Chronic diuretic use was associated with increased long-term mortality and hospitalizations in a wide spectrum of ambulatory chronic systolic and diastolic HF patients. The findings of the current study challenge the wisdom of routine chronic use of diuretics in HF patients who are asymptomatic or minimally symptomatic without fluid retention, and are on complete neurohormonal blockade. These findings, based on a non-randomized design, need to be further studied in randomized trials.

Summary Background Antenatal corticosteroids for pregnant women at risk of preterm birth are among the most effective hospital-based interventions to reduce neonatal mortality. We aimed to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of antenatal corticosteroids at all levels of health care in low-income and middle-income countries. Methods In this 18-month, cluster-randomised trial, we randomly assigned (1:1) rural and semi-urban clusters within six countries (Argentina, Guatemala, India, Kenya, Pakistan, and Zambia) to standard care or a multifaceted intervention including components to improve identification of women at risk of preterm birth and to facilitate appropriate use of antenatal corticosteroids. The primary outcome was 28-day neonatal mortality among infants less than the 5th percentile for birthweight (a proxy for preterm birth) across the clusters. Use of antenatal corticosteroids and suspected maternal infection were additional main outcomes. This trial is registered with ClinicalTrials.gov, number NCT01084096. Findings The ACT trial took place between October, 2011, and March, 2014 (start dates varied by site). 51 intervention clusters with 47 394 livebirths (2520 [5%] less than 5th percentile for birthweight) and 50 control clusters with 50 743 livebirths (2258 [4%] less than 5th percentile) completed follow-up. 1052 (45%) of 2327 women in intervention clusters who delivered less-than-5th-percentile infants received antenatal corticosteroids, compared with 215 (10%) of 2062 in control clusters (p<0·0001). Among the less-than-5th-percentile infants, 28-day neonatal mortality was 225 per 1000 livebirths for the intervention group and 232 per 1000 livebirths for the control group (relative risk [RR] 0·96, 95% CI 0·87–1·06, p=0·65) and suspected maternal infection was reported in 236 (10%) of 2361 women in the intervention group and 133 (6%) of 2094 in the control group (odds ratio [OR] 1·67, 1·33–2·09, p<0·0001). Among the whole population, 28-day neonatal mortality was 27·4 per 1000 livebirths for the intervention group and 23·9 per 1000 livebirths for the control group (RR 1·12, 1·02–1·22, p=0·0127) and suspected maternal infection was reported in 1207 (3%) of 48 219 women in the intervention group and 867 (2%) of 51 523 in the control group (OR 1·45, 1·33–1·58, p<0·0001). Interpretation Despite increased use of antenatal corticosteroids in low-birthweight infants in the intervention groups, neonatal mortality did not decrease in this group, and increased in the population overall. For every 1000 women exposed to this strategy, an excess of 3·5 neonatal deaths occurred, and the risk of maternal infection seems to have been increased. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Context Saw palmetto fruit extracts are widely used for treating lower urinary tract symptoms attributed to benign prostatic hyperplasia. However, recent clinical trials have questioned their efficacy, at least at standard doses (320 mg daily). Objective To determine the effect of a saw palmetto extract at up to three times the standard dose on lower urinary tract symptoms attributed to benign prostatic hyperplasia. Design Multicenter placebo-controlled randomized trial conducted from June, 2008 through October, 2010. Setting Eleven North American clinical sites. Participants Were men at least 45 years old, with a peak urinary flow rate ≥ 4 ml/sec, an AUA Symptom Index (AUASI) score ≥ 8 and ≤ 24, and no exclusions. Interventions One, two, and then three 320 mg daily doses of saw palmetto extract or placebo, with dose increases at 24 and 48 weeks. Main Outcome Measures Primary outcome was the difference in AUASI score from baseline to 72 weeks. Secondary outcomes were measures of urinary bother; nocturia; uroflow; postvoid residual; prostate-specific antigen; participants’ global assessments; and indices of sexual function, continence, sleep quality, and prostatitis symptoms. Results From baseline to 72 weeks, mean AUASI scores decreased from 14.4 to 12.2 points with saw palmetto and from 14.7 to 11.7 points with placebo. The group mean difference in AUASI score change from baseline to 72 weeks between the saw palmetto and placebo groups was 0.79 points favoring placebo (bound of the 95% confidence interval most favorable to saw palmetto was 1.77 points, one-sided P=0.91). Saw palmetto was no more effective than placebo for any secondary outcome. No attributable side effects were identified. Conclusions Increasing doses of a saw palmetto fruit extract did not reduce lower urinary tract symptoms more than placebo. (CAMUS study number NCT00603304 http://www.ClinicalTrials.gov)

