Tyler Hartwell

The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: Contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis☆

Abstract Patients with diabetes mellitus experience a more adverse outcome after acute myocardial infarction compared with nondiabetic patients, although the mechanisms responsible for these findings are not clear. From the Multicenter Investigation of the Limitation of Infarct Size (MILIS) study, the course of acute infarction in 85 diabetic patients was compared with that in 415 nondiabetic patients, all of whom had serial assessments of left ventricular function. The diabetic patients experienced a more complicated in-hospital and postdischarge course than did the nondiabetic patients, including a higher incidence of postinfarction angina, infarct extension, heart failure and death, despite the development of a smaller infarct size and similar levels of left ventricular ejection fraction. Although diabetic patients had a worse profile of cardiovascular risk factors at the time of the index infarction, the increased incidence of adverse outcomes among them persisted despite adjustment for these baseline imbalances. Diabetic women had a poor baseline risk profile compared with the other groups categorized by gender and diabetic status, and experienced an almost twofold increase in cardiac mortality despite development of the smallest infarct size during the index event. The duration of diabetes and the use of insulin at the time of the index infarction were associated with a better in-hospital mortality rate, but the duration of diabetes did not exert a major influence on the outcome of the diabetic patients. The factors responsible for the increased incidence of adverse outcomes among diabetic patients may be related to an acceleration of the atherosclerotic process, diastolic left ventricular dysfunction associated with diabetic cardiomyopathy or other unidentified unfavorable processes.

Oral misoprostol in preventing postpartum haemorrhage in resource-poor communities: a randomised controlled trial

BACKGROUND Postpartum haemorrhage is a major cause of maternal mortality in the developing world. Although effective methods for prevention and treatment of such haemorrhage exist--such as the uterotonic drug oxytocin--most are not feasible in resource-poor settings where many births occur at home. We aimed to investigate whether oral misoprostol, a potential alternative to oxytocin, could prevent postpartum haemorrhage in a community home-birth setting. METHODS In a placebo-controlled trial undertaken between September, 2002, and December, 2005, 1620 women in rural India were randomised to receive oral misoprostol (n=812) or placebo (n=808) after delivery. 25 auxiliary nurse midwives undertook the deliveries, administered the study drug, and measured blood loss. The primary outcome was the incidence of acute postpartum haemorrhage (defined as > or =500 mL bleeding) within 2 h of delivery. Analysis was by intention-to-treat. The trial was registered with the US clinical trials database (http://www. clinicaltrials.gov) as number NCT00097123. FINDINGS Oral misoprostol was associated with a significant reduction in the rate of acute postpartum haemorrhage (12.0% to 6.4%, p<0.0001; relative risk 0.53 [95% CI 0.39-0.74]) and acute severe postpartum haemorrhage (1.2% to 0.2%, p<0.0001; 0.20 [0.04-0.91]. One case of postpartum haemorrhage was prevented for every 18 women treated. Misoprostol was also associated with a decrease in mean postpartum blood loss (262.3 mL to 214.3 mL, p<0.0001). Postpartum haemorrhage rates fell over time in both groups but remained significantly higher in the placebo group. Women taking misoprostol had a higher rate of transitory symptoms of chills and fever than the control. INTERPRETATION Oral misoprostol was associated with significant decreases in the rate of acute postpartum haemorrhage and mean blood loss. The drugs low cost, ease of administration, stability, and a positive safety profile make it a good option in resource-poor settings.

The Team Study - Personal Exposures to Toxic-Substances in Air, Drinking-Water, and Breath of 400 Residents of New-Jersey, North-Carolina, and North-Dakota:

EPAs TEAM Study has measured exposures to 20 volatile organic compounds in personal air, outdoor air, drinking water, and breath of approximately 400 residents of New Jersey, North Carolina, and North Dakota. All residents were selected by a probability sampling scheme to represent 128,000 inhabitants of Elizabeth and Bayonne, New Jersey, 131,000 residents of Greensboro, North Carolina, and 7000 residents of Devils Lake, North Dakota. Participants carried a personal monitor to collect two 12-hr air samples and gave a breath sample at the end of the day. Two consecutive 12-hr outdoor air samples were also collected on identical Tenax cartridges in the backyards of some of the participants. About 5000 samples were collected, of which 1500 were quality control samples. Ten compounds were often present in personal air and breath samples at all locations. Personal exposures were consistently higher than outdoor concentrations for these chemicals and were sometimes 10 times the outdoor concentrations. Indoor sources appeared to be responsible for much of the difference. Breath concentrations also often exceeded outdoor concentrations and correlated more strongly with personal exposures than with outdoor concentrations. Some activities (smoking, visiting dry cleaners or service stations) and occupations (chemical, paint, and plastics plants) were associated with significantly elevated exposures and breath levels for certain toxic chemicals. Homes with smokers had significantly increased benzene and styrene levels in indoor air. Residence near major point sources did not affect exposure.

