Background-Because of the prevalence and expense of congestive heart failure (CHF), significant efforts have been made to develop disease management (DM) programs that will improve clinical and financial outcomes. The effectiveness of such programs in a large, heterogeneous population of CHF patients remains unknown. Methods and Results-We randomized 1069 patients (aged 70.9Ϯ10.3 years) with systolic (ejection fraction 35Ϯ9%) or echocardiographically confirmed diastolic heart failure (HF) to assess telephonic DM over an 18-month period. Data were collected at baseline and at 6-month intervals. Survival analysis was performed by Kaplan-Meier and Cox regression methods. Healthcare utilization was defined after extensive record review, with an attempt to account for all inpatient and outpatient visits, medications, and diagnostic tests. We obtained data on 92% of the patients, from nearly 53 000 health-related encounters. Total cost per patient was defined by adding estimated costs for the observed encounters, excluding the cost of the DM. Kaplan-Meier analysis showed that DM patients had a reduced mortality rate (Pϭ0.037), with DM patients surviving an average of 76 days longer than controls. Subgroup analysis showed that DM had beneficial outcomes in patients with systolic HF (hazard ratio 0.62; Pϭ0.040), which was more pronounced in NYHA classes III and IV. Although improvements in NYHA class were more likely with DM (PϽ0.001), 6-minute walk data from 217 patients in whom data were available at each visit showed no significant benefit from DM (Pϭ0.08). Total and CHF-related healthcare utilization, including medications, office or emergency department visits, procedures, or hospitalizations, was not decreased by DM. Repeated-measures ANOVA for cost by group showed no significant differences, even in the higher NYHA class groups. Conclusions-Participation in DM resulted in a significant survival benefit, most notably in symptomatic systolic HF patients. Although DM was associated with improved NYHA class, 6-minute walk test results did not improve.

Background: Escherichia coli causes over one third of the bacteraemia cases in England each year, and the incidence of these infections is increasing.

Background Evidence for the effectiveness of vitiligo treatments is limited. Objectives To determine the effectiveness of (i) handheld narrowband UVB (NB-UVB) and (ii) a combination of potent topical corticosteroid (TCS) and NB-UVB, compared with TCS alone, for localized vitiligo. Methods A pragmatic, three-arm, placebo-controlled randomized controlled trial (9-month treatment, 12-month follow-up). Adults and children, recruited from secondary care and the community, aged ≥ 5 years and with active vitiligo affecting < 10% of skin, were randomized 1 : 1 : 1 to receive TCS (mometasone furoate 0Á1% ointment + dummy NB-UVB), NB-UVB (NB-UVB + placebo TCS) or a combination (TCS + NB-UVB). TCS was applied once daily on alternating weeks; NB-UVB was administered on alternate days in escalating doses, adjusted for erythema. The primary outcome was treatment success at 9 months at a target patch assessed using the participant-reported Vitiligo Noticeability Scale, with

Prognosis and survival for malignant melanoma is highly dependent on early diagnosis and treatment. While the American Joint Committee on Cancer (AJCC) criterion provides a means of staging melanomas and guiding treatment approaches, it is unable to identify the risk of disease progression of early stage tumors or provide reliable stratification for novel adjuvant therapies. The demand for credible prognostic/companion biomarkers able to identify high-risk melanoma subgroups as well as guide more effective personalized/precision-based therapy is therefore of paramount importance. Autophagy, the principle lysosomal-mediated process for the degradation/recycling of cellular debris, is a hot topic in cancer medicine, and observations of its deregulation in melanoma have brought its potential as a prognostic biomarker to the forefront of current research. Key regulatory proteins, including Atg8/microtubule-associated light chain 3 (LC3) and BECN1 (Beclin 1), have been proposed as potential prognostic biomarkers. However, given the dynamic nature of autophagy, their expression in vitro does not translate to their use as a prognostic biomarker for melanoma in vivo. We have recently identified the expression levels of Sequestosome1/SQSTM1 (p62) and activating molecule in Beclin 1-regulated autophagy protein 1 (AMBRA1) as novel independent prognostic biomarkers for early stage melanomas. While increasing followed by subsequent decreasing levels of p62 expression reflects the paradoxical role of autophagy in melanoma, expression levels additionally define a novel prognostic biomarker for AJCC stage II tumors. Conversely, loss of AMBRA1 in the epidermis overlying primary melanomas defines a novel prognostic biomarker for AJCC stage I tumors. Collectively, the definition of AMBRA1 and p62 as prognostic biomarkers for early stage melanomas provides novel and accurate means through which to identify tumors at risk of disease progression, facilitating earlier patient therapeutic intervention and stratification tools for novel personalized therapeutic approaches to improve clinical outcome.

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The coronavirus disease 2019 (COVID‐19) pandemic has rapidly challenged the pharmaceutical industry to implement remote clinical trials. The industry’s lack of extensive experience with remote measurements initiates multiple questions about how to select candidates for remote collection, their validity, and regulatory implications of moving certain assessments to a remote mode. We propose a decision tree for migration of clinic to remote assessments and highlight activities required to ensure that these measurements are valid, safe, and usable.

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The incidence of unsatisfactory death certificates within a hospital setting is high. Increased education and better documentation leads to improvements in accuracy and legitimacy.