Early to mid-pregnancy HbA1c levels and its association with adverse pregnancy outcomes in three low middle-income countries in Asia and Sub-Saharan Africa.

BACKGROUND: Hyperglycemia during pregnancy leads to adverse maternal and fetal outcomes. Thus, strict monitoring of blood glucose levels is warranted. This study aims to determine the association of early to mid-pregnancy HbA1c levels with the development of pregnancy complications in women from three countries in South Asia and Sub-Saharan Africa. METHODS: We performed a secondary analysis of the AMANHI (Alliance for Maternal and Newborn Health Improvement) cohort, which enrolled 10,001 pregnant women between May 2014 and June 2018 across Sylhet-Bangladesh, Karachi-Pakistan, and Pemba Island-Tanzania. HbA1c assays were performed at enrollment (8 to < 20 gestational weeks), and epidemiological data were collected during 2-3 monthly household visits. The women were followed-up till the postpartum period to determine the pregnancy outcomes. Multivariable logistic regression models assessed the association between elevated HbA1c levels and adverse events while controlling for potential confounders. RESULTS: A total of 9,510 pregnant women were included in the analysis. The mean HbA1c level at enrollment was found to be the highest in Bangladesh (5.31 ± 0.37), followed by Tanzania (5.22 ± 0.49) and then Pakistan (5.07 ± 0.58). We report 339 stillbirths and 9,039 live births. Among the live births were 892 preterm births, 892 deliveries via cesarean section, and 532 LGA babies. In the multivariate pooled analysis, maternal HbA1c levels of ≥ 6.5 were associated with increased risks of stillbirths (aRR = 6.3, 95% CI = 3.4,11.6); preterm births (aRR = 3.5, 95% CI = 1.8-6.7); and Large for Gestational Age (aRR = 5.5, 95% CI = 2.9-10.6). CONCLUSION: Maternal HbA1c level is an independent risk factor for predicting adverse pregnancy outcomes such as stillbirth, preterm birth, and LGA among women in South Asia and Sub-Saharan Africa. These groups may benefit from early interventional strategies.

Neurodevelopmental outcomes following possible serious bacterial infection in early infancy in Karachi, Pakistan: a prospective cohort study.

BACKGROUND: Pakistan reports a significant burden of neonatal mortality, with infections as one of the major causes. We aim to assess the long-term impact of early infancy infections on neurodevelopmental outcomes during later childhood. METHODS: We conducted a prospective follow-up study of the cohort enrolled at the Karachi site of the Aetiology of Neonatal Infection in South Asia (ANISA) during 2019-2020. Children with a possible serious bacterial infection (based on the WHO IMCI algorithm) at early infancy were assessed for neurodevelopment at 6-9 years of age and compared with healthy controls. The Ten Questions (TQS) questionnaire, Strengths and Difficulties Questionnaire (SDQ), and Parent's Evaluation of Developmental Stage Assessment Level (PEDS: DM-AL) neurodevelopmental assessment tools, were administered and scored by the research staff who were blinded to the child's exposure status. Generalized Structural Equation Modelling (GSEM) was employed to verify relationships and associations among developmental milestones, anthropometry, and sociodemographic variables. RESULTS: A total of 398 children (241 cases and 157 controls) completed neurodevelopmental and growth assessments. Cases had a significantly higher rate of abnormal TQS scores (54.5% vs. 35.0%, p-value 0.001), greater delays in motor milestones (21.2% vs. 12.1%, p-value 0.02), lower fine motor skills (78.4 ± 1.4 vs. 83.2 ± 1.5, p-value 0.02). The receptive language skills were well-developed in both groups. According to the logistic regression model, exposure to infection during the first 59 days of life was associated with delayed TQS milestones (ß = -0.6, 95% CI -1.2,-0.04), TQS hearing domain (ß = -0.3, 95% CI: -1.2 to 0.7), PEDS: DM-AL fine motor domain (ß = -1.3, 95% CI: -4.4 to 1.7), PEDS: DM-AL receptive language development (ß = -1.1, 95% CI: -3.7 to 1.4) and child anthropometric measurements such as weight and height (ß = -0.2, 95% CI: -0.4 to 0.01 and ß = -0.2, 95% CI: -0.4 to -0.01, respectively). Early pSBI exposure was positively associated with PEDS: DM-AL self-help domain (ß = 0.6, 95% CI: -1.2 to 2.4) and SDQ-P overall score (ß = 0.02, 95% CI: -0.3 to 0.3). CONCLUSION: Children exposed to PSBI during early infancy have higher rates of abnormal development, motor delays, and lower fine motor skills during later childhood in Pakistan. Socioeconomic challenges and limited healthcare access contribute to these challenges, highlighting the need for long-term follow-ups with integrated neurodevelopment assessments.

