Search

Background: Acute diarrhoea is a common cause of illness and death among children in low- to middle-income settings. World Health Organization guidelines for the clinical management of acute watery diarrhoea in children focus on oral rehydration, supplemental zinc and feeding advice. Routine use of antibiotics is not recommended except when diarrhoea is bloody or cholera is suspected. Young children who are undernourished or have a dehydrating diarrhoea are more susceptible to death at 90 days after onset of diarrhoea. Given the mortality risk associated with diarrhoea in children with malnutrition or dehydrating diarrhoea, expanding the use of antibiotics for this subset of children could be an important intervention to reduce diarrhoea-associated mortality and morbidity. We designed the Antibiotics for Childhood Diarrhoea (ABCD) trial to test this intervention.Methods: ABCD is a double-blind, randomised trial recruiting 11,500 children aged 2-23 months presenting with acute non-bloody diarrhoea who are dehydrated and/or undernourished (i.e. have a high risk for mortality). Enrolled children in Bangladesh, India, Kenya, Malawi, Mali, Pakistan and Tanzania are randomised (1:1) to oral azithromycin 10 mg/kg or placebo once daily for 3 days and followed-up for 180 days. Primary efficacy endpoints are all-cause mortality during the 180 days post-enrolment and change in linear growth 90 days post-enrolment.Discussion: Expanding the treatment of acute watery diarrhoea in high-risk children to include an antibiotic may offer an opportunity to reduce deaths. These benefits may result from direct antimicrobial effects on pathogens or other incompletely understood mechanisms including improved nutrition, alterations in immune responsiveness or improved enteric function. The expansion of indications for antibiotic use raises concerns about the emergence of antimicrobial resistance both within treated children and the communities in which they live. ABCD will monitor antimicrobial resistance. The ABCD trial has important policy implications. If the trial shows significant benefits of azithromycin use, this may provide evidence to support reconsideration of antibiotic indications in the present World Health Organization diarrhoea management guidelines. Conversely, if there is no evidence of benefit, these results will support the current avoidance of antibiotics except in dysentery or cholera, thereby avoiding inappropriate use of antibiotics and reaffirming the current guidelines.Trial Registration: Clinicaltrials.gov, NCT03130114. Registered on April 26 2017. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the effect of Bifidobacterium lactis HN019 and prebiotic- fortified milk on iron status, anemia, and growth among 1- to 4 year-old children. PATIENTS AND METHODS: In a [...]

BACKGROUND: Recent reviews suggest common infectious diseases continue to be a major cause of death among preschool children in developing countries. Identification Of feasible strategies to combat this disease burden [...]

In a community-based double-blind randomized trial in children aged 6-35 months, both intervention and control groups received a multi-vitamin syrup containing vitamin A, while the intervention group had zinc gluconate [...]

Community-based data relating to factors influencing zinc deficiency among preschool children in India are inadequate. Data of a large, double-blinded, randomized, controlled zinc-supplementation trial were used for assessing the descriptive epidemiology of zinc deficiency among children aged 6-35 months (n = 940). In total, 609 children were followed up for 120 days for information on morbidity. Of these children, 116 from the control group belonging to the upper and the lower 25th quartile of plasma zinc status at baseline were selected for assessing the association of zinc deficiency with prospective morbidity. At baseline, demographic, socioeconomic and dietary information was collected, and anthropometric measurements and levels of plasma zinc were assessed. At baseline, 73.3% of the children were zinc-deficient (plasma zinc < 70 microg/dL), of which 33.8% had levels of plasma zinc below 60 microg/dL. A significantly higher risk of morbidity was prevalent among the subjects with lower plasma zinc compared to those with higher levels of plasma zinc. [ABSTRACT FROM AUTHOR]

In an empiric approach to develop the definition of persistent diarrhea, we evaluated the relationship between diarrheal duration and risk of ensuing clinically significant decline in nutritional status, in a cohort of 395 children < 24 mo. Weights were obtained at the onset of diarrhea (wt I) and after three months interval (wt II). The occurrence of an adverse outcome (AO) was defined as a decline of -- 5% in NCHS weight for age (% WFA) between weights I and II or death in this interval. The risk of AO was similar for episodes of / or > 7 days while it was substantially higher in episodes with > 14 days duration (45%) than for shorter duration episodes, relative risk (RR) = 2.5 (p < 0.001). Relative risk remained similar for duration thresholds of 21 (2.3) and 28 days (2.6). As episode durations greater than 14 days are associated with substantial elevation of the risk of clinically cogent sequelae, such episodes may be termed 'persistent' at least in terms of poor prognostic expectations. [ABSTRACT FROM AUTHOR]

