Evaluation of subcutaneous proleukin (Interleukin-2) in a randomized international trial (ESPRIT): Geographical and gender differences in the baseline characteristics of participants

Background: ESPRIT, is a phase III, open-label, randomized, international clinical trial evaluating the effects of subcutaneous recombinant interleukin-2 (rIL-2) plus antiretroviral therapy (ART) versus ART alone on HIV-disease progression and death in HIV-1-infected individuals with CD4+ T-cells ≥300 cells/μL. Objectives: To describe the baseline characteristics of participants randomized to ESPRIT overall and by geographic location. Method: Baseline characteristics of randomized participants were summarized by region. Results: 4,150 patients were enrolled in ESPRIT from 254 sites in 25 countries. 41%, 27%, 16%, 11%, and 5% were enrolled in Europe, North America, South America, Asia, and Australia, respectively. The median age was 40 years, 81% were men, and 76%, 11%, and 9% were Caucasian, Asian, and African American or African, respectively. 44% of women enrolled (n = 769) were enrolled in Thailand and Argentina. Overall, 55% and 38% of the cohort acquired HIV through male homosexual and heterosexual contact, respectively. 25% had a prior history of AIDS-defining illness; Pneumocystis jirovecii pneumonia, M. tuberculosis, and esophageal candida were most commonly reported. Median nadir and baseline CD4+ T-cell counts were 199 and 458 cells/μL, respectively. 6% and 13% were hepatitis B or C virus coinfected, respectively. Median duration of antiretroviral therapy (ART) was 4.2 years; the longest median duration was in Australia (5.2 years) and the shortest was in Asia (2.3 years). 17%, 13%, and 69% of participants began ART before 1995, between 1996 and 1997, and from 1998 onward, respectively. 86% used ART from two or more ART classes, with 49% using a protease inhibitor-based regimen and 46% using a nonnucleoside reverse transcriptase inhibitor-based regimen. 78% had plasma HIV RNA below detection (<500 cp/mL). Conclusion: ESPRIT has enrolled a diverse population of HIV-infected individuals including large populations of women and patients of African-American/African and Asian ethnicity often underrepresented in HIV research. As a consequence, the results of the study may have wide global applicability

Combination antiretroviral therapy improves cognitive performance and functional connectivity in treatment-naïve HIV-infected individuals.

Our study aimed to investigate the short-term effect of combination antiretroviral therapy (cART) on cognitive performance and functional and structural connectivity and their relationship to plasma levels of antiretroviral (ARV) drugs. Seventeen ARV treatment-naïve HIV-infected individuals (baseline mean CD4 cell count, 479 ± 48 cells/mm3) were age matched with 17 HIV-uninfected individuals. All subjects underwent a detailed neurocognitive and functional assessment and magnetic resonance imaging. HIV-infected subjects were scanned before starting cART and 12 weeks after initiation of treatment. Uninfected subjects were assessed once at baseline. Functional connectivity (FC) was assessed within the default mode network while structural connectivity was assessed by voxel-wise analysis using tract-based spatial statistics (TBSS) and probabilistic tractography within the DMN. Tenofovir and emtricitabine blood concentration were measured at week 12 of cART. Prior to cART, HIV-infected individuals had significantly lower cognitive performance than control subjects as measured by the total Z-score from the neuropsychological tests assessing six cognitive domains (p = 0.020). After 12 weeks of cART treatment, there remained only a weak cognitive difference between HIV-infected and HIV-uninfected subjects (p = 0.057). Mean FC was lower in HIV-infected individuals compared with those uninfected (p = 0.008), but FC differences became non-significant after treatment (p = 0.197). There were no differences in DTI metrics between HIV-infected and HIV-uninfected individuals using the TBSS approach and limited evidence of decreased structural connectivity within the DMN in HIV-infected individuals. Tenofovir and emtricitabine plasma concentrations did not correlate with either cognitive performance or imaging metrics.ConclusionsTwelve weeks of cART improves cognitive performance and functional connectivity in ARV treatment-naïve HIV-infected individuals with relatively preserved immune function. Longer periods of observation are necessary to assess whether this effect is maintained

Sexual Intercourse for Induction of Spontaneous Onset of Labor: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

INTRODUCTION: Sexual intercourse during pregnancy is commonly believed to trigger the onset of contractions and, therefore, labor. However, in low-risk pregnancies, there is neither association with preterm birth, premature rupture of membranes, or low birth weight, nor with spontaneous onset of labor at term. AIM: To evaluate the effectiveness of sexual intercourse for spontaneous onset of labor at term in singleton pregnancies. METHODS: The systematic search was conducted using electronic databases from inception of each database to June 2019. Review of articles also included the abstracts of all references retrieved from the search. Inclusion criteria were randomized controlled trials comparing sexual intercourse in singleton low-risk pregnancies at term with controls (either reduced number of coitus or no coitus) for spontaneous onset of labor. Estimates were pooled using random-effects meta-analysis. MAIN OUTCOME MEASURES: The primary outcome was the incidence of spontaneous onset of labor. The summary measures were reported as summary relative risk with 95% CI using the random-effects model of DerSimonian and Laird. RESULTS: Data extracted from 3 trials, including 1,483 women with singleton pregnancy at term and cephalic presentation, were analyzed. Women who were randomized in the sexual intercourse group had similar incidence of spontaneous onset of labor compared with control subjects (0.82% vs 0.80%; relative risk 1.02, 95% CI 0.98-1.07). CLINICAL IMPLICATION: Sexual intercourse should not be restricted in low-risk term pregnancies. Further studies are needed to properly evaluate the impact of orgasm, penetration, condom use, frequency of intercourse and other factors on induction of labor at term. STRENGTH & LIMITATIONS: Our study has several strengths. The three included trials had low risk of allocation bias; intention-to-treat analysis was used; this is the first meta-analysis on this issue so far. Limitations mainly depend on the design of the included studies. Firstly, compliance to the protocol relied on self-reporting by patients; in addition, not all the features of sexual intercourse could be adequately assessed (orgasm, nipple stimulation, sexual positions, etc.). CONCLUSION: In women with singleton, cephalic, low-risk pregnancies, sexual intercourse at term does not significantly increase the incidence of spontaneous onset of labor