Mobile healthcare simulation units: a narrative review.

For healthcare professionals working and living in geographical isolation, there are few opportunities to maintain skills and knowledge, and to update themselves with recent advances in care compared to their citydwelling peers. It is known that within a short period and limited practice, clinical skills erode. A mobile healthcare simulation unit provides high-quality, technologicallyenhanced, convenient, and affordable training for healthcare professionals under expert supervision in any remote setting. The current narrative review was planned to summarise the outcomes and challenges related to developing and effectively utilising mobile healthcare simulation units as experienced globally. A literature search was performed on PubMed, Google Scholar and Cochrane databases for relevant articles published between 2000 and 2020, which resulted in 18 articles that were shortlisted and three major themes. The identification of common strengths, weaknesses and challenges will be a starting point for those engaged in planning and operating such a centre in any location.

Factors associated with medical students' career choices at a private university: a cross-sectional study.

This study aimed to identify the factors associated with students' career choices and the decision whether they wanted to be trained abroad or in Pakistan. The study utilised a cross-sectional design and was conducted between July 2021 and February 2022. An anonymous survey was distributed among the medical students at Aga Khan University, Karachi, Pakistan. All analysis was carried out using Stata 17. A total of 269 students participated in the study. The most sought-after specialties were surgery 68 (25.3%), medicine 25(9.3%), and paediatrics 14(5.2%), and the decision was highly influenced by positive mentors and lifestyle. In addition, 259 (96%) of the students expressed a desire to practice abroad for training due to higher financial prospects and quality of training. This study revealed that providing enthusiastic mentors may encourage medical students to pursue a broader range of specialties. Furthermore, there is a need for advances in postgraduate training and increase in salaries to restore trust in Pakistan's healthcare system.

Student experiences of simulation-based learning and its impact on their performance in Objective Structured Clinical Examination in Pediatrics - A mixed method study.

Objective: This study aims to assess the effectiveness of integrating simulation for teaching pediatric clinical examination skills to undergraduate, MBBS Year-IV medical students at The Aga Khan University, Karachi, Pakistan. Methods: In this mixed method study, the Objective Structured Clinical Examination (OSCE) scores of the students who were taught using simulation (batch 2017-2018) were compared with the batch of the academic year 2016 -2017 (taught via traditional methods). In order to explore the experiences of the intervention group, a questionnaire with four open-ended questions was administered at the end of the clerkship. Results: Students who were taught by simulation, scored significantly higher on the clinical skills stations in Objective Structured Clinical Examination, than in the pre-intervention group (p-value <0.01). The students quoted safety of the learning environment, opportunities for deliberate practice, debriefing and facilitation skills maximized quoted that their experience of learning through simulation, however, some challenges were identified for future improvement. Conclusion: The result of the study suggested simulation as a useful instructional strategy for teaching examination skills to students in their early years. The student gained confidence through deliberate practice and feedback without compromising patient safety, which translated into improved performance in the high-stakes OSCE examination at the end of the clerkship.

Advance care plan discussion among parents of children with cerebral palsy.

