The growing rural–urban divide in US life expectancy : contribution of cardiovascular disease and other major causes of death

Background The US rural disadvantage in life expectancy (LE) relative to urban areas has grown over time. We measured the contribution of cardiovascular disease (CVD), drug-overdose deaths (DODs) and other major causes of death to LE trends in rural and urban counties and the rural–urban LE gap. Methods Counterfactual life tables and cause-of-death decompositions were constructed using data on all US deaths in 1999–2019 (N = 51 998 560) from the Centers for Disease Control and Prevention. Results During 1999–2009, rural and urban counties experienced robust LE gains, but urban LE increased by 1.19 years more in women and 0.86 years more in men compared with rural LE. During 2010–2019, rural counties experienced absolute declines in LE (women −0.20, men −0.30 years), whereas urban counties experienced modest increases (women 0.55, men 0.29 years). Counterfactual analysis showed that slowed CVD-mortality declines, particularly in ages 65+ years, were the main reason why rural LE stopped increasing after 2010. However, slow progress in CVD-mortality influenced LE trends more in urban areas. If CVD-mortality had continued to decline at its pre-2010 pace, the rural–urban LE gap would have grown even more post 2010. DODs and other causes of death also contributed to the LE trends and differences in each period, but their impact in comparison to that of CVD was relatively small. Conclusions Rural disadvantage in LE continues to grow, but at a slower pace than pre 2010. This slowdown is more attributable to adverse trends in CVD and DOD mortality in urban areas than improvements in rural areas.Peer reviewe

Rejoinder to “The Prevalence of Cognitive Impairment Is Not Increasing in the United States: A Critique of Hale et al. (2020)”

Non peer reviewe

Life expectancy with and without cognitive impairment by diabetes status among older Americans

Peer reviewe

Multiplanar strain quantification for assessment of right ventricular dysfunction and non-ischemic fibrosis among patients with ischemic mitral regurgitation

Background: Ischemic mitral regurgitation (iMR) predisposes to right ventricular (RV) pressure and volume overload, providing a nidus for RV dysfunction (RVDYS) and non-ischemic fibrosis (NIF). Echocardiography (echo) is widely used to assess iMR, but performance of different indices as markers of RVDYS and NIF is unknown. Methods: iMR patients prospectively underwent echo and cardiac magnetic resonance (CMR) within 72 hours. Echo quantified iMR, assessed conventional RV indices (TAPSE, RV-S’, fractional area change [FAC]), and strain via speckle tracking in apical 4-chamber (global longitudinal strain [RV-GLS]) and parasternal long axis orientation (transverse strain). CMR volumetrically quantified RVEF, and assessed ischemic pattern myocardial infarction (MI) and septal NIF. Results: 73 iMR patients were studied; 36% had RVDYS (EF<50%) on CMR among whom LVEF was lower, PA systolic pressure higher, and MI size larger (all p<0.05). CMR RVEF was paralleled by echo results; correlations were highest for RV-GLS (r = 0.73) and lowest for RV-S’ (r = 0.43; all p<0.001). RVDYS patients more often had CMR-evidenced NIF (54% vs. 7%; p<0.001). Whereas all RV indices were lower among NIF-affected patients (all p≤0.006), percent change was largest for transverse strain (48.3%). CMR RVEF was independently associated with RV-GLS (partial r = 0.57, p<0.001) and transverse strain (r = 0.38, p = 0.002) (R = 0.78, p<0.001). Overall diagnostic performance of RV-GLS and transverse strain were similar (AUC = 0.93[0.87–0.99]|0.91[0.84–0.99], both p<0.001), and yielded near equivalent sensitivity and specificity (85%|83% and 80%|79% respectively). Conclusion: Compared to conventional echo indices, RV strain parameters yield stronger correlation with CMR-defined RVEF and potentially constitute better markers of CMR-evidenced NIF in iMR

