The influence of left ventricular hypertrophyon survival in patients with coronaryartery disease: do race and gender matter?

AbstractObjectivesWe sought to determine the overall prognostic importance of left ventricular hypertrophy (LVH) among patients with coronary artery disease (CAD), as well as to determine whether this risk varies as a function of race or gender.BackgroundLeft ventricular hypertrophy is more prevalent among blacks and women than their counterparts. Blacks and women also have higher mortality with coronary disease.MethodsWe studied records of 2,461 patients (19% black, 42% women) diagnosed with CAD at cardiac catheterization between 1990 and 1998 from a single academic center. Left ventricular hypertrophy was defined using standard echocardiographic measures. Cox proportional hazards models were used for adjusted survival analyses. Mean patient follow-up was three years.ResultsPatients with LVH were older (68 vs. 65 years, p < 0.01), more often women (54% vs. 36%, p < 0.01), and black (25% vs. 16%, p < 0.01), and had higher unadjusted three-year mortality rates than patients without LVH (42% vs. 34%, p < 0.01). Left ventricular hypertrophy remained an independent predictor of mortality after adjusting for other clinical risk factors (hazard ratio 1.56, 95% confidence interval 1.35 to 1.80) with prognostic importance equivalent to that of left ventricular ejection fraction. Although the relative risk of LVH did not vary by race or gender, the attributable risk of LVH was greater in blacks and women.ConclusionsClinicians should consider the prognostic importance of LVH when assessing risk in patients with CAD. Because LVH is more common among black and women patients with CAD, it partially accounts for racial and gender differences in survival

Incentivizing preventive services in primary care: perspectives on Local Enhanced Services

Background: General practitioners in the UK play a key role in prevention but provision of preventive services is variable. The 2004 General Medical Services contract allows Primary Care Trusts (PCTs) to address health needs through providing locally agreed payments for Local Enhanced Services (LESs). This study identifies how this contractual flexibility is used for preventive services and explores its perceived effectiveness. Methods: Semi-structured interviews were carried out (2008–09) in 10 purposively selected case study sites in England. Details of LESs for these sites were collected (2009) through Freedom of Information requests or local contacts. A national on-line survey of PCTs (2009) provided a national context for case study findings. Results: LESs were considered to be effective in incentivizing preventive activity. However, specifications and performance management were often weak, awareness of how to optimize incentives was low and, as optional services, LESs were perceived to be at risk in a financial downturn. Conclusions: Using LESs for preventive services highlights gaps in ‘core’ primary care responsibilities and in the national pay-for-performance framework. Current incentive arrangements are complex, could increase inequalities and provide only a partial, short-term solution to developing a proactive approach to prevention in primary care

Validation of Risk Prediction Models to Inform Clinical Decisions After Acute Kidney Injury

Wellcome Trust Research Training Fellowship: 102729/Z/13/Z Academy of Medical Sciences Starter Grant for Clinical Lecturers: SGL020\1076 We acknowledge the support of the Grampian Data Safe Haven (DaSH) facility within the Aberdeen Centre for Health Data Science and the associated financial support of the University of Aberdeen, and NHS Research Scotland (through NHS Grampian investment in DaSH). More information is available at the DaSH website: http://www.abdn.ac.uk/iahs/facilities/grampian-data-safe-haven.phpPeer reviewedPublisher PD

770-5 Chamber Specific Regulation of the Sarcoplasmic Reticulum Calcium ATPase Pump In Human Heart Failure

