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Chronic hepatitis C (HCV) in women of childbearing age is a major public health concern with ∼15 million women aged 15-49 years living with HCV globally in 2019. Evidence suggests HCV in pregnancy is associated with adverse pregnancy and infant outcomes. This includes ∼6% risk of infants acquiring HCV vertically, and this is the leading cause of HCV in children globally. However, few countries offer routine universal antenatal HCV screening, and direct-acting antivirals (DAAs) are not approved for pregnant or breastfeeding women although small clinical trials are ongoing. We conducted a survey of pregnant and postpartum women in 3 high HCV burden lower-middle-income countries to assess the acceptability of universal antenatal HCV screening and DAA treatment in the scenario that DAAs are approved for use in pregnancy. Pregnant and postpartum women attending antenatal clinics in Egypt, Pakistan, and Ukraine were invited to complete a survey and provide demographic and clinical data on their HCV status. Among the 630 women included (n=210 per country), 73% were pregnant and 27% postpartum, 27% were ever HCV antibody or PCR positive. Overall, 586 (93%) reported acceptability of universal antenatal HCV screening and 544 (88%) would take DAAs in pregnancy (92%, 98%, and 73% in Egypt, Pakistan, and Ukraine, respectively). Most said they would take DAAs in pregnancy to prevent vertical acquisition and other risks for the baby, and a smaller proportion would take DAAs for maternal cure. Our findings suggest that should DAAs be approved for use in pregnancy, the uptake of both HCV screening and DAA treatment may be high in women living in lower-middle-income countries., Competing Interests: Sarah Pett received institutional grants from Gilead, ViiV Healthcare, Janssen-Cilag, MRC, NIHR, and EDCTP. Manal H. El-Sayed received grants from Gilead. Ali Judd received institutional grants from Gilead. Intira Jeannie Collins received institutional grants from Gilead and ViiV Healthcare. The remaining authors have no conflicts to report., (Copyright © 2024 American Association for the Study of Liver Diseases.)