Serum methylarginines and spirometry-measured lung function in older adults

Rationale: Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans. Objectives: This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures. Methods: Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity. Measurements and Main Results: In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function. Conclusions: After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function

Control of Vancomycin-Resistant Enterococcus in Health Care Facilities in a Region

Background In late 1996, vancomycin-resistant enterococci were first detected in the Siouxland region of Iowa, Nebraska, and South Dakota. A task force was created, and in 1997 the assistance of the Centers for Disease Control and Prevention was sought in assessing the prevalence of vancomycin-resistant enterococci in the region’s facilities and implementing recommendations for screening, infection control, and education at all 32 health care facilities in the region. Methods The infection-control intervention was evaluated in October 1998 and October 1999. We performed point-prevalence surveys, conducted a case– control study of gastrointestinal colonization with vancomycin-resistant enterococci, and compared infection-control practices and screening policies for vancomycin-resistant enterococci at the acute care and long-term care facilities in the Siouxland region. Results Perianal-swab samples were obtained from 1954 of 2196 eligible patients (89 percent) in 1998 and 1820 of 2049 eligible patients (89 percent) in 1999. The overall prevalence of vancomycin-resistant enterococci at 30 facilities that participated in all three years of the study decreased from 2.2 percent in 1997 to 1.4 percent in 1998 and to 0.5 percent in 1999 (P Conclusions An active infection-control intervention, which includes the obtaining of surveillance cultures and the isolation of infected patients, can reduce or eliminate the transmission of vancomycinresistant enterococci in the health care facilities of a region. (N Engl J Med 2001;344:1427-33.

Use of routine ureteral stents in cesarean hysterectomy for placenta accreta

OBJECTIVE: To evaluate benefits of use of ureteral stents in association with cesarean hysterectomy in case of placenta accreta. METHODS: This was a single center, cohort study. Clinical records of singleton pregnancies with placenta accreta who underwent cesarean hysterectomy were included in the study. For this study, pregnancies with diagnoses of placenta accreta, increta, or percreta were considered under the umbrella term of placenta accreta. For all women with placenta accreta, delivery was planned via cesarean hysterectomy at 340-356 weeks, without any attempt to remove the placenta. Reasons for earlier delivery included vaginal bleeding and spontaneous onset of labor. The primary outcome was the incidence of unintentional urinary tract injury. Outcomes were compared in a cohort of women who had planned the placement of ureteral stents and in those who did not. RESULTS: Forty-four singleton gestations with confirmed placenta accreta at the time of cesarean hysterectomy were included in the study. Twenty-four (54.5%) of the included women had the placing of ureteral stents prior to cesarean, while 20 (45.5%) did not. At histological confirmation, most of them had placenta accreta (17/44, 38.6%), 14 placenta increta (31.8%), and 13 placenta percreta (29.6%). Urinary tract injuries occurred in eight cases (18.2%), six in the ureteral stents and two in the non-ureteral stents group (25 versus 10%; p = .21). All the injuries were bladder injuries, while no cases of ureteral injury were recorded. All injuries were recognized intraoperatively. CONCLUSION: In case of placenta accreta, the use of ureteral stents in association with cesarean hysterectomy does not reduce the risk of urinary tract injury

Staphylococcus aureus infections following knee and hip prosthesis insertion procedures

BackgroundStaphylococcus aureus is the most common and most important pathogen following knee and hip arthroplasty procedures. Understanding the epidemiology of invasive S. aureus infections is important to quantify this serious complication.MethodsThis nested retrospective cohort analysis included adult patients who had undergone insertion of knee or hip prostheses with clean or clean-contaminated wound class at 11 hospitals between 2003&ndash;2006. Invasive S. aureus infections, non-superficial incisional surgical site infections (SSIs) and blood stream infections (BSIs), were prospectively identified following each procedure. Prevalence rates, per 100 procedures, were estimated.Results13,719 prosthetic knee (62%) and hip (38%) insertion procedures were performed. Of 92 invasive S. aureus infections identified, SSIs were more common (80%) than SSI and BSI (10%) or BSI alone (10%). The rate of invasive S. aureus infection/100 procedures was 0.57 [95% CI: 0.43-0.73] for knee insertion and 0.83 [95% CI: 0.61-1.08] for hip insertion. More than half (53%) were methicillin-resistant. Median time-to-onset of infection was 34 and 26 days for knee and hip insertion, respectively. Infection was associated with higher National Healthcare Safety Network risk index (p&thinsp;&le;&thinsp;0.0001).ConclusionsPost-operative invasive S. aureus infections were rare, but difficult-to-treat methicillin-resistant infections were relatively common. Optimizing preventative efforts may greatly reduce the healthcare burden associated with S. aureus infections