Diagnosis, Treatment and Prevention of Nutritional Anemia in Children: Recommendations of the Joint Committee of Pediatric Hematology-Oncology Chapter and Pediatric and Adolescent Nutrition Society of the Indian Academy of Pediatrics.

JUSTIFICATION: Anemia in children is a significant public health problem in our country. Comprehensive National Nutrition Survey 2016-18 provides evidence that more than 50% of childhood anemia is due to an underlying nutritional deficiency. The National Family Health Survey-5 has reported an increase in the prevalence of anemia in the under-five age group from 59% to 67.1% over the last 5 years. Clearly, the existing public health programs to decrease the prevalence of anemia have not shown the desired results. Hence, there is a need to develop nationally acceptable guidelines for the diagnosis, treatment and prevention of nutritional anemia. OBJECTIVE: To review the available literature and collate evidence-based observations to formulate guidelines for diagnosis, treatment and prevention of nutritional anemia in children. PROCESS: These guidelines have been developed by the experts from the Pediatric Hematology-Oncology Chapter and the Pediatric and Adolescent Nutrition (PAN) Society of the Indian Academy of Pediatrics (IAP). Key areas were identified as: epidemiology, nomenclature and definitions, etiology and diagnosis of iron deficiency anemia (IDA), treatment of IDA, etiology and diagnosis of vitamin B12 and/or folic acid deficiency, treatment of vitamin B12 and/or folic acid deficiency anemia and prevention of nutritional anemia. Each of these key areas were reviewed by at least 2 to 3 experts. Four virtual meetings were held in November, 2021 and all the key issues were deliberated upon. Based on review and inputs received during meetings, draft recommendations were prepared. After this, a writing group was constituted which prepared the draft guidelines. The draft was circulated and approved by all the expert group members. RECOMMENDATIONS: We recommend use of World Health Organization (WHO) cut-off hemoglobin levels to define anemia in children and adolescents. Most cases suspected to have IDA can be started on treatment based on a compatible history, physical examination and hemogram report. Serum ferritin assay is recommended for the confirmation of the diagnosis of IDA. Most cases of IDA can be managed with oral iron therapy using 2-3 mg/kg elemental iron daily. The presence of macro-ovalocytes and hypersegmented neutrophils, along with an elevated mean corpuscular volume (MCV), should raise the suspicion of underlying vitamin B12 (cobalamin) or folic acid deficiency. Estimation of serum vitamin B12 and folate level are advisable in children with macrocytic anemia prior to starting treatment. When serum vitamin B12 and folate levels are unavailable, patients should be treated using both drugs. Vitamin B12 should preferably be started 10-14 days ahead of oral folic acid to avoid precipitating neurological symptoms. Children with macrocytic anemia in whom a quick response to treatment is required, such as those with pancytopenia, severe anemia, developmental delay and infantile tremor syndrome, should be managed using parenteral vitamin B12. Children with vitamin B12 deficiency having mild or moderate anemia may be managed using oral vitamin B12 preparations. After completing therapy for nutritional anemia, all infants and children should be advised to continue prophylactic iron-folic acid (IFA) supplementation as prescribed under Anemia Mukt Bharat guidelines. For prevention of anemia, in addition to age-appropriate IFA prophylaxis, routine screening of infants for anemia at 9 months during immunization visit is recommended.

Electroencephalogram versus Magnetic Resonance Imaging Brain as the Initial Investigation of Choice in Neurologically Normal Children with First Afebrile Seizure in India.

BACKGROUND AND PURPOSE: To compare the rates of clinically relevant information provided by electroencephalogram (EEG) and magnetic resonance imaging (MRI) brain in first afebrile seizure (FAS) in children. METHODS: In this prospective randomized controlled trial, neurologically normal children between the age of 2 and 14 years, presenting with first episode of unprovoked, afebrile generalized or partial seizures, were included. Enrolled patients were randomized into two groups. After stabilization, initial workup and management, group I-patients underwent an EEG followed by MRI, whereas group II-patients underwent an initial MRI brain followed by an EEG. The patients were followed up after results of both the investigations and then every 3 months for seizure recurrence. The primary outcome was the proportion of investigations, providing clinically relevant information. The secondary outcomes were to determine the etiological diagnosis of FAS and record adverse events associated with EEG and MRI. RESULTS: Out of 170 enrolled patients, 52 patients (61.2%) in initial EEG group and 53 patients (70.6%) in initial MRI group had abnormal results on first investigation. An etiological diagnosis could not be made in any patient in initial EEG group. Neuroimaging revealed an etiological diagnosis in 53 patients (70.6%) in initial MRI group. Inflammatory granuloma was found to be the most common cause of FAS, followed by idiopathic epilepsy. CONCLUSIONS: The results of our study done in neurologically normal children with FAS showed a high diagnostic yield with an initial MRI. We recommend MRI brain to be considered as the initial investigation for evaluation of FAS in children.

