Effect of 3 Days of Oral Azithromycin on Young Children With Acute Diarrhea in Low-Resource Settings: A Randomized Clinical Trial.

Importance: World Health Organization (WHO) guidelines do not recommend routine antibiotic use for children with acute watery diarrhea. However, recent studies suggest that a significant proportion of such episodes have a bacterial cause and are associated with mortality and growth impairment, especially among children at high risk of diarrhea-associated mortality. Expanding antibiotic use among dehydrated or undernourished children may reduce diarrhea-associated mortality and improve growth. Objective: To determine whether the addition of azithromycin to standard case management of acute nonbloody watery diarrhea for children aged 2 to 23 months who are dehydrated or undernourished could reduce mortality and improve linear growth. Design, Setting, and Participants: The Antibiotics for Children with Diarrhea (ABCD) trial was a multicountry, randomized, double-blind, clinical trial among 8266 high-risk children aged 2 to 23 months presenting with acute nonbloody diarrhea. Participants were recruited between July 1, 2017, and July 10, 2019, from 36 outpatient hospital departments or community health centers in a mixture of urban and rural settings in Bangladesh, India, Kenya, Malawi, Mali, Pakistan, and Tanzania. Each participant was followed up for 180 days. Primary analysis included all randomized participants by intention to treat. Interventions: Enrolled children were randomly assigned to receive either oral azithromycin, 10 mg/kg, or placebo once daily for 3 days in addition to standard WHO case management protocols for the management of acute watery diarrhea. Main Outcomes and Measures: Primary outcomes included all-cause mortality up to 180 days after enrollment and linear growth faltering 90 days after enrollment. Results: A total of 8266 children (4463 boys [54.0%]; mean [SD] age, 11.6 [5.3] months) were randomized. A total of 20 of 4133 children in the azithromycin group (0.5%) and 28 of 4135 children in the placebo group (0.7%) died (relative risk, 0.72; 95% CI, 0.40-1.27). The mean (SD) change in length-for-age z scores 90 days after enrollment was -0.16 (0.59) in the azithromycin group and -0.19 (0.60) in the placebo group (risk difference, 0.03; 95% CI, 0.01-0.06). Overall mortality was much lower than anticipated, and the trial was stopped for futility at the prespecified interim analysis. Conclusions and Relevance: The study did not detect a survival benefit for children from the addition of azithromycin to standard WHO case management of acute watery diarrhea in low-resource settings. There was a small reduction in linear growth faltering in the azithromycin group, although the magnitude of this effect was not likely to be clinically significant. In low-resource settings, expansion of antibiotic use is not warranted. Adherence to current WHO case management protocols for watery diarrhea remains appropriate and should be encouraged. Trial Registration: ClinicalTrials.gov Identifier: NCT03130114.

Uterine and ovarian parameters in healthy North Indian girls from 5 to 16 years by ultrasonography.

INTRODUCTION: Knowledge of uterine and ovarian growth patterns during early age and puberty helps in investigating disorders of pubertal development i.e. precocious puberty, premature thelarche, or pubarche. There is a paucity of data for uterine and ovarian parameters. Aim of the study: The aim of this study is to present normative data for Uterine length, Mean ovarian volume (MOV), and fundo cervical ratio (FCR) from 5 to 16 years in healthy girls from north India and to correlate these parameters with age, weight, height, and pubertal Tanner staging. MATERIAL AND METHODS: A cross-sectional observational study was performed on 130 healthy girls age 5 to 16 years. Age, anthropometric parameters were measured and the pubertal stage was categorized using Tanner staging. All subjects underwent pelvic ultrasonography for the measurement of uterine and ovarian parameters. RESULTS: Normative data of uterine length, MOV, and FCR were presented as mean, SD, median, and 95% confidence interval as per age and Tanner stage. A progressive increase in uterine length, MOV & FCR was observed with increasing age, weight, height, and Tanner stage (p < 0.001). A sudden significant increment in uterine length and MOV was observed between the age of 11-12 and 12-13 years (p < 0.001). Uterine length of < 4 cm, MOV < 2 cm3 and FCR < 1 were specific to identify pre-pubertal girls. CONCLUSIONS: Normative data of uterine and ovarian parameters generated in our study by ultrasonography would be useful for screening girls with abnormalities of pubertal development.

