International Occupational Health Research on an Invisible Workforce

There are many professions in which employees are located in remote locations. International maritime workers make up one such occupation. They are a vulnerable, underserved and neglected population of approximately 1.2 million people with high rates of disease and injury. During their typical nine month deployments, they live in relative isolation with no health care professional on board. To understand the root causes of disease and injury among this remote workforce, strategies to collect information, analyze data, and report results and recommendations have been developed. These strategies, which include gathering of data through an alliance of companies involved in seafaring, have yielded initial results as to the predictors of serious illness and injury on board vessels requiring the repatriation of the employee. These same methods should be applicable to other isolated international workforces

Lead-Based Paint Awareness, Work Practices, and Compliance During Residential Construction and Renovation

The U.S. Environmental Protection Agency recently implemented the Renovation, Repair and Painting (RRP) rule that applies to pre-1978 residences because of the potential presence of lead-based paint. Enforcement of this rule may be difficult and therefore it is crucial to understand the awareness and beliefs of contractors and the general public because these will likely be major determinants of exposures resulting from residential renovation work. The study described in this article utilized two mailed surveys: one directed to the general public and the other directed to contractors. The surveys were conducted in New Jersey and Virginia. Field observations were also recorded for work sites in New Jersey. Results indicated a high awareness among the general public about the hazards of lead, a low level of screening by children\u27s doctors for lead exposure, frequent use of work practices that generate lots of dust, poor hygiene among contractors, and the potential for low compliance of contractors with the RRP rule. In particular, contractors who do not believe lead is a serious health hazard are expected to have the lowest compliance with the RRP rule. These findings serve as targets for effective public health interventions through education and outreach

Regulation of Membrane Targeting of the G Protein-coupled Receptor Kinase 2 by Protein Kinase A and Its Anchoring Protein AKAP79

The beta 2 adrenergic receptor (beta 2AR) undergoes desensitization by a process involving its phosphorylation by both protein kinase A (PKA) and G protein-coupled receptor kinases (GRKs). The protein kinase A-anchoring protein AKAP79 influences beta 2AR phosphorylation by complexing PKA with the receptor at the membrane. Here we show that AKAP79 also regulates the ability of GRK2 to phosphorylate agonist-occupied receptors. In human embryonic kidney 293 cells, overexpression of AKAP79 enhances agonist-induced phosphorylation of both the beta 2AR and a mutant of the receptor that cannot be phosphorylated by PKA (beta 2AR/PKA-). Mutants of AKAP79 that do not bind PKA or target to the beta 2AR markedly inhibit phosphorylation of beta 2AR/PKA-. We show that PKA directly phosphorylates GRK2 on serine 685. This modification increases Gbeta gamma subunit binding to GRK2 and thus enhances the ability of the kinase to translocate to the membrane and phosphorylate the receptor. Abrogation of the phosphorylation of serine 685 on GRK2 by mutagenesis (S685A) or by expression of a dominant negative AKAP79 mutant reduces GRK2-mediated translocation to beta 2AR and phosphorylation of agonist-occupied beta 2AR, thus reducing subsequent receptor internalization. Agonist-stimulated PKA-mediated phosphorylation of GRK2 may represent a mechanism for enhancing receptor phosphorylation and desensitization

Risk factors for merchant seafarer repatriation due to injury or illness at sea

Background: Repatriation represents a serious outcome of illness or injury among seafarers at sea. The aim of this study was to describe repatriation patterns due to injury and illness in a seafarer cohort, and determine risk factors for repatriation. Materials and methods: The study analysed a telemedicine database of 3,921 seafarer injury and illness cases over a 4 year period using descriptive statistics and logistic regression. Results: There were 61 repatriations over the study period (1.6% of cases). Most repatriations were due to illness (38; 62.3%) as opposed to injury (23; 37.7%). Back injuries and gastrointestinal illness were the most frequent causes of repatriations. Using logistic regression, nationality was identified as a significant risk factor for repatriation. Conclusions: This study emphasizes illness as a major cause of seafarer repatriation, and suggests opportunities for future studies to identify potentially modifiable risk factors