The prevalence of cardiovascular disorders among healthcare providers have been increasing in the past few years and research conducted in this aspect have identified various risk factors that affect cardiovascular health: like shift work, high stress, anxiety, work environment, obesity, high basal metabolic index, and others. PRISMA guidelines were followed and data search was conducted on PubMed, PMC, MEDLINE, and Google Scholar wherein the identification and screening led to 31 selected studies on identification of knowledge, perception and attitude of the healthcare providers regarding their cardiovascular disorders. Results reveal that knowledge level even although high in healthcare providers regarding their cardiovascular health, the attitude or perception differs among them. Lack of time, stigma, fear of unknown, access to healthcare, not wishing to burden co-workers are some of the identified factors which are affecting their decision making regarding proper actions to be taken to address their cardiovascular issues., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Maternal sepsis is the third leading cause of maternal mortality globally. WHO and collaborators developed a care bundle called FAST-M ( F luids, A ntibiotics, S ource identification and treatment, T ransfer and M onitoring) for early identification and management of maternal sepsis in low-resource settings. This study aimed to determine feasibility of FAST-M intervention in a low-resource setting in Pakistan. The FAST-M intervention consists of maternal sepsis screening tools, treatment bundle and implementation programme., Design and Setting: A feasibility study with before and after design was conducted in women with suspected maternal sepsis admitted at the Liaquat University of Medical and Health Sciences hospital Hyderabad. The study outcomes were compared between baseline and intervention phases. In the baseline phase (2 months), the existing sepsis care practices were recorded, followed by a training programme for healthcare providers on the application of FAST-M tools. These tools were implemented in the intervention phase (4 months) to assess any change in clinical practices compared with the baseline phase., Results: During the FAST-M implementation, 439 women were included in the study. 242/439 were suspected maternal infection cases, and 138/242 were women with suspected maternal sepsis. The FAST-M bundle was implemented in women with suspected maternal sepsis. Following the FAST-M intervention, significant changes were observed. Improvements were seen in the monitoring of oxygen saturation measurements (25.5% vs 100%; difference: 74%; 95% CI: 68.4% to 80.5%; p<0.01), fetal heart rate assessment (58% vs 100%; difference: 42.0%; 95% CI: 33.7% to 50.3%; p≤0.01) and measurement of urine output (76.5% vs 100%; difference: 23.5%; 95% CI: 17.6% to 29.4%; p<0.01). Women with suspected maternal sepsis received all components of the treatment bundle within 1 hour of sepsis recognition (0% vs 70.5%; difference: 70.5%; 95% CI: 60.4% to 80.6%; p<0.01)., Conclusion: Implementation of the FAST-M intervention was considered feasible and enhanced early identification and management of maternal sepsis at the study site., Trial Registration Number: ISRCTN17105658., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: The World Health Organization and partners developed and evaluated a maternity-specific sepsis care bundle called 'FAST-M' for low-resource settings. However, this bundle has not yet been studied in Asia. Our study sought to evaluate the perceptions of healthcare providers about the implementation of the FAST-M intervention in Pakistan., Materials and Methods: The study was conducted at a public sector hospital in Hyderabad. We conducted three focus group discussions with healthcare providers including doctors, nurses, and healthcare administrators (n = 22) who implemented the FAST-M intervention. The Consolidated Framework for Implementation Research was used as a guiding framework for data collection and analysis. The data were analyzed using a thematic analysis approach and deductive methods., Results: Five overarching themes emerged: (I) FAST-M intervention and its significance including HCPs believing in the advantages of using the intervention to improve clinical practices; (II) Influence of outer and inner settings including non-availability of resources in the facility for sepsis care; (III) HCPs perceptions about sustainability, which were positive (IV) Integration into the clinical setting including HCPs views on the existing gaps, for example, shortage of HCPs and communication gaps, and their recommendations to improve these; and (V) Outcomes of the intervention including improved clinical processes and outcomes using the FAST-M intervention. Significant improvement in patient monitoring and FAST-M bundle completion within an hour of diagnosis of sepsis was reported by the HCPs., Conclusions: The healthcare providers' views were positive about the intervention, its outcomes, and long-term sustainability. The qualitative data provided findings on the acceptability of the overall implementation processes to support subsequent scaling up of the intervention., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2023 Ahmed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Borrelia burgdorferi is regarded as an extremely dangerous bacteria causing infectious disease in humans, resulting in musculoskeletal pain, fatigue, fever and cardiac symptom. Because of all alarming concerns, no such prophylaxis setup has been available against Borrelia burgdorferi till now. In fact, vaccine construction using traditional methods is so expensive and time-consuming. Therefore, considering all concerns, we designed a multi-epitope-based vaccine design against Borrelia burgdorferi using in silico approaches., Objective: To design an effective and safe vaccine that can activate cell-mediated and humoral immunity against Borrelia burgdorferi by using various bioinformatics tools., Methods: The present study utilized different computational methodologies, covering different ideas and elements in bioinformatics tools. The protein sequence of Borrelia burgdorferi was retrieved from the NCBI database. Different B and T cell epitopes were predicated using the IEDB tool. Efficient B and T cell epitopes were further assessed for vaccine construction using linkers AAY, EAAAK and GPGPG, respectively. Furthermore, the tertiary structure of constructed vaccine was predicated, and its interaction was determined with TLR9 using ClusPro software. In addition, further atomic level detail of docked complex and their immune response were further determined by MD simulation and C-ImmSim tool, respectively., Results: A protein with immunogenic potential and good vaccine properties (candidate) was identified based on high binding scores, low percentile rank, non-allergenicity and good immunological properties, which were further used to calculate epitopes. Additionally, molecular docking possesses strong interaction; seventeen H-bonds interactions were reported, such as THR101-GLU264, THR185-THR270, ARG 257-ASP210, ARG 257-ASP 210, ASP259-LYS 174, ASN263-GLU237, CYS 265-GLU 233, CYS 265-TYR 197, GLU267- THR202, GLN 270-THR202, TYR345-ASP 210, TYR345-THR 213, ARG 346-ASN209, SER350- GLU141, SER350-GLU141, ASP 424-ARG220 and ARG426-THR216 with TLR-9. Finally, high expression was determined in E. coli (CAI = (0.9045), and GC content = (72%)). Using the IMOD server, all-atom MD simulations of docked complex affirmed its significant stability. The outcomes of immune simulation indicate that both T and B cells represent a strong response to the vaccination component., Conclusion: This type of in-silico technique may precisely decrease valuable time and expenses in vaccine designing against Borrelia burgdorferi for experimental planning in laboratories. Currently, scientists frequently utilize bioinformatics approaches that speed up their vaccine-based lab work., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Numerous malignancies, including metastatic triple-negative breast cancer (TNBC), which has long been associated with a poor prognosis, have been transformed by the widespread use of immunotherapy. Immune checkpoint inhibitors (ICIs) that target and block programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have demonstrated encouraging outcomes in the treatment of patients with metastatic TNBC. The PD-1 inhibitor pembrolizumab is the first-line treatment of metastatic PD-L1+ TNBC in combination with chemotherapy, and the PD-L1 inhibitor atezolizumab has also shown clinical activity. The median progression-free survival for pembrolizumab or atezolizumab combined with chemotherapy increased by 4.1 months and 2.5 months, respectively, with the addition of immunotherapy. Despite this progress, there is still more to be desired. The addition of immunotherapy to chemotherapy improved the pathological complete response (PCR) rate compared to chemotherapy with placebo in landmark phase III trials in the early-stage neoadjuvant context, whereas others reported no meaningful improvement in PCR. There are various ongoing trials that show that more research and studies are needed for components in the TNBC microenvironment and to further explore its importance in the treatment of TNBC., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, K Patel et al.)