The influence of personal activities on exposure to volatile organic compounds

Seven persons volunteered to perform 25 common activities thought to increase personal exposure to volatile organic chemicals (VOCs) during a 3-day monitoring period. Personal, indoor, and outdoor air samples were collected on Tenax cartridges three times per day (evening, overnight, and daytime) and analyzed by GC-MS for 17 target VOCs. Samples of exhaled breath were also collected before and after each monitoring period. About 20 activities resulted in increasing exposure to one or more of the target VOCs, often by factors of 10, sometimes by factors of 100, compared to exposures during the sleep period. These concentrations were far above the highest observed outdoor concentrations during the length of the study. Breath levels were often significantly correlated with previous personal exposures. Major exposures were associated with use of deodorizers (p-dichlorobenzene); washing clothes and dishes (chloroform); visiting a dry cleaners (1,1,1-trichloroethane, tetrachloroethylene); smoking (benzene, styrene); cleaning a car engine (xylenes, ethylbenzene, tetrachloroethylene); painting and using paint remover (n-decane, n-undecane); and working in a scientific laboratory (many VOCs). Continuously elevated indoor air levels of p-dichlorobenzene, trichloroethylene, 1,1,1-trichloroethane, carbon tetrachloride, decane, and undecane were noted in several homes and attributed to unknown indoor sources. Measurements of exhaled breath suggested biological residence times in tissue of 12-18 hr and 20-30 hr for 1,1,1-trichloroethane and p-dichlorobenzene, respectively.

Cohort Profile: The international epidemiological databases to evaluate AIDS (IeDEA) in sub-Saharan Africa

In response to the HIV/AIDS pandemic in sub-Saharan Africa the African networks of IeDEA (International epidemiologic databases to Evaluate AIDS) aim to inform the scale-up of ART in the region through clinical and epidemiologic research. Funded by the National Institutes of Allergy and Infectious Diseases (NIAID) the objectives across the four African IeDEA regions (West Africa Central Africa East Africa and Southern Africa) are similar and cover all populations including pregnant women infants children adolescents and adult patients. They can be summarized as follows: (1) To prove robust evaluation of the delivery of ART in children adolescents and adults in sub-Saharan Africa with a focus on long-term program effectiveness and outcomes; (2) to describe the long-term temporal trends in regimen durability and tolerability and to examine monitoring strategies; (3) to describe important comorbidities and co-infections of HIV infection including malaria tuberculosis and cancer; (4) to examine the pregnancy- and HIV-related outcomes of women initiating ART during pregnancy and of infants exposed to HIV or ART in utero; (5) to develop and apply novel statistical methods to deal with missing data loss to follow-up competing risks and time-dependent confounding; (6) to establish procedures to link the HIV cohort data with other databases at local or national level. The present report provides an indicative summary of some of the major research themes and key findings as well as a discussion of the program’s strengths and weaknesses.

Comparison of enzymatic and anatomic estimates of myocardial infarct size in man.

Enzymatic estimates of myocardial infarct size based on plasma levels of MB creatine kinase (MB-CK) were compared with anatomic infarct size in 49 human hearts obtained at autopsy. The patients studied had been enrolled in the Multicenter Investigation of Limitation of Infarct Size (MILIS) study program within 18 hr of the onset of acute infarction and were treated at one of five participating hospitals. Infarct size was estimated from serial measurements of plasma MB-CK made at the core laboratory for CK analysis. Hearts obtained at autopsy were studied independently by the core pathology laboratory without knowledge of the MB-CK levels or clinical results. Data from the two laboratories were compared at the data coordinating center. Of 49 hearts, 12 were excluded either because anatomic infarct size could not be established or because the infarct occurring at the time of enrollment in the MILIS study could not be distinguished with certainty from other infarcts. Of the remaining 37 hearts, peak MB-CK level was available in 36, but samples sufficient for estimation of infarct size were available in only 25. The overall correlation coefficient (Spearman) was .87 for these 25 hearts, indicating that enzymatic estimates of infarct size correlate closely with anatomic measurements. The results indicate that CK estimates of myocardial infarct size represent a valid clinical end point for assessing myocardial infarct size, and the effect of therapy thereon, in groups of treated and control patients.