Abstract Background Verbal autopsy methods are critically important for evaluating the leading causes of death in populations without adequate vital registration systems. With a myriad of analytical and data collection approaches, it is essential to create a high quality validation dataset from different populations to evaluate comparative method performance and make recommendations for future verbal autopsy implementation. This study was undertaken to compile a set of strictly defined gold standard deaths for which verbal autopsies were collected to validate the accuracy of different methods of verbal autopsy cause of death assignment. Methods Data collection was implemented in six sites in four countries: Andhra Pradesh, India; Bohol, Philippines; Dar es Salaam, Tanzania; Mexico City, Mexico; Pemba Island, Tanzania; and Uttar Pradesh, India. The Population Health Metrics Research Consortium (PHMRC) developed stringent diagnostic criteria including laboratory, pathology, and medical imaging findings to identify gold standard deaths in health facilities as well as an enhanced verbal autopsy instrument based on World Health Organization (WHO) standards. A cause list was constructed based on the WHO Global Burden of Disease estimates of the leading causes of death, potential to identify unique signs and symptoms, and the likely existence of sufficient medical technology to ascertain gold standard cases. Blinded verbal autopsies were collected on all gold standard deaths. Results Over 12,000 verbal autopsies on deaths with gold standard diagnoses were collected (7,836 adults, 2,075 children, 1,629 neonates, and 1,002 stillbirths). Difficulties in finding sufficient cases to meet gold standard criteria as well as problems with misclassification for certain causes meant that the target list of causes for analysis was reduced to 34 for adults, 21 for children, and 10 for neonates, excluding stillbirths. To ensure strict independence for the validation of methods and assessment of comparative performance, 500 test-train datasets were created from the universe of cases, covering a range of cause-specific compositions. Conclusions This unique, robust validation dataset will allow scholars to evaluate the performance of different verbal autopsy analytic methods as well as instrument design. This dataset can be used to inform the implementation of verbal autopsies to more reliably ascertain cause of death in national health information systems.

Background - Diarrhoea is still the major cause of childhood morbidity and mortality; estimated to cause more than 3 million deaths among children globally. Any non-invasive easily administrable intervention that may affect these morbidities would have very important implications for child health and survival. In recent years there has been increasing evidence for the role of probiotics in treatment of diarrhoea. There are very sparse data on prophylactic probiotic therapy and its effects. Objective - To evaluate the impact of milk fortified with pre- and probiotics in prevention of diarrhoea and on iron status and growth. Design - The study was conducted in Sangam Vihar, a peri-urban population in south Delhi. Healthy children aged 1- 3 years, permanent residents in the area and without any chronic illnesses or severe malnutrition were invited to participate. After informed consent 634 children were enrolled and randomly allocated to either receive a milk formulation containing Bifidobacterium lactis HN019 (DR-10) minimum of 107-108 CFU/100 g and galactooligosaccharides 2.5 g/100 g (PP Milk), or the same milk without these two. The milk was provided in sachets of 32 g and children were advised to consume up to 3 sachets per day for 12 months. A blood sample was taken to measure the detailed haemogram, ZPP and retic count at baseline and end study. Twice weekly home visitations were done to collect data on morbidity and compliance. At baseline, six months and one year anthropometric measurements (weight, height) were made. Outcomes - Baseline characteristics of subjects in the two groups were comparable. Compliance was above 80%, with most children consuming at least two serves per day. Supplementation with PP milk resulted in a significant reduction in the incidence of dysentery OR 0.78 (95% CI 0.61, 1.00) as well as prevalence of dysentery OR 0.85 (95% CI 0.71, 1.01). Reduction in incidence of diarrhoea was 10%, but was not statistically significant. Consistent with improved immunity PP milk supplementation caused a significant reduction in the prevalence of severe illness days OR 0.84 (95%CI 0.74- 0.95, p<0.001), days with fever OR 0.68 (95%CI 0.54-0.84) and prevalence of ear infections OR 0.93 (95%CI 0.87- 1.00). Data on haematological parameters indicate a significant increase in the proportion of children with Hb levels above 10 g/L in the PP milk group. There was also a 35 % reduction in the proportion of iron deficient children and a significant reduction in stress of bone marrow as observed by a increase in the proportion of children with normal retic count, in the PP milk group. Children fed PP milk had significantly better growth at six month and one year assessments. After 1 year the children in the PP milk group had significantly better z scores for WAZ (mean diff 0.22, 95%CI 0.02- 0.41; p=0.03) and WHZ (mean diff 0.18, p=0.05), and higher weight gain (mean diff: 130g, 95%CI 30-230; p=0.02). Conclusions - Bifidobacterium lactis HN019 (DR-10) and galacto-oligosaccharide fortified milk resulted in better iron status even when both groups were receiving iso-caloric diets with the same iron content. This effect could be either due to better absorption due to effects on gut flora or more likely secondary to morbidity prevention effects. There was a significant reduction in bloody diarrhoea and a non significant 10% reduction in all diarrhoea. The magnitude of significant reduction in non diarrheal morbidity suggests effects are most likely on both viral and bacterial infections. This study was funded by New Zealand Milk Ltd, who also provided the milk products [ABSTRACT FROM AUTHOR]