Objective: A maternal sepsis management bundle for resource-limited settings was developed through a synthesis of evidence and international consensus. This bundle, called 'FAST-M' consists of: Fluids, Antibiotics, Source control, assessment of the need to Transport/Transfer to a higher level of care and ongoing Monitoring (of the mother and neonate). The study aimed to adapt the FAST-M intervention including the bundle care tools for early identification and management of maternal sepsis in a low-resource setting of Pakistan and identify potential facilitators and barriers to its implementation., Setting: The study was conducted at the Liaquat University of Medical and Health Sciences, which is a tertiary referral public sector hospital in Hyderabad., Design and Participants: A qualitative exploratory study comprising key informant interviews and a focus group discussion was conducted with healthcare providers (HCPs) working in the study setting between November 2020 and January 2021, to ascertain the potential facilitators and barriers to the implementation of the FAST-M intervention. Interview guides were developed using the five domains of the Consolidated Framework for Implementation Research: intervention characteristics, outer setting, inner setting, characteristics of the individuals and process of implementation., Results: Four overarching themes were identified, the hindering factors for implementation of the FAST-M intervention were: (1) Challenges in existing system such as a shortage of resources and lack of quality assurance; and (2) Clinical practice variation that includes lack of sepsis guidelines and documentation; the facilitating factors identified were: (3) HCPs' perceptions about the FAST-M intervention and their positive views about its execution and (4) Development of HCPs readiness for FAST-M implementation that aided in identifying solutions to potential hindering factors at their clinical setting., Conclusion: The study has identified potential gaps and probable solutions to the implementation of the FAST-M intervention, with modifications for adaptation in the local context TRIAL REGISTRATION NUMBER: ISRCTN17105658., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Subclinical hypothyroidism (SCH) is a commonly encountered condition in women with polycystic ovary syndrome (PCOS). Nevertheless, it is unclear whether SCH has any potential impact on the metabolic and reproductive profiles of women with PCOS. Hence, this literature review explores and establishes the link between these two conditions. In women with PCOS, SCH was found to aggravate insulin resistance and dyslipidemia. It was also linked to hormonal imbalances leading to higher infertility rates among the PCOS-SCH group. Therefore, women with PCOS must be screened for thyroid function frequently and managed accordingly., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Peddemul et al.)

Torsades de Pointes (TdP) is a rare form of tachyarrhythmia which can potentially be fatal due to its tendency to degenerate into ventricular fibrillation. It is described as a polymorphic ventricular tachycardia characterized by twisting of the QRS complexes around the electrocardiogram (ECG) baseline in patients with a prolonged QT interval. Prolonged QT interval is known as long QT syndrome. Torsades de Poccurs most commonly in patients with an extended QT interval duration, and even though monitoring an ECG can assist in its prevention, there is no defined duration of a QT interval that can lead to an increased risk of Torsades de Pointes. So, it is hard to determine what QT interval constitutes enough risk for Torsades de Pointes to require intervention. The QT interval duration also depends on other factors, namely heart rate (HR) and other factors such as drugs, congenital diseases, and a combination of both. In this study, we considered various causes of QT prolongation but mainly focused on congenital diseases, drugs, or perioperative risk of QT prolongation and the correlation with the risk of impending TdP. By following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and researching studies on various databases, namely PubMed, Science Direct, Medline, and CiNii we were able to find various systematic reviews and articles showing the association between prolonged QT interval and its degeneration into TdP. This review encourages further research into this topic to understand the implications of QT prolongation and how it can help save the lives of patients with known long QT syndrome, or those on QT prolonging drugs with simple ECG monitoring and treatment for the respective cause., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Kahlon et al.)