AIM: To evaluate parental perception of advance care plan (ACP) discussions in families of Malaysian children with bilateral cerebral palsy (CP) classified in Gross Motor Function Classification System levels IV or V for (1) acceptance of the ACP discussion, (2) feedback on the usefulness of ACP discussion, and (3) exploration of possible factors related to parental acceptance of ACP. METHOD: This was a prospective pre- and post-ACP discussion questionnaire study for parents of children with bilateral CP. RESULTS: Sixty-nine patients were recruited to the study; 64 (93%) had at least one additional comorbidity. The median age was 8 years (interquartile range 5 years 1 month-11 years 6 months). Fifty-seven (82.6%) parents found the ACP discussion acceptable, and most reported positive feedback on various components of the discussion (88.4-97.1%). One-third of participants were not comfortable discussing end-of-life care plans. On multivariate analysis, parents who were comfortable discussing end-of-life care plans were more likely to find the ACP discussion acceptable (odds ratio 27.78, 95% confidence interval 2.9-265.1, p = 0.004). INTERPRETATION: Most parents of Malaysian children with bilateral CP reported the ACP discussion as both acceptable and beneficial. Parents need to be comfortable about discussing end-of-life care plans for their child to enable the ACP discussion to be an acceptable experience.

DISCUSIÓN SOBRE EL PLAN ANTICIPADO DE CUIDADOS CON PADRES DE NIÑOS CON PARÁLISIS CEREBRAL: OBJETIVO: Evaluar la percepción parental al discutir el Plan Anticipado de Cuidados (PAC) en familias de niños Malasios con parálisis cerebral bilateral (PC) niveles IV o V según el Sistema de Clasificación de la Función Motora Gruesa (GMFCS) para 1) Aceptación de la propuesta sobre el PAC, 2) opinión sobre la utilidad de discusión sobre el PAC y 3) exploración de posibles factores relacionados a la aceptación parental del PAC. MÉTODO: Se utilizó un estudio prospectivo con un cuestionario pre y post discusión sobre el PAC con padres de niños con PC bilateral. RESULTADOS: Se reclutaron sesenta y nueve pacientes para este estudio; 64 (93%) tenían como mínimo una comorbilidad adicional. La edad mediana fue 8 años (rango intercuartilo 5 años y 1 mes - 11 años y 6 meses). Cincuenta y siete (82,6%) padres hallaron aceptable la discusión sobre el PAC y la mayoría reportó una opinión positiva sobre varios componentes de la discusión (88,4 - 97,1%). Un tercio de los participantes no se sintieron bien discutiendo planes sobre cuidados del paciente terminal. Utilizando análisis multivariable, los padres que se sintieron cómodos discutiendo planes sobre cuidados del paciente terminal, con mayor probabilidad hallaron aceptable la discusión sobre el PAC (relación de probabilidades 27,78 (95%) Intervalo de confidencia 2,9-265,1, p=0,004). INTERPRETACIÓN: La mayoría de los padres de niños Malasios con PC bilateral reportaron la discusión sobre el PAC como aceptable y beneficioso. Los padres necesitan sentirse cómodos discutiendo planes sobre cuidados del paciente con múltiples comorbilidades, referidos a su hijo, a fin de permitir que la discusión sobre el PAC sea una experiencia aceptable.

'Mammy's supposed to be strong and supportive - not sitting in a corner rocking and crying': an interpretative phenomenological analysis of British mothers' experiences of postnatal depression.

OBJECTIVE: To gain an in-depth understanding of the lived experience of women with postnatal depression (PND). BACKGROUND: Although there is a small body of existing research which explores subjective experience of this phenomenon, relatively little research has been carried out and is prior to the publication of the NICE guidelines for PND in 2007. METHOD: Semi-structured interviews were carried out with six mothers (aged 23-40 years), who had taken part in a PND support group. Verbatim transcripts were analysed using Interpretative Phenomenological Analysis (IPA). RESULTS: One broad superordinate theme of 'the conflicted mother' emerged from the data, with four corresponding sub-themes (own mother as absent and judgemental; internalised mother; pregnancy on the road to motherhood as an unpleasant stranger; the ideal mother). CONCLUSION: It is argued that a broad umbrella construct of 'the conflicted mother' exists in PND experience. This study highlights the importance of the mother's own maternal relationship in living with depression. The authors discuss limitations of the study, make service recommendations to improve current clinical practice for women with PND, and provide future research directions.

Compassionate Healthcare for Parents of Children with Life-limiting Illnesses: A Qualitative Study.

