Effect of dexamethasone on newborn survival at different administration-to-birth intervals: A secondary analysis of the who action (Antenatal corticosteroids for improving outcomes in preterm newborn)-I trial

Background: The WHO ACTION-I trial demonstrated that dexamethasone significantly reduced neonatal mortality when administered to women at risk of early preterm birth in low-resource countries. We conducted a secondary analysis to determine how these benefits can be optimised, by evaluating the effect of dexamethasone compared to placebo on newborn mortality and severe respiratory distress outcomes at different administration-to-birth intervals, and identifying the interval with the greatest benefits.Methods: The WHO ACTION-I trial was a multi-country, individually-randomised, parallel-group, double-blind, placebo-controlled trial. It was conducted in 29 hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan. Women with a viable singleton or multiple pregnancy who presented to participating hospitals at a gestational age of 26 weeks 0 days-33 weeks 6 days and who were at risk of imminent preterm birth were eligible. In this secondary analysis, 2638 women and their newborns treated with single course of dexamethasone or placebo were analysed. Multivariate logistic regression was used to assess the effect of dexamethasone versus placebo on neonatal death, stillbirth or neonatal death, and severe respiratory distress at 24 h and at 168 h, by administration-to-birth interval (from 0 through 28 days), adjusting for gestational age at first dose. We used relative risks to identify the administration-to-birth interval with the greatest benefits of dexamethasone compared to placebo on the newborn outcomes.Findings: Between 24 December 2017 and 21 November 2019, 2852 women and their 3070 babies were enrolled in the WHO ACTION-I trial; 1332 women (1464 babies) in the dexamethasone group and 1306 women (1440 babies) in the placebo group were included in this secondary analysis. Neonatal mortality risk was lower with increasing time between initiating dexamethasone and birth, achieving peak mortality reduction by days 13 and 14 and then diminishing as the interval approached 28 days, regardless of gestational age at administration. For other outcomes, the overall pattern of risk reduction extending into the second week was consistent with that of neonatal death.Interpretation: In women at risk of preterm birth prior to 34 weeks\u27 gestation, the neonatal benefits of antenatal dexamethasone appear to increase with longer administration-to-birth intervals than previously thought. This knowledge can support clinical assessment and estimation of the risks of adverse preterm newborn outcomes at the time of birth, and the potential benefits of antenatal dexamethasone treatment for a known administration-to-birth interval.Funding: Bill and Melinda Gates Foundation; World Health Organization

Comparative satisfaction of receiving medical abortion service from nurses and auxiliary nurse-midwives or doctors in Nepal: results of a randomized trial

Background: Early first-trimester medical abortion (MA) service (≤ 63 days) has been provided by doctors and nurses under doctors’ supervision since 2009 in Nepal. This paper assesses whether MA services provided by specifically trained and certified nurses and auxiliary nurse-midwives independently from doctors’ supervision, is considered as satisfactory by women as those provided by doctors. Methods: The data come from a multi-center, randomized, controlled equivalence trial conducted between April 2009 and March 2010 in five district hospitals in Nepal. Women seeking MA were randomly assigned to doctors or nurses and auxiliary nurse-midwives(ANMs).Eligible women were administered 200 mg mifepristone orally followed by 800 μg misoprostol vaginally two days later by their assigned providers and followed up 10–14 days later. At the follow-up visit women’s reported satisfaction with MA service they received was measured. Results: Of 1295 women screened for eligibility, 535 were randomly assigned to a doctor and 542 to a nurse or ANM. Nineteen women were lost-to-follow up in the former group and 27 were lost-to-follow up or did not complete the acceptability interview in the latter group. This study is, therefore, based on516womenin the doctor’s group and 515 women in the nurse or ANM group. All women in the nurse or ANM group reported being satisfied or highly satisfied by MA compared to 99% in the doctor’s group. Satisfaction was similar regardless of the type of provider; 38% among nurse or ANM and 35% among the doctor group were “highly satisfied”, and 62% and 64%, respectively, were “satisfied”. Women’s experiences such as ‘less than expected amount or duration of bleeding following MA’, ‘shorter than expected duration of the abortion process’, and ‘able to manage symptoms’, were found to be associated with women’s higher satisfaction with MA. Counseling and information on the method, potential complications of MA and post-abortion contraception was nearly universal. No statistically significant differences were found in the level of satisfaction by age, parity, marital status, education or occupation of women. Conclusions: Women’s satisfaction with MA service provided by trained nurses or auxiliary nurse-midwives was similar to that provided by doctors. The findings, therefore, provide support for extending safe and accessible medical abortion services by government-trained nurses and auxiliary nurse midwives to women seeking early first trimester pregnancy termination. Trial registration The trial was retrospectively registered with ClinicalTrials.gov (identifier: NCT01186302). Registered August 20, 2010

