Abstract
Objective
The objective of this study is to systematically synthesize the currently available literature on various modes of transmission (congenital, intrapartum, and postpartum), clinical ...features and outcomes of SARS-CoV-2 infection in neonates.
Methods
We conducted a comprehensive literature search using PubMed, EMBASE, and Web of Science until 9 June 2020. A combination of keywords and MeSH terms, such as COVID-19, coronavirus, SARS-CoV-2, 2019-nCoV, severe acute respiratory syndrome coronavirus 2, neonates, newborn, infant, pregnancy, obstetrics, vertical transmission, maternal–foetal transmission and intrauterine transmission, were used in the search strategy. We included studies reporting neonatal outcomes of SARS-CoV-2 proven pregnancies or neonatal cases diagnosed with SARS-CoV-2 infection.
Results
Eighty-six publications (45 case series and 41 case reports) were included in this review. Forty-five case series reported 1992 pregnant women, of which 1125 (56.5%) gave birth to 1141 neonates. A total of 281 (25%) neonates were preterm, and caesarean section (66%) was the preferred mode of delivery. Forty-one case reports describe 43 mother-baby dyads of which 16 were preterm, 9 were low birth weight and 27 were born by caesarean section. Overall, 58 neonates were reported with SARS-CoV-2 infection (4 had a congenital infection), of which 29 (50%) were symptomatic (23 required ICU) with respiratory symptoms being the predominant manifestation (70%). No mortality was reported in SARS-CoV-2-positive neonates.
Conclusion
The limited low-quality evidence suggests that the risk of SARS-CoV-2 infections in neonates is extremely low. Unlike children, most COVID-positive neonates were symptomatic and required intensive care. Postpartum acquisition was the commonest mode of infection in neonates, although a few cases of congenital infection have also been reported.
To synthesize the current evidence for the presence of SARS-CoV-2 RNA in the human milk of mothers with confirmed COVID-19 and its potential role in neonatal SARS-CoV-2 infection.
Using terms related ...to novel coronavirus 2019 and human milk, a systematic search was performed in three electronic databases (PubMed, EMBASE, and Web of Science) for studies published between December 2019 and 15 October 2020. Published peer-reviewed studies reporting the results of RT-PCR for SARS-CoV-2 RNA in human milk in mothers with confirmed COVID-19 were included. Proportion meta-analysis of case series and prospective cohort studies was performed using STATA version 14.2 (StataCorp, College Station, TX) and pooled estimate (with 95% confidence interval) of overall incidence of SARS-CoV-2 transmission was calculated.
We identified 936 records, of which 34 studies (24 case-reports, 10 cohort studies) were eligible for this systematic review. A total of 116 confirmed COVID-19 lactating women (88 in cohort and 28 in case-reports) underwent RT-PCR testing in human milk, and 10 (six in case reports) were detected to have SARS-CoV-2 RNA. The overall pooled proportion (from cohort studies) for SARS-CoV-2 RNA detection in human milk was 2.16% (95% CI: 0.0-8.81%, I
2
: 0%). Four studies (six patients) also reported the presence of SARS-CoV-2 specific antibodies (along with RT-PCR) in human milk.
The limited low-quality evidence suggests that SARS-CoV-2 RNA is detected in human milk in an extremely low proportion, however, based on current evidence no conclusion can be drawn about its infectivity and impact on the infants. In concordance with World Health Organization recommendations, exclusive breastfeeding should be considered in all cases unless any other contraindication exists.
RNA-binding proteins (RBPs) are critical regulators of post-transcriptional gene expression, and aberrant RBP-RNA interactions can promote cancer progression. Here, we interrogate the function of ...RBPs in cancer using pooled CRISPR-Cas9 screening and identify 57 RBP candidates with distinct roles in supporting MYC-driven oncogenic pathways. We find that disrupting YTHDF2-dependent mRNA degradation triggers apoptosis in triple-negative breast cancer (TNBC) cells and tumors. eCLIP and m6A sequencing reveal that YTHDF2 interacts with mRNAs encoding proteins in the MAPK pathway that, when stabilized, induce epithelial-to-mesenchymal transition and increase global translation rates. scRibo-STAMP profiling of translating mRNAs reveals unique alterations in the translatome of single cells within YTHDF2-depleted solid tumors, which selectively contribute to endoplasmic reticulum stress-induced apoptosis in TNBC cells. Thus, our work highlights the therapeutic potential of RBPs by uncovering a critical role for YTHDF2 in counteracting the global increase of mRNA synthesis in MYC-driven breast cancers.
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•RBP CRISPR screening identifies 57 candidates that maintain MYC-driven cell survival•YTHDF2 depletion triggers apoptosis in triple-negative breast cancer cells and tumors•YTHDF2 maintains mRNA homeostasis by limiting the number of translating mRNAs•scRibo-STAMP reveals proteomic heterogeneity in triple-negative breast tumors in vivo
RNA-binding proteins (RBPs) are aberrantly expressed in cancer, but they remain largely unexplored as drug targets. Using RBP-focused CRISPR-Cas9 screening, Einstein et al. uncover an essential and selective role for YTHDF2 in MYC-driven breast cancer, highlighting the utility of discovering RBPs as safe and effective therapeutic targets.