Stretched Penile Length and Testicular Size from Birth to 18 Years in Boys from Western Maharashtra.

BACKGROUND: Genital stage and testicular volume examination and assessment are essential for assessment of growth puberty in boys. There is paucity of Indian data for penile and testicular parameters particularly in pubertal years. AIM: The aim of this study is to present normative data for penile length, testicular volume, and testicular length from birth to 18 years in boys from western Maharashtra and to correlate these parameters with sexual maturity staging (SMR) (Tanner staging). MATERIALS AND METHODS: A cross-sectional observational study was undertaken in apparently healthy boys from 0 to 18 years of age from western Maharashtra from October 2016 to October 2017. Age, anthropometric parameters, stretched penile length (SPL), testicular volume, and testicular length were measured. Pubertal stage was categorized using Tanner staging. Data were entered in Microsoft excel 2013 and using SPSS version 16. LMS method was used to construct age-specific Z-scores for SPL, testicular volume, and testicular length. RESULTS: A total of 843 boys were enrolled in the study. Mean SPL was 4.1 ± 0.4, 5.4 ± 0.8, and 10.2 ± 1.7 cm at 1, 10, and 18 years of age, respectively, and showed a gradual rise from birth to 18 years. Mean testicular volume was 1.8 ± 0.5, 3.3 ± 1.2, and 24.1 ± 3.5 ml, whereas testicular length was 1.3 ± 0.4, 2.1 ± 0.5, and 4.4 ± 0.7 cm respectively, at 1, 10, and 18 years, respectively. The magnitude of increase for SPL and testicular volume was greater around 9-10 years. The increase in SPL and testicular size was hand in hand with SMR for genital development as well as for axillary and pubic hair stages. CONCLUSION: Normative data on SPL, testicular volume, and testicular length from western Maharashtra are presented. These data may be useful in disorders of puberty and genitalia in boys.

Serum Zinc Levels as a Predictor of Severity of Acute Diarrhea.

OBJECTIVE: To determine relationship between serum zinc levels and severity of diarrhea as determined by hydration status, duration of diarrhea and requirement for hospitalization. Also, to compare serum zinc levels in relation to rotavirus status. METHODS: A prospective observational study which included 254 children aged 6 mo to 5 y with diarrhea was conducted. RESULTS: Serum zinc levels could be estimated in 198 children. Median (IQR) serum zinc levels of study population were 73.5 (59.11-92.86)µg/dl. Median (IQR) of serum zinc levels in children with dehydration and without dehydration were 69.64 (54.57-81.62) and 82.86 (64.1-103.48) µg/dl respectively (p < 0.001). Median (IQR) of serum zinc levels in hospitalised and non-hospitalished children were 63.28 (51.81-85.37) and 74.86 (61.75-95.78) µg/dl, respectively (p 0.013). Median (IQR) of total duration of diarrhea was 4.8 (3.5-6.0) d and it did not correlate with serum zinc levels. Median (IQR) of serum zinc levels in children, with rotavirus diarrhea was 66.8 (49.7-82.48) and non-rotavirus diarrhea was 80.0 (62.42-100.12) µg/dl (p < 0.001). CONCLUSIONS: Children with dehydration and those with rotavirus diarrhea tend to have significantly lower serum zinc levels. Hospitalized children also have lower serum zinc levels than non-hospitalized children. Duration of diarrhea does not relate with serum zinc levels.

Screening for Hypoglycemia in Exclusively Breastfed High-risk Neonates.

OBJECTIVE: To determine incidence of hypoglycemia in exclusively breastfed, high-risk but healthy newborns, and risk factors for its development. METHODS: This observational study enrolled 407 exclusively breastfed high-risk (low birth weight newborns (1800-2499 g), late preterms, small-for-gestation, large-for-gestation and infant of diabetic mother), who did not require admission to neonatal intensive care unit and were kept in postnatal wards with mother. Hypoglycemia was defined as blood glucose £46 mg/dL (2.6 mmol/L). Blood glucose was monitored till 48 hours of life. RESULTS: 27% of the screened newborns developed hypoglycemia in first 48 hours. 31 (7.6%) developed recurrent (>2) episodes, 28 (6.8%) had moderate (<37mg/dL) while 8 (1.9%) developed symptomatic hypoglycemia. With increase in birthweight, risk of hypoglycemia reduced significantly (P=0.003). Hypoglycemia was observed more frequently in first 2 hours as compared to next 48 hours (P=0.0001). Low birth- weight, preterm gestation and male gender was significantly associated with increased risk of hypoglycemia. CONCLUSION: Healthy, high-risk exclusively breastfed newborns in postnatal wards need close monitoring for hypoglycemia in first 24 hrs of life.

