Induced sputum inflammatory mediator concentrations in chronic cough

Previous studies have shown evidence of airway inflammation in patients with chronic cough and have suggested that the cough may be due to release of tussive mediators and activation of afferent sensory nerve endings. We measured the concentration of various proinflammatory and tussive mediators in induced sputum supernatants from 20 patients with cough variant asthma or eosinophilic bronchitis, 20 patients with nonasthmatic chronic cough, 22 patients with idiopathic chronic cough, and 18 healthy control subjects. We measured histamine, cysteinyl-leukotrienes, prostanoids (prostaglandin D2 and prostaglandin E2), and interleukin-8 by enzyme immunoassay. The median sputum histamine concentrations were significantly higher in patients with idiopathic chronic cough (8.0 ng/ml) and cough variant asthma/eosinophilic bronchitis (10.2 ng/ml) than in normal subjects (2.6 ng/ml; 95% confidence interval of difference from idiopathic chronic cough, 0.8 to 25.8 [p = 0.009] and 95% confidence interval of difference from cough variant asthma/eosinophilic bronchitis, 1.1 to 20.1 [p = 0.01]). Median sputum prostaglandin D2 and prostaglandin E2 concentrations were significantly higher in all categories of chronic cough. Our findings support the view that there is release of inflammatory and tussive mediators in patients with chronic cough and suggest that there might be similarities in the mechanism of cough in a diverse range of conditions.     

Alcohol in a social context: findings from event-contingent recording studies of everyday social interactions

Background:  Data concerning the effects of alcohol on social interaction in everyday life are limited.
Methods:  Healthy volunteers in 4 studies of social behaviors and mood were instructed to complete record forms immediately after a social interaction had occurred, a method known as event-contingent recording. Record forms asked questions about quarrelsome, agreeable, dominant, and submissive behaviors; about aspects of mood; and, in 3 studies, about perceptions of others. Each form also contained a question about alcohol consumption prior to a social interaction. For the present report, only social interactions taking place in the evening and outside the work setting were included. Only individuals who consumed alcohol at least once in these circumstances were included ( n  = 171).
Results:  Social interactions involving alcohol were primarily characterized by higher levels of agreeable behaviors, by perceptions of greater agreeableness in others, and by more positive mood. Alcohol consumption was not associated with higher levels of quarrelsomeness.
Conclusions:  Alcohol consumption in a social context may have predominantly positive effects, an observation which is at odds with most alcohol-induced aggression experiments performed in laboratory settings. Drinking in everyday life may be less likely to result in aggression because, unlike in most laboratory experiments, individuals can choose among a variety of behaviors in response to social cues and the alcohol dose consumed is usually lower. Event-contingent recording provides a new approach for the study of alcohol's effects in everyday life and the conditions in which alcohol might result in interpersonal aggression.     

A clinical trial to investigate the effect of silver nylon dressings on mediastinitis rates in postoperative cardiac sternotomy incisions

Mediastinitis is a rare but serious postoperative complication of cardiac surgery that increases mortality rates, hospital length of stay, and medical costs. A clinical trial was conducted to investigate whether the type of postoperative surgical dressing (silver nylon or standard gauze) affects the rate of mediastinal infections. The sample consisted of 1,600 surgical cardiac patients. Infection rates in the standard gauze group (control, n = 1,235) were collected retrospectively from 24 months of infection control records. In the prospective treatment arm of the study, the wounds of all consecutive surgical patients (n = 365) were covered with a silver nylon dressing and patients were assessed during the 3-week postoperative visit. Thirteen (13) patients in the control group (1%) and none of the patients in the treatment group developed mediastinitis (chi2 [1, N = 1,600] = 3.88, P <0.05). Study findings support the need for a large, prospective, controlled clinical study to confirm the effects of these dressings on mediastinitis, resultant morbidity, and costs of care.     

An assessment of linezolid utilization in selected canadian provinces.

BACKGROUND: Linezolid is approved for the treatment of designated infections caused by methicillin-resistant and -susceptible Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. OBJECTIVE: To characterize linezolid utilization since its launch in Canada in 2001. METHODS: Demographics, antimicrobial regimens, and clinical and resource utilization data for linezolid-treated patients were collected retrospectively by hospital pharmacists at nine tertiary care hospitals in four provinces. Statistics describing linezolid utilization were calculated and the appropriateness of use was assessed according to a treatment algorithm based on recommendations of the Infectious Diseases Pharmacy Specialty Network in 2001. RESULTS: Ninety-nine linezolid courses were prescribed for 103 infections in 95 patients (mean age 57.8 years, 52.6% male) with an average length of hospital stay of 40.6 days. Fifty-three per cent of patients had an allergy to at least one antibiotic other than linezolid. The major use of linezolid was for treatment of skin and soft tissue infections (32.0%), followed by bacteremia (15.5%). The most prevalent pathogen was methicillin-resistant S aureus, identified in 44.7% of infections. Linezolid was primarily prescribed as the oral form following other intravenous anti-infectives (55.6% of courses) for an average duration of 14.4 days. The rate of appropriate utilization was 53% (range 25% to 75% by site). In 93.5% of courses deemed inappropriate, recommended first-line therapies were not attempted before linezolid. CONCLUSIONS: Linezolid was prescribed appropriately in approximately one-half of cases reviewed. The rate of appropriate utilization is similar to those rates reported in other Canadian antibiotic reviews.     