Objectives: Premature death of a child from a serious illness is probably one of the most painful experiences for a parent. This study examined the clinical experiences of bereaved parents of children with a life-limiting illness to provide recommendations for quality care. Materials and Methods: Data were collected using semi-structured in-depth interviews with bereaved parents whose children had died at least 3 months before the interview. Parents were purposively sampled from two institutions offering end-of-life care to children with life-limiting illnesses. Data were analysed using thematic analysis. Results: Data analysis revealed three main themes: (1) Clinical communication, (2) Healthcare infrastructure and (3) Non-physical aspects of healthcare. The seven subthemes uncovered were as follows: (1) Honesty and clarity, (2) empathy, (3) interdisciplinary communication, (4) inconveniences in hospital, (5) home palliative care, (6) financial burden of illness and (7) psychosocial and spiritual support. Conclusion: Strategies to improve healthcare for children and their families are multifold. Underlying the provision of quality care is compassion; a child and family-friendly healthcare system with compassionate providers and compassionate institutional policies are vital components to achieving quality healthcare. Culturally sensitive psychosocial, emotional and spiritual support will need to be integrated as standard care.

Machine learning guided postnatal gestational age assessment using new-born screening metabolomic data in South Asia and sub-Saharan Africa.

BACKGROUND: Babies born early and/or small for gestational age in Low and Middle-income countries (LMICs) contribute substantially to global neonatal and infant mortality. Tracking this metric is critical at a population level for informed policy, advocacy, resources allocation and program evaluation and at an individual level for targeted care. Early prenatal ultrasound examination is not available in these settings, gestational age (GA) is estimated using new-born assessment, last menstrual period (LMP) recalls and birth weight, which are unreliable. Algorithms in developed settings, using metabolic screen data, provided GA estimates within 1-2 weeks of ultrasonography-based GA. We sought to leverage machine learning algorithms to improve accuracy and applicability of this approach to LMICs settings. METHODS: This study uses data from AMANHI-ACT, a prospective pregnancy cohorts in Asia and Africa where early pregnancy ultrasonography estimated GA and birth weight are available and metabolite screening data in a subset of 1318 new-borns were also available. We utilized this opportunity to develop machine learning (ML) algorithms. Random Forest Regressor was used where data was randomly split into model-building and model-testing dataset. Mean absolute error (MAE) and root mean square error (RMSE) were used to evaluate performance. Bootstrap procedures were used to estimate confidence intervals (CI) for RMSE and MAE. For pre-term birth identification ROC analysis with bootstrap and exact estimation of CI for area under curve (AUC) were performed. RESULTS: Overall model estimated GA had MAE of 5.2 days (95% CI 4.6-6.8), which was similar to performance in SGA, MAE 5.3 days (95% CI 4.6-6.2). GA was correctly estimated to within 1 week for 85.21% (95% CI 72.31-94.65). For preterm birth classification, AUC in ROC analysis was 98.1% (95% CI 96.0-99.0; p < 0.001). This model performed better than Iowa regression, AUC Difference 14.4% (95% CI 5-23.7; p = 0.002). CONCLUSIONS: Machine learning algorithms and models applied to metabolomic gestational age dating offer a ladder of opportunity for providing accurate population-level gestational age estimates in LMICs settings. These findings also point to an opportunity for investigation of region-specific models, more focused feasible analyte models, and broad untargeted metabolome investigation.

Red blood cell transfusion in critically-ill children and its association with outcome.

OBJECTIVE: To determine the indications and threshold of haemoglobin levels for packed red blood cell transfusion and its association with outcomes in a paediatric intensive care setting. METHODS: The retrospective study was conducted in the paediatric intensive care unit of the Aga Khan University Hospital, Karachi, and comprised medical records of all inpatients with age between 1 month and 16 years who received packed red blood cell transfusions between January and December 2017. Data was retrieved from the hospital database and was analyzed using SPSS 22. RESULTS: Of the 147 subjects with a mean age of 67.89±65.8 months, 76(51.7%) were males. Mean paediatric risk of mortality score was 11.72±7.86. Major admitting diagnosis included sepsis and multiorgan dysfunction 50(34%), respiratory diseases 26(17.7%) and haematology/oncology diseases 22(15%). The indications for transfusion was low haemoglobin in 90(61.2%) patients, shock 29(19.7%) and hypoxia 28(19%). Acute transfusion reaction was observed in 1(0.7%) patient; 120(82%) required mechanical ventilation; and 94(64%) required inotropic support. Of the total, 88(59.9%) patients survived. Paediatric risk of mortality score, need for inotropic support and mechanical ventilation were associated with mortality (p<0.05). CONCLUSIONS: Packed red blood cell transfusion, which is frequently prescribed in intensive care settings, was not found to be associated with favourable outcome.