Drug-Resistant Aspergillus flavus Is Highly Prevalent in the Environment of Vietnam: A New Challenge for the Management of Aspergillosis?

The burden of aspergillosis, especially Chronic Pulmonary Aspergillosis, is increasingly recognized, and the increasing presence of azole-resistant environmental Aspergillus fumigatus has been highlighted as a health risk. However, a sizable minority of aspergillosis is caused by Aspergillus flavus, which is assumed to be sensitive to azoles but is infrequently included in surveillance. We conducted environmental sampling at 150 locations in a rural province of southern Vietnam. A. flavus isolates were identified morphologically, their identity was confirmed by sequencing of the beta-tubulin gene, and then they were tested for susceptibility to azoles and amphotericin B according to EUCAST methodologies. We found that over 85% of A. flavus isolates were resistant to at least one azole, and half of them were resistant to itraconazole. This unexpectedly high prevalence of resistance demands further investigation to determine whether it is linked to agricultural azole use, as has been described for A. fumigatus. Clinical correlation is required, so that guidelines can be adjusted to take this information into account

Evaluation of the Luminex xTAG Respiratory Viral Panel FAST v2 assay for detection of multiple respiratory viral pathogens in nasal and throat swabs in Vietnam

Background Acute respiratory infections (ARI) are among the leading causes of hospitalization in children ≤5 years old. Rapid diagnostics of viral pathogens is essential to avoid unnecessary antibiotic treatment, thereby slowing down antibiotic-resistance. We evaluated the diagnostic performance of the Luminex xTAG Respiratory Viral Panel FAST v2 against viral specific PCR as reference assays for ARI in Vietnam. Methods Four hundred and forty two nose and throat swabs were collected in viral transport medium, and were tested with Luminex xTAG Respiratory Viral Panel FAST v2. Multiplex RT-PCR and single RT-PCR were used as references. Results Overall, sensitivity of the Luminex against reference assays was 91.8%, 95% CI 88.1-94.7 (270/294), whilst 112/6336 (1.8%, 95% CI, 1.4-2.1) of pathogens were detected by the Luminex, but not by reference assays. Frequency of pathogens detected by Luminex and reference assays was 379 and 292, respectively. The diagnostic yield was 66.7% (295/442, 95%CI 62.1-71.1%) for the Luminex assay and 54.1% (239/442, 95% CI, 49.3-58.8%) for reference assays. The Luminex kit had higher yields for all viruses except influenza B virus, respiratory syncytial virus, and human bocavirus. High agreements between both methods [mean (range): 0.91 (0.83-1.00)] were found for 10/15 viral agents. Conclusions The Luminex assay is a high throughput multiplex platform for rapid detection of common viral pathogens causing ARI. Although the current high cost may prevent Luminex assays from being widely used, especially in limited resource settings where ARI are felt most, its introduction in clinical diagnostics may help reduce unnecessary use of antibiotic prescription.</p

Non-Pneumatic Anti-Shock Garment (NASG), a First-Aid Device to Decrease Maternal Mortality from Obstetric Hemorrhage: A Cluster Randomized Trial

