Effect of Maternal and Newborn Care Service Package on Perinatal and Newborn Mortality: A Cluster Randomized Clinical Trial.

Importance: In resource-constrained settings where the neonatal mortality rate (NMR) is high due to preventable causes and health systems are underused, community-based interventions can increase newborn survival by improving health care practices. Objectives: To develop and evaluate the effectiveness of a community-based maternal and newborn care services package to reduce perinatal and neonatal mortality in rural Pakistan. Design, Setting, and Participants: This cluster randomized clinical trial was conducted between November 1, 2012, and December 31, 2013, in district Rahim Yar Khan in the province of Punjab. A cluster was defined as an administrative union council. Any consenting pregnant resident of the study area, regardless of gestational age, was enrolled. An ongoing pregnancy surveillance system identified 12 529 and 12 333 pregnancies in the intervention and control clusters, respectively; 9410 pregnancies were excluded from analysis due to continuation of pregnancy at the end of the study, loss to follow-up, or miscarriage. Participants were followed up until the 40th postpartum day. Statistical analysis was performed from January to May 2014. Intervention: A maternal and newborn health pack, training for community- and facility-based health care professionals, and community mobilization through counseling and education sessions. Main Outcomes and Measures: The primary outcome was perinatal mortality, defined as stillbirths per 1000 births and neonatal death within 7 days per 1000 live births. The secondary outcome was neonatal mortality, defined as death within 28 days of life per 1000 live births. Systematic random sampling was used to allocate 10 clusters each to intervention and control groups. Analysis was conducted on a modified intention-to-treat basis. Results: For the control group vs the intervention group, the total number of households was 33 188 vs 34 315, the median number of households per cluster was 3092 (IQR, 3018-3467) vs 3469 (IQR, 3019-4075), the total population was 229 155 vs 234 674, the mean (SD) number of residents per household was 6.9 (9.5) vs 6.8 (9.6), the number of males per 100 females (ie, the sex ratio) was 104.2 vs 103.7, and the mean (SD) number of children younger than 5 years per household was 1.0 (4.2) vs 1.0 (4.3). Altogether, 7598 births from conrol clusters and 8017 births from intervention clusters were analyzed. There was no significant difference in perinatal mortality between the intervention and control clusters (rate ratio, 0.86; 95% CI, 0.69-1.08; P = .19). The NMR was lower among the intervention than the control clusters (39.2/1000 live births vs 52.2/1000 live births; rate ratio, 0.75; 95% CI, 0.58-0.95; P = .02). The frequencies of antenatal visits and facility births were similar between the 2 groups. However, clean delivery practices were higher among intervention clusters than control clusters (63.2% [2284 of 3616] vs 13.2% [455 of 3458]; P < .001). Chlorhexidine use was also more common among intervention clusters than control clusters (55.9% [4271 of 7642] vs 0.3% [19 of 7203]; P < .001). Conclusions and Relevance: This pragmatic cluster randomized clinical trial demonstrated a reduction in NMR that occurred in the background of improved household intrapartum and newborn care practices. However, the effect of the intervention on antenatal visits, facility births, and perinatal mortality rates was inconclusive, highlighting areas requiring further research. Nevertheless, the improvement in NMR underscores the effectiveness of community-based programs in low-resource settings. Trial Registration: ClinicalTrials.gov Identifier: NCT01751945.

Outcomes of oncoplastic breast surgery compared to breast-conserving surgery in breast cancer patients in a developing country: a retrospective cohort study.

Background and Objective: Breast-conserving surgery (BCS) with adjuvant radiotherapy remains the standard of care for early breast cancers in Pakistan. We sought to compare the outcomes of BCS with oncoplastic surgery (OPS), a relatively infrequent approach to breast cancer treatment in the country. Methods: This retrospective cohort study was conducted at Aga Khan University Hospital and Ziauddin Hospital in Karachi. Patients who had biopsy-proven Stage-I to III breast cancer and underwent either OPS or BCS between August 1, 2016, and December 31, 2021, were identified and followed for 30 days. Data were collected by reviewing patient files and electronic records. Results: A total of 481 patients were included in the study, where 204 (42.4%) underwent BCS and 277 (57.6%) underwent OPS. Mean tumor volume (146.8 vs. 90.4 cm3), and postoperative complications (2.2 % vs. 0%) were higher in OPS while the frequency of positive margins was greater in the BCS group (15.7 % vs. 2.2 %). There were no significant differences in the histologic type of tumor between the two groups. Conclusion: OPS is a valid alternative approach to breast cancer treatment that can be offered to women with early stage, locally advanced, multifocal or tumors at complex locations owing to the reduced occurrence of positive margins and thus lowered re-excision rates.