Hydroxychloroquine (HCQ)/Chloroquine (CQ) has been evaluated for treatment and prophylaxis against SARS-CoV-2 infection in various studies with conflicting results. We performed a systematic review ...to synthesize the currently available evidence over the efficacy and safety of HCQ/CQ therapy alone against SARS-CoV-2 infection.
We searched Embase, PubMed, Web of Science, and Cochrane central for randomized controlled trials (RCTs) and prospective cohort studies published until October 15, 2020 and assessing the efficacy of HCQ alone against SARS-CoV-2 infection. We included studies evaluating HCQ/CQ alone as intervention and placebo/standard care as a control group. Retrospective studies and studies using other drugs (namely azithromycin, corticosteroids, immunomodulators, etc.) we excluded. Thirteen RCTs and three prospective cohort studies were included in this review. We pooled data using a random-effect model.
Pooled data from 12 studies (9917 participants) showed that HCQs increase mortality as compared to placebo/standard of care (RR 1.10; 95% CI:1.00–1.20). Hydroxychloroquine did not reduce the need for hospitalization in out-patients (RR 0.57; 95% CI 0.31–1.02). HCQ group has a significantly higher rate of any adverse event (RR 2.68; 95% CI 1.55–4.64), as compared to the control group. Also, using HCQ for prophylaxis against SARS-CoV-2 infection did not reduce the risk of acquiring SARS-CoV-2 infection (RR 1.04; 95% CI 0.58–1.88).
HCQ therapy for COVID-19 is associated with an increase in mortality and other adverse events. The negative effects are more pronounced in hospitalized patients. Therefore, with the available evidence, HCQ should not be used in prophylaxis or treatment of patients with COVID-19.
Background
The overall cost of managing chronic diseases is a significant barrier to accessing complete and timely healthcare, especially in rural and geographically isolated areas. This cost ...disparity becomes more pronounced in the case of children and more so in under-resourced regions of the world. In the era of COVID-19, as the need for physical distancing increased, there was a transition in approach to healthcare provision to telemedicine consultations. This study evaluates the cost saving using teleconsultations in a paediatric nephrology clinic.
Methods
This prospective cohort study was conducted at AIIMS Jodhpur, a tertiary care centre in western Rajasthan from March 2021 to October 2022. All consecutive paediatric (29 days–18 years) patients attending telemedicine services for kidney-related illness were enrolled. Basic demographic details were collected. Cost analysis was done after 6 months, regarding perceived cost savings for the patient and family by using telehealth for follow-up during 6 months starting from enrolment.
Results
A total of 112 patients were enrolled; 266 teleconsultations attended; 109 patients who could be followed up saved INR 457,900 during 6 months of follow-up. The average cost saving was INR − 1577/patient/visit. Patients saved 4.99% of the family income (median 2.16% (IQR 0.66–5.5)). The highest expenditure per visit was incurred for food and transport. The median distance from the residence to the clinic was 122.5 km (IQR 30–250). Over the 6-month study period, patients saved a travel distance of 83,274 km (743 km/patient).
Conclusions
The use of telemedicine as a follow-up method helps save significant costs and distances travelled by patients.
Graphical abstract
A higher-resolution version of the Graphical abstract is available as
Supplementary information
Background and Aims: The risk of contracting infection while intubating a coronavirus disease 2019 (COVID-19)-positive patient can be reduced by the use of personal protective equipment (PPE), video ...laryngoscope (VL) and aerosol-preventing intubation box. We compared two VLs (C-MAC and King Vision laryngoscope KVL) for ease of intubation and time taken to intubate the manikin using an intubation box. Methods: This randomised study involved healthcare workers having experience in using both C-MAC and KVL. After explaining the study and five practice sessions, a total of 63 volunteers were included; 61 participants gave consent and were enroled. The participants were allowed to intubate initially with one VL as per random sequence. Each participant performed three tracheal intubations with each device (C-MAC VL and KVL) on a manikin using an aerosol-prevention box over the head end at the time of intubation. Results: Time taken, percentage of glottic opening (POGO) score and the number of attempts taken for successful intubation with C-MAC and KVL were comparable in any of the three attempts (P > 0.05). The participants reported more difficulty in using KVL compared to C-MAC, and insertion of laryngoscope blade into the mouth of manikin for intubation was easy in group C-MAC compared to KVL in all three intubations (P < 0.01). Conclusion: C-MAC and KVL take comparable time for successful intubation under COVID-19 simulation conditions. But C-MAC is more user-friendly.