Alterations in the expression of Ca2+ channels have been described in failing human left ventricle, including down regulation of the ryanodine receptor (RyR)/Ca2+ release channel and the sarcoplasmic reticulum Ca2+ ATPase pump (SERCA) which are involved in excitation-contraction coupling and relaxation (Cir Res 71: 18, 1992). We previously reported chamber specific regulation of the RyR during end-stage human heart failure (Clin Res 42(2):166A. 1994). We investigated whether SERCA is also regulated in the other cardiac chambers during human heart failure. Total RNA and protein homogenates were isolated from the left and right atria (LA, RA) and left and right ventricles (LV, RV) obtained prospectively from 32 cardiac transplant patients and 4 normal controls. Messenger RNA (mRNA) levels of SERCA were quantified using Northern and slot blot hybridizations with a 1.6kb rat cardiac SERCA cDNA probe and normalized to 28S ribosomal levels. Protein levels of SERCA were quantified using enzyme-linked immunosorbent assays with monoclonal antibodies directed against dog cardiac SERCA. Northern analyses detected a single ≈4 kb mRNA in all regions. Compared to controls. SERCA mRNA expression in failing hearts was decreased in LV by 39% (p&lt;0.005), unchanged in RV, and increased in LA by 255% (p&lt;0.005) and in RA by 338% (p&lt;0.025). Consistent with the mRNA data. immunodetectable levels of SERCA were also reduced in LV by 30% (p&lt;0.05) and unchanged in RV; however, protein levels appeared unchanged or reduced in both atria in contrast to the mRNA. This is the first study reporting simultaneous measurements of SERCA mRNA and protein levels in the human heart. We conclude that chamber specific regulation of SERCA mRNA occurs during end-stage heart failure. corroborated by protein expression in the ventricles. Down regulations of SERCA may contribute to impaired relaxation and increased diastolic tone during heart failure

Safety and Pharmacokinetics of a Four Monoclonal Antibody Combination Against Botulinum C and D Neurotoxins.

Botulism is caused by botulinum neurotoxin (BoNT), the most poisonous substance known. BoNTs are also classified as Tier 1 biothreat agents due to their high potency and lethality. The existence of seven BoNT serotypes (A-G), which differ between 35% to 68% in amino acid sequence, necessitates the development of serotype specific countermeasures. We present results of a Phase 1 clinical study of an anti-toxin to BoNT serotypes C and D, NTM-1634, which consists of an equimolar mixture of four fully human IgG1 monoclonal antibodies (mAbs), each binding to non-overlapping epitopes on BoNT serotypes C and D resulting in potent toxin neutralization in rodents. This first-in-human study evaluated the safety and pharmacokinetics of escalating doses of NTM-1634 administered intravenously to healthy adults (NCT03046550). Three cohorts of eight healthy subjects received a single intravenous dose of NTM-1634 or placebo at 0.33 mg/kg, 0.66 mg/kg or 1 mg/kg. Follow-up examinations and pharmacokinetic evaluations were continued up to 121 days post-infusion. Subjects were monitored using physical examinations, hematology and chemistry blood tests, and electrocardiograms. Pharmacokinetic parameters were estimated using noncompartmental methods. The results demonstrated that the materials were safe and well-tolerated with the expected half-lives for human mAbs and with minimal anti-drug antibodies detected over the dose ranges and duration of the study

Correction of Electronic Record for Weighing Bucket Precipitation Gauge Measurements

Electronic sensors generate valuable streams of forcing and validation data for hydrologic models but are often subject to noise which must be removed as part of model input and testing database development. We developed an automated precipitation correction program (APCP) for weighing bucket precipitation gauge records, which are subject to several types of mechanical and electronic noise and discontinuities, including gauge maintenance, missing data, wind vibration, and sensor drift. Corrected cumulative water year precipitation from APCP did not exhibit an error bias and matched measured water year total precipitation within 2.1% for 58 station years tested. Removal of low-amplitude periodic noise was especially important for developing accurate instantaneous precipitation records at subdaily time steps. Model flexibility for use with other data types is demonstrated through application to time domain reflectometry soil moisture content data, which are also frequently subject to substantial noise

Point-of-care tests for syphilis and yaws in a low-income setting: a qualitative study of healthcare worker and patient experiences