Exploring the long-term seroprevalence of SARS-CoV-2 antibodies in infants born to women with clinical or laboratory-confirmed COVID-19.

INTRODUCTION: Infants are at a higher risk of severe illness with COVID-19 infection compared to older children. While COVID-19 vaccination is not recommended for young infants, they can acquire maternally-derived anti-SARS-CoV-2 antibodies passively through the placenta and breastmilk. We described the persistence of infection-induced maternal antibodies in infant circulation at 9-12 months of age. METHODOLOGY: This was a cross-sectional study nested within the INTERCOVID multinational cohort study. For each COVID positive pregnant woman, two unmatched consecutive COVID negative pregnant women were enrolled between April and September 2020. Women with a positive PCR test, radiographic signs consistent with COVID-19, or at least 2 predefined symptoms of COVID-19 were considered as COVID positive. For this nested cross-sectional study, all COVID positive and either one of the COVID negative participants recruited from the Aga Khan University, Pakistan were approached 9-12 months after delivery, and maternal and infant sera were collected for antibody detection. RESULTS: Altogether, 83 mothers provided consent, of whom 32 (38.6 %) were COVID positive and 51 (61.4 %) were COVID negative during pregnancy. Anti-SARS-CoV-2 antibodies were present in 13 (41 %) infants born to COVID positive and 19 (39 %) infants born to COVID negative mothers (p = 0.87). The presence of reactive antibodies in infants at follow-up was associated with maternal antibodies at follow-up (OR:9.50, 95 % CI:2.03-44.42; p = 0.004). COVID infection occurred in 3 (6 %) infants born to COVID negative mothers while no infant born to a COVID positive mother had a history of infection (p = 0.27). CONCLUSION: The presence of reactive anti-SARS-CoV-2 antibodies in infants at 9-12 months of age is associated with maternal seropositivity 9-12 months after delivery rather than maternal infection during pregnancy. Further studies are required to validate these findings and assess whether passive immunity in infants is protective against COVID-19 infection.

Risk factors for acute diarrhoea in children between 0 and 23 months of age in a peri-urban district of Pakistan: a matched case-control study.

BACKGROUND: Diarrhoea is a leading cause of preventable childhood morbidity and mortality worldwide. Unfortunately, Pakistan has the third-highest burden of diarrhoea-related deaths in children <5 y of age. Therefore we aimed to evaluate factors associated with diarrhoea among Pakistani children. METHODS: A retrospective 1:2 matched case-control study nested in a baseline cross-sectional survey was conducted from October to December 2018 in Taluka Kotri, a two-thirds urban locality in the Jamshoro district. Children between the ages of 0 and 23 months with a history of diarrhoea in the 2 weeks preceding the survey were labelled as cases. Age-matched controls were children without symptoms of diarrhoea. Univariate and multivariable conditional logistic regression was performed to identify diarrhoea-related factors. RESULTS: A total of 1558 cases were matched with 3116 controls. Factors significantly associated with lower odds of diarrhoea in the multivariate analysis included increasing maternal age (odds ratio [OR] 0.78 [95% confidence interval {CI} 0.67 to 0.90]), breastfeeding (OR 0.77 [95% CI 0.66 to 0.90]), higher paternal education (OR 0.79 [95% CI 0.65 to 0.97]) and belonging to the rich (OR 0.66 [95% CI 0.54 to 0.80]) and richest quintiles (OR 0.54 [95% CI 0.44 to 0.66]). CONCLUSIONS: This study identifies risk factors associated with diarrhoea in children <23 months of age, including younger maternal age, higher paternal education, not breastfeeding and poverty, which has implications for developing preventive programs and strategies that target populations with a higher risk of diarrhoea.