Background - Given the high prevalence of micronutrient deficiencies and infectious diseases in children of developing countries, interventions to reduce infant and pre-school morbidity are a public health priority. With failure of iron supplementation programs for prevention of anaemia, fortification has been suggested as potential strategy for delivery of micronutrients that would reduce interactions and have multiple health benefits. Objective - To evaluate the efficacy of micronutrient fortification of milk in prevention of diarrhoea, acute respiratory infections, iron deficiency and other childhood morbidity, and it's impact on growth. Design - The study was undertaken in peri-urban Delhi. Children aged 1-3 years, resident in the area and without any chronic illness or severe malnutrition were invited to participate. After informed consent 633 children were randomly allocated to either receive a milk formulation (MN milk) with a blend of micronutrients ('Nutri-careTM') including per 100 g powder: zinc 10 mg, iron 10 mg, vitamin A 350 µg, vitamin E 8.3 mg, vitamin C 50 mg, selenium 7 µg and copper 0.3 mg, or the same milk without the fortification. The milk was provided in sachets of 32 g and children were advised to reconstitute and consume 3 sachets per day for 12 months. A field assistant delivered the milk weekly to the homes. At baseline and end study a blood sample was collected and a detailed haemogram, plasma zinc, ferritin and zinc protoporphyrin were measured. Children were visited twice weekly in the home to record compliance and morbidity. At baseline, six months and one year anthropometric measures were made. Outcomes - Compliance was above 80% with most children consuming at least 2 serves of milk per day. MN milk fed children had significantly lower incidences of diarrhoea (OR 0.78, 95% CI 0.66-0.9; 1 p<0.001), days of diarrhoea (OR 0.80, 95% CI 0.74 -0.84; p<0.001), severe illness (OR 0.85,95% CL 0.76-0.96, p=0.01), high fever (OR 0.93, 95%CI 0.90-0.98; p=.003), measles (OR 0.12 p=.02) and acute lower respiratory infection (OR 0.72 95% CL 0.60-0.87; p=.01). They also had a significant increase in both height velocity (diff mean: 0.51; 95% CI: 0.27, 0.75, p= 0.00) and weight velocity (diff mean: 0.21; 95% CI: 0.12, 0.31, p= 0.00). There were also greater changes in height for age (HAZ) Z scores (mean diff 0.19 95%CI 0.12-0.26, p<0.001), weight for age (WAZ) Z scores (diff mean 0.24, 95%CI 0.11-0.36; p<0.001), and weight for height (WHZ) Z scores (diff mean 0.16, 95% CI 0.03-0.30; p=0.02) in the MN milk fed group. There was a significant change in mean Hb of 1.26 g (95%CI 1.11-1.60; p<0.001) in the MN milk group. As well as a significant increase in the proportion of non anaemic children with Hb levels above 10 g/L (OR 3.42, 95% CI 2.43-4.83; P<0.001) there was also an 87% decrease (95% CI 44%-99%; p=0.001) in children with severe anaemia, an increase in mean hematocrit 3.34 (95% CI 2.68, 3.99; p= 0.00), MCV, 6.97 (95% CI 5.53, 8.42; p= 0.00), mean RDW -2.49 (95% CI -2.92,-2.05; p= 0.00) and retic count -0.19 (95% CI, -0.27, 0.11; p= 0.00) in the MN milk group. Conclusions - This study is the largest double blind trial showing fortified milk can reduce morbidity from diarrhoea, respiratory infections and other illnesses, as well as improve iron status and growth. Improvements in anaemia and iron status were greater than that documented with therapeutic iron supplementation in most trials. [ABSTRACT FROM AUTHOR]