West-central African chimpanzees (Pan troglodytes troglodytes) harbor strains of simian immunodeficiency virus (SIVcpz) that are closely related to all three groups of human immunodeficiency virus 1 (HIV-1) (M, N, and 0) and have thus been implicated as a A reservoir for human infection (1). Yet, because all SIVcpz strains identified to date have been derived from captive chimpanzees, little is known about the prevalence, geographic distribution, and genetic diversity of SIVcpz in the wild. B Here, we describe a prevalence study g9 and detection of SIVcpz in wild-living 9 apes.Sampling blood from endangered pri-c mates is generally neither feasible nor ethical. We therefore developed noninvasive methods to detect and characterize SIVcpz in wild chimpanzees by analyzing fecal and urine samples for SIVcpz antibodies and virion RNA (2). The sensitivity of antibody detection by enhanced chemilu-Fig minescent immunoblot was tested in cap-ze tive chimpanzees of known HIV-l1/SIVcpz Re infection status and found to be 100% for in urine and 65% for feces (specificity in (6 each instance was 100%). The sensitivity lik ofpolymerase chain reaction amplification sic of virion RNA from feces of SIVcpz-in-rec fected chimpanzees was 66%. Using these de techniques, we studied 28 P. t. verus from the Tai Forest, Cote d'Ivoire, 24 P. t. schweinfurthii from Kibale National Park, Uganda, and 6 P. t. schweinfurthii from Gombe National Park, Tanzania (Fig. 1A). Of the 58 wild-living chimpanzees tested, only one healthy 23-year-old sexually active male (Ch-06) from Gombe was positive for SIVcpz infection. Two different urine samples from Ch-06 contained SIVcpz antibodies (Fig. 1B), and three fecal samples were positive for SIVcpz virion RNA. Sequence analysis of a 2195-base pair pol/vif fragment amplified from fecal samples revealed a highly divergent SIVcpz strain (TAN1) that differed from west-central African SIVcpz and HIV-1 groups M, N, and O by 28 to 30% of amino acid sequences. The most similar sequence was SIVcpzANT from a captive P. t. schwein-furthii (3), which differed by 23%. In a phylogenetic tree, SIVcpzTAN1 and SIVcpzANT clustered together in a statistically highly significant manner (Fig. 1C).. . u B, p31 I .,-SIVcpzCAM3 J1~l. SIV'cpzUS _I SIVcpzGAB1 SIVcpzANT g. 1. (A) Locations of Tai, Kibale, and Gombe chimpa es and the four recognized chimpanzee subspecies ( d asterisks indicate the origins of four captive SIVcI ected P. t. troglodytes apes (6, 7). (B) Urine immur )ts of Ch-06, two infected captive chimpanzees CAP ) and ch-No (3), and negative samples. (C) Maxim elihood tree of TAN1 Pol/Vif sequences (GenBank accE >n number AF382822) and other SIVcpz (P. t. troglodyt d; P. t. schweinfurthii, blue) and HIV-1 strains (asteri. note >95% bootstrap values). The discovery of SIVcpzTAN1 in a single wild-living Gombe chimpanzee provides insight into the origins and evolutionary history of HIV-1 and SIVcpz. First, the geographic boundaries for SIVcpz must now be extended from Gabon and Cameroon in west-central Africa to the ea...

BackgroundThe first minutes after birth are critical to reducing neonatal mortality. Helping Babies Breathe (HBB) is a simulation-based neonatal resuscitation program for low resource settings. We studied the impact of initial HBB training followed by refresher training on the knowledge and skills of the birth attendants in facilities.MethodsWe conducted HBB trainings in 71 facilities in the NICHD Global Network research sites (Nagpur and Belgaum, India and Eldoret, Kenya), with a 6:1 ratio of facility trainees to Master Trainers (MT). Because of staff turnover, some birth attendants (BA) were trained as they joined the delivery room staff, after the initial training was completed (catch-up initial training). We compared pass rates for skills and knowledge pre- and post- initial HBB training and following refresher training among active BAs. An Objective Structured Clinical Examination (OSCE) B tested resuscitation skill retention by comparing post-initial training performance with pre-refresher training performance. We identified factors associated with loss of skills in pre-refresher training performance using multivariable logistic regression analysis. Daily bag and mask ventilation practice, equipment checks and supportive supervision were stressed as part of training.ResultsOne hundred five MT (1.6 MT per facility) conducted initial and refresher HBB trainings for 835 BAs; 76% had no prior resuscitation training. Initial training improved knowledge and skills: the pass percentage for knowledge tests improved from 74 to 99% (p < 0.001). Only 5% could ventilate a newborn mannequin correctly before initial training but 97% passed the post-initial ventilation training test (p < 0.0001) and 99% passed the OSCE B resuscitation evaluation. During pre-refresher training evaluation, a mean of 6.7 (SD 2.49) months after the initial training, 99% passed the knowledge test, but the successful completion rate fell to 81% for the OSCE B resuscitation skills test. Characteristics associated with deterioration of resuscitation skills were BAs from tertiary care facilities, no prior resuscitation training, and the timing of training (initial vs. catch-up training).ConclusionsHBB training significantly improved neonatal resuscitation knowledge and skills. However, skills declined more than knowledge over time. Ongoing skills practice and monitoring, more frequent retesting, and refresher trainings are needed to maintain neonatal resuscitation skills.Trial registrationClinicalTrials.gov Identifier: NCT01681017; 04 September 2012, retrospectively registered.Electronic supplementary materialThe online version of this article (doi:10.1186/s12884-016-1141-3) contains supplementary material, which is available to authorized users.