Diagnostic accuracy of artificial intelligence for detecting gastrointestinal luminal pathologies: A systematic review and meta-analysis.

Background: Artificial Intelligence (AI) holds considerable promise for diagnostics in the field of gastroenterology. This systematic review and meta-analysis aims to assess the diagnostic accuracy of AI models compared with the gold standard of experts and histopathology for the diagnosis of various gastrointestinal (GI) luminal pathologies including polyps, neoplasms, and inflammatory bowel disease. Methods: We searched PubMed, CINAHL, Wiley Cochrane Library, and Web of Science electronic databases to identify studies assessing the diagnostic performance of AI models for GI luminal pathologies. We extracted binary diagnostic accuracy data and constructed contingency tables to derive the outcomes of interest: sensitivity and specificity. We performed a meta-analysis and hierarchical summary receiver operating characteristic curves (HSROC). The risk of bias was assessed using Quality Assessment for Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Subgroup analyses were conducted based on the type of GI luminal disease, AI model, reference standard, and type of data used for analysis. This study is registered with PROSPERO (CRD42021288360). Findings: We included 73 studies, of which 31 were externally validated and provided sufficient information for inclusion in the meta-analysis. The overall sensitivity of AI for detecting GI luminal pathologies was 91.9% (95% CI: 89.0-94.1) and specificity was 91.7% (95% CI: 87.4-94.7). Deep learning models (sensitivity: 89.8%, specificity: 91.9%) and ensemble methods (sensitivity: 95.4%, specificity: 90.9%) were the most commonly used models in the included studies. Majority of studies (n = 56, 76.7%) had a high risk of selection bias while 74% (n = 54) studies were low risk on reference standard and 67% (n = 49) were low risk for flow and timing bias. Interpretation: The review suggests high sensitivity and specificity of AI models for the detection of GI luminal pathologies. There is a need for large, multi-center trials in both high income countries and low- and middle- income countries to assess the performance of these AI models in real clinical settings and its impact on diagnosis and prognosis. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=288360], identifier [CRD42021288360].

Impact of a standardised parenteral nutrition protocol: a quality improvement experience from a NICU of a developing country.

OBJECTIVE: Nutrition societies recommend using standardised parenteral nutrition (SPN) solutions. We designed evidence-based SPN formulations for neonates admitted to our neonatal intensive care unit (NICU) and evaluated their outcomes. DESIGN: This was a quality improvement initiative. Data were collected retrospectively before and after the intervention. SETTING: A tertiary-care level 3 NICU at the Aga Khan University in Karachi, Pakistan. PATIENTS: All NICU patients who received individualised PN (IPN) from December 2016 to August 2017 and SPN from October 2017 to June 2018. INTERVENTIONS: A team of neonatologists and nutrition pharmacists collaborated to design two evidence-based SPN solutions for preterm neonates admitted to the NICU. MAIN OUTCOME MEASURES: We recorded mean weight gain velocity from days 7 to 14 of life. The other outcomes were change in weight expressed as z-scores, metabolic abnormalities, PN-associated liver disease (PNALD), length of NICU stay and episodes of sepsis during hospital stay. RESULTS: Neonates on SPN had greater rate of change in weight compared with IPN (ß=13.40, 95% CI: 12.02 to 14.79) and a smaller decrease in z-scores (p<0.001). Neonates in the SPN group had fewer hyperglycemic episodes (IPN: 37.5%, SPN: 6.2%) (p<0.001), electrolyte abnormalities (IPN: 56.3%, SPN: 21%) (p<0.001), PNALD (IPN: 52.5%, SPN: 18.5%) (p<0.001) and sepsis (IPN: 26%, SPN: 20%) (p<0.05). The median length of stay in NICU was 14.0 (IQR 12.0-21.0) for the IPN and 8.0 (IQR 5.0-13.0) days for the SPN group. CONCLUSIONS: We found that SPN was associated with shorter NICU stay and greater weight gain. In-house preparation of SPN can be used to address the nutritional needs in resource-limited settings where commercially prepared SPN is not available.