Genomic and biological characteristics of Avian Orthoavulavirus-1 strains isolated from multiple wild birds and backyard chickens in Pakistan.

Circulation of the dominant sub-genotype VII.2 of Avian Orthoavulavirus-1 (AOAV-1) is affecting multiple poultry and non-poultry avian species and causing significant economic losses to the poultry industry worldwide. In countries where ND is endemic, continuous monitoring and characterization of field strains are necessary. In this study, genetic characteristics of eleven AOAV-1 strains were analyzed isolated from wild birds including parakeets (n = 3), lovebird parrot (n = 1), pheasant (n = 1), peacock (n = 1), and backyard chickens (n = 5) during 2015-2016. Genetic characterization (genome size [15,192 nucleotides], the presence of typical cleavage site [112-RRQKRF-117]) and biological assessment (HA log 27 to 29 and intracerebral pathogenicity index [ICPI] value ranging from 1.50 to 1.86) showed virulent AOAV-1. Phylogenetic analysis showed that the studied isolates belonged to sub-genotype VII.2 and genetically very closely related (> 98.9%) to viruses repeatedly isolated (2011-2018) from commercial poultry. These findings provide evidence for the existence of epidemiological links between poultry and wild bird species in the region where the disease is prevalent. The deduced amino acid analysis revealed several substitutions in critical domains of fusion and hemagglutinin-neuraminidase genes. The pathogenesis and transmission potential of wild bird-origin AOAV-1 strain (AW-Pht/2015) was evaluated in 21-day-old chickens that showed the strain was highly virulent causing clinical signs and killed all chickens. High viral loads were detected in different organs of the infected chickens correlating with the severity of lesions developed. The continuous monitoring of AOAV-1 isolates in different species of birds will improve our knowledge of the evolution of these viruses, thereby preventing possible panzootic.

Possibility of extending biopharmaceutics classification system based biowaiver to BCS class IIa drug.

Biowaiver studies have been performed to assess the bioequivalence of two drug products. Ibuprofen is a Biopharmaceutics Classification System (BCS) class IIa drug (Low solubility - High permeability) used as analgesic, antipyretic and anti-inflammatory agent. World Health Organization (WHO) placed ibuprofen in the category of biowaiver drugs but Food and drug authority (FDA) and International Council for Harmonization (ICH) has not issued yet any guidelines regarding the biowaiver of BCS class II drugs. Present study was aimed to formulate immediate release (IR) Ibuprofen 600 mg tablets with variable disintegrants. All trial film coated formulations were evaluated physicochemically with in-vitro bioequivalence studies in three buffer mediums (pH 6.8, pH 4.5 and pH 1.2). Samples were analyzed spectrophotometrically at 221 nm and model independent approaches (dissimilarity (f1), similarity (f2;) and Boot strap) was applied to assess the observed similarity. The similarity factor (f2;) was achieved only in pH 1.2 in three trial formulations and met acceptance criteria (f2; 50-100) although the amount of drug release was negligible. This investigation revealed that for BCS class IIa drug (ibuprofen), subsequent analysis of excipients used, pKa of drug and method of manufacturing should also be considered to ensure bioequivalence for a successful biowaiver study.

National Pediatric Palliative Care Needs from Hospital Deaths.