Purpose: The early post-transplant period after liver transplantation is critical, as recipients are highly susceptible to sepsis due to their immune-compromised state. This study aimed to identify the association between preoperative procalcitonin and early post-transplant sepsis and mortality at one month after living donor liver transplantation (LDLT)., Methodology: All patients who underwent LDLT from July 2021 to December 2021 were recruited prospectively. Participants were divided into two groups based on preoperative PCT levels: elevated (>0.5 ng/ml) and low levels (<0.5 ng/ml). Serum procalcitonin (PCT) levels were measured on the day of transplant and on postoperative days 3 and 7. The relationship between preoperative PCT and post-transplant sepsis was evaluated using a Chi-square test, and receiver operating characteristic (ROC) curves were generated., Results: Sepsis occurred in 48.3% of patients, with a significant association between elevated preoperative PCT levels and early post-transplant sepsis (p=0.023). The ROC curve for preoperative PCT showed moderate predictive ability (area under curve (AUC)=0.664), while PCT levels on postoperative day 3 demonstrated better discriminatory power (AUC=0.790). PCT levels measured on day 7 also had good diagnostic accuracy, with an AUC of 0.843 and a significant difference between the sepsis and non-sepsis groups (p=0.002). The length of ICU stay was significantly longer in the sepsis group (p=0.009).  Conclusion: Elevated preoperative PCT levels can predict early post-transplant sepsis in LDLT patients. PCT monitoring may enhance risk stratification and guide perioperative management, improving post-transplant outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee at Institute of Liver and Biliary sciences, New Delhi issued approval IEC/2020/73/NA05. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Satija et al.)

Background: Approximately 12% of all diarrhoeal episodes last for 7-13 days. As such, they are termed prolonged diarrhoea, and are associated with over two-thirds of all diarrhoeal deaths. Due to a lack of robust data, we aimed to evaluate a comparative background characteristics of young children with acute and prolonged diarrhoea, and their outcomes at day 90 follow-up., Methods: We performed a secondary analysis of data from the Antibiotics for Children with Diarrhea (ABCD) trial. Children aged 2-23 months were enrolled between July 2017 and July 2019 from seven Asian and sub-Saharan African countries. For this analysis, we divide diarrhoea into two categories: acute diarrhoea (duration <7 days) and prolonged diarrhoea (duration ≥7-13 days). We used logistic regression to observe baseline crude and adjusted associations and linear regression to compare post-discharge outcomes., Results: We analysed data on 8266 children, of whom 756 (9%) had prolonged diarrhoea and 7510 (91%) had acute diarrhoea. Pakistan had the highest proportion of children with prolonged diarrhoea (n/N = 178/1132, 16%), while Tanzania had the lowest (n/N = 12/1200, 1%). From an analysis that adjusted for sex, breastfeeding, nutritional status, clinical presentation, housing, water supply, sanitation, and country, we observed that presentation at a health facility with prolonged diarrhoea was associated with low age (2-12 months) (adjusted odds ratio (aOR) = 1.25; 95% confidence interval (CI) = 1.02, 1.53; P = 0.028), presence of three or more under-five children in the family (aOR = 1.54; 95% CI = 1.26, 1.87; P < 0.001), maternal illiteracy (aOR = 1.45; 95% CI = 1.21, 1.74, P < 0.001), moderate underweight (aOR = 1.25; 95% CI = 1.01, 1.55; P = 0.042) and pathogen (Campylobacter) (aOR = 1.27; 95% CI = 1.12, 1.44; P < 0.001). At day 90 follow-up, children with prolonged diarrhoea had significantly lower weight-for-age z-score compared to children with acute diarrhoea (-1.62, standard deviation (SD) = 1.11 vs -1.52, SD = 1.20; P = 0.032), as well as significantly higher frequency of hospital admission (6.1% vs 4.5%; P = 0.042)., Conclusions: Prolonged diarrhoea was more common in children of younger age, those who were moderately underweight, those with Campylobacter in stool, those with three or more under-five children in a family, and those with illiterate mothers compared to those who had acute diarrhoea. Children with prolonged diarrhoea more often required hospitalisation during the three-month follow-up period compared to their counterparts., Competing Interests: Disclosure of interests: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background: Hypertensive disorders of pregnancy (HDP) are a significant cause of maternal mortality worldwide. The classification and treatment of hypertension in pregnancy remain debated. We aim to compare the effectiveness of the revised 2017 ACC/AHA blood pressure threshold in predicting adverse pregnancy outcomes., Methods: We conducted a secondary data analysis of the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, including 10,001 pregnant women from Bangladesh, Pakistan, and Tanzania. Blood pressure was measured using validated devices at different antenatal care visits. The blood pressure readings were categorized as: normal blood pressure (systolic blood pressure (sBP) < 120 mm Hg and diastolic blood pressure (dBP) < 80 mm Hg), elevated blood pressure (sBP 120-129 and dBP < 80), stage 1 hypertension (sBP 130-139 or dBP 80-89, or both), and stage 2 hypertension (sBP ≥ 140 or dBP ≥ 90, or both). We estimated risk ratios for stillbirths and preterm births, as well as diagnostic test properties of both the pre-existing JNC7 (≥ 140/90) and revised ACC/AHA (≥ 130/80) thresholds using normal blood pressure as reference group., Results: From May 2014 to June 2018, blood pressure readings were available for 9,448 women (2,894 in Bangladesh, 2,303 in Pakistan, and 4,251 in Tanzania). We observed normal blood pressure in 70%, elevated blood pressure in 12.4%, stage 1 hypertension in 15.2%, and stage 2 hypertension in 2.5% of the pregnant women respectively. Out of these, 310 stillbirths and 9,109 live births were recorded, with 887 preterm births. Using the ACC/AHA criteria, the stage 1 hypertension cut-off revealed 15.3% additional hypertension diagnoses as compared to JNC7 criteria. ACC/AHA defined hypertension was significantly associated with stillbirths (RR 1.8, 95% CI 1.4, 2.3). The JNC 7 hypertension cut-off of ≥ 140/90 was significantly associated with a higher risk of preterm births (RR 1.6, 95% CI 1.2, 2.2) and stillbirths (RR 3.6, 95% CI 2.5, 5.3). Both criteria demonstrated low sensitivities (8.4 for JNC-7 and 28.1 for ACC/AHA) and positive predictive values (11.0 for JNC7 and 5.2 for ACC/AHA) in predicting adverse outcomes., Conclusion: The ACC/AHA criteria (≥ 130/80) identified additional cases of hypertension but had limited predictive accuracy for stillbirths and preterm births, highlighting the ongoing need for improved criteria in managing pregnancy-related hypertension., (© 2024. The Author(s).)