Background: Burkholderia pseudomallei is an infectious agent causing severe disease melioidosis resulting in pneumonia, fever, and acute septicemia in humans. B. pseudomallei show resistance to drugs. No such FDA-approved vaccine is available against B. pseudomallei, and treatment is limited to therapy. Therefore, the scientific study was designed to develop a vaccine for B. pseudomallei. The protein sequence of B. pseudomallei was retrieved from NCBI. B-cell and T-cell epitopes were identified and further screened for allergenicity, antigenicity docking, and simulation., Results: Here, in this study, in silico approach was applied to design a multi-epitope subunit vaccine peptide consisting of linear B-cell and T-cell epitopes of proteins considered to be potential novel vaccine candidates. Peptide epitopes were joined by adjuvant and EAAAK, CPGPG, and AAY linkers. This constructed vaccine was subjected to in silico immune simulations by C-ImmSim. The protein construct was cloned into PET28a (+) vector for expression study in Escherichia coli using SnapGene., Conclusion: The designed multi-epitope vaccine was analyzed for its physicochemical, structural, and immunological characteristics, and it was found to be antigenic, soluble, stable, nonallergenic, and have a high affinity to its target receptor. The immune simulation studies were carried out on the C-ImmSim showing increased production of cellular and humoral responses indicating that the constructed vaccine proved effective and able to provoke humoral and cell-mediated response immune responses. In silico study could be a breakthrough in designing effective vaccines to eradicate B. pseudomallei globally., (© 2022. The Author(s).)

Rheumatoid arthritis (RA) is an autoimmune disease that, if untreated or poorly controlled, can cause significant morbidity in terms of loss of physical function and higher mortality due to higher cardiovascular risk. The standard of care for this disease is the use of disease-modifying antirheumatic drugs (DMARDs). However, patients unable to reach low disease activity or remission and patients unable to tolerate conventional DMARDs will be switched to biologic therapy, a subset of which includes anti-tumor necrosis factor-alpha inhibitors. Since tumor necrosis factor-alpha inhibitors (TNFi) inhibit the inflammatory cascade, they also play an essential role in dampening the progression of atherosclerosis and altering the risk of cardiovascular outcomes in RA. In this study, we assessed the risk of cardiovascular diseases, namely, congestive heart failure, nonfatal myocardial infarction, cerebrovascular disease, and coronary artery disease. We carried out the analysis by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and conducted a literature search utilizing the following databases: PubMed, Science Direct, and Cochrane Library. Using the search strategy, we found a total of 19 articles that fit the inclusion and exclusion criteria, in addition to passing the risk of bias assessment. This is composed of three systematic reviews with meta-analyses, three randomized control studies, four narrative reviews, and nine cohort studies. In this systematic review, it was found that treatment with TNFi causes a corresponding reduction in the risk of cardiovascular events. This review encourages further dissection into the inner workings of TNFi in reducing the risk of cardiovascular disease among patients with RA., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Nair et al.)

Background: Maternal sepsis is a life-threatening condition, defined by organ dysfunction caused by infection during pregnancy, childbirth, and the postpartum period. It is estimated to account for between one-tenth and half (4.7% to 13.7%) of all maternal deaths globally. An international stakeholder group, including the World Health Organization, developed a maternal sepsis management bundle called "FAST-M" for resource-limited settings through a synthesis of evidence and international consensus. The FAST-M treatment bundle consists of five components: Fluids, Antibiotics, Source identification and control, assessment of the need to Transport or Transfer to a higher level of care and ongoing Monitoring (of the mother and neonate). This study aims to adapt the FAST-M intervention and evaluate its feasibility in Pakistan., Methods: The proposed study is a mixed method, with a before and after design. The study will be conducted in two phases at the Liaquat University of Medical and Health Sciences, Hyderabad. In the first phase (formative assessment), we will adapt the bundle care tools for the local context and assess in what circumstances different components of the intervention are likely to be effective, by conducting interviews and a focus group discussion. Qualitative data will be analyzed considering a framework method approach using NVivo version 10 (QSR International, Pty Ltd.) software. The qualitative results will guide the adaptation of FAST-M intervention in local context. In the second phase, we will evaluate the feasibility of the FAST-M intervention. Quantitative analyses will be done to assess numerous outcomes: process, organizational, clinical, structural, and adverse events with quantitative comparisons made before and after implementation of the bundle. Qualitative analysis will be done to evaluate the outcomes of intervention by conducting FGDs with HCPs involved during the implementation process. This will provide an understanding and validation of quantitative findings., Discussion: The utilization of care bundles can facilitate recognition and timely management of maternal sepsis. There is a need to adapt, integrate, and optimize a bundled care approach in low-resource settings in Pakistan to minimize the burden of maternal morbidities and mortalities due to sepsis., (© 2022. The Author(s).)