OBJECTIVE: The objective of this study was to estimate palliative care needs and to describe the cohort of children with life-limiting illnesses (LLI) dying in hospitals. DESIGN: This study was a retrospective cohort study. The national hospital admissions database was reviewed and children who had died who had life-limiting illnesses were identified. SETTING: This study was conducted at Ministry of Health hospitals, Malaysia. PATIENTS: Children aged 18 years and below who had died between January 1, 2012 and December 31, 2014. MAIN OUTCOME MEASURES: Life-limiting diagnoses based on Hain et al.'s directory of LLI or the ACT/RCPCH categories of life-limiting disease trajectories. RESULTS: There were 8907 deaths and 3958 (44.4%) were that of children with LLI. The majority, 2531 (63.9%) of children with LLI were neonates, and the most common diagnosis was extreme prematurity <28 weeks with 676 children (26.7%). For the nonneonatal age group, the median age at admission was 42 months (1-216 months). A majority, 456 (32.0%) had diagnoses from the ICD-10 chapter "Neoplasms" followed by 360 (25.3%) who had a diagnoses from "Congenital malformations, deformations, and chromosomal abnormalities" and 139 (9.7%) with diagnoses from "Disease of the nervous system." While a majority of the terminal admissions were to the general ward, there were children from the nonneonatal age group, 202 (14.2%) who died in nonpediatric wards. CONCLUSION: Understanding the characteristics of children with LLI who die in hospitals could contribute toward a more efficient pediatric palliative care (PPC) service development. PPC service should include perinatal and neonatal palliative care. Palliative care education needs to extend to nonpediatric healthcare providers who also have to manage children with LLI.

Formulation design, characterization and optimization of cinitapride (1mg) immediate release tablets using direct compression technology.

Cinitapride hydrogen tartarate is relatively a new prokinetic agent that widely prescribed for GERD and epigastric pain. Present study was aimed to develop and optimize cinitapride (1 mg) immediate release (IR) tablet formulation(s) by direct compression using central composite rotatable technique. Overall nine formulations (FC1-FC9) were generated by varying the composition of binder avicel PH 102 (X1) and superdisintegrant crospovidone (X2). The effect of interaction of excipients on hardness (Y1), friability (Y2), disintegration (Y3) and dissolution at 15 min (Y4) were analyzed by RSM plotting. On the basis of physico-chemical evaluation FC3, FC4 and FC6 were found to be the optimized formulations however; FC3 was selected to be the best trial owing to excellent drug release (100.17%) with least friability (0.14%). These IR tablets showed the release pattern similar to the Weibull model with r2 value of 0.978-0.998. The dissimilarity (f1) and similarity indexes (f2) of FC3, FC4, FC6 with the marketed product were estimated to be 2.57 and 76.51, 4.51 and 64.46, 4.32 and 66.78 respectively. Trial optimized formulations were highly stable with the shelf lives of 58-64 months. So, keeping in view the results of present investigation, it is concluded that the technique of manufacturing and optimization is found to be excellent for developing immediate release cinitapride tablets.

The Six-Food Elimination Diet for Eosinophilic Esophagitis Increases Grocery Shopping Cost and Complexity.

The six-food elimination diet (SFED), where dairy, wheat, eggs, soy, nuts, and seafood are avoided, is an effective treatment for eosinophilic esophagitis (EoE). Patient-related costs of this approach, however, are unknown. We aimed to assess the cost of and ease of shopping for an SFED compared to an unrestricted diet. A dietitian with expertise in EoE generated menus meeting dietary requirements for a week's worth of meals for the SFED and an unrestricted diet. We compared prices and the number of missing items for both diets at standard and specialty grocery stores. The average weekly price of the SFED at a standard supermarket was $92.54 compared to $79.84 for an unrestricted diet (p = 0.0001). A patient shopping at a standard grocery store needed a higher proportion of items from a second store compared to an unrestricted diet (32 vs. 3 %, p = 0.0001). The prices of the SFED and unrestricted diet using a specialty supermarket were comparable ($106.47 vs. $105.96, p = 0.81), as was the percentage of items requiring a trip to a second store (6 vs. 2 % items, p = 0.03). Shopping at a specialty grocery store increased weekly grocery costs by $13.93 (p = 0.04) for the SFED and $26.12 (p = 0.03) for the unrestricted diet. In conclusion, for patients shopping at standard grocery stores, the cost of an SFED is higher, and an SFED requires more items from a second store. These differences disappear at specialty grocery stores, but costs were significantly higher. This cost and logistical burden can inform patients when selecting dietary therapy.