A prospective study of catch-up growth among Indian children with celiac disease.

OBJECTIVES: The study was done to investigate the response of the gluten-free diet (GFD) on growth and other biochemical parameters in newly diagnosed children with celiac disease (CD). We also determined the association of Marsh biopsy classification and the response in haematological parameters among the children with GFD over the follow-up time. METHODS: A prospective observational study was conducted for 1.5 years where children aged 1-10 years with newly confirmed CD (as per Marsh classification) without pre-existing chronic disease were enrolled. Individual anthropometry, biochemical and haematological parameters were recorded on enrolment and compared with 1, 3 and 6 months (follow-up) after initiating GFD (as per World Health Organization growth charts). STATISTICAL ANALYSIS: The data were entered in MS Excel spreadsheet and analysis was done using Statistical Package for Social Sciences version 21.0. A P value of < 0.05 was considered significant. RESULTS: A total of 51 (out of 55) children with CD completed 6-month follow-up. A significant improvement in the growth and biochemical parameters was seen at 6-month follow-up with the GFD (P < 0.05). There was a significantly decreasing Hb (at enrolment and at 3 months) with increasing Marsh biopsy grade-it was significantly less with Marsh 3C and more with Marsh 3A. A significantly better %Hb improvement was seen in children with Marsh biopsy 3C as compared to 3A and 3B (P < 0.05). We found no significant association of Marsh biopsy with Malabsorption, type of anaemia and Serum ferritin levels (P > 0.05). CONCLUSIONS: GFD showed significant improvement in the growth and development of the child with a significant reduction in anaemia at 6 months. With increasing grade of Marsh biopsy, the severity of anaemia increases but after the initiation of GFD, such children show significantly better improvement in %Hb over time.

Pediatric Appropriate Evaluation Protocol for India (PAEP-India): Tool for Assessing Appropriateness of Pediatric Hospitalization.

OBJECTIVE: To develop and assess Pediatric Appropriateness Evaluation Protocol for India (PAEP-India) for inter-rater reliability and appropriateness of hospitalization. DESIGN: Cross-sectional study. SETTING: The available PAEP tools were reviewed and adapted for Indian context by ten experienced pediatricians following semi-Delphi process. Two PAEP-India tools; newborn (≤28 days) and children (>28 days-18 years) were developed. These PAEP-India tools were applied to cases to assess appropriateness of admission and inter-rater reliability between assessors. PARTICIPANTS: Two sets of case records were used: (i) 274 cases from five medical colleges in Delhi-NCR [≤28 days (n=51); >28 days to 18 years (n=223)]; (ii) 622 infants who were hospitalized in 146 health facilities and were part of a cohort (n= 30688) from two southern Indian states. INTERVENTIONS: Each case-record was evaluated by two pediatricians in a blinded manner using the appropriate PAEP-India tools, and 'admission criteria' were categorized as appropriate, inappropriate or indeterminate. OUTCOME MEASURES: The proportion of appropriate hospitalizations and inter-rater reliability between assessors (using kappa statistic) were estimated for the cases. RESULTS: 97.8% hospitalized cases from medical colleges were labelled as appropriate by both reviewers with inter-rater agreement of 98.9% (k=0.66). In the southerm Indian set of infants, both reviewers labelled 80.5% admissions as appropriate with inter-rater agreement of 96.1% (k= 0.89). CONCLUSIONS: PAEP-India (newborn and child) tools are simple, objective and applicable in diverse settings and highly reliable. These tools can potentially be used for deciding admission appropriateness and hospital stay and may be evaluated later for usefulness for cost reimbursements for insurance proposes.

Safety and immunogenicity of Bio Pox™, a live varicella vaccine (Oka strain) in Indian children: A comparative multicentric, randomized phase II/III clinical trial.

