Role of combination of mifepristone and misoprostol versus misoprostol alone in the management of late intrauterine fetal death

Background: Intrauterine fetal death (IUFD) occurs in 1% of pregnancies and has devastating consequences. Previous methods for inducing labor in IUFD involved oxytocin and prostaglandins. The combination of mifepristone and misoprostol is commonly used for early first-trimester termination. This study aimed to compare the effectiveness of mifepristone and misoprostol combination versus misoprostol alone for labor induction in intrauterine fetal death. Methods: A randomized controlled clinical trial was conducted at Sir Salimullah Medical College, Mitford Hospital, Dhaka, from January 2017 to June 2017. Sixty-four pregnant women with intrauterine fetal death after 28 weeks of gestation were included. Participants were randomly assigned to either group-I (mifepristone and misoprostol) or group-II (misoprostol alone). Statistical analyses were performed using statistical package for the social sciences (SPSS) version 20.0 for Windows. Results: The mean age was 27.7±5.6 years in group I and 27.5±4.3 years in group II. Majority of patients in group I were housewives (87.5%), while in group II, it was 78.1%. Most patients in group I (56.3%) came from lower-income families, compared to 65.6% in group II. The gestational age did not significantly differ between the groups. The induction to delivery interval was significantly shorter in group I (8.6±2.0 hours) compared to group II (15.1±3.5 hours). The dose administration pattern of misoprostol differed significantly between the groups. Conclusions: Both methods are equally safe and effective for managing intrauterine fetal death. However, the combination of mifepristone and misoprostol showed greater efficacy in terms of reducing the induction to delivery interval and requiring a lower dose of misoprostol

Risk factors of mortality in hospitalized children with severe acute malnutrition

Background: Severe acute malnutrition (SAM) is a major cause of morbidity and mortality in children around the world. It is critical to identify the factors that contribute to mortality to reduce SAM related mortality. This study aimed to analyze the risk factors of mortality in hospitalized children with SAM. Methods: This case-control study was conducted in the SAM unit, department of pediatrics, institute of child and mother health, Matuail-1362, Dhaka, from January 2021 to December 2021. Data analysis was conducted using SPSS version 22. Univariate analysis was done to determine factors affecting mortality, and multivariate logistic regression was used to determine significant independent risk factors. Results: Mean age of the study subject was 6.38±3.45 months and 10.90±10.00 months in the case and control groups respectively. So, death was more common in younger children. The percentage of death was more (61.5% vs 54.6%) in males. Mortality was more common in family income <10,000 Tk/ month, 53.8% in the case group and 21.9% in the control group. The mean age of the mother was 19.23±0.60 years and 21.78±4.78 years in the death and survived group. Among risk factors of mortality, dermatosis (46.2% vs 4.9%), oral ulcer (46.2% vs 5.5%), hypoglycemia (46.2% vs 3.8%), severe anemia (38.5% vs 2.2%), septicemia (76.9% vs 29.5%) in case and control group respectively. These risk factors were significantly higher in the death group compared to the surviving group. After doing multivariate logistic regression analysis it was observed that hypoglycemia (OR=9.17 with 95% CI 1.44 to 58.29) and severe anemia (OR=13.42 with 95% CI 1.42 to 126.13) were the strongest predictors of mortality among the hospitalized children with SAM. Conclusions: Hypoglycemia and severe anemia were the main contributing factors of mortal among the children with SAM in the hospital

Best time to assess complete clinical response after chemoradiotherapy in squamous cell carcinoma of the anus (ACT II): a post-hoc analysis of randomised controlled phase 3 trial