Introduction Endoscopic retrograde cholangiopancreatography (ERCP) is vital for diagnosing and treating biliary and pancreatic diseases, necessitating deep sedation typically achieved through total intravenous anesthesia. Propofol, with its favorable pharmacokinetic profile, is the preferred sedative, but conventional administration methods of mg/kg boluses or infusion rates pose challenges. Target-controlled infusion (TCI) systems offer a solution that ensures precise dose delivery of propofol. Despite its widespread use, the literature lacks specific guidance on the target plasma concentration (Cp) of propofol for sedation in patients undergoing ERCP. Methods A prospective interventional study was conducted at the Institute of Liver and Biliary Sciences, Delhi, India to determine the target Cp of propofol for sedation during ERCP. The study enrolled 86 American Society of Anesthesiologists (ASA) grade I and II patients aged 18-70 years. The primary objective was to establish the optimal propofol concentration for sedation as guided by a bispectral index (BIS) value of 60-70. Secondary outcomes included induction time, recovery time, total propofol consumption, and the occurrence of adverse events (if any). The Marsh pharmacokinetic model guided the TCI pump, adjusting Cp until the target sedation was achieved. Results The mean Cp of propofol to maintain the BIS value 60-70 was 2.21 ± 0.42 µg/ml. Age-wise analysis revealed variations, emphasizing the need for individualized dosing. Induction time was 4.21 ± 0.68 minutes; recovery times were seven minutes (median, IQR: 5-10 minutes) for BIS >80 and seven minutes (median, IQR: 5-10 minutes) for achieving a Modified Observer's Assessment of Alertness/Sedation score of ≥5. The mean propofol consumption was 6.24 mg/kg/hr. Side effects were minimal, with 1.16% experiencing transient hypoxia and hypotension. Conclusion The study establishes a mean target propofol concentration of 2.21 ± 0.42 µg/ml for sedation in ASA I and II patients undergoing ERCP., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee, Institute of Liver and Biliary Sciences issued approval IEC/2023/102/MA07. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, S et al.)