Secondary attack rates and determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) household transmission in Pakistan: A case-ascertained prospective, longitudinal study.

BACKGROUND: Households are considered ideal settings for studying the transmission dynamics of an infectious disease. METHODS: A prospective study was conducted, based on the World Health Organization FFX protocol from October 2020 to January,2021. Household contacts of laboratory-confirmed index cases were followed up for their symptomatic history, nasal swabs for RT-PCR,and blood samples for anti-SARS CoV-2 antibodies were collected at enrollment and days 7, 14 and 28. We estimated secondary attack rate (SAR), effective household case cluster size and determinants of secondary infection among susceptible household contacts using multivariable logistic regression. RESULTS: We enrolled 77 index cases and their 543 contacts. Out of these, 252 contacts were susceptible at the time of enrollment. There were 77 household clusters, out of which, transmission took place in 20 (25.9%) giving rise to 34 cases. The acquired secondary attack rate (SAR) was 14.0% (95% CI 9.0-18.0). The effective household case cluster size was 0.46 (95%CI 0.33,0.56). Reported symptoms of nausea and vomiting (aOR, 7.9; 95% CI, 1.4-45.5) and fatigue (aOR, 9.3; 95% CI, 3.8-22.7) were associated with SARS-CoV-2 transmission. CONCLUSIONS: We observed a low SARS-CoV-2 secondary attack rate in the backdrop of high seroprevalence and asymptomatic transmission among households in Karachi, Pakistan.

Environmental surveillance for COVID-19 using SARS-CoV-2 RNA concentration in wastewater - a study in District East, Karachi, Pakistan.

Background: Wastewater-based surveillance is used to track the temporal patterns of the SARS-CoV-2 virus in communities. Viral RNA particle detection in wastewater samples can indicate an outbreak within a catchment area. We describe the feasibility of using a sewage network to monitor SARS-CoV-2 trend and use of genomic sequencing to describe the viral variant abundance in an urban district in Karachi, Pakistan. This was among the first studies from Pakistan to demonstrate the surveillance for SARS-CoV-2 from a semi-formal sewage system. Methods: Four sites draining into the Lyari River in District East, Karachi, were identified and included in the current study. Raw sewage samples were collected early morning twice weekly from each site between June 10, 2021 and January 17, 2022, using Bag Mediated Filtration System (BMFS). Secondary concentration of filtered samples was achieved by ultracentrifugation and skim milk flocculation. SARS-CoV-2 RNA concentrations in the samples were estimated using PCR (Qiagen ProMega kits for N1 & N2 genes). A distributed-lag negative binomial regression model within a hierarchical Bayesian framework was used to describe the relationship between wastewater RNA concentration and COVID-19 cases from the catchment area. Genomic sequencing was performed using Illumina iSeq100. Findings: Among the 151 raw sewage samples included in the study, 123 samples (81.5%) tested positive for N1 or N2 genes. The average SARS-CoV-2 RNA concentrations in the sewage samples at each lag (1-14 days prior) were associated with the cases reported for the respective days, with a peak association observed on lag day 10 (RR: 1.15; 95% Credible Interval: 1.10-1.21). Genomic sequencing showed that the delta variant dominated till September 2022, while the omicron variant was identified in November 2022. Interpretation: Wastewater-based surveillance, together with genomic sequencing provides valuable information for monitoring the community temporal trend of SARS-CoV-2. Funding: PATH, Bill & Melinda Gates Foundation, and Global Innovation Fund.

Maternal and Paternal Attachment Patterns in Pakistani Internet Users During COVID-19.

With ever-growing Internet penetration and increasing numbers of social media applications, the apprehensions around problematic use of the Internet among young adults are rising. Among the determinants of problematic Internet use (PIU), parental attachment toward both fathers and mothers is considered significant. However, research in Pakistan, despite growing numbers of Internet users, is either insufficient or methodologically challenged. This study aims to address these gaps by using improved methodology to study PIU and parental attachment among young adults while also accounting for the impact of psychological distress due to COVID-19. Using a correlational quantitative research design, we recruited a total of 142 young adults (>18 years) residing in Pakistan, with no previous psychiatric history, who were asked to complete the Generalized Problematic Internet Use Scale-2, Experiences in Closed Relationships-Relationships Structures scale, and Kessler Psychological Distress Scale-10 (K10). Results showed that psychological distress had a significant positive association with PIU and paternal attachment had a significant positive association with PIU. Regression analysis showed that only duration of Internet use and psychological distress were significant predictors in the model and that parental attachment was nonsignificant. Furthermore, securely attached individuals reported significantly less psychological distress than those with fearful-avoidant and dismissive attachment styles. Therefore, our results show that general parental attachments are associated with psychological distress and psychological distress is associated with PIU. The implications of these findings are discussed.

