A Correlative Study of Epidemiological Mortality and Morbidity Rates: Appalachian vs Non-Appalachian Counties within Kentucky

In this study, differences in mortality rates were statistically analyzed between Kentucky Appalachian County Populations (KACP) and Kentucky Non-Appalachian County Populations (KnACP) for 2013. Health – risk factors and socio – economic conditions were also assessed to determine if they put KACP at a higher risk of the five most common causes of death in Kentucky. Estill County, a KACP, was also specifically examined for its mortality and health – risk factor rates. By examining the 2013 database provided by the Kentucky Department for Public Health (KDPH) and the Center for Disease Control and Prevention (CDC), it was determined that there is a significant increase in mortality rates of malignant neoplasms and heart disease in the KACP population compared to KnACP. The KACP population also has significantly increased rates of hypertension, diabetes, smoking, and obesity; all of which contribute to the significance of KACP mortality rates. Subsequently, socio – economic factors such as median house – hold income showed a significant decrease for KACP compared to KnACP which indirectly affects the mortality rates of KACP. Estill County also showed an increase in mortality rates, as well as, health-risk factors compared to KACP. These findings indicate that the populations of KACP are at higher risk of dying from malignant neoplasms and heart disease due to a significant increase in hypertension, smoking, diabetes, and obesity. To correct this overwhelming health issue, improving the quality of and access to healthcare for the KACP’s needs to be a focus. Projects including government resources such as more funding for free clinics, as well as community based efforts to reduce smoking, etc. is of utmost importance

View point: gaps in the current guidelines for the prevention of Methicillin-resistant Staphylococcus aureus surgical site infections

The authors advocate the addition of two preventative strategies to the current United State’s guidelines for the prevention of surgical site infections. It is known that Staphylococcus aureus, including Methicillin-resistant Staphylococcus aureus (MRSA), carriers are at a higher risk for the development of infections and they can easily transmit the organism. The carriage rate of Staph. aureus in the general population approximates 33%. The CDC estimates the carriage rate of MRSA in the United States is approximately 2%. The first strategy is preoperative screening of surgical patients for Staph. aureus, including MRSA. This recommendation is based upon the growing literature which shows a benefit in both prevention of infections and guidance in preoperative antibiotic selection. The second is performing MRSA active surveillance screening on healthcare workers. The carriage rate of MRSA in healthcare workers approximates 5% and there are concerns of transmission of this pathogen to patients. MRSA decolonization of healthcare workers has been reported to approach a success rate of 90%. Healthcare workers colonized with dangerous pathogens, including MRSA, should be assigned to non-patient contact work areas. In addition, there needs to be implemented a safety net for both the worker’s economic security and healthcare. Finally, a reporting system for the healthcare worker acquisition and infections with dangerous pathogens needs to be implemented. These recommendations are needed because Staph. aureus including MRSA is endemic in the United States. Policies regarding endemic pathogens which are to be implemented only upon the occurrence of a facility defined “outbreak” have to be questioned, since absence of infections does not mean absence of transmission. Optimizing these policies will require further research but until then we should error on the side of patient safety

The incidence of MRSA infections in the United States: is a more comprehensive tracking system needed?

A review of epidemiological studies on the incidence of MRSA infections overtime was performed along with an analysis of data available for download from Hospital Compare (https://data.medicare.gov/data/hospital-compare). We found the estimations of the incidence of MRSA infections varied widely depending upon the type of population studied, the types of infections captured and in the definitions and terminology used to describe the results. We could not find definitive evidence that the incidence of MRSA infections in U.S. community or facilities is decreasing significantly. Of concern are recent data reported to the National Healthcare Safety Network (NHSN) on MRSA bloodstream infections which indicate that by the end of 2015 there had been little change in the average facility Standardized Infection Ratio (0.988), compared to a 2010-2011 baseline and is significantly increased compared to the previous year. This is in contradistinction to the recent Veterans Administration study which reported over an 80% reduction in MRSA infections. However, this discrepancy may be due to the inability to reconcile the baselines of the two data sets; and the observed increase may be artifactual due to aberrations in the NHSN tracking system. Our review supports the need for implementation of a comprehensive tracking and monitoring system involving all types of healthcare facilities for multi-drug resistant organisms, along with concomitant funding for both staff and infrastructure. Without such a system, determining the effectiveness of interventions such as antibiotic stewardship and chlorhexidine bathing will be hindered