Randomized controlled trial of topical EMLA and vapocoolant spray for reducing pain during wDPT vaccination.

BACKGROUND: Intramuscular vaccination is among the most common source of iatrogenic pain in infants. Vapocoolant sprays are rapid-acting alternative to topical anesthetics. They provide transient anesthesia via evaporation induced skin cooling, and reduce pain due to vaccine injection in children and adults. The objective was to compare the synergistic analgesic effect of eutectic mixture of local anesthetics (EMLA) with breastfeeding (EB group) and vapocoolant spay with breastfeeding (VB group) to that of only breastfeeding (BO group) during whole cell diptheria, pertussis and tetanus (wDPT) vaccination. METHODS: A double blind randomized controlled trial was done to include infants up to 3 months of age who came for their first wDPT vaccination. The primary outcome variable was the duration of cry after vaccination. Secondary outcome variables were Modified Facial Coding Score, Neonatal Infant Pain Scale and latency of onset of cry. RESULTS: Of the 201 eligible participants, 111 babies were excluded and remaining 90 babies were randomized into three groups of thirty each. The groups did not differ significantly in baseline characteristics. Median (interquartile range, IQR) of duration of cry was lesser [35.86 (21.07-107.75) seconds] in babies receiving EMLA cream with breast feeding (EB group) and in babies receiving vapocoolant spray with breast feeding (VB group) [32.58 (21.25-106.21) seconds] as compared to babies receiving only breast feeding (BO group) [67.5 (27.6-180) seconds] (P=0.147). Difference in median (IQR) of latency of cry was not statistically significant. Modified Facial Coding Score and Neonatal Infant Pain Scale at 1 minute and 3 minutes was significantly lower in the EB and VB group, as compared to the BO group (P<0.05). CONCLUSION: Addition of topical EMLA application or vapocoolant spray to breastfeeding during wDPT vaccination does not reduce duration of cry in infants up to 3 months of age. However, they are able to show reduction in pain score and further studies are warranted to assess their efficacy as pain relief measures in infants and children.

Randomised control trial showed that delayed cord clamping and milking resulted in no significant differences in iron stores and physical growth parameters at one year of age.

AIM: Placental redistribution has been shown to improve haematological outcomes in the immediate neonatal period and early infancy. This study compared the effects of delayed cord clamping (DCC) and umbilical cord milking (UCM) on haematological and growth parameters at 12 months of age. METHODS: This was a follow-up study of a randomised control trial, conducted in a tertiary care paediatric centre from August 2013 to August 2014. We studied 200 apparently healthy Indian infants randomised at birth to receive DCC for 60-90 seconds or UCM. The outcome measures were iron status and physical growth parameters at 12 months. RESULTS: Of the 200 babies, 161 completed the follow-up and baseline characteristics were comparable in both groups. The mean haemoglobin in the DCC group (102.2 (17.2) g/L and serum ferritin 16.44 (2.77) µg/L) showed no significant differences to the UCM group (98.6 (17.1) g/L and 18.2 (2.8) µg/L) at one year. In addition, there were no significant differences in weight, height and mid-upper arm circumference in the two groups. CONCLUSION: Term-born Indian infants who had DCC at 60-90 seconds or UCM showed no significant differences in ferritin and haemoglobin levels and growth parameters at 12 months of age.

Validity of non-invasive point-of-care hemoglobin estimation in healthy and sick children-a method comparison study.

