Detection and Characterisation of Lactobacillus spp. in the Bovine Uterus and Their Influence on Bovine Endometrial Epithelial Cells In Vitro

Bacterial infections and inflammation of the uterus are common in dairy cattle after parturition. In particular, pathogenic bacteria that cause endometritis have been the focus of research in cattle reproduction in the last ten years. The aim of the present study was to identify commensal lactobacilli in the bovine uterus and to examine their influence on the synthesis of pro- inflammatory factors in bovine endometrial epithelial cells in vitro. Lactobacillus species were isolated from healthy bovine uteri and further characterised. Bovine endometrial epithelial cells in the second passage (n = 5 animals) were co-cultured with the autochthonous isolates L. buchneri, L. ruminis and L. amylovorus as well as with a commercially available L. vaginalis in different multiplicities of infection (MOI = 1, 5 and 10, respectively). Endometrial epithelial cells cultured without bacteria served as controls. At distinct points in time (2, 4 and 6 h) total RNA was extracted from co-cultured epithelial cells and subjected to reverse transcription quantitative PCR of pro-inflammatory factors. Furthermore, the release of such factors by co-cultured epithelial cells was measured by ELISA or EIA after 24 and 48 h. L. ruminis and L. amylovorus induced increased interleukin (IL) IL1A, IL6, IL8 and prostaglandin-endoperoxide synthase 2 mRNA levels and the release of IL8 and prostaglandin F2α in endometrial epithelial cells compared with control cells. In contrast, L. buchneri did not significantly influence the expression and release of these factors. Toll-like receptors 2 and 6 transcripts were found unchanged in co-cultured and untreated epithelial cells in vitro. However, endometrial epithelial cells of each animal showed individual differences in the response to bacterial load. These results suggest that Lactobacillus species are present in the bovine uterus, revealing immunomodulatory properties

Effect of ICU Strain on Timing of Limitations in Life-Sustaining Therapy and Death

Purpose: The effect of capacity strain in an ICU on the timing of end-of-life decision making is unknown. We sought to determine how changes in strain impact timing of new DNR orders and of death. Methods: Retrospective cohort study of 9,891 patients dying in the hospital following an ICU stay ≥ 72 hours in Project IMPACT, 2001-2008. We examined the effect of ICU capacity strain (measured by standardized census, proportion of new admissions, and average patient acuity) on time to initiation of DNR orders and time to death for all ICU decedents using fixed-effects linear regression. Results: Increases in strain were associated with shorter time to DNR for patients with limitations in therapy (predicted time to DNR 6.11 days for highest versus 7.70 days for lowest quintile of acuity, p=0.02; 6.50 days for highest versus 7.77 days for lowest quintile of admissions, p<0.001), and shorter time to death (predicted time to death 7.64 days for highest versus 9.05 days for lowest quintile of admissions, p<0.001; 8.28 days for highest versus 9.06 days for lowest quintile of census, only in closed ICUs, p=0.006). Time to DNR order significantly mediated relationships between acuity and admissions and time to death, explaining the entire effect of acuity, and 65% of the effect of admissions. There was no association between strain and time to death for decedents without a limitation in therapy. Conclusions: Strains in ICU capacity are associated with end-of-life decision making, with shorter times to placement of DNR orders and death for patients admitted during high-strain days

Race and sex differences in response to endothelin receptor antagonists for pulmonary arterial hypertension

Background Recently studied therapies for pulmonary arterial hypertension (PAH) have improved outcomes among populations of patients, but little is known about which patients are most likely to respond to specific treatments. Differences in endothelin-1 biology between sexes and between whites and blacks may lead to differences in patients' responses to treatment with endothelin receptor antagonists (ERAs). Methods We conducted pooled analyses of deidentified, patient-level data from six randomized placebo-controlled trials of ERAs submitted to the US Food and Drug Administration to elucidate heterogeneity in treatment response. We estimated the interaction between treatment assignment (ERA vs placebo) and sex and between treatment and white or black race in terms of the change in 6-min walk distance from baseline to 12 weeks. Results Trials included 1,130 participants with a mean age of 49 years; 21% were men, 74% were white, and 6% were black. The placebo-adjusted response to ERAs was 29.7 m (95% CI, 3.7-55.7 m) greater in women than in men (P = .03). The placebo-adjusted response was 42.2 m for whites and −1.4 m for blacks, a difference of 43.6 m (95% CI, −3.5-90.7 m) (P = .07). Similar results were found in sensitivity analyses and in secondary analyses using the outcome of absolute distance walked. Conclusions Women with PAH obtain greater responses to ERAs than do men, and whites may experience a greater treatment benefit than do blacks. This heterogeneity in treatment-response may reflect pathophysiologic differences between sexes and races or distinct disease phenotypes

Examining the Prevalence of Financial Exploitation of Individuals Suffering from Alzheimer’s and Dementia Related Diseases in Texas

The Alzheimer’s Association of Houston and Southeast Texas (Association) is committed to expanding care and services for individuals with Alzheimer’s disease through awareness, research, and legislation. The Association has asked the Bush School capstone team to examine the prevalence of elder financial exploitation in Texas, specifically among individuals with Alzheimer’s and dementia-related diseases. The result of this examination will assist the Association’s policy and recommendation agenda during the 2019 Texas Legislative Session