Evaluation the Effectiveness of Abridged IMNCI (7-Day) Course v Standard (11-Day) Course in Pakistan.

BACKGROUND: The conventional IMCI training for healthcare providers is delivered in 11 days, which can be expensive and disruptive to the normal clinical routines of the providers. An equally effective, shorter training course may address these challenges. METHODS: We conducted a quasi-experimental study in two provinces (Sindh and Punjab) of Pakistan. 104 healthcare providers were conveniently selected to receive either the abridged (7-day) or the standard (11-day) training. Knowledge and clinical skills of the participants were assessed before, immediately on conclusion of, and six months after the training. RESULTS: The improvement in mean knowledge scores of the 7-day and 11-day training groups was 31.6 (95% CI 24.3, 38.8) and 29.4 (95% CI 23.9, 34.9) respectively, p = 0.630 while the improvement in mean clinical skills scores of the 7-day and 11-day training groups was 23.8 (95% CI: 19.3, 28.2) and 23.0 (95% CI 18.9, 27.0) respectively, p = 0.784. The decline in mean knowledge scores six months after the training was - 12.4 (95% CI - 18.5, - 6.4) and - 6.4 (95% CI - 10.5, - 2.3) in the 7-day and 11-day groups respectively, p = 0.094. The decline in mean clinical skills scores six months after the training was - 6.3 (95% CI - 11.3, - 1.3) in the 7-day training group and - 9.1 (95% CI - 11.5, - 6.6) in the 11-day group, p = 0.308. CONCLUSION: An abridged IMNCI training is equally effective as the standard training. However, training for certain illnesses may be better delivered by the standard course.

Outcomes of preterm neonates with patent ductus arteriosus: A retrospective review from a tertiary care hospital.

The management of patent ductus arteriosus (PDA) in preterm neonates remains controversial. A retrospective review was conducted to determine the outcomes in preterm neonates with PDA. Data of neonates admitted to the Aga Khan University Hospital from January 2012 to December 2016 were retrieved from patient records. Of the 208 neonates included in the study, 143 (68.7%) received no treatment, while 65 (31.2%) underwent pharmacotherapy and/or surgical ligation for PDA closure. PDA closure was spontaneous in 109 (52.4%) neonates. The mean ±SD gestational age (GA) of neonates with spontaneous ductal closure was greater as compared to those who required some form of treatment [33±3.3 vs 29.7±3.1weeks, p=0.001]. Apnoea (OR:4.47; 95% CI:1.21-16.44), sepsis (OR:3.81; 95% CI:1.33-10.87), pulmonary haemorrhage (OR:4.88; 95% CI:1.24-19.19), and lower APGAR (OR:0.69; 95% CI:0.54-0.90) were associated with higher odds of mortality in our cohort. Our findings demonstrate that PDA resolves spontaneously in most preterm neonates and provide evidence that conservative treatment is not associated with mortality.

Diagnostic Accuracy of Machine Learning Models to Identify Congenital Heart Disease: A Meta-Analysis.

Background: With the dearth of trained care providers to diagnose congenital heart disease (CHD) and a surge in machine learning (ML) models, this review aims to estimate the diagnostic accuracy of such models for detecting CHD. Methods: A comprehensive literature search in the PubMed, CINAHL, Wiley Cochrane Library, and Web of Science databases was performed. Studies that reported the diagnostic ability of ML for the detection of CHD compared to the reference standard were included. Risk of bias assessment was performed using Quality Assessment for Diagnostic Accuracy Studies-2 tool. The sensitivity and specificity results from the studies were used to generate the hierarchical Summary ROC (HSROC) curve. Results: We included 16 studies (1217 participants) that used ML algorithm to diagnose CHD. Neural networks were used in seven studies with overall sensitivity of 90.9% (95% CI 85.2-94.5%) and specificity was 92.7% (95% CI 86.4-96.2%). Other ML models included ensemble methods, deep learning and clustering techniques but did not have sufficient number of studies for a meta-analysis. Majority (n=11, 69%) of studies had a high risk of patient selection bias, unclear bias on index test (n=9, 56%) and flow and timing (n=12, 75%) while low risk of bias was reported for the reference standard (n=10, 62%). Conclusion: ML models such as neural networks have the potential to diagnose CHD accurately without the need for trained personnel. The heterogeneity of the diagnostic modalities used to train these models and the heterogeneity of the CHD diagnoses included between the studies is a major limitation.

