Plasma Concentrations of Myeloperoxidase Predict Mortality After Myocardial Infarction

ObjectivesThis study investigated relationships between plasma myeloperoxidase (MPO), protein oxidation markers, and clinical outcome retrospectively in patients after acute myocardial infarction (MI).BackgroundReactive oxidants are implicated in cardiovascular disease, and elevated plasma MPO is reported to predict adverse outcome in acute coronary syndromes.MethodsDetailed demographic information, radionuclide ventriculography, neurohormone measurements, and clinical history were obtained for 512 acute MI patients at hospital admission. Plasma levels of MPO and protein carbonyls were measured in patients and 156 heart-healthy control subjects. 3-Chlorotyrosine was measured in selected patients. Patient mortality was followed for 5 years.ResultsPlasma MPO and protein carbonyl concentrations were higher in MI patients 24 h to 96 h after admission than in control subjects (medians: MPO 55 ng/ml vs. 39 ng/ml, and protein carbonyls 48 pmol/mg vs. 17 pmol/mg protein, p < 0.001 for each). Both markers were significantly correlated with each other and with cardiovascular hormone levels. Chlorotyrosine was not elevated in patients with high MPO or carbonyl levels. Above-median levels of MPO but not protein carbonyls were independently predictive of mortality (odds ratio 1.8, 95% confidence interval 1.0 to 3.0, p = 0.034). Patients with above-median MPO levels in combination with above-median plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP) or below-median left ventricular ejection fraction (LVEF) had significantly greater mortality compared with other patients.ConclusionsMyeloperoxidase and protein carbonyl levels are elevated in plasma after acute MI, apparently via independent mechanisms. High MPO is a risk factor for long-term mortality and adds prognostic value to LVEF and plasma NT-proBNP measurements

A nurse-led education and cognitive behaviour therapy-based intervention among adults with uncontrolled type 2 diabetes: A randomised controlled trial

Rationale, aims and objectives: Diabetes mellitus is associated with significant morbidity, mortality and escalating healthcare costs. Research has consistently demonstrated the importance of glycaemic control in delaying the onset, and decreasing the incidence, of both the short- and long-term complications of diabetes. Although glycaemic control is difficult to achieve and challenging to maintain, it is key to reducing negative disease outcomes.&nbsp; The aim of this study was to determine whether a nurse-led educational intervention alone or a nurse-led intervention using education and acceptance and commitment therapy (ACT) were effective in reducing HbA1c in people living with uncontrolled type 2 diabetes compared to usual care.&nbsp; Methods: Adults over the age of 18 years, with a confirmed diagnosis of type 2 diabetes and HbA1c outside of the recommended range (4-7%, 20-53 mmol/mol) for 12 months or more were eligible to participate.&nbsp; Participants were randomised to either a nurse-led education intervention, a nurse-led education plus ACT intervention or usual care. One hundred and eighteen participants completed baseline data collection (N=34 education group, N=39 education plus ACT, N=45 control group). An intention to treat analysis was employed.&nbsp; Results: A statistically significant reduction in HbA1c in the education intervention group was found (p=.011 [7.48, 8.14]). At 6 months, HbA1c was reduced in both intervention groups (Education group -0.21, education and ACT group -0.04) and increased in the control group (+0.32). A positive change in HbA1c (HbA1c reduced) was noted in 50 participants overall. Twice as many participants in the intervention groups demonstrated an improvement as compared to the control group (56% of the education group, 51% education plus ACT, and 24% control group.&nbsp; Conclusions: At 6 months post intervention, HbA1c was reduced in both intervention groups with a greater reduction noted in the nurse-led education intervention

A nurse-led interdisciplinary approach to promote self-management of type 2 diabetes: A process evaluation of post intervention experiences

