optimize the impact of HTA in an era of investment and expansion and to encourage debate and implementation.

Understanding Pathways into Care homes using Data (UnPiCD study): a retrospective cohort study using national linked health and social care data.

BACKGROUND: Pathways into care are poorly understood but important life events for individuals and their families. UK policy is to avoid moving-in to care homes from acute hospital settings. This assumes that moves from secondary care represent a system failure. However, those moving to care homes from community and hospital settings may be fundamentally different groups, each requiring differing care approaches. OBJECTIVE: To characterise individuals who move-in to a care home from hospital and compare with those moving-in from the community. DESIGN AND SETTING: A retrospective cohort study using cross-sectoral data linkage of care home data. METHODS: We included adults moving-in to care homes between 1/4/13 and 31/3/16, recorded in the Scottish Care Home Census. Care home data were linked to general and psychiatric hospital admissions, community prescribing and mortality records to ascertain comorbidities, significant diagnoses, hospital resource use, polypharmacy and frailty. Multivariate logistic regression identified predictors of moving-in from hospital compared to from community. RESULTS: We included 23,892 individuals moving-in to a care home, 13,564 (56.8%) from hospital and 10,328 (43.2%) from the community. High frailty risk adjusted Odds Ratio (aOR) 5.11 (95% Confidence Interval (CI): 4.60-5.68), hospital discharge with diagnosis of fracture aOR 3.91 (95%CI: 3.41-4.47) or stroke aOR 8.42 (95%CI: 6.90-10.29) were associated with moving-in from hospital. Discharge from in-patient psychiatry was also a highly significant predictor aOR 19.12 (95%CI: 16.26-22.48). CONCLUSIONS: Individuals moving-in to care homes directly from hospital are clinically distinct from those from the community. Linkage of cross-sectoral data can allow exploration of pathways into care at scale.

Propensity score methods for comparative-effectiveness analysis: A case study of direct oral anticoagulants in the atrial fibrillation population.

OBJECTIVE: To explore methodological challenges when using real-world evidence (RWE) to estimate comparative-effectiveness in the context of Health Technology Assessment of direct oral anticoagulants (DOACs) in Scotland. METHODS: We used linkage data from the Prescribing Information System (PIS), Scottish Morbidity Records (SMR) and mortality records for newly anticoagulated patients to explore methodological challenges in the use of Propensity score (PS) matching, Inverse Probability Weighting (IPW) and covariate adjustment with PS. Model performance was assessed by standardised difference. Clinical outcomes (stroke and major bleeding) and mortality were compared for all DOACs (including apixaban, dabigatran and rivaroxaban) versus warfarin. Patients were followed for 2 years from first oral anticoagulant prescription to first clinical event or death. Censoring was applied for treatment switching or discontinuation. RESULTS: Overall, a good balance of patients' covariates was obtained with every PS model tested. IPW was found to be the best performing method in assessing covariate balance when applied to subgroups with relatively large sample sizes (combined-DOACs versus warfarin). With the IPTW-IPCW approach, the treatment effect tends to be larger, but still in line with the treatment effect estimated using other PS methods. Covariate adjustment with PS in the outcome model performed well when applied to subgroups with smaller sample sizes (dabigatran versus warfarin), as this method does not require further reduction of sample size, and trimming or truncation of extreme weights. CONCLUSION: The choice of adequate PS methods may vary according to the characteristics of the data. If assumptions of unobserved confounding hold, multiple approaches should be identified and tested. PS based methods can be implemented using routinely collected linked data, thus supporting Health Technology decision-making.

A two-part model to estimate inpatient, outpatient, prescribing and care home costs associated with atrial fibrillation in Scotland.

OBJECTIVE: This study aimed to estimate global inpatient, outpatient, prescribing and care home costs for patients with atrial fibrillation using population-based, individual-level linked data. DESIGN: A two-part model was employed to estimate the probability of resource utilisation and costs conditional on positive utilisation using individual-level linked data. SETTINGS: Scotland, 5 years following first hospitalisation for AF between 1997 and 2015. PARTICIPANTS: Patients hospitalised with a known diagnosis of AF or atrial flutter. PRIMARY AND SECONDARY OUTCOME MEASURES: Inpatient, outpatient, prescribing and care home costs. RESULTS: The mean annual cost for a patient with AF was estimated at £3785 (95% CI £3767 to £3804). Inpatient admissions and outpatient visits accounted for 79% and 8% of total costs, respectively; prescriptions and care home stay accounted for 7% and 6% of total costs. Inpatient cost was the main driver across all age groups. While inpatient cost contributions (~80%) were constant between 0 and 84 years, they decreased for patients over 85 years. This is offset by increasing care home cost contributions. Mean annual costs associated with AF increased significantly with increasing number of comorbidities. CONCLUSION: This study used a contemporary and representative cohort, and a comprehensive approach to estimate global costs associated with AF, taking into account resource utilisation beyond hospital care. While overall costs, considerably affected by comorbidity, did not increase with increasing age, care home costs increased proportionally with age. Inpatient admission was the main contributor to the overall financial burden of AF, highlighting the need for improved mechanisms of early diagnosis to prevent hospitalisations.

Risk of grade 3-4 diarrhea and mucositis in colorectal cancer patients receiving anti-EGFR monoclonal antibodies regimens: A meta-analysis of 18 randomized controlled clinical trials.

The anti-Epidermal Growth Factor Receptor monoclonal antibodies (anti-EGFR MoAbs) are beneficial in the treatment of wild type (WT) KRAS colorectal cancer, but are burdened by serious toxicities. We conducted a systematic review and meta-analysis to determine incidence and relative risk (RR) of severe and life-threatening diarrhoea and mucositis in colorectal cancer patients and WT-KRAS subpopulation. PubMed and Embase were searched for trials comparing the same therapeutic regimens with or without anti-EGFR for colorectal cancer. Data on severe and life-threatening diarrhoea and mucositis were extracted from 18 studies involving 13,382 patients. Statistical analyses calculated incidence of AEs, RRs and 95% confidence intervals by using either random or fixed effects models. Patients receiving anti-EGFR MoAbs showed an increased risk of diarrhoea (RR: 1.66, CI 1.52-1.80) and mucositis (RR: 3.44, CI 2.66-4.44). The risk was similar among WT-KRAS patients. Prevention and risk reduction strategies of these AEs are mandatory to optimize clinical outcomes.