Maternal and perinatal morbidity and mortality in severe pre-eclampsia and eclampsia in a tertiary care hospital: a prospective study

Background: Hypertensive disorders of pregnancy are a leading cause of maternal and perinatal morbidity and mortality worldwide. In India, they account for the third most important cause of maternal mortality. The objective of this study was to evaluate maternal and perinatal outcome and complications in cases with severe pre-eclampsia and eclampsia and measures to prevent them.Methods: A prospective study was carried out on 100 patients with severe pre-eclampsia and eclampsia in tertiary care referral hospital over a period of one year i.e. from November 2017 to October 2018. Only those cases with initial blood pressure reading of ≥160/110mmHg or presenting with eclampsia were in included in the study. Detailed history and examination was carried out. Investigations and management were carried out as per standardized department protocol and maternal and fetal outcomes were analyzed.Results: 48% of women were between 21-25 years age, 82% were from rural area, and 86% cases were unbooked, 68% cases were primigravida. Liver Function Tests were deranged in 18% of the patients and 19% had abnormal Renal Function Tests. Labetalol was the most commonly used antihypertensive. Lower segment cesarean section was the mode of delivery in 59% of the cases. Most common maternal complication was Eclampsia. There were 5 maternal deaths i.e. maternal death rate was 5%. 54.3% of live births needed NICU admission and out of these 50% were preterm deliveries.Conclusions: Accessible healthcare and health education and awareness regarding antenatal checkup for all women will lead to early detection of severe pre-eclampsia. Hence, early treatment and management of patient’s complications will certainly improve the maternal and perinatal outcome

Ciprofloxacin-Resistant Neisseria meningitidis, Delhi, India

Decreased susceptibility of Neisseria meningitidis isolates to ciprofloxacin emerged from an outbreak in Delhi, India. Results of antimicrobial susceptibility testing of the meningococcal isolates to ciprofloxacin and further sequencing of DNA gyrase A quinolone-resistance–determining region confirmed the emergence of ciprofloxacin resistance in the outbreak

Global, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019

Background Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. Methods We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (USMR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. Findings Global U5MR decreased from 71.2 deaths per 1000 livebirths (95% uncertainty interval WI] 68.3-74-0) in 2000 to 37.1 (33.2-41.7) in 2019 while global NMR correspondingly declined more slowly from 28.0 deaths per 1000 live births (26.8-29-5) in 2000 to 17.9 (16.3-19-8) in 2019. In 2019,136 (67%) of 204 countries had a USMR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030,154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9.65 million (95% UI 9.05-10.30) in 2000 and 5.05 million (4.27-6.02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3.76 million 95% UI 3.53-4.021) in 2000 to 48% (2.42 million; 2.06-2.86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0.80 (95% UI 0.71-0.86) deaths per 1000 livebirths and U5MR to 1.44 (95% UI 1-27-1.58) deaths per 1000 livebirths, and in 2019, there were as many as 1.87 million (95% UI 1-35-2.58; 37% 95% UI 32-43]) of 5.05 million more deaths of children younger than 5 years than the survival potential frontier. Interpretation Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve USMR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

Design, Synthesis, and Identification of Silicon Incorporated Oxazolidinone Antibiotics with Improved Brain Exposure

Therapeutic options for brain infections caused by pathogens with a reduced sensitivity to drugs are limited. Recent reports on the potential use of linezolid in treating brain infections prompted us to design novel compounds around this scaffold. Herein, we describe the design and synthesis of various oxazolidinone antibiotics with the incorporation of silicon. Our findings in preclinical species suggest that silicon incorporation is highly useful in improving brain exposures. Interestingly, three compounds from this series demonstrated up to a 30-fold higher brain/plasma ratio when compared to linezolid thereby indicating their therapeutic potential in brain associated disorders

<i>Cissampelos pareira</i> Linn: Natural Source of Potent Antiviral Activity against All Four Dengue Virus Serotypes