This study was conducted at a tertiary care center in northern India to evaluate the validity of non-invasive transcutaneous hemoglobin estimation in healthy and sick children in comparison to hemoglobin estimation by traditional lab method. A method comparison study was conducted including 150 subjects. Enrolled patients included 80 neonates with average age of 3.9 ± 2.1 days, and 70 children with average age of 5.8 ± 2 years. Each population (newborn and children) comprised of almost equal numbers of healthy and critically ill patients with shock. Hemoglobin (Hb) was estimated on enrolment by transcutaneous spectrophotometry (SpHb) and traditional automated lab analyzer (Hb-Lab). Difference between Hb levels by the two methods (called bias) was measured and analyzed using Bland-Altman method. Out of 148 data pairs analyzed, bias between SpHb and Hb-Lab was -1.52 ± 1.91 g/dl (mean ± SD). SpHb showed excellent positive correlation with Hb-Lab (r = 0.94 (p < 0.001)) and good visual agreement on Bland-Altman plots. Bias was higher in sick subjects with shock as compared to healthy ones in both neonatal and pediatric population (-2.31 ± 2.21 g/dl versus -0.77 ± 1.2 g/dl, respectively). CONCLUSIONS: SpHb showed good accuracy and correlated well with lab estimated Hb levels in healthy children. However, in children with impaired peripheral perfusion, its diagnostic accuracy was inadequate to justify routine use for quantification of severity of anemia and making transfusion decisions solely on non-invasive estimation of hemoglobin. WHAT IS KNOWN: Non-invasive hemoglobin estimation is a relatively new and novel method which has given mixed results regarding its potential efficacy in adults. There is limited data regarding usefulness and accuracy of non-invasive Hb estimation by SpHb in sick neonates and children. WHAT IS NEW: Non-invasive Hb estimation by SpHb monitor is reasonably accurate in healthy neonates and children. It can be used in critically ill children and neonates, but in conjunction with lab confirmation of Hb values.

Umbilical Cord Milking and Hematological Parameters in Moderate to Late Preterm Neonates: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effect of umbilical cord milking on hematological parameters at 6 weeks of age in late preterm neonates. DESIGN: Randomized controlled trial. SETTING: A tertiary care center of Northern India during 2013-14. PARTICIPANTS: 200 moderate to late preterm neonates randomly allocated to early cord clamping or umbilical cord milking group (100 in each). INTERVENTION: In milking group, 25 cm length of cord was milked towards the baby thrice after separating (within 30 s) it from placenta. MAIN OUTCOME MEASURES: Hemoglobin and serum ferritin at 6 weeks of age. RESULTS: Mean (SD) serum ferritin [428.9 (217.6) vs. 237.5 (118.6) ng/mL; P< 0.01] and hemoglobin [12.1 (1.5) vs. 10.4 (1.2) gm/dL; P<0.01] at 6 weeks were significantly higher in umbilical cord milking group. In early neonatal period, hemodynamic and hematological parameters were not significantly different. Higher incidence of jaundice with higher phototherapy rates (33% vs. 9%; P<0.01) were noted in umbilical cord milking group. CONCLUSIONS: In preterm neonates, umbilical cord milking at birth enhances iron stores at 6 weeks of age. Higher phototherapy rates with this intervention are a matter of concern.

Lactobacillus GG for treatment of acute childhood diarrhoea: an open labelled, randomized controlled trial.

BACKGROUND & OBJECTIVES: Randomized controlled trials in developed countries have reported benefits of Lactobacillus GG (LGG) in the treatment of acute watery diarrhoea, but there is paucity of such data from India. The study was aimed to evaluate the efficacy and safety of Lactobacillus GG in the treatment of acute diarrhoea in children from a semi-urban city in north India. METHODS: In this open labelled, randomized controlled trial 2000 children with acute watery diarrhoea, aged between 6 months to 5 years visiting outpatient department and emergency room of a teaching hospital in north India were enrolled. The children were randomized into receiving either Lactobacillus GG in dose of 10 billion cfu/day for five days or no probiotic medication in addition to standard WHO management of diarrhoea. Primary outcomes were duration of diarrhoea and time to change in consistency of stools. RESULTS: Median (inter quartile range) duration of diarrhoea was significantly shorter in children in LGG group [60 (54-72) h vs. 78 (72-90) h; P<0.001]. Also, there was faster improvement in stool consistency in children receiving Lactobacillus GG than control group [36 (30-36) h vs. 42 (36-48) h; P<0.001]. There was significant reduction in average number of stools per day in LGG group (P<0.001) compared to the control group. These benefits were seen irrespective of rotavirus positivity in stool tests. INTERPRETATION & CONCLUSIONS: Our results showed that the use of Lactobacillus GG in children with acute diarrhoea resulted in shorter duration and faster improvement in stool consistency as compared to the control group.

Effect of oil massage on growth in preterm neonates less than 1800 g: a randomized control trial.