Questionable Validity of the Catheter-associated Urinary Tract Infection Metric Used for Value-based Purchasing

Catheter-associated urinary tract infections (CAUTIs) occur in 290,000 US hospital patients annually, with an estimated cost of $290 million. Two different measurement systems are being used to track the US health care system\u27s performance in lowering the rate of CAUTIs. Since 2010, the Agency for Healthcare Research and Quality (AHRQ) metric has shown a 28.2% decrease in CAUTI, whereas the Centers for Disease Control and Prevention metric has shown a 3%-6% increase in CAUTI since 2009. Differences in data acquisition and the definition of the denominator may explain this discrepancy. The AHRQ metric analyzes chart-audited data and reflects both catheter use and care. The Centers for Disease Control and Prevention metric analyzes self-reported data and primarily reflects catheter care. Because analysis of the AHRQ metric showed a progressive change in performance over time and the scientific literature supports the importance of catheter use in the prevention of CAUTI, it is suggested that risk-adjusted catheter-use data be incorporated into metrics that are used for determining facility performance and for value-based purchasing initiatives

Reporter\u27s Occupation and Source of Adverse Device Event Reports Contained in the FDA\u27s MAUDE Database

Introduction: A review of the medical device adverse events submitted to the United States Food & Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database was undertaken to determine the major sources of the information. Methods: The reporter’s occupation and source of the medical device report were determined for acquisition dates Jan 1, 1997 to Dec 31, 2018. A total of 7,766,737 adverse event records were analyzed. Results: 96.6% of reports originated with the manufacturer. Patients (patients/family/friend) were the most frequent submitter of reports directly to the FDA, almost five times as often as physicians. Nurses submitted reports directly to the FDA 2.77 times as often as physicians. Only 0.49% of physician reports were submitted directly to the FDA, representing 0.09% of total MAUDE reports. Conclusion: Increasing physician reporting directly to the FDA and MAUDE through the MedWatch reporting system is an imperative. Incorporating information from the perspective of the physician has the potential of increasing the quality of the data and improving the reliability of post-market surveillance

iPLA2β Overexpression in Smooth Muscle Exacerbates Angiotensin II-Induced Hypertension and Vascular Remodeling

Calcium independent group VIA phospholipase A(2) (iPLA(2)β) is up-regulated in vascular smooth muscle cells in some diseases, but whether the up-regulated iPLA(2)β affects vascular morphology and blood pressure is unknown. The current study addresses this question by evaluating the basal- and angiotensin II infusion-induced vascular remodeling and hypertension in smooth muscle specific iPLA(2)β transgenic (iPLA(2)β-Tg) mice.Blood pressure was monitored by radiotelemetry and vascular remodeling was assessed by morphologic analysis. We found that the angiotensin II-induced increase in diastolic pressure was significantly higher in iPLA(2)β-Tg than iPLA(2)β-Wt mice, whereas, the basal blood pressure was not significantly different. The media thickness and media∶lumen ratio of the mesenteric arteries were significantly increased in angiotensin II-infused iPLA(2)β-Tg mice. Analysis revealed no difference in vascular smooth muscle cell proliferation. In contrast, adenovirus-mediated iPLA(2)β overexpression in cultured vascular smooth muscle cells promoted angiotensin II-induced [(3)H]-leucine incorporation, indicating enhanced hypertrophy. Moreover, angiotensin II infusion-induced c-Jun phosphorylation in vascular smooth muscle cells overexpressing iPLA2β to higher levels, which was abolished by inhibition of 12/15 lipoxygenase. In addition, we found that angiotensin II up-regulated the endogenous iPLA(2)β protein in-vitro and in-vivo.The present study reports that iPLA(2)β up-regulation exacerbates angiotensin II-induced vascular smooth muscle cell hypertrophy, vascular remodeling and hypertension via the 12/15 lipoxygenase and c-Jun pathways