Therapeutic Options for the Management of Postprandial Glucose in Patients With Type 2 Diabetes on Basal Insulin

In Brief For patients with type 2 diabetes who require add-on therapy to metformin plus basal insulin, GLP-1 receptor agonists may be a favorable option because they effectively manage postprandial glucose, reduce body weight, and have an overall favorable safety profile compared to other agents. Given the wide range of treatment combinations available for type 2 diabetes management, health professionals must partner with patients to determine the best choices based on patients’ individual lifestyle, resources, and treatment goals.Providing patients with optimal strategies for the management of hyperglycemia associated with type 2 diabetes is challenging. This is especially true as type 2 diabetes progresses and patients require two- and three-drug combinations or complex insulin regimens to achieve glycemic targets (1). Current consensus guidelines from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), as well as the 2015 diabetes management algorithm of the American Association of Clinical Endocrinologists, recognize that many different drug combinations can be used to achieve A1C goals (Figure 1) (1,2). Given this range of available therapeutic options, ADA/EASD guidelines emphasize the importance of individualized, patient-centered care (1). If patients are able to be involved with treatment decisions, health care professionals (HCPs) must use a shared decision-making process to increase patient satisfaction and adherence to treatment (3). HCPs should emphasize treatment outcomes that are also important to the patient (3). Factors to consider in such individualized type 2 diabetes treatment plans include patients’ attitudes and willingness to make lifestyle changes and risk factors for hypoglycemia and other adverse events. HCPs should also consider patients’ body weight, duration of disease, life expectancy, comorbidities, established vascular complications, overall level of support, and economic burdens of treatment (1). All treatment plans should include strategies for controlling obesity, blood pressure, and hyperlipidemia and emphasize smoking cessation, regular exercise, and healthy eating habits (4).Open in a separate windowFIGURE 1.ADA/EASD general recommendations for type 2 diabetes management (1). DPP-4-i, DPP-4 inhibitor; Fx’s, fractures; GLP-1-RA, GLP-1 receptor agonist; HF, heart failure; SU, sulfonylurea.^aConsider beginning at this stage in patients with a very high A1C level (e.g., ≥9%).^bConsider rapid-acting, nonsulfonylurea secretagogues (meglitinides) in patients with irregular meal schedules or who develop late postprandial hypoglycemia on sulfonylureas.^cUsually a basal insulin (NPH, glargine, or detemir) in combination with noninsulin agents.^dCertain noninsulin agents may be continued with insulin. Consider beginning at this stage if patient presents with severe hyperglycemia (≥300−350 mg/dL; A1C level ≥10.0−12.0%) with or without catabolic features (e.g., weight loss or ketosis).     

Worsening of cerebral hyperemia by the administration of terlipressin in acute liver failure with severe encephalopathy

There is increasing evidence that terlipressin is useful in patients with cirrhosis and hepatorenal syndrome, but there are no data of its use in patients with acute liver failure (ALF) in whom hepatorenal syndrome is common. Although terlipressin produces systemic vasoconstriction, it produces cerebral vasodilatation and may increase cerebral blood flow (CBF). Increased CBF contributes to intracranial hypertension in patients with ALF. The aim of this study was to evaluate the safety of terlipressin in patients with ALF with respect to cerebral hemodynamics. Six successive patients with ALF were ventilated electively for grade IV hepatic encephalopathy. Patients were monitored invasively and CBF was measured (Kety-Schmidt technique). Measurements were made before and at 1, 3, and 5 hours after intravenous (single bolus) administration of terlipressin (0.005 mg/kg), median, 0.25 mg (range, 0.2-0.3 mg). There was no significant change in heart rate, mean arterial pressure, or cardiac output. CBF and jugular venous oxygen saturation both increased significantly at 1 hour (P = 0.016). Intracranial pressure increased significantly at 1 hour (P = 0.031), returning back to baseline values at 2 hours. In conclusion, administration of terlipressin, at a dose that did not alter systemic hemodynamics, resulted in worsening of cerebral hyperemia and intracranial hypertension in patients with ALF and severe hepatic encephalopathy. These data suggest the need to exercise extreme caution in the use of terlipressin in these patients in view of its potentially deleterious consequences on cerebral hemodynamics.     

Associations of Mortality with Long-Term Exposures to Fine and Ultrafine Particles,Species and Sources: Results from the California Teachers Study Cohort

Background

Although several cohort studies report associations between chronic exposure to fine particles (PM_2.5) and mortality, few have studied the effects of chronic exposure to ultrafine (UF) particles. In addition, few studies have estimated the effects of the constituents of either PM_2.5 or UF particles.