OBJECTIVE: To study the effect of oil massage on growth in preterm babies less than 1800 g. METHODS: This randomised controlled trial was conducted in Neonatal intensive care unit of a level II hospital. Neonates with birth weight < 1800 g, gestation < 35 wk and < 48 h of age at enrolment were included in the studies. Eligible neonates were randomized to one of the two groups (a) Oil massage along with standard care of low birth weight (b) Standard care of low birth weight without massage. Weight, length and head circumference was measured in the two groups at 7 d intervals. Serum triglyceride levels were measured at enrolment and at completion of study. Primary outcome variable was weight gain at 28 d after enrolment. RESULTS: A total of forty-eight neonates were randomisd to either oil massage group (n = 25) or standard care of low birth weight without massage group (n = 23). Mean (SD) weight of babies in the two groups was 1466.4 ± 226.8 g in oil massage group and 1416.6 ± 229.9 g in the control group. At 28 d, weight gain in the oil massage group (476.76 ± 47.9 g) was higher compared to the control group (334.96 ± 46.4 g) (p < 0.05). At 7 d, less weight loss (7.80 ± 9.8 g) was observed in babies in oil massage group compared to control group (21.52 ± 19.4 g) (p = 0.003). However, there was no significant difference in serum triglycerides and other anthropometric parameters. CONCLUSIONS: Oil application has a potential to improve weight gain and cause less weight loss in first 7 d in low birth weight neonates.

The microbiological and clinical characteristics of invasive salmonella in gallbladders from cholecystectomy patients in kathmandu, Nepal.

Gallbladder carriage of invasive Salmonella is considered fundamental in sustaining typhoid fever transmission. Bile and tissue was obtained from 1,377 individuals undergoing cholecystectomy in Kathmandu to investigate the prevalence, characteristics and relevance of invasive Salmonella in the gallbladder in an endemic area. Twenty percent of bile samples contained a Gram-negative organism, with Salmonella Typhi and Salmonella Paratyphi A isolated from 24 and 22 individuals, respectively. Gallbladders that contained Salmonella were more likely to show evidence of acute inflammation with extensive neutrophil infiltrate than those without Salmonella, corresponding with higher neutrophil and lower lymphocyte counts in the blood of Salmonella positive individuals. Antimicrobial resistance in the invasive Salmonella isolates was limited, indicating that gallbladder colonization is unlikely to be driven by antimicrobial resistance. The overall role of invasive Salmonella carriage in the gallbladder is not understood; here we show that 3.5% of individuals undergoing cholecystectomy in this setting have a high concentration of antimicrobial sensitive, invasive Salmonella in their bile. We predict that such individuals will become increasingly important if current transmission mechanisms are disturbed; prospectively identifying these individuals is, therefore, paramount for rapid local and regional elimination.

Inequity in health care delivery in India: the problem of rural medical practitioners.

A considerable section of the population in India accesses the services of individual private medical practitioners (PMPs) for primary level care. In rural areas, these providers include MBBS doctors, practitioners of alternative systems of medicine, herbalists, indigenous and folk practitioners, compounders and others. This paper describes the profile, knowledge and some practices of the rural doctor in India and then discusses the reasons for lack of equity in health care access in rural areas and possible solutions to the problem.

Is prophylactic placement of drains necessary after subtotal gastrectomy?

AIM: To determine the evidence-based values of prophylactic drainage in gastric cancer surgery. METHODS: One hundred and eight patients, who underwent subtotal gastrectomy with D1 or D2 lymph node dissection for gastric cancer between January 2001 and December 2005, were divided into drain group or no-drain group. Surgical outcome and post-operative complications within four weeks were compared between the two groups. RESULTS: No significant differences were observed between the drain group and no-drain group in terms of operating time (171 +/- 42 min vs 156 +/- 39 min), number of post-operative days until passage of flatus (3.7 +/- 0.5 d vs 3.5 +/- 1.0 d), number of post-operative days until initiation of soft diet (4.9 +/- 0.7 d vs 4.8 +/- 0.8 d), length of post-operative hospital stay (9.3 +/- 2.2 d vs 8.4 +/- 2.4 d), mortality rate (5.4% vs 3.8%), and overall post-operative complication rate (21.4% vs 19.2%). CONCLUSION: Prophylactic drainage placement is not necessary after subtotal gastrectomy for gastric cancer since it does not offer additional benefits for the patients.