Objective: The primary objective was to compare the rates of early allograft dysfunction (EAD) in patients undergoing elective adult live donor liver transplantation (ALDLT) with and without graft portal inflow modulation (GIM) for portal hyper-perfusion. The secondary objectives were to compare time to normalization of bilirubin and International Normalized Ratio (INR), day 14 ascitic output more than 1liter, small-for-size syndrome (SFSS), intensive care unit / high dependency unit and total hospital stay, and 90 day morbidity and mortality., Background: GIM can prevent EAD in ALDLT patients with portal hyper-perfusion., Methods: A single-center randomized trial with and without GIM for portal hyper-perfusion by splenic artery ligation (SAL) in ALDLT was performed. After reperfusion, patients with portal venous pressure (PVP)>15 mm Hg with a gradient (PVP - central venous pressure) of ≥ 7 mm Hg and/or portal venous flow (PVF)>250 mL/min/100 grams of liver were randomized into two groups: GIM and No GIM., Results: 75 of 209 patients satisfied the inclusion criteria, and 38 underwent GIM. Baseline PVF and PVP were comparable between the GIM and no GIM groups. SAL significantly reduced the PVF and PVP (P<0.001). There were no differences in the primary and secondary outcomes between the two groups. In the subgroup analysis, with a Graft to Recipient Weight Ratio (GRWR)≤0.8, there were no significant differences in the primary and secondary outcomes., Conclusion: SAL significantly decreased PVP and PVF, but did not decrease rates of EAD in adult LDLT., Competing Interests: Conflict of Interest: The authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare intraoperative hemodynamic parameters, blood loss, renal function, and duration of surgery with and without temporary portocaval shunt (TPCS) in live donor liver transplantation (LT) recipients. Secondary objectives were postoperative early graft dysfunction, morbidity, mortality, total intensive care unit, and hospital stay., Background: Blood loss during recipient hepatectomy for LT remains a major concern. Routine use of TPCS during LT is not yet elucidated., Methods: This study is a single-center, open-label, randomized control trial. The sample size was calculated based on intraoperative blood loss. After exclusion, a total of 60 patients, 30 in each arm (TPCS vs no TPCS) were recruited in the trial., Results: The baseline recipient and donor characteristics were comparable between the groups. The median intraoperative blood loss ( P = 0.004) and blood product transfusions ( P < 0.05) were significantly less in the TPCS group. The TPCS group had significantly improved intraoperative hemodynamics in the anhepatic phase as compared with the no TPCS group ( P < 0.0001), requiring significantly less vasopressor support. This led to significantly better renal function as evidenced by higher intraoperative urine output in the TPCS group ( P = 0.002). Because of technical simplicity, the TPCS group had significantly fewer inferior vena cava injuries (3.3 vs 26.7%, P = 0.026) and substantially shorter hepatectomy time and total duration of surgery (529.4 ± 35.54 vs 606.83 ± 48.13 min, P < 0.0001). The time taken for normalization of lactate in the immediate postoperative period was significantly shorter in the TPCS group (median, 6 vs 13 h; P = 0.04). Although postoperative endotoxemia, major morbidity, 90-day mortality, total intensive care unit, and hospital stay were comparable between both groups, tolerance to enteral feed was earlier in the TPCS group., Conclusions: In live donor LT, TPCS is a simple and effective technique that provides superior intraoperative hemodynamics and reduces blood loss and duration of surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Bacterial pathogens cause substantial diarrhea morbidity and mortality among children living in endemic settings, yet antimicrobial treatment is only recommended for dysentery or suspected cholera., Methods: AntiBiotics for Children with severe Diarrhea was a 7-country, placebo-controlled, double-blind efficacy trial of azithromycin in children 2-23 months of age with watery diarrhea accompanied by dehydration or malnutrition. We tested fecal samples for enteric pathogens utilizing quantitative polymerase chain reaction to identify likely and possible bacterial etiologies and employed pathogen-specific cutoffs based on genomic target quantity in previous case-control diarrhea etiology studies to identify likely and possible bacterial etiologies., Results: Among 6692 children, the leading likely etiologies were rotavirus (21.1%), enterotoxigenic Escherichia coli encoding heat-stable toxin (13.3%), Shigella (12.6%), and Cryptosporidium (9.6%). More than one-quarter (1894 [28.3%]) had a likely and 1153 (17.3%) a possible bacterial etiology. Day 3 diarrhea was less common in those randomized to azithromycin versus placebo among children with a likely bacterial etiology (risk difference [RD]likely, -11.6 [95% confidence interval {CI}, -15.6 to -7.6]) and possible bacterial etiology (RDpossible, -8.7 [95% CI, -13.0 to -4.4]) but not in other children (RDunlikely, -0.3% [95% CI, -2.9% to 2.3%]). A similar association was observed for 90-day hospitalization or death (RDlikely, -3.1 [95% CI, -5.3 to -1.0]; RDpossible, -2.3 [95% CI, -4.5 to -.01]; RDunlikely, -0.6 [95% CI, -1.9 to .6]). The magnitude of risk differences was similar among specific likely bacterial etiologies, including Shigella., Conclusions: Acute watery diarrhea confirmed or presumed to be of bacterial etiology may benefit from azithromycin treatment., Clinical Trials Registration: NCT03130114., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: The objective was to assess the association between nutritional and clinical characteristics and quantitative PCR (qPCR)-diagnosis of bacterial diarrhoea in a multicentre cohort of children under 2 years of age with moderate to severe diarrhoea (MSD)., Design: A secondary cross-sectional analysis of baseline data collected from the AntiBiotics for Children with Diarrhoea trial (NCT03130114)., Patients: Children with MSD (defined as > 3 loose stools within 24 hours and presenting with at least one of the following: some/severe dehydration, moderate acute malnutrition (MAM) or severe stunting) enrolled in the ABCD trial and collected stool sample., Study Period: June 2017-July 2019., Interventions: None., Main Outcome Measures: Likely bacterial aetiology of diarrhoea. Secondary outcomes included specific diarrhoea aetiology., Results: A total of 6692 children with MSD had qPCR results available and 28% had likely bacterial diarrhoea aetiology. Compared with children with severe stunting, children with MAM (adjusted OR (aOR) (95% CI) 1.56 (1.18 to 2.08)), some/severe dehydration (aOR (95% CI) 1.66 (1.25 to 2.22)) or both (aOR (95% CI) 2.21 (1.61 to 3.06)), had higher odds of having likely bacterial diarrhoea aetiology. Similar trends were noted for stable toxin-enterotoxigenic Escherichia coli aetiology. Clinical correlates including fever and prolonged duration of diarrhoea were not associated with likely bacterial aetiology; children with more than six stools in the previous 24 hours had higher odds of likely bacterial diarrhoea (aOR (95% CI) 1.20 (1.05 to 1.36)) compared with those with fewer stools., Conclusion: The presence of MAM, dehydration or high stool frequency may be helpful in identifying children with MSD who might benefit from antibiotics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Moderate acute malnutrition (MAM) affects over 30 million children aged < 5 years worldwide. MAM may confer a greater risk of developing severe malnutrition and even mortality in children. Assessing risk factors for MAM may allow for earlier recognition of children at risk of deleterious health outcomes., Objective: To determine risk factors associated with the prevalence and development of MAM among children aged 6 to 59 months with acute diarrhoea who received treatment with oral rehydration solution and zinc supplementation., Methods: We conducted a secondary analysis of data from a randomized, dose-finding trial of zinc among children with acute diarrhoea in India and Tanzania. We used regression models to assess risk factors for prevalent MAM at the start of diarrhoea treatment and to identify risk factors associated with the development of MAM at 60 days. MAM was defined as weight for length (or height) Z score ≤-2 and > -3 or mid-upper arm circumference < 12.5 and ≥ 11.5 cm., Results: A total of 4,500 children were enrolled; 593 (13.2%) had MAM at the baseline. MAM at baseline was significantly less common among children in Tanzania than in India (adjusted risk ratio [aRR] 0.37, 95% confidence interval [CI]: 0.30, 0.44, P < 0.001), in children aged 24- < 60 months versus 6- < 12 months (aRR 0.46, 95% CI: 0.38, 0.56, P < 0.001), and in families with household wealth index higher than the median (aRR 0.79, 95% CI: 0.68, 0.92, P = 0.002). Sixty days after outpatient treatment and follow-up, 87 (2.5%) children developed MAM. When compared to children aged 6- < 12 months, children aged 24- < 60 months had a 52% lower risk of developing MAM. Every one unit increase in weight for length (or height) Z score at enrolment was associated with a 93% lower risk of developing MAM during follow-up., Conclusions: Among children with diarrhoea, younger children and those from households with lower wealth were at greater risk of MAM. These children may benefit from targeted interventions focusing on feeding (targeted nutrition support for at-risk households) and follow up in order to reduce the occurrence of MAM and its consequences., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Background: Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB)., Objectives: This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations., Methods: Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort., Results: The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 μg/mL and standard deviation of 0.43 μg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 μg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration., Conclusions: Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB., (Copyright © 2023. Published by Elsevier Inc.)

