Association between Class III Obesity (BMI of 40–59 kg/m2) and Mortality: A Pooled Analysis of 20 Prospective Studies

Background: The prevalence of class III obesity (body mass index [BMI]≥40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity. Methods and Findings: In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19–83 y at baseline, classified as obese class III (BMI 40.0–59.9 kg/m2) compared with those classified as normal weight (BMI 18.5–24.9 kg/m2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976–2009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively) and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40–44.9, 45–49.9, 50–54.9, and 55–59.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.7–7.3), 8.9 (95% CI: 7.4–10.4), 9.8 (95% CI: 7.4–12.2), and 13.7 (95% CI: 10.5–16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report. Conclusions: Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight. Please see later in the article for the Editors' Summar

Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study

BACKGROUND: Postmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood. METHODS: We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays. We examined the relationship between HRT-regulated gene profiles, tumor characteristics, and recurrence-free survival in 72 postmenopausal women. RESULTS: HRT use in patients with estrogen receptor (ER) protein positive tumors (n = 72) was associated with an altered regulation of 276 genes. Expression profiles based on these genes clustered ER-positive tumors into two molecular subclasses, one of which was associated with HRT use and had significantly better recurrence free survival despite lower ER levels. A comparison with external data suggested that gene regulation in tumors associated with HRT was negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen. CONCLUSION: Our findings suggest that post-menopausal HRT use is associated with a distinct gene expression profile related to better recurrence-free survival and lower ER protein levels. Tentatively, HRT-associated gene expression in tumors resembles the effect of tamoxifen exposure on MCF-7 cells

Acute coronary syndrome in a hemophilia patient: A clinical challenge

Case Presentation: A 68 year old male with a history of severe hemophilia (factor VIII \u3c1%) and hypertension presented with symptoms of nausea, vomiting, severe dyspnea, diaphoresis and substernal chest pain for several days prior to admission. On initial presentation, electrocardiogram revealed ST-segment depressions in leads V5 and V6, with a troponin elevation to 24, so he was started on a nitroglycerin infusion and his symptoms of chest pain and dyspnea began to improve. Given his history of frequent bleeding in the setting of hemophilia, patient initially refused treatment with any antiplatelet agents or anticoagulation. The hematology service was consulted for recommendations for anticoagulation in the setting of factor VIII deficiency. Care was coordinated between the cardiology and hematology services, and percutaneous coronary intervention (PCI) and stenting was planned for treatment of his non-ST-segment elevation myocardial infarction (NSTEMI). The patient agreed to the treatment plan and was started on both heparin and factor VIII replacement with a goal of 80% correction prior to PCI. Left heart catheterization revealed severe multi-vessel coronary artery disease. He was deemed a poor surgical candidate by cardiac surgery, so underwent high risk PCI with two drug eluting stents to the ostial left anterior descending artery. Once heparin was discontinued, he remained on dual antiplatelet therapy with continued factor VIII replacement at a goal of 60% correction. He did not have any bleeding complications during his hospital course, and was instructed to follow up for regular factor VIII level checks with hematology after discharge. Discussion: The management of cardiovascular disease in patients with hemophilia is often difficult for clinicians, and there are few studies addressing specific treatment guidelines for these patients. As life expectancy for patients with hemophilia has increased, the incidence of acute coronary syndromes (ACS) in this population has also grown. Despite the fact that studies have shown successful revascularization with PCI in hemophilia patients, one retrospective study showed that in 25% of cases, initial management of ACS was altered due to the fact that the patients had hemophilia, often with delays in treatment. This demonstrates the challenge that clinicians perceive when viewing the balance between bleeding and ischemic risks in patients with this condition. Even so, data suggests that hemophilia patients with ACS should receive the same treatments and interventions as the general population and success rates are similar. Treatment with antiplatelet agents, heparin, and PCI with stenting should be used, however clotting factor replacement should often be given to prevent any associated bleeding risk in patients with severe disease. European guidelines suggest bare-metal stenting may be favored over drug-eluting stents given the shorter duration for antiplatelet agents. Conclusions: Treatment of ACS in patients with bleeding disorders, particularly hemophilia, is a challenge, however using a multidisciplinary approach involving cardiologists, hematologists, and internists, can provide good cardiac outcomes with minimal adverse events, with rates comparable to the general population

Car Coupling.

Patent for a simple, durable, and safe car-coupling that will not accidentally uncouple, and can uncouple without the operator stepping between the cars. It "consists principally of a knuckle pivoted in the drawhead and provided with cam surfaces, and an arm mounted to swing and adapted to engage the said cam surfaces to open and close the knuckle" (lines 14-18). The coupling can also couple cars of different heights

Multiple sclerosis : case report from Henry Ford Hospital

Etude de l'évolution de la sclérose en plaques et des effets de différents exercices physiques sur la maladie (entraînement cardio-respiratoire, ergométrie et musculation) chez une patiente entraîneuse d'athlétisme

Scientism, trust, value alignment, views of nature, and U.S. public opinion about gene drive mosquitos.

Gene drive could be a powerful tool for addressing problems of conservation, agriculture, and human health caused by insect and animal pests but is likely to be controversial as it involves the release of genetically modified organisms. This study examined the social determinants of opinion of gene drive. We asked a representative sample of the U.S. public to respond to a description of a hypothetical application of a gene-drive mosquito to the problem of malaria and examined the relationship of these responses with demographic and ideological beliefs. We found strong general approval for the use of gene-drive mosquitos to address malaria, coinciding with the concern about a possible environmental impact of modified mosquitos and that gene drives represent "too much power over nature." Among the determinants we measured, respondent acceptance of scientism and trust that scientists are advancing the public's interest were the greatest predictors of views of gene drive