Four new Donor-Acceptor (D-A) type oligothiophenes based structures (C1-C4) were designed by substituting different acceptors moieties around tetrahedral silicon core to simulate their photovoltaic properties. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) quantum analysis were carried out to reconnoiter various parameters of solar cells. A comparative analysis has conducted between designed structures and reference molecule R to conclude our simulated results. Among all the structures, C2 has displayed highest absorption values (380 nm) with red shift and minimum band gap (Δ H-L ) of 4.11 eV in dichloromethane at DFT-CAM-B3LYP/6-31G (d,p) using IEFPCM model. The C2 has also shown the lowest values of electron reorganization energy (λe = 0.018eV) and hole reorganization energy (λh = 0.015eV) therefore, could be suggested for use in organic solar cells because of its most noteworthy charge carrier mobilities. Again, C2 has the different trend in TDM graph because the electron density is present in the lower right part of core unit and in the acceptor moiety due to high electron affinities of end capped acceptor having cyanide groups., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The safety and efficacy of antenatal glucocorticoids in women in low-resource countries who are at risk for preterm birth are uncertain., Methods: We conducted a multicountry, randomized trial involving pregnant women between 26 weeks 0 days and 33 weeks 6 days of gestation who were at risk for preterm birth. The participants were assigned to intramuscular dexamethasone or identical placebo. The primary outcomes were neonatal death alone, stillbirth or neonatal death, and possible maternal bacterial infection; neonatal death alone and stillbirth or neonatal death were evaluated with superiority analyses, and possible maternal bacterial infection was evaluated with a noninferiority analysis with the use of a prespecified margin of 1.25 on the relative scale., Results: A total of 2852 women (and their 3070 fetuses) from 29 secondary- and tertiary-level hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan underwent randomization. The trial was stopped for benefit at the second interim analysis. Neonatal death occurred in 278 of 1417 infants (19.6%) in the dexamethasone group and in 331 of 1406 infants (23.5%) in the placebo group (relative risk, 0.84; 95% confidence interval [CI], 0.72 to 0.97; P = 0.03). Stillbirth or neonatal death occurred in 393 of 1532 fetuses and infants (25.7%) and in 444 of 1519 fetuses and infants (29.2%), respectively (relative risk, 0.88; 95% CI, 0.78 to 0.99; P = 0.04); the incidence of possible maternal bacterial infection was 4.8% and 6.3%, respectively (relative risk, 0.76; 95% CI, 0.56 to 1.03). There was no significant between-group difference in the incidence of adverse events., Conclusions: Among women in low-resource countries who were at risk for early preterm birth, the use of dexamethasone resulted in significantly lower risks of neonatal death alone and stillbirth or neonatal death than the use of placebo, without an increase in the incidence of possible maternal bacterial infection. (Funded by the Bill and Melinda Gates Foundation and the World Health Organization; Australian and New Zealand Clinical Trials Registry number, ACTRN12617000476336; Clinical Trials Registry-India number, CTRI/2017/04/008326.)., (Copyright © 2020 Massachusetts Medical Society.)

Lapatinib (LPT) is an orally administered drug for the treatment of metastatic breast cancer. For expanding its therapeutic horizon, we have prepared its nanocrystals (LPT-NCs) that were subsequently coated with hyaluronic acid (HA) to produce LPT-HA-NCs. The detailed in-vitro and in-vivo investigation of LPT-HA-NCs showed the superior anticancer activity due to active targeting to CD44 receptors than the counterparts LPT-NCs and free LPT. In the triple negative 4T1 cells induced breast tumor bearing female Balb/C mice; LPT-HA-NCs treatment caused significant retardation of tumor growth and overall increase in animal survival probability because of their higher tumor localization, increased residence time. Our findings clearly suggest that HA coated LPT-NCs formulation enhances the activity of LPT against triple negative breast cancer. It exhibited magnificent therapeutic outcome at low dose thus presenting a strategy to reduce dose administrations and minimize dose related toxicity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To improve health outcomes through the implementation of national early warning sign tool for babies delivered through emergency caesarean section in off-work hours., Methods: This comparative clinical study was conducted at the Aga Khan Hospital for Women and Children, Karachi, from April to August 2014, and comprised women who had an emergency caesarean section. Maternal and perinatal outcomes were compared of patients in Group A and Group B which represented individuals before and after the implementation of the national early warning score respectively., Results: Of the 200 participants, there were 100(50%) in each group. The overall mean age was 26.79±5.10 years. The mean age was 26.3±5 years in Group A, and 27.2±5 years in Group B (p=0.25). The two groups were also comparable in terms of parity (p=0.77) and co-morbidities (p =0.51). There was no stillbirth or maternal death, but decline in complications due to post-partum haemorrhage (p=0.00) was observed due to early recognition and timely management. None of the women required referral to higher facility., Conclusions: National early warning score was found to be a practical early warning tool for obstetric population.