A Randomized Trial of Nighttime Physician Staffing in an Intensive Care Unit

Background Increasing numbers of intensive care units (ICUs) are adopting the practice of nighttime intensivist staffing despite the lack of experimental evidence of its effectiveness. Methods We conducted a 1-year randomized trial in an academic medical ICU of the effects of nighttime staffing with in-hospital intensivists (intervention) as compared with nighttime coverage by daytime intensivists who were available for consultation by telephone (control). We randomly assigned blocks of 7 consecutive nights to the intervention or the control strategy. The primary outcome was patients’ length of stay in the ICU. Secondary outcomes were patients’ length of stay in the hospital, ICU and in-hospital mortality, discharge disposition, and rates of readmission to the ICU. For length-of-stay outcomes, we performed time-to-event analyses, with data censored at the time of a patient’s death or transfer to another ICU. Results A total of 1598 patients were included in the analyses. The median Acute Physiology and Chronic Health Evaluation (APACHE) III score (in which scores range from 0 to 299, with higher scores indicating more severe illness) was 67 (interquartile range, 47 to 91), the median length of stay in the ICU was 52.7 hours (interquartile range, 29.0 to 113.4), and mortality in the ICU was 18%. Patients who were admitted on intervention days were exposed to nighttime intensivists on more nights than were patients admitted on control days (median, 100% of nights [interquartile range, 67 to 100] vs. median, 0% [interquartile range, 0 to 33]; P\u3c0.001). Nonetheless, intensivist staffing on the night of admission did not have a significant effect on the length of stay in the ICU (rate ratio for the time to ICU discharge, 0.98; 95% confidence interval [CI], 0.88 to 1.09; P=0.72), ICU mortality (relative risk, 1.07; 95% CI, 0.90 to 1.28), or any other end point. Analyses restricted to patients who were admitted at night showed similar results, as did sensitivity analyses that used different definitions of exposure and outcome. Conclusions In an academic medical ICU in the United States, nighttime in-hospital intensivist staffing did not improve patient outcomes. (Funded by University of Pennsylvania Health System and others; ClinicalTrials.gov number, NCT01434823.

Dealing with heterogeneity of treatment effects: is the literature up to the challenge?

<p>Abstract</p> <p>Background</p> <p>Some patients will experience more or less benefit from treatment than the averages reported from clinical trials; such variation in therapeutic outcome is termed heterogeneity of treatment effects (HTE). Identifying HTE is necessary to individualize treatment. The degree to which heterogeneity is sought and analyzed correctly in the general medical literature is unknown. We undertook this literature sample to track the use of HTE analyses over time, examine the appropriateness of the statistical methods used, and explore the predictors of such analyses.</p> <p>Methods</p> <p>Articles were selected through a probability sample of randomized controlled trials (RCTs) published in <it>Annals of Internal Medicine</it>, <it>BMJ</it>, <it>JAMA</it>, <it>The Lancet</it>, and <it>NEJM </it>during odd numbered months of 1994, 1999, and 2004. RCTs were independently reviewed and coded by two abstractors, with adjudication by a third. Studies were classified as reporting: (1) HTE analysis, utilizing a formal test for heterogeneity or treatment-by-covariate interaction, (2) subgroup analysis only, involving no formal test for heterogeneity or interaction; or (3) neither. Chi-square tests and multiple logistic regression were used to identify variables associated with HTE reporting.</p> <p>Results</p> <p>319 studies were included. Ninety-two (29%) reported HTE analysis; another 88 (28%) reported subgroup analysis only, without examining HTE formally. Major covariates examined included individual risk factors associated with prognosis, responsiveness to treatment, or vulnerability to adverse effects of treatment (56%); gender (30%); age (29%); study site or center (29%); and race/ethnicity (7%). Journal of publication and sample size were significant independent predictors of HTE analysis (p < 0.05 and p < 0.001, respectively).</p> <p>Conclusion</p> <p>HTE is frequently ignored or incorrectly analyzed. An iterative process of exploratory analysis followed by confirmatory HTE analysis will generate the data needed to facilitate an individualized approach to evidence-based medicine.</p

Active Choice Intervention Increases Advance Directive Completion: A Randomized Trial

Background. Many people recognize the potential benefits of advance directives (ADs), yet few actually complete them. It is unknown whether an active choice intervention influences AD completion. Methods. New employees were randomized to an active choice intervention (n = 642) or usual care (n = 637). The active choice intervention asked employees to complete an AD, confirm prior AD completion, or fill out a declination form. In usual care, participants could complete an AD, confirm prior completion, or skip the task. We used multivariable logistic regression to assess the relationship between the intervention arm and both AD completion online and the return of a signed AD by mail, as well as assess interactions between intervention group and age, gender, race, and clinical degree status. Results. Participants assigned to the active choice intervention more commonly completed ADs online (35.1% v. 20.4%, P 0.10). Limitations. A young and healthy participant may not benefit from AD completion as an older or seriously ill patient would. Conclusions. The active choice intervention significantly increased the proportion of participants completing an AD without changing the choices in ADs. This relationship was especially strong among men and may be a useful method to increase AD completion rates without altering choices