Methods

We used a statewide cohort of > 100,000 women from the California Teachers Study who were followed from 2001 through 2007. Exposure data at the residential level were provided by a chemical transport model that computed pollutant concentrations from > 900 sources in California. Besides particle mass, monthly concentrations of 11 species and 8 sources or primary particles were generated at 4-km grids. We used a Cox proportional hazards model to estimate the association between the pollutants and all-cause, cardiovascular, ischemic heart disease (IHD), and respiratory mortality.

Results

We observed statistically significant (p < 0.05) associations of IHD with PM_2.5 mass, nitrate, elemental carbon (EC), copper (Cu), and secondary organics and the sources gas- and diesel-fueled vehicles, meat cooking, and high-sulfur fuel combustion. The hazard ratio estimate of 1.19 (95% CI: 1.08, 1.31) for IHD in association with a 10-μg/m³ increase in PM_2.5 is consistent with findings from the American Cancer Society cohort. We also observed significant positive associations between IHD and several UF components including EC, Cu, metals, and mobile sources.

Conclusions

Using an emissions-based model with a 4-km spatial scale, we observed significant positive associations between IHD mortality and both fine and ultrafine particle species and sources. Our results suggest that the exposure model effectively measured local exposures and facilitated the examination of the relative toxicity of particle species.

Citation

Ostro B, Hu J, Goldberg D, Reynolds P, Hertz A, Bernstein L, Kleeman MJ. 2015. Associations of mortality with long-term exposures to fine and ultrafine particles, species and sources: results from the California Teachers Study cohort. Environ Health Perspect 123:549–556; http://dx.doi.org/10.1289/ehp.1408565     

HIV Sexual Risk and Syndemics among Women in Three Urban Areas in the United States: Analysis from HVTN 906

Limited data are available on the longitudinal occurrence of syndemic factors among women at risk for HIV infection in the USA and how these factors relate to sexual risk over time. HVTN 906 was a longitudinal study enrolling 799 HIV-uninfected women in three cities. Assessments were done at baseline, 6, 12, and 18 months to assess syndemic factors (low education, low income, unemployment, lack of health insurance, housing instability, substance use, heavy alcohol use, partner violence, incarceration) and sexual risk outcomes. For each sexual risk outcome, a GEE model was fit with syndemic factors or syndemic score (defined as sum of binary syndemics, ranging from 0 to 9), visit, study site, age and race/ethnicity as predictors to examine the multivariable association between syndemic factors and outcomes over time. Odds of unprotected sex while drunk or high were significantly higher when women reported lack of health insurance, substance and heavy alcohol use and partner violence. Housing instability, substance and heavy alcohol use, partner violence and recent incarceration were associated with higher odds of having multiple sexual partners. Odds of sex exchange were significantly higher in the presence of unemployment, housing instability, low education, lack of health insurance, substance and heavy alcohol use, partner violence and incarceration. Housing instability, substance and heavy alcohol use, and partner violence were significantly associated with higher odds of unprotected anal sex. Odds of having a recent STI were significantly higher when women reported housing instability and partner violence. There were significantly higher odds of the reporting of any risk outcomes during follow-up with higher syndemic score. This study highlights a group of women experiencing multiple poor social and health outcomes who need to be the focus of comprehensive interventions.     

Determinants of Intima-Media Thickness in the Young: The ALSPAC Study

ObjectivesThis study characterized the determinants of carotid intima-media thickness (cIMT) in a large (n > 4,000) longitudinal cohort of healthy young people age 9 to 21 years.BackgroundGreater cIMT is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood.MethodsAssociations between cardiovascular risk factors and cIMT were investigated in both longitudinal (ages 9 to 17 years) and cross-sectional (ages 17 and 21 years) analyses, with the latter also related to other measures of carotid structure and stress. Additional use of ultra-high frequency ultrasound in the radial artery at age 21 years allowed investigation of the distinct layers (i.e., intima or media) that may underlie observed differences.ResultsFat-free mass (FFM) and systolic blood pressure were the only modifiable risk factors positively associated with cIMT (e.g., mean difference in cIMT per 1-SD increase in FFM at age 17: 0.007 mm: 95% confidence interval [CI]: 0.004 to 0.010; p < 0.001), whereas fat mass was negatively associated with cIMT (difference: ?0.0032; 95% CI: 0.004 to ?0.001; p = 0.001). Similar results were obtained when investigating cumulative exposure to these factors throughout adolescence. An increase in cIMT maintained circumferential wall stress in the face of increased mean arterial pressure when increases in body mass were attributable to increased FFM, but not fat mass. Risk factor?associated differences in the radial artery occurred in the media alone, and there was little evidence of a relationship between intimal thickness and any risk factor.ConclusionsSubtle changes in cIMT in the young may predominantly involve the media and represent physiological adaptations as opposed to subclinical atherosclerosis. Other vascular measures may be more appropriate for the identification of arterial disease before adulthood.