Care processes and clinical outcomes of continuous outpatient support with inotropes (COSI) in patients with refractory endstage heart failure

BACKGROUND: This study describes the process and outcomes of continuous outpatient support with inotropes (COSI) in patients with Stage D heart failure (HF). Although Stage D HF has recently been defined as end-stage disease requiring special interventions for survival such as COSI or ventricular assist devices, concern has been raised regarding the safety, efficacy, mortality outcomes, and ethics of COSI. METHODS AND RESULTS: Inotrope dependence was defined as worsening of the patient's clinical status with attempted inotrope withdrawal such that the patient was deemed unlikely to survive to permit hospital discharge. A care process for COSI was designed; baseline and outcome variables were evaluated. COSI was administered to 36 inotrope-dependent patients (age 55.4 +/- 9.5 years, 24 males). Baseline characteristics (mean +/- SD) were consistent with Stage D HF: left ventricular ejection fraction 19.9 +/- 8.5, left ventricular end-diastolic dimension (LVEDD) 70 +/- 10 mm, systolic blood pressure 97.4 +/- 13.4 mm Hg, serum creatinine 1.5 +/- 0.6, serum sodium 131.7 +/- 5.3; 69 HF hospitalizations (mean 1.9 +/- 1.8) 6 months before COSI initiation. Symptomatic hypotension, increasing dyspnea, renal dysfunction, and hypoperfusion most commonly prevented inotrope withdrawal. Despite Stage D HF, patients were discharged with COSI ambulatory, oriented, and pain free. Rehospitalizations were 46; 6 subjects accounted for 24 hospitalizations; 23 had 0 or 1 rehospitalization. Median survival was 3.4 months (range 0.2-26.3 months); and 3-, 6-, and 12-month Kaplan Meier survival was 51%, 26%, and 6%, respectively. The majority of patients died at home and chose to not undergo resuscitation attempts. CONCLUSION: COSI may be an acceptable treatment option for Stage D HF.     

Aerobic Reduction of Cytochrome b566 in Pigeon-Heart Mitochondria

In anaerobic, uncoupled pigeon-heart mitochondria treated with oxidizable substrate, the cytochrome b(566) remains largely oxidized. In the presence of antimycin A, addition of oxygen induces a reduction of this cytochrome. The rate of cytochrome b(566) reduction is comparable to and dependent on the rate of cytochrome c(1) oxidation. Kinetic data suggest that either ubiquinone or another donor of similar potential provides electrons for the reduction of cytochrome b(566). It is postulated that the aerobic reduction of cytochrome b(566) is directly related to the energy conservation at site II.     

Chemoreceptor influence on pulmonary blood flow during unilateral hypoxia in dogs

Dogs anesthetized with 30 mg/kg pentobarbital were artificially respired after differential cannulation of the main stem bronchi. Following median sternotomy, blood flow was monitored by electromagnetic flow probes on the left pulmonary artery (QL) and on the pulmonary trunk or aorta, QT. Following 10 min of bilateral 100% O2, QL was 42.5 +/- 7% of QT. When 6% O2, was substituted as the gas mixture inspired by the left lung while the right lung remained on 100% O2, PaO2 was above 70 mm Hg and QL fell to 24.5 +/- 5% of QT. Room air was then used to ventilate the right lung while the left lung remained on 6% O2. This caused PaO2 to fall to 42.3 +/- 3 MM Hg and QL to rise to 38.3 +/- 6% QT. This increase in blood flow to the unilaterally hypoxic lung during systemic hypoxemia did not occur in dogs after peripheral chemoreceptor denervation. Therefore, interference with the local response to alveolar hypoxia during systemic hypoxemia appears to be mediated by the arterial chemoreceptors.     

Differential effects of hormones on precocious yolk sac retraction in chick embryos following administration by a new technique.

A simple new technique allowing continuous application of hormones to the chorioallantoic membrane of the embryonated chicken egg is described. By use of this technique, by grafting the pars distalis, and by monitoring the hormonal response, with inhibitors and with induction of glucocorticoid-dependent liver enzymes, yolk sac retraction has been shown to be linked with thyroidal and not with adrenocortical or several other hormones. Evidence is also presented that the pars distalis, from chickens up to at least 18 months old, is capable of autonomous performance of certain adrenocorticotrophic or thyrotrophic functions when grafted on the chorioallantoic membrane of embryonated eggs.     

Combating an invisible enemy:The American military response to global pandemics

The present moment is not the first time that America has found itself at war with a pathogen during a time of international conflict.Between crowded barracks at home and trenches abroad,wartime conditions helped enable the spread of influenza in the fall of 1918 during World War Ⅰ such that an estimated 20％-40％ of U.S.military members were infected.While the coronavirus disease 2019 (COVID-19) pandemic is unparalleled for most of today's population,it is essential to not view it as unprecedented lest the lessons of past pandemics and their effect on the American military be forgotten.This article provides a historical perspective on the effect of the most notable antecedent pandemic,the Spanish Influenza epidemic,on American forces with the goal of understanding the interrelationship of global pandemics and the military,highlighting the unique challenges of the current pandemic,and examining how the American military has fought back against pandemics both at home and abroad,both 100 years ago and today.     

Is multiple SNP testing in BRCA2 and BRCA1 female carriers ready for use in clinical practice? Results from a large Genetic Centre in the UK

BRCA1 and BRCA2 are major breast cancer susceptibility genes. Nineteen single nucleotide polymorphisms (SNPs) at 18 loci have been associated with breast cancer. We aimed to determine whether these predict breast cancer incidence in women with BRCA1/BRCA2 mutations. BRCA1/2 mutation carriers identified through the Manchester genetics centre between 1996 and 2011 were included. Using published odds ratios (OR) and risk allele frequencies, we calculated an overall breast cancer risk SNP score (OBRS) for each woman. The relationship between OBRS and age at breast cancer onset was investigated using the Cox proportional hazards model, and predictive ability assessed using Harrell's C concordance statistic. In BRCA1 mutation carriers we found no association between OBRS and age at breast cancer onset: OR for the lowest risk quintile compared to the highest was 1.20 (95% CI 0.82–1.75, Harrell's C = 0.54), but in BRCA2 mutation carriers the association was significant (OR for the lowest risk quintile relative to the highest was 0.47 (95% CI 0.33–0.69, Harrell's C = 0.59). The 18 validated breast cancer SNPs differentiate breast cancer risks between women with BRCA2 mutations, but not BRCA1. It may now be appropriate to use these SNPs to help women with BRCA2 mutations make maximally informed decisions about management options.     

Parkinson’s disease: considerations for dental hygienists

Abstract: The prevalence of Parkinson’s disease (PD) is expected to double over the next 20 years owing to the increase in life expectancy. This progressive disease has several implications relating to oral health, and many are manageable with proper awareness and knowledge about the disease. This article reviews the epidemiology, pathophysiology, and characteristics of PD, as well as the treatments and oral health considerations to enable dental hygienists to undertake an informed approach to patient management strategies and provide optimal care.