Objective: To analyse referral pattern of high-risk obstetric cases from secondary to tertiary care hospitals and to assess their maternal and neonatal outcomes., Methods: This retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised all referred obstetric cases from secondary-level hospitals to tertiary-level care within and outside the Hospital between January 2011 and December 2014. Day and time of referral, reason for referral as well as maternal and neonatal outcomes were collected. SPSS 19 was used for data analysis., Results: Of the 634 obstetric referrals, 279(44%) patients were referred to the study site, while 355(56%) sought care in other hospitals. Of those patients who were referred to the AKUH, medical records of 195(69.9%) were available for review. The mean age of the participants was 28±4.7 years. Obstetric complications led to 122(61%) referrals. The top three reasons among these were pregnancy-induced hypertension, preterm labour and foetal causes. Medical causes such as viral infections were the cause of 50(27%) referrals. Moreover, 177(91%) patients were pregnant at the time of referral and the remaining 18(9%) were referred after delivery. Of the pregnant women, 133(75%) delivered at the study site. Caesarean section was the mode in 92(69%) deliveries. There was 1(0.75%) maternal death due to puerperal sepsis while 9(7%) neonatal deaths were recorded., Conclusions: The most common reason for referrals was obstetric indications. Moreover, a quarter of referrals were initiated due to medical conditions, most of which were due to infections.

Objective: To determine prevalence and severity of menopausal symptoms and to investigate any correlation of sociodemographic and reproductive characteristics with menopausal symptoms in rural women., Methods: The cross-sectional study was conducted in 2007-08 in rural Sindh, Pakistan, and comprised women of age 40-70 years who were selected through multistage random sampling. Sociodemographic information was collected on a predesigned proforma. Menopause Rating Scale was used to collect information regarding the prevalence and severity of menopausal symptoms. Multivariate logistic regression was used to adjust prevalence odds ratio for demographic and reproductive characteristics., Results: From among a population of 525,082, the study selected 3062(0.5%) women. The prevalence of menopausal symptoms was mostly higher except bladder problems 1138(37.7%) and dryness of vagina 1008(34%). The frequency of symptoms - all mild in nature - were hot flushes 1287(42%), sleep problems 1251(40.9%), depressive mode 1169(38.2%), physical and mental exertion 1169(38.2%), and muscle and joint pain 861(28.1%). Significant association of the symptoms was found with age, education and menopausal status (p<0.05 each)., Conclusions: The prevalence of most of the menopausal symptoms was high except for bladder problems and dryness of vagina. Majority of the symptoms were categorised as mild.

Objective: To assess the incremental value of blood oxygen saturation (SpO(2)) as a predictor in the miniPIERS model, a risk prediction model for adverse outcomes among women with a diagnosis of hypertensive disorder of pregnancy (HDP) in low-resourced settings., Methods: Using data from a prospective cohort including 852 women admitted to hospital for a HDP, the association between SpO(2) and adverse maternal outcome was assessed using logistic regression. The miniPIERS model was recalibrated and extended to include SpO(2). The incremental value of adding SpO(2) to the model was measured using a net reclassification index (NRI), sensitivity, specificity, positive and negative predictive values, and likelihood ratios., Results: SpO(2) of < 93% was associated with a 30-fold increase in risk (95% CI 14 to 68) of adverse maternal outcome compared to women with SpO(2) > 97%. After recalibration and extension, the miniPIERS model including SpO(2) (vs. not including SpO(2)) had improved sensitivity (32.8% vs. 49.6%) at the cost of minimally decreased specificity (91.5% vs. 96.2%) with a NRI of 0.122., Conclusion: SpO(2) is a significant independent predictor of risk in women with a HDP. Adding SpO(2) to the miniPIERS model improved the model's ability to correctly identify high-risk patients who would benefit most from interventions.

Background: Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications., Methods and Findings: From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability., Conclusions: The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care.

Objectives: To determine the prevalence of Group B Streptococcus genital tract infection in pregnant women and to determine the risk factors for its colonisation., Methods: The cross-sectional study was conducted at the Aga Khan University Hospital, Karachi and Sobhraj Hospital, Karachi, from May to August 2007. Pregnant women at 35-37 weeks gestation attending antenatal clinic at these hospitals constituted the study population. Based on stratified sampling, 405 patients were recruited. High vaginal swabs of these patients were taken in order to calculate the prevalence of infection at each hospital. Logistic regression was used to evaluate the risk factor association. SPSS 11.5 was used for statistical analysis., Results: The overall prevalence of colonisation was 17% (n = 69) (95% CI: 13.4-20.7). Of the 155 (38.27%) women at the Aga Khan Hospital, 35 (22.6%) were positive, while among the 250 (61.72%) women at Sobhraj Hospital, the prevalence was 13.6% (n = 34). The colonisation was found to be significantly associated inversely with the body mass index of the patient (OR 0.91; 95% CI: 0.08-1.0)., Conclusion: Group B Streptococcus screening should be an integral part of antenatal care and should be offered to all pregnant women.