<div><p>Background</p><p>Obstetric hemorrhage is the leading cause of maternal mortality. Using a cluster randomized design, we investigated whether application of the Non-pneumatic Anti-Shock Garment (NASG) before transport to referral hospitals (RHs) from primary health care centers (PHCs) decreased adverse outcomes among women with hypovolemic shock. We hypothesized the NASG group would have a 50% reduction in adverse outcomes.</p><p>Methods and Findings</p><p>We randomly assigned 38 PHCs in Zambia and Zimbabwe to standard obstetric hemorrhage/shock protocols or the same protocols plus NASG prior to transport. All women received the NASG at the RH. The primary outcomes were maternal mortality; severe, end-organ failure maternal morbidity; and a composite mortality/morbidity outcome, which we labeled extreme adverse outcome (EAO). We also examined whether the NASG contributed to negative side effects and secondary outcomes. The sample size for statistical power was not reached; of a planned 2400 women, 880 were enrolled, 405 in the intervention group. The intervention was associated with a non-significant 46% reduced odds of mortality (OR 0.54, 95% CI 0.14–2.05, p = 0.37) and 54% reduction in composite EAO (OR 0.46, 95% CI 0.13–1.62, p = 0.22). Women with NASGs recovered from shock significantly faster (HR 1.25, 95% CI 1.02–1.52, p = 0.03). No differences were observed in secondary outcomes or negative effects. The main limitation was small sample size.</p><p>Conclusions</p><p>Despite a lack of statistical significance, the 54% reduced odds of EAO and the significantly faster shock recovery suggest there might be treatment benefits from earlier application of the NASG for women experiencing delays obtaining definitive treatment for hypovolemic shock. As there are no other tools for shock management outside of referral facilities, and no safety issues found, consideration of NASGs as a temporizing measure during delays may be warranted. A pragmatic study with rigorous evaluation is suggested for further research.</p><p>Trial Registration</p><p>ClinicalTrials.gov NCT00488462 </p></div

Schematic of the NASG.

<p>This figure shows an opened NASG. The articulated leg segments (1, 2, 3) are attached to the pelvic segment (4), and the abdominal segments (5, 6) contain a foam ball for extra pressure.</p

Non-pneumatic Anti-Shock Garment (NASG) Photo.

<p>A model in an NASG.</p

Clinic and Women’s Characteristics and Outcome Assessment during Baseline Period.

a<p>Variables used for randomization, using Phase 1 clinic statistics.</p>b<p>Mean (Standard Deviation).</p>c<p>N° of women in the Intervention Group: 113; N° of women in the Control Group: 99.</p>d<p>Median (Interquartile Range) is reported.</p>e<p>N° of women in the Intervention Group: 104; N° of women in the Control Group: 90.</p>f<p>For those ≥24 weeks; does not include cases with molar or ectopic pregnancies or abortion. N° of women in the Intervention Group: 92; N° of women in the Control Group: 69.</p>g<p>MAP was measured as ([(2 * diastolic BP)+systolic BP]/3); includes women with non-palpable BP.</p>h<p>Includes acute renal failure, acute respiratory distress syndrome, heart failure, cerebral impairment (seizures, unconsciousness, motor/cognitive loss) among women who survived.</p

Primary and Secondary Outcomes.

a<p>Includes acute renal failure, acute respiratory distress syndrome, heart failure, cerebral impairment (seizures, unconsciousness, motor/cognitive loss) among women who survived.</p>b<p>The blood loss in transit was measured in 155 women in the Intervention Group and 175 women in the Control Group.</p>c<p>For each group the median and the interquartile range is reported.</p>d<p>For estimation of the effect the variable was transformed into the log metric for normality and the ratio of the mean is reported.</p>e<p>Blood loss after arrival was measured in 267 women in the Intervention Group and 269 women in the Control Group at post-randomization.</p>f<p>Total blood loss was measured in 125 women in the Intervention Group and 123 women in the Control Group at post-randomization.</p>g<p>Hysterectomy among women with diagnosis of uterine atony and complications of abortion.</p>h<p>Shock Index was calculated by (heart rate/systolic blood pressure). For each group the median and interquartile range and hazard ratio is reported. Shock Index was measured in 326 women in the Intervention Group and 358 women in the Control Group at post-randomization.</p>i<p>Hazard ratio.</p