Incidence of Respiratory Syncytial Virus Infection in Older Adults: Limitations of Current Data.

INTRODUCTION: Respiratory syncytial virus (RSV) is an important cause of severe respiratory illness in older adults and adults with respiratory or cardiovascular comorbidities. Published estimates of its incidence and prevalence in adult groups vary widely. This article reviews the potential limitations affecting RSV epidemiology studies and suggests points to consider when evaluating or designing them. METHODS: Studies reporting the incidence or prevalence of RSV infection in adults in high-income Western countries from 2000 onwards were identified via a rapid literature review. Author-reported limitations were recorded, together with presence of other potential limitations. Data were synthesized narratively, with a focus on factors affecting incidence estimates for symptomatic infection in older adults. RESULTS: A total of 71 studies met the inclusion criteria, most in populations with medically attended acute respiratory illness (ARI). Only a minority used case definitions and sampling periods tailored specifically to RSV; many used influenza-based or other criteria that are likely to result in RSV cases being missed. The great majority relied solely on polymerase chain reaction (PCR) testing of upper respiratory tract samples, which is likely to miss RSV cases compared with dual site sampling and/or addition of serology. Other common limitations were studying a single season, which has potential for bias due to seasonal variability; failure to stratify results by age, which underestimates the burden of severe disease in older adults; limited generalizability beyond a limited study setting; and absence of measures of uncertainty in the reporting of results. CONCLUSIONS: A significant proportion of studies are likely to underestimate the incidence of RSV infection in older adults, although the effect size is unclear and there is also potential for overestimation. Well-designed studies, together with increased testing for RSV in patients with ARI in clinical practice, are required to accurately capture both the burden of RSV and the potential public health impact of vaccines.

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.

Impact of novel agents on patient-relevant outcomes in patients with previously untreated chronic lymphocytic leukemia who are not eligible for fludarabine-based therapy.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is an orphan disease that primarily affects the elderly. The majority of symptomatic patients eligible for frontline treatment are unfit for fludarabine based chemoimmunotherapy. Historical treatment includes chlorambucil (Chl), bendamustine/rituximab (BR), and chlorambucil/rituximab/ChlR combination. Clinical guidelines now recommend the use of novel agents, such as ibrutinib (Ibr), in both frontline and relapse settings and other novel agents, such as idelalisib (with rituximab), in relapse settings. Despite compelling clinical results for novel agents, follow-up in clinical trials is relatively short and, thus, the comparative long-term benefits are still unknown. MATERIALS AND METHODS: The authors developed a simulation model to generate treatment specific lifetime estimates of Overall Survival (OS) and Quality Adjusted Life Years (QALYs) for treatment with BR, Chl, ChlR, and Ibr. Two potential clinical scenarios were modelled: with and without novel agents for treating CLL. The model was based on health states relating to first- and second-line progression-free survival (PFS), post-progression survival, and death. RESULTS: Where novel agents were assumed unavailable, mean OS ranged from 5.4-8.5 years and QALYs from 3.5-6.1. Where novel agents were available, the mean OS increased to 10.0 years, with a corresponding increase in QALYs to 7.6. Frontline Ibr use followed by Physician's Choice, including novel agents at relapse, resulted in projected increase in OS of between 18% (1.5 years) and 85% (4.6 years), corresponding to a 25-117% increase in QALYs, compared with currently available traditional therapies. LIMITATIONS: The limitations of this analysis include immature OS data and the assumption of equivalent efficacy across all novel agents in terms of their impact on PFS and OS. CONCLUSIONS: The use of novel agents is predicted to yield substantive gains in predicted lifetime OS and QALY improvements compared to traditional therapies in CLL patients who are ineligible for fludarabine-based chemoimmunotherapy.

Stapled peptide induces cancer cell death.

Hydrocarbon stapling could enable peptides from the key domains of natural proteins to be used therapeutically. Using the technique on a peptide involved in apoptosis, researchers have succeeded in destroying cancer cells in a mouse model of leukaemia.

Actin strange.

Actin, an abundant protein forming part of the cytoskeleton, can act as a co-factor for viral enzymes and could thus be the key to a potential new class of anti-viral drugs.