Background: Age at menopause and symptoms vary among populations and societies. Scarce data is available about menopausal age, symptoms and socio-demographic and reproductive factors from rural women of Sindh, Pakistan. The present study was conducted to find out the self reported age at natural menopause, prevalence of menopausal symptoms, and to identify sociodemographic and reproductive factors that may influence the onset of menopause., Methods: A survey was carried out on women aged 40-70. A multistage random sampling technique was used to retrieve 1,355 women with natural menopause from 10 union councils of district Matiari. These women were further categorised into 3 groups, I, II, and III having menopause for 1-5, 6-10, > 10 years respectively. Pearson's chi-square test was used to analyse the percentage of symptoms distribution. ANOVA was used to analyse the relationship between demographic, reproductive factors and the age at natural menopause., Results: Age at menopause in our subjects was 46.2 +/- 6.4 years. The prevalence of menopausal symptoms ranges from 26 % to 83%. Frequency of somatic, psychological and urogenital symptoms was high in group II. No significant association was found between parity, socioeconomic status and age at natural menopause., Conclusion: The results have shown the early age at menopause. The prevalence of menopausal symptoms is high. Results regarding correlation of age at menopause with socio-demographic and reproductive characteristics were different from literature.

Background: We hypothesized that pre-eclampsia (PE) can be predicted early in primiparas by measuring serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF)., Methods: All normotensive primiparas attending the antenatal clinics of Aga Khan University Hospital and Aga Khan Hospital for Women, Karachi, Pakistan without any known risk factor for PE were invited to participate in the study. They were divided into two groups based on the development of PE. Their blood samples were collected at 8-15, 16-22, 23-28, 29v34 weeks of pregnancy and once within 1 week of delivery. All samples were analysed for sFlt-1 and PlGF., Results: Six hundred and eleven (46.7%) of 1307 recruited primiparas completed the study according to the protocol. Of these, 39 (6.4%) women developed PE. The difference in serum sFlt-1 was evident as early as 15 weeks of gestation. Higher levels of serum sFlt-1 were present in women who later developed PE. Relatively higher levels of PlGF were observed in non-PE women compared to PE women up to 22 weeks of gestation. However, after 23 weeks of pregnancy, PlGF levels increased in both the groups, but less so in the PE group. Receiver operator characteristics (ROC) curve analysis showed that even in early pregnancy (<15 weeks of gestation), serum sFlt-1 alone has the potential to predict PE with area under the curve (AUC), sensitivity and specificity of 0.81, 75.9 and 72.4, respectively., Conclusion: PE can be predicted in primiparas in the early part of second trimester with serum levels of sFlt-1 and in the later part of second trimester with serum levels of PlGF., (Copyright 2012, NMJI.)

Sirenomelia, the Mermaid Syndrome is a rare and lethal congenital anomaly with an incidence of one in 60,000 to 70,000 pregnancies. Sirenomelia is characterized by complete fusion of the lower limbs, commonly associated with renal agenesis, absent external genitalia and other gastrointestinal defects. Another pathognomonic finding is the presence of single umbilical, persistent vitelline artery which is the chief distinguishing anatomic finding from Caudal Regression Syndrome. We report a case of termination of pregnancy done on the basis of ultrasound diagnosis of bilateral renal agenesis with no liquor volume. The foetus was identified to have characteristic features of Sirenomelia at the time of termination.

Restless legs syndrome (RLS) is more common in pregnant women. The objective of our study was to determine frequency of RLS in pregnant women and predictors of RLS in pregnancy in Pakistan. All pregnant women admitted at The Aga Khan University Hospital for delivery from June to July 2005 were enrolled. Eighty-one of 271 (30%) interviewed women fulfilled the diagnostic criteria of RLS. One hundred seventeen (43%) of the subjects dropped their haemoglobin during the pregnancy. No significant difference in haemoglobin drop was noted between the RLS group and healthy group. On multivariate analysis family history of RLS (OR: 8.43, CI: 2.32-30.57, p value<0.001), history of RLS in prior pregnancy (OR: 53.74, CI: 6.72-429.8, p value<0. 001), history of RLS in past even when non-pregnant (OR: 12.91, CI: 3.34-49.87, p value<0.001) and haemoglobin of 11g/dL or less (OR: 2.05, CI: 1.04-4.04, p value 0.036) were found to be independent predictors of RLS during pregnancy. Subgroup analysis revealed that family history of RLS (OR: 3.06, CI: 1.2-7.83, p value 0.019) and anemia (OR: 1.89, CI: 0.96-3.71, p value 0.06) were associated with de novo RLS, and family history of RLS (OR: 12.39, CI: 4.45-35.54, p value<0.001) and multiparity (OR: 6.84, CI: 2.15-21.71, p value 0.001) were predictors of pre-existing RLS.

