Estimating the Health and Economic Impact of Improved Management in Prevalent Chronic Obstructive Pulmonary Disease Populations in England, Germany, Canada, and Japan: A Modelling Study.

Introduction: COPD is a leading cause of morbidity and mortality globally. Management is complex and costly. Although international quality standards for diagnosis and management exist, opportunities remain to improve outcomes, especially in reducing avoidable hospitalisations. Objective: To estimate the potential health and economic impact of improved adherence to guideline-recommended care for prevalent, on-treatment COPD populations in four high-income settings. Methods: A disease simulation model was developed to evaluate the impact of theoretical improvements to COPD management, comparing outcomes for usual care and policy scenarios for interventions that reduce avoidable hospitalisations: 1) increased attendance (50% vs 31-38%) of early follow-up review after severe exacerbation hospitalisation; 2) increased access (30% vs 5-10%) to an integrated disease management (IDM) programme that provides guideline adherent care. Results: For cohorts of 100,000 patients, Policy 1 yielded additional life years (England: 523; Germany: 759; Canada: 1316; Japan: 512) and lifetime cost savings (-£2.89 million; -€6.58 million; -$40.08 million; -¥735.58 million). For Policy 2, additional life years (2299; 3619; 3656) and higher lifetime total costs (£38.15 million; €35.58 million; ¥1091.53 million) were estimated in England, Germany and Japan, and additional life years (4299) and cost savings (-$20.52 million) in Canada. Scenarios found that the cost impact depended on the modelled intervention effect size. Conclusion: Interventions that reduce avoidable hospitalisations are estimated to improve survival and may generate cost savings. This study provides evidence on the theoretical impact of policies to improve COPD care and highlights priority areas for further research to support evidence-based policy decisions.

Comparative Efficacy and Safety of Fostemsavir in Heavily Treatment-Experienced People With HIV-1.

PURPOSE: Heavily treatment-experienced (HTE) people with multidrug-resistant HIV-1 have limited treatment options. Treatment with the first-in-class attachment inhibitor fostemsavir in addition to optimized background therapy (OBT) resulted in sustained virologic and immunologic responses in HTE participants throughout 96 weeks in the BRIGHTE trial. In the absence of long-term direct comparative evidence between fostemsavir-based and other antiretroviral regimens, this analysis indirectly compares efficacy and safety across relevant available trials, adjusting for demographic and baseline characteristics. METHODS: A systematic literature review was conducted to identify trials with designs and populations comparable to BRIGHTE. Using matching-adjusted indirect comparison analyses, individual participant data from BRIGHTE were reweighted to create balanced populations across trials, and efficacy and safety outcomes were compared. FINDINGS: Three comparator trials were identified, 2 of which reflected an optimized therapy without fostemsavir (OBT alone): TMB-301 (ibalizumab and OBT), BENCHMRK-1/-2 (OBT alone), and VIKING-3 (OBT alone). Compared with ibalizumab and OBT (N = 40), fostemsavir and OBT (unadjusted, N = 347; adjusted, N = 236) were associated with numerically higher nonsignificant odds of virologic suppression (odds ratio [OR] = 1.44; 95% CI, 0.74-2.80; P = 0.284) and a similar increase in CD4+ cell count of approximately 65 cells/mm3 from baseline through week 24 (mean difference = 7.05 cells/mm3; 95% CI, -60.88 to 74.98 cells/mm3; P = 0.834). Compared with OBT from BENCHMRK-1/-2 (N = 237), fostemsavir and OBT (adjusted, N = 126) were associated with significantly higher odds of virologic suppression (OR = 3.26; 95% CI, 2.08-5.11; P < 0.001) and increased CD4+ cell count (135.78 cells/mm3; 95% CI, 91.93-179.63 cells/mm3; P < 0.001) at week 96. Compared with OBT from VIKING-3 (N = 183), fostemsavir and OBT (adjusted, N = 78) were associated with numerically higher odds of virologic suppression (OR = 1.34; 95% CI, 0.78-2.30; P = 0.297) and a modest CD4+ cell count increase (26.86 cells/mm3; 95% CI, -10.79 to 64.52; P = 0.162) through week 48; however, differences were not significant. All-cause discontinuations and safety comparisons varied across studies. IMPLICATIONS: Although matching-adjusted indirect comparison analyses have limitations, these results support the use of fostemsavir and OBT as an important treatment option in HTE people with multidrug-resistant HIV-1.