Rationale, aims and objectives&nbsp; Self-management of type 2 diabetes through diet, exercise and for many medications, are vital in achieving and maintaining glycaemic control in type 2 diabetes. A number of interventions have been designed to improve self-management, but the outcomes of these are rarely explored from a qualitative angle and even fewer through a process evaluation.&nbsp; Method&nbsp; A process evaluation was conducted using a qualitative design with participants randomized to an intervention. Seventy-three people living with type 2 diabetes and hyperglycaemia for a minimum of 1 year, randomized to one of two interventions (n = 34 to an education intervention andn = 39 to an education and acceptance and commitment therapy intervention) completed stage one of the process evaluation, immediately following the intervention through written feedback guided by open-ended questions. A purposive sample of 27 participants completed semi-structured interviews at 3 and 6 months post intervention. Interview data were transcribed and data analysed using a thematic analysis.&nbsp; Results&nbsp; The majority of participants described an increase in knowledge around diabetes self-management and an increased sense of personal responsibility. Participants also described changes in self-management activities and reflected on the challenges in instigating and maintaining change to improve diabetes management.&nbsp; Conclusion&nbsp; The complexities of implementing change in daily life to improve glycaemic control indicate the need for ongoing support post intervention, which may increase and maintain the effectiveness of the intervention

Heart Fatty Acid Binding Protein and cardiac troponin: development of an optimal rule-out strategy for acute myocardial infarction

Background: Improved ability to rapidly rule-out Acute Myocardial Infarction (AMI) in patients presenting with chest pain will promote decongestion of the Emergency Department (ED) and reduce unnecessary hospital admissions. We assessed a new commercial Heart Fatty Acid Binding Protein (H-FABP) assay for additional diagnostic value when combined with cardiac troponin (using a high sensitivity assay). Methods: H-FABP and high-sensitivity troponins I (hs-cTnI) and T (hs-cTnT) were measured in samples taken on-presentation from patients, attending the ED, with symptoms triggering investigation for possible acute coronary syndrome. The optimal combination of H-FABP with each hs-cTn was defined as that which maximized the proportion of patients with a negative test (low-risk) whilst maintaining at least 99 % sensitivity for AMI. A negative test comprised both H-FABP and hs-cTn below the chosen threshold in the absence of ischemic changes on the ECG. Results: One thousand seventy-nine patients were recruited including 248 with AMI. H-FABP 99 % sensitivity for AMI whilst classifying 40.9 % of patients as low-risk. The combination of H-FABP < 3.9 ng/mL and hs-cTnT < 7.6 ng/L with a negative ECG maintained the same sensitivity whilst classifying 32.1 % of patients as low risk. Conclusions: In patients requiring rule-out of AMI, the addition of H-FABP to hs-cTn at presentation (in the absence of new ischaemic ECG findings) may accelerate clinical diagnostic decision making by identifying up to 40 % of such patients as low-risk for AMI on the basis of blood tests performed on presentation. If implemented this has the potential to significantly accelerate triaging of patients for early discharge from the ED

Hand-rolled cigarette smoking patterns compared with factory-made cigarette smoking in New Zealand men

<p>Abstract</p> <p>Background</p> <p>Roll-your-own (RYO) cigarettes have increased in popularity, yet their comparative potential toxicity is uncertain. This study compares smoking of RYO and factory-made (FM) cigarettes on smoking pattern and immediate potential toxicity.</p> <p>Methods</p> <p>At a research clinic, 26 RYO and 22 FM volunteer male cigarette smokers, (addicted and overnight-tobacco-abstinent) each smoked 4 filter cigarettes, one half-hourly over 2 hours, either RYO or FM according to usual habit, using the CReSSMicro flowmeter. First cigarette smoked was their own brand. Subsequent cigarettes, all Holiday regular brand, were RYOs (0.5 g tobacco with filter), or FM with filter. Cravings on 100 mm visual analogue scale, and exhaled carbon monoxide (CO) were measured before and after each cigarette smoked.</p> <p>Results</p> <p>Smokers reported similar daily cigarette consumption (RYO 19.0, FM 17.4, p = 0.45), and similar time after waking to first cigarette. (RYO 6.1 minutes, FM 8.6 minutes, p = 0.113). First cigarette's RYO tobacco (0.45 g) weighed less than for FM (0.7 g, p < 0.001); less tobacco was burnt (0.36 g, FM 0.55 g, p < 0.001) but smoking patterns were no different. RYO smokers smoked subsequent cigarettes more intensively; inhaled 28% more smoke per cigarette (RYO 952 mL, FM 743 mL, p = 0.025); took 25% more puffs (RYO 16.9, FM 13.6, p = 0.035); puffed longer (RYO 28 seconds, FM 22 seconds, p = 0.012), taking similar puffs (RYO 57 mL, FM 59 mL). Over four cigarettes, RYOs boosted alveolar CO (RYO 13.8 ppm, FM 13.8 ppm), and reduced cravings (RYO 53%, FM 52%) no differently from FM cigarettes.</p> <p>Conclusion</p> <p>In these smokers, RYO smoking was associated with increased smoke exposure per cigarette, and similar CO breath levels, and even with filters is apparently no less and possibly more dangerous than FM smoking. Specific package warnings should warn of RYO smoking's true risk. RYOs are currently taxed much less than FM cigarettes in most countries; similar harm merits similar excise per cigarette.</p