Efficacy of sacubitril/valsartan relative to a prior decompensation: the PARADIGM-HF trial

Objectives: This study assessed whether the benefit of sacubtril/valsartan therapy varied with clinical stability. Background: Despite the benefit of sacubitril/valsartan therapy shown in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, it has been suggested that switching from an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker should be delayed until occurrence of clinical decompensation. Methods: Outcomes were compared among patients who had prior hospitalization within 3 months of screening (n = 1,611 [19%]), between 3 and 6 months (n = 1,009 [12%]), between 6 and 12 months (n = 886 [11%]), >12 months (n = 1,746 [21%]), or who had never been hospitalized (n = 3,125 [37%]). Results: Twenty percent of patients without prior HF hospitalization experienced a primary endpoint of cardiovascular death or heart failure (HF) hospitalization during the course of the trial. Despite the increased risk associated with more recent hospitalization, the efficacy of sacubitril/valsartan therapy did not differ from that of enalapril according to the occurrence of or time from hospitalization for HF before screening, with respect to the primary endpoint or with respect to cardiovascular or all-cause mortality. Conclusions: Patients with recent HF decompensation requiring hospitalization were more likely to experience cardiovascular death or HF hospitalization than those who had never been hospitalized. Patients who were clinically stable, as shown by a remote HF hospitalization (>3 months prior to screening) or by lack of any prior HF hospitalization, were as likely to benefit from sacubitril/valsartan therapy as more recently hospitalized patients. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255)

Risk of prostate cancer after isolated high-grade prostatic intraepithelial neoplasia (HGPIN) detected on extended core needle biopsy : a UK hospital experience.

Background High-grade prostatic intraepithelial neoplasia (HGPIN) is a precursor lesion to prostate cancer (CaP). UK-based studies examining the occurrence of isolated HGPIN and subsequent risk of CaP are lacking. Our aim was to assess the occurrence of HGPIN in a regional UK population and to determine whether in a retrievable cohort of such patients that had repeat extended core biopsies, there was an elevated risk of CaP. Methods A retrospective analysis of the pathology database was conducted at our institution (Lancashire Teaching Hospitals NHS Foundation Trust) for prostate biopsies recorded between January 2001 and December 2005 (all extended core biopsies). Those patients with isolated HGPIN on 1st set of biopsies were identified and, their clinical characteristics and pathological findings from subsequent biopsies (if any) were determined. The risk of CaP on subsequent biopsies based on presenting baseline PSA was stratified. Results Of 2,192 biopsied patients, there were 88 cases of isolated HGPIN of which 67 patients underwent one or more repeat biopsies. In this repeat-biopsy group, 28 CaP diagnoses were made. Age at first biopsy (P 20 ng/ml – 87.5%. Conclusion Based on our results, we recommend delaying the 1st repeat biopsy at low PSA range but to have a shorter interval to repeat biopsies at intermediate and higher PSA ranges

Influence of Sacubitril/Valsartan (LCZ696) on 30-day readmission after heart failure hospitalization