Objective: To determine the reasons underlying the refusals to participate and drop outs from a follow up study involving primigravidae., Design: A descriptive study., Methods: Aga Khan University and Aga Khan Hospital for Women, Karachi, jointly initiated a nested case-control study on primigravidae for determining the predictability of preeclampsia using various biochemical markers in blood. The protocol-eligible study subjects were counseled along with their accompanying family members to participate in the study. All women recruited in this study were followed up throughout their pregnancy till delivery., Results: One thousand six hundred and sixty-five primigravidae were identified as the potential study subjects. Out of which, 1,307 (78.5%) consented and 358 (21.5%) refused to participate in the study. The most common reason underlying the refusal was inability to get permission from the family members (n=84; 34.4%) followed by fear of prick (n=51; 20.9%). For 114 refusals, either the reason was not mentioned by the counseled women (n=60) or the data was missing (n=54). Out of 1,307 women recruited in the research, only 611 (46.7%) women completed the study according to the prescribed protocol. Among the rest, 102 (7.8%) subsequently withdrew from the research, 503 (38.5%) were dropped out, and 91 (7.0%) were lost to follow up., Conclusions: Refusal to participate and drop out from the research program are two significant factors hindering the smooth flow of a study. In Pakistan, the major reason for the refusal by the protocol-eligible pregnant women for participating in a research program is the unwillingness of the family members.

Pregnancy and puerperium are most prevalent prothrombotic states leading to cerebral venous thrombosis. Likelihood of stroke to be of venous origin is greater in stroke associated with pregnancy compared to stroke unrelated to pregnancy. Pregnancy induces several changes in coagulation system, which persists at least during early puerperium, rendering it a prothrombotic state. Hypercoaguability worsens further after delivery as a result of volume depletion and trauma. During puerperium additional risk factors include infection and instrumental delivery or Caesarean section. The management follows general rules as for the venous thrombosis unrelated to pregnancy, however the prognosis is different.

Objective: To determine the success rate of intrauterine insemination (IUI), following controlled ovarian hyperstimulation (COH) and to identify the prognostic factors associated with successful outcome in couples undergoing this form of assisted reproduction., Design: Case series., Place and Duration of Study: Concept Fertility Centre, Karachi, Pakistan from January - December 2004., Patients and Methods: A total of 290 IUI procedures carried out for the treatment of unexplained and male factor subfertility were included. The age of women ranged from 20 to 44 years and the duration of subfertility were variable. All women had tubal patency confirmed before undergoing COH with one of the three regimens. IUI was performed at follicular maturity of > 16 mm and endometrial thickness of > 7 mm. Main outcome measures analyzed were pregnancy rate per cycle of IUI, miscarriage rate and ongoing pregnancy rate. Other variables observed were the various prognostic factors associated with successful outcome in IUI, such as maternal age, effect of different regimen of COH, motile sperm count and numbers of pre-ovulatory mature follicles > 16 mm. Data was collected and entered in SPSS version 10. Chi- square test of significance was applied and p-value determined., Results: The cycle pregnancy rate (CPR), miscarriage rate and ongoing pregnancy rate was 10%, 13.8% and 8.6% respectively. CPR was 12% in women <35 years compared to 3% in >35 years (p-value 0.03). Significant difference was not observed in the CPR with three different COH regimes. CPR increased dramatically with motile sperm count of >10 millions/ml compared with < 10 millions/ml (12.3% vs. 2.8%, p-value 0.02). Significantly higher pregnancy rate was observed with increasing number of mature follicles >16 mm (6.2%, 12.9% and 30% with one, two and three follicles, p-value 0.0019). There was no case of OHSS and only one case of twin gestation., Conclusion: The overall CPR in patients undergoing IUI following COH at our clinic is comparable to the pregnancy rates as shown in different studies. Younger age, motile sperm count of > 10 millions/ml and two or three mature follicles >16 mm are good prognostic factors for successful outcome. However, no significant difference was observed in CPR with different COH regimes.