Study of Constrained Minimal Supersymmetry

Taking seriously phenomenological indications for supersymmetry, we have made a detailed study of unified minimal SUSY, including effects at the few percent level in a consistent fashion. We report here a general analysis without choosing a particular unification gauge group. We find that the encouraging SUSY unification results of recent years do survive the challenge of a more complete and accurate analysis. Taking into account effects at the 5-10% level leads to several improvements of previous results, and allows us to sharpen our predictions for SUSY in the light of unification. We perform a thorough study of the parameter space. The results form a well-defined basis for comparing the physics potential of different facilities. Very little of the acceptable parameter space has been excluded by LEP or FNAL so far, but a significant fraction can be covered when these accelerators are upgraded. A number of initial applications to the understanding of the SUSY spectrum, detectability of SUSY at LEP II or FNAL, BR($b\to s\gamma$), Width($Z\to b\bar b$), dark matter, etc, are included in a separate section. We formulate an approach to extracting SUSY parameters from data when superpartners are detected. For small tan(beta) or large $m_top$ both $M_half$ and $M_0$ are entirely bounded from above at O(1 tev) without having to use a fine-tuning constraint.Comment: Michigan preprint UM-TH-93-24, LaTeX, 60 pages without figures. Complete paper with inline figures available by anonymous ftp to williams.physics.lsa.umich.edu in /pub/preprints/UM-TH-93-24.ps.Z (uncompresses to 10MB / 77 pages), or by e-mailing reques

Effectiveness of EDACS Versus ADAPT Accelerated Diagnostic Pathways for Chest Pain: A Pragmatic Randomized Controlled Trial Embedded Within Practice

Study objective A 2-hour accelerated diagnostic pathway based on the Thrombolysis in Myocardial Infarction score, ECG, and troponin measures (ADAPT-ADP) increased early discharge of patients with suspected acute myocardial infarction presenting to the emergency department compared with standard care (from 11% to 19.3%). Observational studies suggest that an accelerated diagnostic pathway using the Emergency Department Assessment of Chest Pain Score (EDACS-ADP) may further increase this proportion. This trial tests for the existence and size of any beneficial effect of using the EDACS-ADP in routine clinical care. Methods This was a pragmatic randomized controlled trial of adults with suspected acute myocardial infarction, comparing the ADAPT-ADP and the EDACS-ADP. The primary outcome was the proportion of patients discharged to outpatient care within 6 hours of attendance, without subsequent major adverse cardiac event within 30 days. Results Five hundred fifty-eight patients were recruited, 279 in each arm. Sixty-six patients (11.8%) had a major adverse cardiac event within 30 days (ADAPT-ADP 29; EDACS-ADP 37); 11.1% more patients (95% confidence interval 2.8% to 19.4%) were identified as low risk in EDACS-ADP (41.6%) than in ADAPT-ADP (30.5%). No low-risk patients had a major adverse cardiac event within 30 days (0.0% [0.0% to 1.9%]). There was no difference in the primary outcome of proportion discharged within 6 hours (EDACS-ADP 32.3%; ADAPT-ADP 34.4%; difference −2.1% [−10.3% to 6.0%], P=.65). Conclusion There was no difference in the proportion of patients discharged early despite more patients being classified as low risk by the EDACS-ADP than the ADAPT-ADP. Both accelerated diagnostic pathways are effective strategies for chest pain assessment and resulted in an increased rate of early discharges compared with previously reported rates