Background: Patients with heart failure (HF) are at high risk for hospital readmission in the first 30 days following HF hospitalization. Objectives: This study sought to determine if treatment with sacubitril/valsartan (LCZ696) reduces rates of hospital readmission at 30-days following HF hospitalization compared with enalapril. Methods: We assessed the risk of 30-day readmission for any cause following investigator-reported hospitalizations for HF in the PARADIGM-HF trial, which randomized 8,399 participants with HF and reduced ejection fraction to treatment with LCZ696 or enalapril. Results: Accounting for multiple hospitalizations per patient, there were 2,383 investigator-reported HF hospitalizations, of which 1,076 (45.2%) occurred in subjects assigned to LCZ696 and 1,307 (54.8%) occurred in subjects assigned to enalapril. Rates of readmission for any cause at 30 days were 17.8% in LCZ696-assigned subjects and 21.0% in enalapril-assigned subjects (odds ratio: 0.74; 95% confidence interval: 0.56 to 0.97; p = 0.031). Rates of readmission for HF at 30-days were also lower in subjects assigned to LCZ696 (9.7% vs. 13.4%; odds ratio: 0.62; 95% confidence interval: 0.45 to 0.87; p = 0.006). The reduction in both all-cause and HF readmissions with LCZ696 was maintained when the time window from discharge was extended to 60 days and in sensitivity analyses restricted to adjudicated HF hospitalizations. Conclusions: Compared with enalapril, treatment with LCZ696 reduces 30-day readmissions for any cause following discharge from HF hospitalization

The Post-Apoptotic Fate of RNAs Identified Through High-Throughput Sequencing of Human Hair

The hair of all mammals consists of terminally differentiated cells that undergo a specialized form of apoptosis called cornification. While DNA is destroyed during cornification, the extent to which RNA is lost is unknown. Here we find that multiple types of RNA are incompletely degraded after hair shaft formation in both mouse and human. Notably, mRNAs and short regulatory microRNAs (miRNAs) are stable in the hair as far as 10 cm from the scalp. To better characterize the post-apoptotic RNAs that escape degradation in the hair, we performed sequencing (RNA-seq) on RNA isolated from hair shafts pooled from several individuals. This hair shaft RNA library, which encompasses different hair types, genders, and populations, revealed 7,193 mRNAs, 449 miRNAs and thousands of unannotated transcripts that remain in the post-apoptotic hair. A comparison of the hair shaft RNA library to that of viable keratinocytes revealed surprisingly similar patterns of gene coverage and indicates that degradation of RNA is highly inefficient during apoptosis of hair lineages. The generation of a hair shaft RNA library could be used as months of accumulated transcriptional history useful for retrospective detection of disease, drug response and environmental exposure

Effects of sacubitril/valsartan in the PARADIGM-HF Trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) according to background therapy

Background—In the PARADIGM-HF trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan was more effective than the angiotensin-converting enzyme inhibitor enalapril in patients with heart failure and reduced ejection fraction. We examined whether this benefit was consistent irrespective of background therapy. Methods and Results—We examined the effect of study treatment in the following subgroups: diuretics (yes/no), digitalis glycoside (yes/no), mineralocorticoid receptor antagonist (yes/no), and defibrillating device (implanted defibrillating device, yes/no). We also examined the effect of study drug according to β-blocker dose (≥50% and <50% of target dose) and according to whether patients had undergone previous coronary revascularization. We analyzed the primary composite end point of cardiovascular death or heart failure hospitalization, as well as cardiovascular death. Most randomized patients (n=8399) were treated with a diuretic (80%) and β-blocker (93%); 47% of those taking a β-blocker were treated with ≥50% of the recommended dose. In addition, 4671 (56%) were treated with a mineralocorticoid receptor antagonist, 2539 (30%) with digoxin, and 1243 (15%) had a defibrillating device; 2640 (31%) had undergone coronary revascularization. Overall, the sacubitril/valsartan versus enalapril hazard ratio for the primary composite end point was 0.80 (95% confidence interval, 0.73–0.87; P<0.001) and for cardiovascular death was 0.80 (0.71–0.89; P<0.001). The effect of sacubitril/valsartan was consistent across all subgroups examined. The hazard ratio for primary end point ranged from 0.74 to 0.85 and for cardiovascular death ranged from 0.75 to 0.89, with no treatment-by-subgroup interaction. Conclusions—The benefit of sacubitril/valsartan, over an angiotensin-converting enzyme inhibitor, was consistent regardless of background therapy and irrespective of previous coronary revascularization or β-blocker dose