The impact of a computerized decision aid on empowering pregnant women for choosing vaginal versus cesarean section delivery: study protocol for a randomized controlled trial

Cesarean delivery on maternal request (CDMR) is one of the main reasons for cesarean delivery in Iran, and women often need help in making a decision about the delivery options available to them. The main objective of this study is to evaluate the effect of a computerized decision aid (CDA) system on empowering pregnant women in choosing an appropriate mode of delivery. This CDA contrasts the advantages and disadvantages of vaginal versus cesarean section delivery in terms of their value to the individual woman. The protocol concerns a randomized trial study that will be performed among Iranian women. Four hundred pregnant women will be recruited from two private and two public prenatal centers in Mashhad, Iran. They will be randomly assigned to either an intervention or a control group. The designed CDA will be provided to the intervention group, whereas the control group will only receive routine care. The CDA provides educational contents as well as some recommendations. The CDA's knowledge base is obtained from the results of studies on predictors of cesarean delivery. The CDA's software will be installed on women's computers for use at home. The two primary outcomes for the study are O'Connor's Decisional Conflict Scale and knowledge as measured by true/false questions. Actual mode of delivery (vaginal versus cesarean) will be compared in the two groups. We investigate the effect of a CDA on empowering pregnant women in terms of reducing their decisional conflict as well as on improving their clinical knowledge pertaining to mode of delivery. This trial is registered with the Iran Trial Registrar under registration number IRCT2015093010777N4 and registration date 26 October 201

NALCN Dysfunction as a Cause of Disordered Respiratory Rhythm With Central Apnea

The sodium leak channel nonselective protein (NALCN) is a regulator of the pacemaker neurons that are responsible for rhythmic behavior (including respiration), maintaining the resting membrane potential, and are required for action potential production. NALCN-null mice show early death associated with disrupted respiratory rhythms, characterized by frequent and profound apneas. We report 3 children (2 siblings) with compound heterozygous mutations in NALCN associated with developmental impairment, hypotonia, and central sleep-disordered breathing causing apneas. Supplemental oxygen normalized the respiratory rhythm. NALCN mutations have been previously reported to cause severe hypotonia, speech impairment, and cognitive delay as well as infantile neuroaxonal dystrophy and facial dysmorphism. Nonsynonymous changes in the 2 affected extracellular loops may be responsible for the deleterious effect on the stability of the respiratory rhythm. Although oxygen is known to be a stabilizer of respiratory rhythm in central apnea in children, its role in NALCN dysfunction requires further investigation.</jats:p

Improved PCR based methods for detecting C9orf72 hexanucleotide repeat expansions

Due to the GC-rich, repetitive nature of C9orf72 hexanucleotide repeat expansions, PCR based detection methods are challenging. Several limitations of PCR have been reported and overcoming these could help to define the pathogenic range. There is also a need to develop improved repeat-primed PCR assays which allow detection even in the presence of genomic variation around the repeat region. We have optimised PCR conditions for the C9orf72 hexanucleotide repeat expansion, using betaine as a co-solvent and specific cycling conditions, including slow ramping and a high denaturation temperature. We have developed a flanking assay, and repeat-primed PCR assays for both 3′ and 5′ ends of the repeat expansion, which when used together provide a robust strategy for detecting the presence or absence of expansions greater than ∼100 repeats, even in the presence of genomic variability at the 3′ end of the repeat. Using our assays, we have detected repeat expansions in 47/442 Scottish ALS patients. Furthermore, we recommend the combined use of these assays in a clinical diagnostic setting

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Novel cystic fibrosis transmembrane conductance (CFTR) variant in a patient with Ghanaian parentage

No abstract available

Meconial amniotic fluid and maternal and neonatal outcomes

Introduction: One of the major problems of the fetus is the excretion of the contents of the fetal intestine in the amniotic fluid sac or the amniotic fluid stained with meconium. If the time of stained with meconium is long or if the meconium is thick, it leads to serious risks for the mother and the fetus. The present study was conducted with aim to investigate the prevalence of babies born with meconial stained amniotic fluid and the associated maternal and fetal complications. Methods: This cross-sectional study was conducted in a period of 6 months (Dec 2014 to June 2015) on 1383 women with a singleton pregnancy and a gestational age of more than 28 weeks who had referred to Omolbanian Hospital in Mashhad due to the onset of labor pains. The investigated information included: mother's age, gestational age, number of pregnancies, mode of delivery, amniotic fluid condition, baby's gender, baby's Apgar, ABG (arterial blood gas), birth weight and the need for baby resuscitation. Data analysis was done using SPSS statistical software (version 22) and t-test and chi-square statistical tests. P< 0.05 was considered statistically significant. Results: In the present study, out of 1383 cases of normal delivery, 114 cases had meconium-stained amniotic fluid (prevalence of 8.2%). The number of cesarean section was higher in the thick meconial group (26 cases (%43.3)) compared to thin meconial group (9 cases (16.7%)) (p=0.002). The amount of abnormal ABG was 10 cases (8.7%) in the meconial group, of which 6 cases (5.2%) were in the fetal distress group. The amount of abnormal ABG was 8%, which was significantly higher in the thick meconial group (p=0.002). First minute Apgar less than 7 was more in the thick meconial group (p=0.01) and 5th minute Apgar had no difference between the two groups. There were no cases of convulsions or death of infant in the two groups. Conclusion: In this study, the prevalence of amniotic fluid stained with meconium was 8.2%. Although the rate of cesarean delivery was higher in the thick meconial group, there was no significant difference in fetal distress in the thick and thin meconial groups. Considering the complications of cesarean section for the mother, natural delivery can be a choice method in these mothers and cesarean section is limited to cases of fetal distress or thick meconium far from delivery