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes

BACKGROUND: Olaparib (Lynparza™) is a PARP inhibitor approved for advanced BRCA-mutated (BRCAm) ovarian cancer. PARP inhibitors may benefit patients whose tumours are dysfunctional in DNA repair mechanisms unrelated to BRCA1/2. We report exploratory analyses, including the long-term outcome of candidate biomarkers of sensitivity to olaparib in BRCA wild-type (BRCAwt) tumours. METHODS: Tumour samples from an olaparib maintenance monotherapy trial (Study 19, D0810C00019; NCT00753545) were analysed. Analyses included classification of mutations in genes involved in homologous recombination repair (HRR), BRCA1 promoter methylation status, measurement of BRCA1 protein and Myriad HRD score. RESULTS: Patients with BRCAm tumours gained most benefit from olaparib; a similar treatment benefit was also observed in 21/95 patients whose tumours were BRCAwt but had loss-of-function HRR mutations compared to patients with no detectable HRR mutations (58/95). A higher median Myriad MyChoice® HRD score was observed in BRCAm and BRCAwt tumours with BRCA1 methylation. Patients without BRCAm tumours derived benefit from olaparib treatment vs placebo although to a lesser extent than BRCAm patients.CONCLUSIONS: Ovarian cancer patients with tumours harbouring loss-of-function mutations in HRR genes other than BRCA1/2 may constitute a small, molecularly identifiable and clinically relevant population who derive treatment benefit from olaparib similar to patients with BRCAm

SARS-CoV-2 lineage B.1.1.7 is associated with greater disease severity among hospitalised women but not men: multicentre cohort study.

BACKGROUND: SARS-CoV-2 lineage B.1.1.7 has been associated with an increased rate of transmission and disease severity among subjects testing positive in the community. Its impact on hospitalised patients is less well documented. METHODS: We collected viral sequences and clinical data of patients admitted with SARS-CoV-2 and hospital-onset COVID-19 infections (HOCIs), sampled 16 November 2020 to 10 January 2021, from eight hospitals participating in the COG-UK-HOCI study. Associations between the variant and the outcomes of all-cause mortality and intensive therapy unit (ITU) admission were evaluated using mixed effects Cox models adjusted by age, sex, comorbidities, care home residence, pregnancy and ethnicity. FINDINGS: Sequences were obtained from 2341 inpatients (HOCI cases=786) and analysis of clinical outcomes was carried out in 2147 inpatients with all data available. The HR for mortality of B.1.1.7 compared with other lineages was 1.01 (95% CI 0.79 to 1.28, p=0.94) and for ITU admission was 1.01 (95% CI 0.75 to 1.37, p=0.96). Analysis of sex-specific effects of B.1.1.7 identified increased risk of mortality (HR 1.30, 95% CI 0.95 to 1.78, p=0.096) and ITU admission (HR 1.82, 95% CI 1.15 to 2.90, p=0.011) in females infected with the variant but not males (mortality HR 0.82, 95% CI 0.61 to 1.10, p=0.177; ITU HR 0.74, 95% CI 0.52 to 1.04, p=0.086). INTERPRETATION: In common with smaller studies of patients hospitalised with SARS-CoV-2, we did not find an overall increase in mortality or ITU admission associated with B.1.1.7 compared with other lineages. However, women with B.1.1.7 may be at an increased risk of admission to intensive care and at modestly increased risk of mortality.This report was produced by members of the COG-UK-HOCI Variant substudy consortium. COG-UK-HOCI is part of COG-UK. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute