Clinical deterioration after sildenafil cessation in patients with pulmonary hypertension

Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE-5). Its chronic administration has been shown to improve exercise capacity, World Health Organization functional class, and haemodynamics in patients with symptomatic pulmonary arterial hypertension (PAH). There is however, no data describing the clinical consequences of sudden cessation of sildenafil treatment. In this series, 9 patients with NYHA Class II–IV PAH who were stable on 2 months of sildenafil monotherapy, had their sildenafil ceased to accommodate a 2-week washout period, required for enrollment in research involving an endothelin receptor antagonist. Six minute walk distance (SMWD) and clinical assessments were performed before cessation of sildenafil, and again 2 weeks later. Over the course of this 2-week washout period, 6 of the 9 patients reported increased breathlessness and fatigue, 1 of these was hospitalized with worsening right heart failure. The SMWD fell in 6 patients, with falls of greater than 100 m recorded in 4 patients. This was accompanied by a worsening of NYHA Class from 2.5 ± 0.2 to 3.1 ± 0.1 (mean ± SEM, p = 0.01). These data indicate that sudden cessation of sildenafil monotherapy, in patients with PAH, carries with it a significant and unpredictable risk of rapid clinical deterioration. We recommend that if sildenafil needs to be ceased, it would be more prudent to consider concurrent vasodilator therapy before the gradual cessation of sildenafil

Use of a Single Coil Transvenous Electrode with an Abdominally Placed Implantable Cardioverter Defibrillator in Children

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73702/1/j.1540-8159.2000.tb00859.x.pd

Erectile Dysfunction Severity as a Risk Marker for Cardiovascular Disease Hospitalisation and All-Cause Mortality: A Prospective Cohort Study

BACKGROUND Erectile dysfunction is an emerging risk marker for future cardiovascular disease (CVD) events; however, evidence on dose response and specific CVD outcomes is limited. This study investigates the relationship between severity of erectile dysfunction and specific CVD outcomes. METHODS AND FINDINGS We conducted a prospective population-based Australian study (the 45 and Up Study) linking questionnaire data from 2006-2009 with hospitalisation and death data to 30 June and 31 Dec 2010 respectively for 95,038 men aged ≥45 y. Cox proportional hazards models were used to examine the relationship of reported severity of erectile dysfunction to all-cause mortality and first CVD-related hospitalisation since baseline in men with and without previous CVD, adjusting for age, smoking, alcohol consumption, marital status, income, education, physical activity, body mass index, diabetes, and hypertension and/or hypercholesterolaemia treatment. There were 7,855 incident admissions for CVD and 2,304 deaths during follow-up (mean time from recruitment, 2.2 y for CVD admission and 2.8 y for mortality). Risks of CVD and death increased steadily with severity of erectile dysfunction. Among men without previous CVD, those with severe versus no erectile dysfunction had significantly increased risks of ischaemic heart disease (adjusted relative risk [RR] = 1.60, 95% CI 1.31-1.95), heart failure (8.00, 2.64-24.2), peripheral vascular disease (1.92, 1.12-3.29), "other" CVD (1.26, 1.05-1.51), all CVD combined (1.35, 1.19-1.53), and all-cause mortality (1.93, 1.52-2.44). For men with previous CVD, corresponding RRs (95% CI) were 1.70 (1.46-1.98), 4.40 (2.64-7.33), 2.46 (1.63-3.70), 1.40 (1.21-1.63), 1.64 (1.48-1.81), and 2.37 (1.87-3.01), respectively. Among men without previous CVD, RRs of more specific CVDs increased significantly with severe versus no erectile dysfunction, including acute myocardial infarction (1.66, 1.22-2.26), atrioventricular and left bundle branch block (6.62, 1.86-23.56), and (peripheral) atherosclerosis (2.47, 1.18-5.15), with no significant difference in risk for conditions such as primary hypertension (0.61, 0.16-2.35) and intracerebral haemorrhage (0.78, 0.20-2.97). CONCLUSIONS These findings give support for CVD risk assessment in men with erectile dysfunction who have not already undergone assessment. The utility of erectile dysfunction as a clinical risk prediction tool requires specific testing.JC has received research grants from Servier, administered through the University of Sydney and The George Institute, as principal investigator for the ADVANCE trial and ADVANCE-ON post trial follow-up study, and have received honoraria from Servier for speaking about ADVANCE at Scientific meetings. PM has received payment from Pfizer for giving a lecture on the treatment of pulmonary hypertension. All other authors have declared that no competing interests exis

Drag in paired electron-hole layers

We investigate transresistance effects in electron-hole double layer systems with an excitonic condensate. Our theory is based on the use of a minimum dissipation premise to fix the current carried by the condensate. We find that the drag resistance jumps discontinuously at the condensation temperature and diverges as the temperature approaches zero.Comment: 12 pages, 1 Figure, .eps file attache

Reversibility of frailty after lung transplantation

Background. Frailty contributes to increased morbidity and mortality in patients referred for and undergoing lung transplantation (LTX). &e study aim was to determine if frailty is reversible after LTX in those classified as frail at LTX evaluation. Methods. Consecutive LTX recipients were included. All patients underwent modified physical frailty assessment during LTX evaluation. For patients assessed as frail, frailty was reassessed on completion of the post-LTX rehabilitation program. Frailty was defined by the presence of ≥ 3 domains of the modified Fried Frailty Phenotype (mFFP). Results. We performed 166 lung transplants (frail patients, n = 27, 16%). Eighteen of the 27 frail patients have undergone frailty reassessment. Eight frail patients died, and one interstate recipient did not return for reassessment. In the 18 (66%) patients reassessed, there was an overall reduction in their frailty score post-LTX ((3.4 ± 0.6 to 1.0 ± 0.7), p < 0.001) with 17/18 (94%) no longer classified as frail. Improvements were seen in the following frailty domains: exhaustion, mobility, appetite, and activity. Handgrip strength did not improve posttransplant. Conclusions. Physical frailty was largely reversible following LTX, underscoring the importance of considering frailty a dynamic, not a fixed, entity. Further work is needed to identify those patients whose frailty is modifiable and establish specific interventions to improve frailty

Publisher Correction: An engineered human Fc domain that behaves like a pH-toggle switch for ultra-long circulation persistence.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Relative efforts of countries to conserve world’s megafauna

Surprisingly little attention has been paid to variation among countries in contributions to conservation. As a first step, we developed a Megafauna Conservation Index (MCI) that assesses the spatial, ecological and financial contributions of 152 nations towards conservation of the world’s terrestrial megafauna. We chose megafauna because they are particularly valuable in economic, ecological and societal terms, and are challenging and expensive to conserve. We categorised these 152 countries as being above- or below-average performers based on whether their contribution to megafauna conservation was higher or lower than the global mean; ‘major’ performers or underperformers were those whose contribution exceeded 1 SD over or under the mean, respectively. Ninety percent of countries in North/Central America and 70% of countries in Africa were classified as major or above-average performers, while approximately one-quarter of countries in Asia (25%) and Europe (21%) were identified as major underperformers. We present our index to emphasize the need for measuring conservation performance, to help nations identify how best they could improve their efforts, and to present a starting point for the development of more robust and inclusive measures (noting how the IUCN Red List evolved over time). Our analysis points to three approaches that countries could adopt to improve their contribution to global megafauna conservation, depending on their circumstances: 1) upgrading or expanding their domestic protected area networks, with a particular emphasis on conserving large carnivore and herbivore habitat, 2) increase funding for conservation at home or abroad, or 3) ‘rewilding’ their landscapes. Once revised and perfected, we recommend publishing regular conservation rankings in the popular media to recognise major-performers, foster healthy pride and competition among nations, and identify ways for governments to improve their performance

Revising evidence of hurricane strikes on Abaco Island (the Bahamas) over the last 700 years

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Winkler, T. S., van Hengstum, P. J., Donnelly, J. P., Wallace, E. J., Sullivan, R. M., MacDonald, D., & Albury, N. A. Revising evidence of hurricane strikes on Abaco Island (the Bahamas) over the last 700 years. Scientific Reports, 10(1), (2020): 16556, doi:10.1038/s41598-020-73132-x.The northern Bahamas have experienced more frequent intense-hurricane impacts than almost anywhere else in the Atlantic since 1850 CE. In 2019, category 5 (Saffir-Simpson scale) Hurricane Dorian demonstrated the destructive potential of these natural hazards. Problematically, determining whether high hurricane activity levels remained constant through time is difficult given the short observational record (< 170 years). We present a 700-year long, near-annually resolved stratigraphic record of hurricane passage near Thatchpoint Blue Hole (TPBH) on Abaco Island, The Bahamas. Using longer sediment cores (888 cm) and more reliable age-control, this study revises and temporally expands a previous study from TPBH that underestimated the sedimentation rate. TPBH records at least 13 ≥ category 2 hurricanes per century between 1500 to 1670 CE, which exceeds the 9 ≥ category 2 hurricanes per century within 50 km of TPBH since 1850 CE. The eastern United States also experienced frequent hurricanes from 1500 to 1670 CE, but frequency was depressed elsewhere in the Atlantic Ocean. This suggests that spatial heterogeneity in Atlantic hurricane activity since 1850 CE could have persisted throughout the last millennium. This heterogeneity is impacted by climatic and stochastic forcing, but additional high-resolution paleo-hurricane reconstructions are required to assess the mechanisms that impact regional variability.Field support was provided by Jody Albury and the staff of Friends of the Environment in Marsh Harbour, The Bahamas, and technical support was provided was provided by M. Horgan and S. Molodtsov. Funding for this project was provided by NSF Awards OCE-1356509, OCE-1356708, OCE-1854917, OCE-1903616, and ICER-1854980. The open access publishing fees for this article have been covered by the Texas A&M University Open Access to Knowledge Fund (OAKFund), supported by the University Libraries