Background: Guidelines for anal cancer recommend assessment of response at 6–12 weeks after starting treatment. Using data from the ACT II trial, we determined the optimum timepoint to assess clinical tumour response after chemoradiotherapy. Methods: The previously reported ACT II trial was a phase 3 randomised trial of patients of any age with newly diagnosed, histologically confirmed, squamous cell carcinoma of the anus without metastatic disease from 59 centres in the UK. We randomly assigned patients (by minimisation) to receive either intravenous mitomycin (one dose of 12 mg/m2 on day 1) or intravenous cisplatin (one dose of 60 mg/m2 on days 1 and 29), with intravenous fluorouracil (one dose of 1000 mg/m2 per day on days 1–4 and 29–32) and radiotherapy (50·4 Gy in 28 daily fractions); and also did a second randomisation after initial therapy to maintenance chemotherapy (fluorouracil and cisplatin) or no maintenance chemotherapy. The primary outcome was complete clinical response (the absence of primary and nodal tumour by clinical examination), in addition to overall survival and progression-free survival from time of randomisation. In this post-hoc analysis, we analysed complete clinical response at three timepoints: 11 weeks from the start of chemoradiotherapy (assessment 1), 18 weeks from the start of chemoradiotherapy (assessment 2), and 26 weeks from the start of chemoradiotherapy (assessment 3) as well as the overall and progression-free survival estimates of patients with complete clinical response or without complete clinical response at each assessment. We analysed both the overall trial population and a subgroup of patients who had attended each of the three assessments by modified intention-to-treat. This study is registered at controlled-trials.com, ISRCTN 26715889. Findings: We enrolled 940 patients from June 4, 2001, until Dec 16, 2008. Complete clinical response was achieved in 492 (52%) of 940 patients at assessment 1 (11 weeks), 665 (71%) of patients at assessment 2 (18 weeks), and 730 (78%) of patients at assessment 3 (26 weeks). 691 patients attended all three assessments and in this subgroup, complete clinical response was reported in 441 (64%) patients at assessment 1, 556 (80%) at assessment 2, and 590 (85%) at assessments 3. 151 (72%) of the 209 patients who had not had a complete clinical response at assessment 1 had a complete clinical response by assessment 3. In the overall trial population of 940 patients, 5 year overall survival in patients who had a clinical response at assessments 1, 2, 3 was 83% (95% CI 79–86), 84% (81–87), and 87% (84–89), respectively and was 72% (66–78), 59% (49–67), and 46% (37–55) for patients who did not have a complete clinical response at assessments 1, 2, 3, respectively. In the subgroup of 691 patients, 5 year overall survival in patients who had a clinical response at assessment 1, 2, 3 was 85% (81–88), 86% (82–88), and 87% (84–90), respectively, and was 75% (68–80), 61% (50–70), and 48% (36–58) for patients who did not have a complete clinical response at assessment 1, 2, 3, respectively. Similarly, progression-free survival in both the overall trial population and the subgroup was longer in patients who had a complete clinical response, compared with patients who did not have a complete clinical response, at all three assessments. Interpretation: Many patients who do not have a complete clinical response when assessed at 11 weeks after commencing chemoradiotherapy do in fact respond by 26 weeks, and the earlier assessment could lead to some patients having unnecessary surgery. Our data suggests that the optimum time for assessment of complete clinical response after chemoradiotherapy for patients with squamous cell carcinoma of the anus is 26 weeks from starting chemoradiotherapy. We suggest that guidelines should be revised to indicate that later assessment is acceptable. Funding: Cancer Research UK

Substantial and sustained reduction in under-5 mortality, diarrhea, and pneumonia in Oshikhandass, Pakistan : Evidence from two longitudinal cohort studies 15 years apart

Funding Information: Study 1 was funded through the Applied Diarrheal Disease Research Program at Harvard Institute for International Development with a grant from USAID (Project 936–5952, Cooperative Agreement # DPE-5952-A-00-5073-00), and the Aga Khan Health Service, Northern Areas and Chitral, Pakistan. Study 2 was funded by the Pakistan US S&T Cooperative Agreement between the Pakistan Higher Education Commission (HEC) (No.4–421/PAK-US/HEC/2010/955, grant to the Karakoram International University) and US National Academies of Science (Grant Number PGA-P211012 from NAS to the Fogarty International Center). The funding bodies had no role in the design of the study, data collection, analysis, interpretation, or writing of the manuscript. Publisher Copyright: © 2020 The Author(s).Peer reviewedPublisher PD