Efficacy and Tolerability of Semaglutide in Patients With Type-2 Diabetes Mellitus: Experience of a Tertiary Care Hospital, Pakistan.

Background: Semaglutide, a Glucagon-like peptide 1 (GLP-1) is highly effective as an anti-diabetic medication along with additional benefits of significant reduction in cardiovascular events and weight. Objectives: There is a lack of reliable evidence confirming the benefits of Semaglutide in the Pakistani cohort. Our study aims to ascertain the efficacy of Semaglutide in the Pakistani cohort and patient satisfaction. Methods: An ambi-directional cohort study was conducted from August 2022 to January 2023 at The Aga Khan University Hospital, Karachi, Pakistan. A chart review was done for all patients with Type 2 diabetes who were prescribed Semaglutide, and baseline data was recorded. Patients were followed prospectively in the endocrinology clinics after at least 3 months for the change in HbA1c, BMI, adverse effects profile, treatment satisfaction questionnaire for medications (TSQM-9) and medication effect score. Mean + STD or median with IQR were computed for continuous data, while categorical variables and percentages were measured. The association between variables was assessed by applying the chi-square test. Results: A total of 112 patients were recruited who took the medication for at least 3 months. The mean age of the patients was 50.9 ± 10.5 years with 51.2% females. The mean difference in weight, body mass index, fasting blood glucose, HbA1c, and medication effect score were decreasing from baseline to follow-up (-4.0 kg, -1.5 kg/m2, -23.1 mg/dl, -1.2%, -0.4) respectively. A decrease in appetite was reported in 72.7% of the participants. The major adverse effects observed were dyspepsia (21.4%) followed by nausea (20.5%) and constipation (19.6%). Medication was discontinued in 9.8% of patients due to gastrointestinal side effects. The majority (72.3%) of patients were satisfied with their medication. Conclusion: Semaglutide is effective in reducing HbA1c and weight in Pakistani population with measurable tolerability and patient satisfaction.

Frequency and Risk Factors of Permanent Hypoparathyroidism After Total Thyroidectomy: An Experience at a Tertiary Care Hospital in Pakistan.

OBJECTIVES: Thyroid surgeries are among the most common operations performed in the world. Hypocalcemia following total thyroidectomy (TT) is a common complication that is sometimes difficult to correct. This study aims to determine the frequency of hypocalcemia and permanent hypoparathyroidism (PtHPT) following TT. METHODS: A total of 363 patient records were reviewed who underwent TT for any reason. Thirty-eight patients did not have a follow-up in the clinic in the postoperative period and were excluded from the final analysis with the final sample as 325. For patients who developed hypocalcemia during the postoperative hospital stay, their lowest calcium levels were recorded and medical records were reviewed for the period of one year for the requirement of oral calcium and active form of vitamin D (calcitriol or alpha calcidiol) in the outpatient setting. Patients who required calcium and vitamin D supplementation for up to 1 year were labeled as having PtHPT. Risk factors were analyzed among those who developed PtHPT. RESULTS: From a total of 325 patients postoperative hypocalcemia developed in 163 (50.2%) patients, and 162 (49.8%) patients remained normocalcemic. Permanent hypoparathyroidism was found in 42(12.9%) patients and transient HPT in 121 (37.2%). Age, severe postoperative hypocalcemia (PoHC), and readmission for hypocalcemia were independent risk factors for PtHPT. CONCLUSIONS: Transient hypoparathyroidism (THPT) is common in our setup. Patients who develop severe hypocalcemia postoperatively and need readmission should be closely followed for the development of PtHPT.