HEROIC: a 5-year observational cohort study aimed at identifying novel factors that drive diabetic kidney disease: rationale and study protocol

Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. INTRODUCTION: Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease worldwide and a major cause of premature mortality in diabetes mellitus (DM). While improvements in care have reduced the incidence of kidney disease among those with DM, the increasing prevalence of DM means that the number of patients worldwide with DKD is increasing. Improved understanding of the biology of DKD and identification of novel therapeutic targets may lead to new treatments. A major challenge to progress has been the heterogeneity of the DKD phenotype and renal progression. To investigate the heterogeneity of DKD we have set up The East and North London Diabetes Cohort (HEROIC) Study, a secondary care-based, multiethnic observational study of patients with biopsy-proven DKD. Our primary objective is to identify histological features of DKD associated with kidney endpoints in a cohort of patients diagnosed with type 1 and type 2 DM, proteinuria and kidney impairment. METHODS AND ANALYSIS: HEROIC is a longitudinal observational study that aims to recruit 500 patients with DKD at high-risk of renal and cardiovascular events. Demographic, clinical and laboratory data will be collected and assessed annually for 5 years. Renal biopsy tissue will be collected and archived at recruitment. Blood and urine samples will be collected at baseline and during annual follow-up visits. Measured glomerular filtration rate (GFR), echocardiography, retinal optical coherence tomography angiography and kidney and cardiac MRI will be performed at baseline and twice more during follow-up. The study is 90% powered to detect an association between key histological and imaging parameters and a composite of death, renal replacement therapy or a 30% decline in estimated GFR. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Bloomsbury Research Ethics Committee (REC 18-LO-1921). Any patient identifiable data will be stored on a password-protected National Health Services N3 network with full audit trail. Anonymised imaging data will be stored in a ISO27001-certificated data warehouse.Results will be reported through peer-reviewed manuscripts and conferences and disseminated to participants, patients and the public using web-based and social media engagement tools as well as through public events

Satisfaction with web-based training in an integrated healthcare delivery network: do age, education, computer skills and attitudes matter?

<p>Abstract</p> <p>Background</p> <p>Healthcare institutions spend enormous time and effort to train their workforce. Web-based training can potentially streamline this process. However the deployment of web-based training in a large-scale setting with a diverse healthcare workforce has not been evaluated. The aim of this study was to evaluate the satisfaction of healthcare professionals with web-based training and to determine the predictors of such satisfaction including age, education status and computer proficiency.</p> <p>Methods</p> <p>Observational, cross-sectional survey of healthcare professionals from six hospital systems in an integrated delivery network. We measured overall satisfaction to web-based training and response to survey items measuring Website Usability, Course Usefulness, Instructional Design Effectiveness, Computer Proficiency and Self-learning Attitude.</p> <p>Results</p> <p>A total of 17,891 healthcare professionals completed the web-based training on HIPAA Privacy Rule; and of these, 13,537 completed the survey (response rate 75.6%). Overall course satisfaction was good (median, 4; scale, 1 to 5) with more than 75% of the respondents satisfied with the training (rating 4 or 5) and 65% preferring web-based training over traditional instructor-led training (rating 4 or 5). Multivariable ordinal regression revealed 3 key predictors of satisfaction with web-based training: Instructional Design Effectiveness, Website Usability and Course Usefulness. Demographic predictors such as gender, age and education did not have an effect on satisfaction.</p> <p>Conclusion</p> <p>The study shows that web-based training when tailored to learners' background, is perceived as a satisfactory mode of learning by an interdisciplinary group of healthcare professionals, irrespective of age, education level or prior computer experience. Future studies should aim to measure the long-term outcomes of web-based training.</p

Ginkgo biloba for the treatment of vitilgo vulgaris: an open label pilot clinical trial