The human treponematoses comprise venereal syphilis and the three non-venereal or endemic treponematoses yaws, bejel, and pinta. Serological assays remain the most common diagnostic method for all treponemal infections. Point-of-care tests (POCTs) for syphilis and yaws allow testing without further development of infrastructure in populations where routine laboratory facilities are not available. Alongside the test’s performance characteristics assessed through diagnostic evaluation, it is important to consider broader issues when rolling out a POCT. Experience with malaria POCT roll-out in sub-Saharan Africa has demonstrated that both healthcare worker and patient beliefs may play a major role in shaping the real-world use of POCTs. We conducted a qualitative study evaluating healthcare worker and patient perceptions of using a syphilis/yaws POCT in clinics in the East Malaita region of Malaita province in the Solomon Islands. Prior to the study serology was only routinely available at the local district hospital

Squirrelpox virus: assessing prevalence, transmission and environmental degradation

Red squirrels (Sciurus vulgaris) declined in Great Britain and Ireland during the last century, due to habitat loss and the introduction of grey squirrels (Sciurus carolinensis), which competitively exclude the red squirrel and act as a reservoir for squirrelpox virus (SQPV). The disease is generally fatal to red squirrels and their ecological replacement by grey squirrels is up to 25 times faster where the virus is present. We aimed to determine: (1) the seropositivity and prevalence of SQPV DNA in the invasive and native species at a regional scale; (2) possible SQPV transmission routes; and, (3) virus degradation rates under differing environmental conditions. Grey (n = 208) and red (n = 40) squirrel blood and tissues were sampled. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) techniques established seropositivity and viral DNA presence, respectively. Overall 8% of squirrels sampled (both species combined) had evidence of SQPV DNA in their tissues and 22% were in possession of antibodies. SQPV prevalence in sampled red squirrels was 2.5%. Viral loads were typically low in grey squirrels by comparison to red squirrels. There was a trend for a greater number of positive samples in spring and summer than in winter. Possible transmission routes were identified through the presence of viral DNA in faeces (red squirrels only), urine and ectoparasites (both species). Virus degradation analyses suggested that, after 30 days of exposure to six combinations of environments, there were more intact virus particles in scabs kept in warm (25°C) and dry conditions than in cooler (5 and 15°C) or wet conditions. We conclude that SQPV is present at low prevalence in invasive grey squirrel populations with a lower prevalence in native red squirrels. Virus transmission could occur through urine especially during warm dry summer conditions but, more notably, via ectoparasites, which are shared by both species

Exenatide extended release in patients with type 1 diabetes with and without residual insulin production

AimsTo test whether a long- acting GLP- 1 receptor agonist would improve glucose control in patients with type 1 diabetes (T1D) and to determine whether the presence of residual beta cell function would affect the response. In addition, we sought to determine whether the drug would affect beta cell function.MethodsWe performed a randomized placebo- controlled trial of exenatide extended release (ER) in participants with T1D with and without detectable levels of C- peptide. Seventy- nine participants were randomized to exenatide ER 2 mcg weekly, or placebo, stratified by the presence or absence of detectable C- peptide levels. The primary outcome was the difference in glycated haemoglobin (HbA1c) levels at 24- weeks. Participants were followed for another 6 months off study drug.ResultsAt week 24, the time of the primary outcome, the least squares (LS) mean HbA1c level was 7.76% (95% confidence interval [CI] 7.42, 8.10) in the exenatide ER group versus 8.0% (95% CI 7.64, 8.35) in the placebo group (P = 0.08). At week 12 the LS mean HbA1c levels were 7.71% (95% CI 7.37, 8.05) in the exenatide ER group versus 8.05% (95% CI 7.7, 8.4) in the placebo group (P = 0.01). The improvement at week 12 was driven mainly by those with detectable levels of C- peptide. Those treated with exenatide ER lost weight at 12 and 24- weeks compared to those treated with placebo (P- <0.001 and P = 0.007). The total insulin dose was lower, but not when corrected for body weight, and was not affected by residual insulin production. Adverse events were more frequent with exenatide ER, but hypoglycaemia was not increased.ConclusionTreatment with exenatide ER may have short- term benefits in some individuals with T1D who are overweight or who have detectable levels of C- peptide, but short- term improvements were not sustained.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163873/1/dom14121_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163873/2/dom14121.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163873/3/dom14121-sup-0001-Supinfo.pd