<div><p>Background</p><p>Dengue, a mosquito-borne viral disease, poses a significant global public health risk. In tropical countries such as India where periodic dengue outbreaks can be correlated to the high prevalence of the mosquito vector, circulation of all four dengue viruses (DENVs) and the high population density, a drug for dengue is being increasingly recognized as an unmet public health need.</p><p>Methodology/Principal findings</p><p>Using the knowledge of traditional Indian medicine, Ayurveda, we developed a systematic bioassay-guided screening approach to explore the indigenous herbal bio-resource to identify plants with pan-DENV inhibitory activity. Our results show that the alcoholic extract of <i>Cissampelos pariera</i> Linn (<i>Cipa</i> extract) was a potent inhibitor of all four DENVs in cell-based assays, assessed in terms of viral NS1 antigen secretion using ELISA, as well as viral replication, based on plaque assays. Virus yield reduction assays showed that <i>Cipa</i> extract could decrease viral titers by an order of magnitude. The extract conferred statistically significant protection against DENV infection using the AG129 mouse model. A preliminary evaluation of the clinical relevance of <i>Cipa</i> extract showed that it had no adverse effects on platelet counts and RBC viability. In addition to inherent antipyretic activity in Wistar rats, it possessed the ability to down-regulate the production of TNF-α, a cytokine implicated in severe dengue disease. Importantly, it showed no evidence of toxicity in Wistar rats, when administered at doses as high as 2g/Kg body weight for up to 1 week.</p><p>Conclusions/Significance</p><p>Our findings above, taken in the context of the human safety of <i>Cipa</i>, based on its use in Indian traditional medicine, warrant further work to explore <i>Cipa</i> as a source for the development of an inexpensive herbal formulation for dengue therapy. This may be of practical relevance to a dengue-endemic resource-poor country such as India.</p></div

Effect of <i>Cipa</i> extract on platelets.

<p>(A) Freshly collected human blood was incubated with saline (white bars) or <i>Cipa</i> extract (at 2 μg/ml: blue bars; or 10 μg/ml: red bars) for up to 4 hours. Aliquots were drawn at the indicated times for determination of platelet counts. (B) Wistar rats were orally administered 0.25% methyl cellulose containing <i>Cipa</i> extract ranging from 0–1000 mg/Kg body weight. Fresh blood collected from these rats at 0 (white bars), 1 (blue bars) and 4 (red bars) hours post-administration, were analysed for platelet counts. For both panels, data shown are mean values (<i>n</i> = 5); the vertical bars represent standard deviation, SD.</p

Evaluation of protective efficacy of <i>Cipa</i> extract <i>in vivo</i>.

<p>AG129 mice (9–12 weeks old) were injected i.p. with 10⁶ PFU brain-passaged DENV-2. Infected mice were treated orally with 0.25% methyl cellulose (solid red squares) or <i>Cipa</i> extract at 125 mg (empty blue circles) and 250 mg/kg body weight (solid blue circles). Treatment was twice daily for the first 5 days. A sham control group that was not virus-infected, but which received the higher dose of <i>Cipa</i> extract orally (solid green squares), was tested in parallel. The mice were monitored daily for mortality and the resultant data plotted as Kaplan-Meier survival curves. The <i>p</i> values to assess the statistical significance in the survival rates on day 35 between the <i>Cipa</i> extract-treated and placebo-treated (0.25% methyl cellulose) groups were determined using the Log-rank test.</p

Schematic representation of the antiviral screening assays.

<p>An outline of the three types of screening assays (indicated by Arabic numbers 1, 2 and 3) is shown. The multi-coloured sphere represents DENV and the Eppendorf tube with green liquid represents the herbal extract. These two were pre-incubated (1) before addition to the monolayer or added sequentially (2, 3) to the monolayer. In assays 1 and 2, the treated-monolayers were overlaid with methyl cellulose-containing growth medium. Shown at the bottom are the possible outcomes of the type 1 and 2 assays. The ‘x’ mark denotes failure of entry into cells. In assay 3, liquid growth medium was added instead of the methyl cellulose overlay, and followed by analysis of NS1 and virus released into the culture supernatant.</p