<p>Abstract</p> <p>Background</p> <p>Vitiligo is a common hypopigmentation disorder with significant psychological impact if occurring before adulthood. A pilot clinical trial to determine the feasibility of an RCT was conducted and is reported here.</p> <p>Methods</p> <p>12 participants 12 to 35 years old were recruited to a prospective open-label pilot trial and treated with 60 mg of standardized <it>G. biloba </it>two times per day for 12 weeks. The criteria for feasibility included successful recruitment, 75% or greater retention, effectiveness and lack of serious adverse reactions. Effectiveness was assessed using the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force (VETF), which are validated outcome measures evaluating the area and intensity of depigmentation of vitiligo lesions. Other outcomes included photographs and adverse reactions. Safety was assessed by serum coagulation factors (platelets, PTT, INR) at baseline and week 12.</p> <p>Results</p> <p>After 2 months of recruitment, the eligible upper age limit was raised from 18 to 35 years of age in order to facilitate recruitment of the required sample size. Eleven participants completed the trial with 85% or greater adherence to the protocol. The total VASI score improved by 0.5 (P = 0.021) from 5.0 to 4.5, range of scale 0 (no depigmentation) to 100 (completely depigmented). The progression of vitiligo stopped in all participants; the total VASI indicated an average repigmentation of vitiligo lesions of 15%. VETF total vitiligo lesion area decreased 0.4% (P = 0.102) from 5.9 to 5.6 from baseline to week 12. VETF staging score improved by 0.7 (P = 0.101) from 6.6 to 5.8, and the VETF spreading score improved by 3.9 (P < 0.001)) from 2.7 to -1.2. There were no statistically significant changes in platelet count, PTT, or INR.</p> <p>Conclusions</p> <p>The criteria for feasibility were met after increasing the maximum age limit of the successful recruitment criterion; participant retention, safety and effectiveness criteria were also met. Ingestion of 60 mg of <it>Ginkgo biloba </it>BID was associated with a significant improvement in total VASI vitiligo measures and VETF spread, and a trend towards improvement on VETF measures of vitiligo lesion area and staging. Larger, randomized double-blind clinical studies are warranted and appear feasible.</p> <p>Trial Registration</p> <p>Clinical trials.gov registration number <a href="http://www.clinicaltrials.gov/ct2/show/NCT00907062">NCT00907062</a></p

HSV-2 glycoprotein gD targets the CC domain of tetherin and promotes tetherin degradation via lysosomal pathway.

BACKGROUND: HSV-2 is the major cause of genital herpes. We previously demonstrated that the host viral restriction factor tetherin restricts HSV-2 release and is antagonized by several HSV-2 glycoproteins. However, the mechanisms underlying HSV-2 glycoproteins mediated counteraction of tetherin remain unclear. In this study, we investigated whether tetherin restricts the cell-to-cell spread of HSV-2 and the mechanisms underlying HSV-2 gD mediated antagonism of tetherin. METHODS: Infectious center assays were used to test whether tetherin could affect cell-to-cell spread of HSV-2. Coimmunoprecipitation assays were performed to map the tetherin domains required for HSV-2 gD-mediated downregulation. Immunoflurence assays were performed to detect the accumulation of tetherin in lysosomes or proteasomes. All experiments were repeated for at least three times and the data were performed statistical analysis. RESULTS: 1) Tetherin restricts cell-to-cell spread of HSV-2; 2) HSV-2 gD specifically interacts with the CC domain of tetherin; 3) HSV-2 gD promotes tetherin to the lysosomal degradation pathway. CONCLUSIONS: Tetherin not only restricts HSV-2 release but also its cell-to-cell spread. In turn, HSV-2 gD targets the CC domain of tetherin and promotes its degradation in the lysosome. Findings in this study have increased our understanding of tetherin restriction and viral countermeasures

The Reno-Vascular A2B Adenosine Receptor Protects the Kidney from Ischemia

Using gene-targeted mice, Holger Eltzschig and colleagues identify the A2B adenosine receptor as a novel therapeutic target for providing protection from renal ischemia