Implications for acute intervention related to time of hospital arrival in acute myocardial infarction.

The time from onset of symptoms to arrival in the hospital emergency room (ER) was studied in 778 patients randomized into a study of acute myocardial infarction (AMI) size limitation. Patients at relatively high risk of death after AMI (including those with preexisting diabetes mellitus, systemic hypertension or congestive heart failure), women and older patients arrived significantly later in the ER than did patients without these characteristics. A significantly higher mortality rate was observed in patients who arrived late, i.e., those who arrived more than 2 hours after the onset of chest pain, even though patients with hemodynamic compromise (bradycardia, hypotension) tended to arrive earlier. The difference in long-term mortality between those who arrived early (within 2 hours of onset of chest pain) and those who arrived late was accounted for by the baseline differences between these 2 groups. These baseline differences may influence the effects of early interventions in AMI. In addition, these findings have implications for education of high-risk patients who could benefit the most from aggressive early intervention.

Effect of propranolol on myocardial-infarct size in a randomized blinded multicenter trial:

A multicenter randomized single-blind study was performed to evaluate the effects of propranolol administered during the evolution of myocardial infarction. Five centers enrolled a total of 269 patients, with 134 receiving propranolol and 135 placebo. Propranolol or placebo was given intravenously upon randomization (0.1 mg per kilogram of body weight) and then orally for nine days to keep the heart rate between 45 and 60 beats per minute. Less than 2 per cent of patients were treated within 4 hours after the onset of symptoms, but 50 per cent received therapy within 8 hours of onset of chest pain, and the remainder between 8 and 18 hours. The heart rates in the propranolol-treated group were significantly lower than those in the placebo group (P less than 0.001). Base-line characteristics, including the mean heart rate (79.6 vs. 81.3) and the left ventricular ejection fraction (49.0 vs. 49.5), were similar in the two groups. The primary end point evaluated--infarct size as estimated from plasma MB creatine kinase activity--was virtually identical in the two groups, averaging 13.3 and 13.6 gram-equivalents of MB creatine kinase per square meter of body-surface area. Peak plasma levels of the enzyme were also similar in the two groups. No significant difference was observed between the propranolol and placebo groups in the change in left ventricular ejection fraction, extent of area involved in pyrophosphate uptake, R-wave loss on electrocardiograms, or mortality (after three years). These results do not support the use of propranolol administered four or more hours after the onset of symptoms to limit infarct size.

Tobacco use and secondhand smoke exposure during pregnancy: An investigative survey of women in 9 developing nations:

OBJECTIVES We examined pregnant womens use of cigarettes and other tobacco products and the exposure of pregnant women and their young children to secondhand smoke (SHS) in 9 nations in Latin America, Asia, and Africa. METHODS Face-to-face surveys were administered to 7961 pregnant women (more than 700 per site) between October 2004 and September 2005. RESULTS At all Latin American sites, pregnant women commonly reported that they had ever tried cigarette smoking (range: 78.3% [Uruguay] to 35.0% [Guatemala]). The highest levels of current smoking were found in Uruguay (18.3%), Argentina (10.3%), and Brazil (6.1%). Experimentation with smokeless tobacco occurred in the Democratic Republic of the Congo and India; one third of all respondents in Orissa, India, were current smokeless tobacco users. SHS exposure was common: between 91.6% (Pakistan) and 17.1% (Democratic Republic of the Congo) of pregnant women reported that smoking was permitted in their home. CONCLUSIONS Pregnant womens tobacco use and SHS exposure are current or emerging problems in several low- and middle-income nations, jeopardizing ongoing efforts to improve maternal and child health.

Childhood Sexual Abuse and Risk Behaviors Among Men at High Risk for HIV Infection

OBJECTIVES This study examined the association between unwanted sexual activity during childhood and risky behaviors among a sample of predominantly African American and Hispanic men. METHODS Data were obtained from baseline interviews completed by 2676 men enrolled in a multisite HIV prevention trial. RESULTS Approximately 25% of the men reported unwanted or uninvited sexual activity before 13 years of age, with Hispanic men more likely than African American men to report unwanted sexual activity during childhood. Men with a history of unwanted sexual activity during childhood were more likely to report unwanted sexual activity since age 13, the buying and selling of sex, problems with alcohol, and drug use. Men who reported unwanted sexual activity during childhood also reported a significantly greater frequency of unprotected sexual acts and more partners. CONCLUSIONS Among men at high risk for HIV infection, unwanted sexual activity during childhood is more widespread than previously described and can increase the risk of participating in harmful health practices during adulthood, including risky sexual behaviors.