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

View point: gaps in the current guidelines for the prevention of Methicillin-resistant Staphylococcus aureus surgical site infections

Abstract The authors advocate the addition of two preventative strategies to the current United State’s guidelines for the prevention of surgical site infections. It is known that Staphylococcus aureus, including Methicillin-resistant Staphylococcus aureus (MRSA), carriers are at a higher risk for the development of infections and they can easily transmit the organism. The carriage rate of Staph. aureus in the general population approximates 33%. The CDC estimates the carriage rate of MRSA in the United States is approximately 2%. The first strategy is preoperative screening of surgical patients for Staph. aureus, including MRSA. This recommendation is based upon the growing literature which shows a benefit in both prevention of infections and guidance in preoperative antibiotic selection. The second is performing MRSA active surveillance screening on healthcare workers. The carriage rate of MRSA in healthcare workers approximates 5% and there are concerns of transmission of this pathogen to patients. MRSA decolonization of healthcare workers has been reported to approach a success rate of 90%. Healthcare workers colonized with dangerous pathogens, including MRSA, should be assigned to non-patient contact work areas. In addition, there needs to be implemented a safety net for both the worker’s economic security and healthcare. Finally, a reporting system for the healthcare worker acquisition and infections with dangerous pathogens needs to be implemented. These recommendations are needed because Staph. aureus including MRSA is endemic in the United States. Policies regarding endemic pathogens which are to be implemented only upon the occurrence of a facility defined “outbreak” have to be questioned, since absence of infections does not mean absence of transmission. Optimizing these policies will require further research but until then we should error on the side of patient safety

Breast Cancer Ca2+-independent Phospholipase A2β Mediates Nicotine-induced Tumor Growth and Metastasis through Matrix Metalloprotease-9 Secretion

Ca2+-independent Phospholipase A2β (iPLA2β) is a member of the phospholipase A2 superfamily has been linked to the regulation of a variety of cellular signaling pathways and functions. This is in part due to the catalytic activity of iPLA2β, cleaving glycerophospholipids at the sn-2 position causing the release of free fatty acids including arachidonic acid and 2-lysophospholipid. However, the ability of iPLA2β to mediate breast cancer cellular functioning including proliferation and migration remains unknown. Our central hypothesis is that suppression of iPLA2β reduces nicotine-induced breast cancer metastasis through attenuating MMP-9 (Matrix Metalloprotease-9) secretion. Our in-vivo preliminary data shows that iPLA2β is overexpressed in 4TI stage four breast cancer tumors grown in-vivo for 2 weeks and nicotine (5mg/kg/day) significantly increased growth at 2weeks and 4 weeks. Additionally, we found Bromoenol lactone, 3uM (BEL) an inhibitor of iPLA2β significantly attenuated nicotine-induced breast cancer cell proliferation. Further, we found that BEL significantly decreased nicotine-induced breast cancer cell migration (gap closure) utilizing a scratch assay. Through the use of gel zymography we elucidated that BEL attenuates nicotine-induced matrix metallopreotease-9 secretion, which, is an important contributor to cancer cell metastasis and the initiation of angiogenesis. Taken together, our in-vivo and in-vitro results indicate that iPLA2β is an important regulator of nicotine-induced breast cancer tumor growth, cell migration, and proliferation. Much work is still to be done in future studies to fully elucidate the full capacity of iPLA2β in mediating breast cancer tumerogenicity, angiogenesis, and its invasive nature.https://encompass.eku.edu/swps_undergraduategallery/1009/thumbnail.jp