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. Methods In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. Findings Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis

جیلانی بانو کے افسانوں میں تانیثی عناصر کی عکاسی

Jilani Banu is a well-known contemporary fiction writer and novelist, his role in strengthening the tradition of fiction in Urdu literature is unforgettable. She not only reflected the best of social realism in her writings but also the feminism movement that was founded at the literary level for the welfare of women in the subcontinent

Changing Indications and Risk Factors for Peripartum Hysterectomy

Background: To determine the changing indications and risk factors for Peripartum Hysterectomy (PH), comparing the present times with the nineteen eighties.Methods: This retrospective comparative study was conducted in the Department of Obstetrics and Gynaecology (Unit-II) at Holy Family Hospital, Rawalpindi. Data of patients undergoing PH over a five-year period in the nineteen eighties, extending from June 1984 to May 1989 was collected. All ladies delivered during this period constituted Group A. The clinical record of all patients undergoing peripartum hysterectomy in the recent five-year period from January 2010 to December 2014 was examined to determine the indications and risk factors which necessitated this surgery. All women delivered in this time period constituted Group B. Peripartum Hysterectomy was defined as hysterectomy performed at the time of delivery or within the immediate postpartum period of 48 hours. All women of more than 28 weeks of gestation undergoing peripartum hysterectomy were enrolled.Results: The total number of deliveries conducted in Group A (1984-89) was 7843. Total vaginal deliveries were 6795(86.6%), while 1048(13.4%) were Caesarean sections(CS).In Group B (2010-14) total deliveries were 45340. Vaginal births were 29948(66%) and Lower Segment Caesarean section was performed in 15392(34%).In Group A, ten women required peripartum hysterectomy with a rate of 1.3/1000 deliveries Five of these (50%) were done for uterine rupture. Four (40%) were done for postpartum haemorrhage. One was done for placenta previa without previous caesarean section.One hundred and thirty six patients in Group B underwent peripartum hysterectomy with a rate of 2.9/1000 deliveries. In this group fifty-six (41%) were for postpartum haemorrhage, and forty-one (30.2%) for morbidly adherent placenta praevia on previous C-section scar (MAPCS). Uterine rupture led to peripartum hysterectomy in twenty (14.7%) cases.Conclusions: Uterine rupture was previously the leading indication for peripartum hysterectomy, followed by postpartum haemorrhage. With a rise in caesarean section rate, placenta praevia on previous scar and postpartum haemorrhage are now the leading risk factors for peripartum hysterectomy

Laparoscopic Surgery in Gynaecology

Background: With the advent of technological advancements, the indications for gynecological laparoscopy are increasing. We evaluated the results of our experiences with gynaecological laparoscopies and assessed rate, indications, complications and benefits in a teaching hospital.Methods: In this retrospective observational study, a total of 137 patients had laparoscopic procedure done during the period January 2011 to December 2014 and were included in the study. Laparoscopic surgeries were performed under general anesthesia. Successful creation of the pneumoperitoneum was created with the help of Veress needle, mostly by closed access technique and occasionally with the open method. Secondary ports were introduced under direct vision. After completing the surgery laparoscope and secondary ports were removed under direct vision to minimize any iatrogenic insult.Results: During the study period, 874 major gynaecological operations and 137 laparoscopies were performed. This gave the rate of 15.6% laparoscopies per 100 operations. Diagnostic laparoscopies were 48 (35%), operative were 89 (65%) and 8 (5.8%) laparoscopies were converted into open surgery due to technical difficulties. Complications were 8 (5.8%), majority being of minor nature except one major complication being a bladder injury.Conclusion: Laparoscopic surgery offers unique benefits. These are establishing definite diagnosis, mobilization and speedy recovery, minimal complications, less cost and shorter hospital stay. In young patients, laparoscopy helps in preserving their fertility with better prognosis in contrast to open surgery