Impact of Delayed Diagnosis and Misdiagnosis for Patients with Transthyretin Amyloid Cardiomyopathy (ATTR-CM): A Targeted Literature Review.

INTRODUCTION: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal and under-recognized disease. This targeted literature review assessed the extent and consequences of diagnostic delay and misdiagnosis in ATTR-CM. METHODS: The Embase database was searched together with proceedings of eight cardiology conferences to identify publications or abstracts on ATTR-CM. Outcomes of interest were time from symptom onset to diagnosis, rates of delayed diagnosis and misdiagnosis, and costs, healthcare resource use or clinical outcomes whilst undiagnosed/misdiagnosed. RESULTS: Twenty-three articles were included. Weighted means of reported mean and median diagnostic delays were 6.1 and 3.4 years for wild-type (ATTRwt-CM) and 5.7 and 2.6 years for hereditary (ATTRv-CM). Misdiagnosis occurred in 34-57% of patients when reported. Evaluation and misdiagnosis by multiple healthcare providers before receiving an ATTR-CM diagnosis was common, and there was evidence that patients undergo unnecessary or inappropriate evaluations or treatments while misdiagnosed. Diagnostic "red flags" were reported to be underused. Data on the consequences of delay for patients and health systems were sparse, but given the progressive nature of ATTR-CM, delay is likely to have adverse consequences. CONCLUSION: ATTR-CM patients commonly experience diagnostic delay and misdiagnosis. Efforts are required to provide timely diagnosis so that patients can benefit from earlier access to new disease-modifying therapies.

Associations between serum potassium and adverse clinical outcomes: A systematic literature review.

BACKGROUND AND OBJECTIVES: Despite the growing body of evidence characterising the association between serum potassium levels and adverse clinical outcomes, a contemporary summary of available evidence is currently lacking. The objective of this study, therefore, was to undertake a systematic literature review to identify all relevant evidence assessing risk factors associated with the incidence of hyperkalaemia (HK) and also quantifying the effect of serum potassium levels on risk of adverse clinical outcomes. METHODS: PubMed (Medline and Medline In-Process), Embase and the Cochrane Library were searched for studies published between January 2002 and November 2018. Search inclusion criteria included studies describing either the incidence of HK events and any associated risk factors, or associations between HK or serum potassium concentration and adverse clinical outcomes including mortality, hospitalisation, major adverse cardiac events (MACE) and renin-angiotensin-aldosterone system inhibitors (RAASi) discontinuation in adult patients with chronic kidney disease (CKD), heart failure (HF), type 2 diabetes (T2DM) or hypertension. RESULTS: The search identified 1,897 publications. From these, a total of 123 studies met the inclusion criteria and were included in the review. The most commonly identified risk factors associated with HK events were the presence of CKD or renal impairment, T2DM, HF, hypertension, RAASi use and mineralocorticoid receptor antagonist use. Potassium levels both above and below the normal range were consistently associated with adverse clinical outcomes, with relative and absolute risks of outcomes increasing with severity of hyper- or hypokalaemia. These associations were consistently reported across a broad range of patient population types and study types. CONCLUSION: The current body of published evidence is compelling in its confirmation of the associations between serum potassium levels and adverse clinical outcomes. This review further highlights the importance of avoiding both hyper- and hypokalaemia, in order to reduce risk of mortality, hospitalisation, MACE and RAASi discontinuation or down-titration.