Many oncogenic insults deregulate RNA splicing, often leading to hypersensitivity of tumors to spliceosome-targeted therapies (STTs). However, the mechanisms by which STTs selectively kill cancers ...remain largely unknown. Herein, we discover that mis-spliced RNA itself is a molecular trigger for tumor killing through viral mimicry. In MYC-driven triple-negative breast cancer, STTs cause widespread cytoplasmic accumulation of mis-spliced mRNAs, many of which form double-stranded structures. Double-stranded RNA (dsRNA)-binding proteins recognize these endogenous dsRNAs, triggering antiviral signaling and extrinsic apoptosis. In immune-competent models of breast cancer, STTs cause tumor cell-intrinsic antiviral signaling, downstream adaptive immune signaling, and tumor cell death. Furthermore, RNA mis-splicing in human breast cancers correlates with innate and adaptive immune signatures, especially in MYC-amplified tumors that are typically immune cold. These findings indicate that dsRNA-sensing pathways respond to global aberrations of RNA splicing in cancer and provoke the hypothesis that STTs may provide unexplored strategies to activate anti-tumor immune pathways.
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•Spliceosome-targeted therapies (STTs) induce widespread mis-spliced mRNA in cancer•Mis-spliced, intron-retained mRNAs are an unexplored source of endogenous dsRNA•STTs trigger antiviral signaling and extrinsic apoptosis in TNBCs via dsRNA sensors•RNA mis-splicing in human breast cancers correlates with immune signatures
Spliceosome-targeted therapies generate intron-retained, double-stranded RNAs that activate downstream antiviral signaling and extrinsic apoptosis in breast cancer.
A considerable proportion of children experience a recurrence of urinary tract infection (UTI) following the first episode. While low-dose antibiotic prophylaxis has been the mainstay for the ...prevention of UTI, recent evidence raised concerns over their efficacy and safety. Hence, we aim to systematically synthesize evidence on the efficacy and safety of non-antibiotic prophylactic interventions for UTI. Using keywords related to study population (children) and intervention (non-antibiotic), we searched CENTRAL, Embase, PubMed, and Web of Science for randomized controlled trials (RCTs) published until August 2020. RCTs comparing any non-antibiotic interventions with placebo/antibiotics for prevention of UTIs in children were considered eligible. We used a random-effect model to provide pooled estimates. Sixteen trials evaluating 1426 participants were included. Cranberry was as effective as antibiotic prophylaxis (RR: 0.92; 95% CI: 0.56–1.50) but better than placebo/no therapy (RR: 0.48; 95% CI: 0.28–0.80) in reducing UTI recurrence. Probiotic therapy was more effective in reducing UTI recurrence (RR: 0.52; 95% CI: 0.29–0.94) when compared with placebo. While probiotic therapy was not better than antibiotics prophylaxis in preventing UTI (RR: 0.82; 95% CI: 0.56–1.21), they have a lower risk of antibiotic resistance (RR: 0.38; 95% CI: 0.21–0.69).
Conclusion
: Cranberry products and probiotics are the two non-antibiotic interventions that have been chiefly evaluated, reduce the risk of UTI recurrence when compared with placebo in children with a normal urinary tract. The findings from this systematic review suggest that while cranberry and probiotics may be used, there is a definite need to identify better and more acceptable non-antibiotic interventions.
What is Known:
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Efficacy of the low-dose antibiotic is controversial in preventing UTI and it is associated with increase in the risk of antimicrobial resistance.
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Non-antibiotic interventions such as cranberry products are effective in preventing UTI recurrence in adults.
What is New:
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Cranberry products are effective in reducing the recurrence of UTI in children with normal urinary tract.
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Low-quality evidence suggests that probiotics can be a potential prophylactic measure to reduce recurrence of UTI in the pediatric population.
ASHAs (Accredited Social Health Activist)role is evolving beyond maternal and child health workers. They are engaged in NCD (Non-communicable Diseases)control activities. This study investigated ...their preparedness for this new task.The aim of the study was to assess the preparedness (knowledge, attitude, practices & patient navigation) of ASHAs in delivering community-based NCD prevention and control services under NPCDCS (National Programme for Prevention & Control of Cancer, Diabetes, Cardiovascular Diseases & Stroke)program. And the study also assessed the challenges faced by ASHAs in fulfilling their roles and responsibilities towards common NCDs.
Cross sectional descriptive conducted in Delhi.
Total 464 ASHAs randomly selected from 54 Primary Health Centres from 3 districts of Delhi. A self-administered, pre-tested, validated and piloted semi structured questionnaire was filled by enrolled ASHAs. It assessed their knowledge, attitude and practices related to NCD screening.
descriptive statistics, chi square test and logistic regression analysis were used.
Two-third ASHAs had moderate to good knowledge about NCDs. They had positive inclination towards NCD screening and risk mitigation. Their practices for hypertension and diabetes screening were adequate but common cancer screening practices were inadequate. Challenges encountered in performing these tasks were lack of appropriate referral linkages, minimal supportive supervision and no ear marked incentives.
ASHAs showed willingness to work for NCD control provided they have optimum training, supportive supervision from their superiors, and screening facilities in functional state and appropriate incentives for the new tasks.
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