Background and objectives Propofol-based sedation is one of the most commonly used methods for endoscopic retrograde cholangiopancreatography (ERCP). The commonest complications during ERCP are in the form of adverse cardiopulmonary events as a result of sedation. Etomidate has a more stable cardiovascular and respiratory profile than propofol and has been used for sedation in simple gastrointestinal endoscopy but has not been studied for procedural sedation in ERCP. The objective of the present study was to compare the safety and feasibility of etomidate and propofol for sedation during ERCP procedures. Methods This single-center, randomized trial included 100 American Society of Anesthesiologists (ASA) physical status class I to II patients who were scheduled for ERCP. All patients received midazolam 0.02 mg/kg, lignocaine (2%) 1 mg/kg, and fentanyl 1 µg/kg intravenously, followed by etomidate or propofol according to the group allocation. The primary outcome was to compare the mean arterial pressure (MAP) at various timepoints between the two groups and secondary outcomes were to compare oxygen saturation, induction and recovery times, and adverse events. Transient hypotension was defined as any decrease in MAP below 60 mmHg or 20% below the baseline. Transient hypoxia was defined as desaturation (saturation of peripheral oxygen (SpO2) <92%) lasting for more than 10 seconds requiring airway intervention. Results Fifty patients were enrolled in each group (Group E: etomidate and Group P: propofol). Transient hypotension occurred in eight (16%) patients in Group P, and two (4%) patients in Group E (P= 0.045). Baseline MAP was comparable between the two groups but was significantly lower in Group P at three timepoints during the study. Nine (18 %) patients in Group P had a transient hypoxic episode, compared to none in Group E (p= 0.006). The induction and recovery times were similar in the two groups. Conclusions Etomidate offers better hemodynamic and respiratory stability than propofol and can be recommended for use during ERCP in ASA I/II patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Dhingra et al.)