Aboard the Smile Train: Outcomes of Primary Cleft Palate Repair at a Tertiary Care Center: À bord du Smile Train : les résultats cliniques de réparations de fentes palatines dans un centre de soins tertiaires.

INTRODUCTION: Cleft palate repair is considered to be a safe procedure, yet still carries a 5% to 30% risk of complications. This study sought to assess the outcomes of this procedure in a high-burden Asian country that partners with the Smile Train to perform cleft surgeries. METHODS: The Aga Khan University medical records database was queried for pediatric patients undergoing cleft surgery between 2014 and 2017. Data were abstracted from the patient medical records, and details of the clinical, demographic factors, and postoperative outcomes were assessed. RESULTS: Among 142 patients with orofacial clefts, 102 (72%) underwent primary cleft palate repair, one-third (n = 36, 35%) of whom were operated as part of the Smile Train. The median preoperative hemoglobin was 11.4 g/dL (interquartile range: 10.7-12.0 g/dL), whereas the median weight was 8.3 kg (7.7-11.4 kg). Nearly two-thirds (n = 64, 63%) of the cohort underwent preoperative cardiology screening, with only a minority undergoing orthodontic treatment (n = 6, 6%). Approximately 15% (n = 15) of patients experienced a postoperative complication, most often a fistula (n = 11, 73%). On multivariable analysis, with each unit increase in hemoglobin levels, there was a 50% reduction in the odds of experiencing a complication (odds ratio: 0.51, 95% CI: 0.28-0.87). There were no in-patient deaths among the cohort. CONCLUSION: The results of the current study provide useful information to key stakeholders including patients, plastic surgeons, and policy makers on the outcomes of cleft palate repair in a developing country.

INTRODUCTION: La réparation des fentes palatines est considérée comme une intervention sécuritaire, mais comporte un risque de complications de 5 % à 30 %. La présente étude vise à évaluer les résultats de cette intervention dans un pays asiatique au fardeau élevé où les partenaires de Smile Train corrigent des fentes palatines. MÉTHODOLOGIE: Les chercheurs ont fouillé la base de données des dossiers de l'université Aga Khan pour en extraire les patients pédiatriques qui ont subi une intervention de fente palatine entre 2014 et 2017. Ils ont résumé les données des dossiers médicaux des patients et évalué le détail des facteurs cliniques et démographiques ainsi que les résultats postopératoires. RÉSULTATS: Sur les 142 patients ayant une fente labiopalatine, 102 (72 %) ont subi une réparation palatine primaire, dont le tiers a été opéré (n = 36, 35 %) par l'équipe de Smile Train. L'hémoglobine préopératoire médiane était de 11,4 g/dl (ratio interquartile de 10,7 à 12,0 g/dl), et le poids médian, de 8,3 kg (7,7 g à 11,4 kg). Près des deux tiers des membres de la cohorte (n = 64, 63 %) ont subi un dépistage préopératoire, et seule une minorité a suivi un traitement orthodontique (n = 6, 6 %). Environ 15 % des patients (n = 15) ont souffert d'une complication postopératoire, la plupart du temps sous forme de fistule (n = 11, 73 %). À l'analyse multivariée, à chaque nouvelle unité d'hémoglobine, le risque de complication diminuait de 50 % (rapport de cotes 0,51, IC à 95 %, 0,28 à 0,87). Aucun patient hospitalisé n'est décédé au sein de la cohorte. CONCLUSION: Les résultats de la présente étude fournissent de l'information utile aux principaux intervenants, y compris les patients, les plasticiens et les décideurs, sur les résultats des réparations de la fente palatine dans un pays industrialisé.