Background: Blood proteins are frequently measured in serum or plasma, because they provide a wealth of information. Differences in the ex vivo processing of serum and plasma raise concerns that proteomic health and disease signatures derived from serum or plasma differ in content and quality. However, little is known about their respective power to predict feto-maternal health outcomes. Predictive power is a sentinel characteristic to determine the clinical use of biosignatures., Objective: This study aimed to compare the power of serum and plasma proteomic signatures to predict a physiological pregnancy outcome., Study Design: Paired serum and plasma samples from 73 women were obtained from biorepositories of a multinational prospective cohort study on pregnancy outcomes. Gestational age at the time of sampling was the predicted outcome, because the proteomic signatures have been validated for such a prediction. Multivariate and cross-validated models were independently derived for serum and plasma proteins., Results: A total of 1116 proteins were measured in 88 paired samples from 73 women with a highly multiplexed platform using proximity extension technology (Olink Proteomics Inc, Watertown, MA). The plasma proteomic signature showed a higher predictive power (R=0.64; confidence interval, 0.42-0.79; P =3.5×10 -6 ) than the serum signature (R=0.45; confidence interval, 0.18-0.66; P =2.2×10 -3 ). The serum signature was validated in plasma with a similar predictive power (R=0.58; confidence interval, 0.34-0.75; P =4.8×10 -5 ), whereas the plasma signature was validated in serum with reduced predictive power (R=0.53; confidence interval, 0.27-0.72; P =2.6×10 -4 ). Signature proteins largely overlapped in the serum and plasma, but the strength of association with gestational age was weaker for serum proteins., Conclusion: Findings suggest that serum proteomics are less informative than plasma proteomics. They are compatible with the view that the partial ex-vivo degradation and modification of serum proteins during sample processing are an underlying reason. The rationale for collecting and analyzing serum and plasma samples should be carefully considered when deriving proteomic biosignatures to ascertain that specimens of the highest scientific and clinical yield are processed. Findings suggest that plasma is the preferred matrix., (© 2023 The Authors.)

Objectives: To address the disproportionate burden of preterm birth (PTB) in low- and middle-income countries, this study aimed to (1) verify the performance of the United States-validated spontaneous PTB (sPTB) predictor, comprised of the IBP4/SHBG protein ratio, in subjects from Bangladesh, Pakistan and Tanzania enrolled in the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, and (2) discover biomarkers that improve performance of IBP4/SHBG in the AMANHI cohort., Study Design: The performance of the IBP4/SHBG biomarker was first evaluated in a nested case control validation study, then utilized in a follow-on discovery study performed on the same samples. Levels of serum proteins were measured by targeted mass spectrometry. Differences between the AMANHI and U.S. cohorts were adjusted using body mass index (BMI) and gestational age (GA) at blood draw as covariates. Prediction of sPTB < 37 weeks and < 34 weeks was assessed by area under the receiver operator curve (AUC). In the discovery phase, an artificial intelligence method selected additional protein biomarkers complementary to IBP4/SHBG in the AMANHI cohort., Results: The IBP4/SHBG biomarker significantly predicted sPTB < 37 weeks ( n  = 88 vs. 171 terms ≥ 37 weeks) after adjusting for BMI and GA at blood draw (AUC= 0.64, 95% CI: 0.57-0.71, p  < .001). Performance was similar for sPTB < 34 weeks ( n  = 17 vs. 184 ≥ 34 weeks): AUC = 0.66, 95% CI: 0.51-0.82, p  = .012. The discovery phase of the study showed that the addition of endoglin, prolactin, and tetranectin to the above model resulted in the prediction of sPTB < 37 with an AUC= 0.72 (95% CI: 0.66-0.79, p -value < .001) and prediction of sPTB < 34 with an AUC of 0.78 (95% CI: 0.67-0.90, p  < .001)., Conclusion: A protein biomarker pair developed in the U.S. may have broader application in diverse non-U.S. populations.