Varicella or chickenpox is a highly contagious disease with a high secondary attack rate. Almost 30% of Indian adolescents lack protective antibodies against varicella, emphasizing the need of routine varicella immunization. The Oka VZV is a well-established, safe and efficacious vaccine strain that is highly immunogenic and produces lifelong protective immunity. The present multicentric, open label, randomized, controlled Phase II/III study, compared the Bio Pox™ (indigenous investigational vaccine) with a licensed vaccine, Varivax™ [a][a] Please note that this article refers to the product named VARIVAX as manufactured by Changchun Keygen Biological Products Ltd., China and marketed in India by VHB Life Sciences Limited, Mumbai, and not the product VARIVAX® owned by Merck Sharp & Dohme Corp., Rahway, New Jersey, USA. Merck Sharp & Dohme Corp. have asked us to make clear that the product manufactured by Changchun Keygen Biological Products Ltd. is unrelated to and is not sponsored, endorsed or otherwise authorised by Merck Sharp & Dohme Corp. , for its safety and immunogenicity profile in 252 healthy subjects in the age group of 1-12 y (cohort I: 6-12 years, II:1-6 years) in 3 tertiary medical institutions. Antibodies were measured by VZV Glycoprotein Enzyme Linked Immunoassay (IgG ELISA) kit. Seroconversion percentage in children having pre-vaccination anti VZV IgG titer <10 mIU/mL (< 5 gp ELISA units/mL) were 80% for Bio Pox™ and 77% for Varivax™ (p = 0.692). The seroconversion rate in the group receiving Bio Pox™ was non-inferior to the group that received Varivax™. There were mild local reactions for both the vaccines; none of the patient had fever or required hospitalization or medication. The Bio Pox™ was found to be safe and immunogenic in children against VZV infection.

Antibody persistence up to 5 y after vaccination with a quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine in adolescents.

Long-term protection against meningococcal disease relies on antibody persistence after vaccination. We report antibody persistence up to 5 y after vaccination in adolescents who received a single dose of either meningococcal serogroups A, C, W, Y tetanus toxoid conjugate vaccine (MenACWY-TT, Pfizer) or MenACWY polysaccharide vaccine (MenPS, GSK Vaccines) at the age of 11-17 y in the randomized controlled primary study NCT00464815. In this phase III, open, controlled, multi-center persistence follow-up study conducted in India and the Philippines (NCT00974363), antibody persistence was evaluated by a serum bactericidal antibody assay using rabbit complement (rSBA) yearly, up to year 5 after vaccination. Serious adverse events (SAEs) related to study participation were recorded. Five years after a single dose of MenACWY-TT, the percentage of participants (N = 236) with rSBA titers ≥1:8 was 97.5% for serogroup A, 88.6% for serogroup C, 86.0% for serogroup W and 96.6% for serogroup Y. The percentages in the MenPS group (N = 86) were 93.0%, 87.1%, 34.9% and 66.3%, respectively. Exploratory analysis indicated a higher percentage of subjects with rSBA titers ≥1:8 for serogroups W and Y, and higher rSBA geometric mean antibody titers for serogroups A, W and Y in the MenACWY-TT group than the MenPS group at each time point (years 3, 4 and 5). No differences between groups were observed for serogroup C. No SAEs related to study participation were reported. In conclusion, the results of this follow-up study indicate that antibodies persisted up to 5 y after a single dose of MenACWY-TT in adolescents.

Persistence of the immune response two years after vaccination with quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) in Asian adolescents.

Invasive meningococcal disease is a serious infection that is most often vaccine-preventable. Long-term protection relies on antibody persistence. Here we report the persistence of the immune response 2 y post-vaccination with a quadrivalent meningococcal serogroups A, C, W, Y tetanus toxoid conjugate vaccine (MenACWY-TT) compared with a MenACWY polysaccharide vaccine (Men-PS), in Asian adolescents aged 11-17 y. We also report a re-analysis of data from the primary vaccination study. This persistence study (NCT00974363) conducted in India and the Philippines included subjects who previously (study NCT00464815) received a single dose of MenACWY-TT or Men-PS. Persistence of functional antibodies was measured in 407 MenACWY-TT recipients and 132 Men-PS recipients (according-to-protocol cohort) using a rabbit complement serum bactericidal assay (rSBA, cut-off 1:8). Vaccine-related serious adverse events (SAEs) occurring since the end of the initial vaccination study were retrospectively recorded. Two y post-vaccination ≥99.3% of adolescents who received MenACWY-TT had persisting antibody titers ≥1:8 against each vaccine serogroup. Antibody persistence was higher (exploratory analysis) in the MenACWY-TT group than the Men-PS group in terms of rSBA titers ≥1:8 for serogroups W and Y; rSBA titers ≥1:128 for serogroups A, W and Y; and rSBA GMTs for serogroups A, W and Y; and was lower in the MenACWY-TT group for rSBA GMTs for serogroup C. No vaccine-related SAEs were reported. The results of this study indicated that antibodies persisted for at least 2 y in the majority of adolescents after vaccination with a single dose of MenACWY-TT.

Immunogenicity and safety of a tetravalent dengue vaccine in healthy adults in India: A randomized, observer-blind, placebo-controlled phase II trial.

Dengue is a mosquito-borne viral disease that is endemic in India. We evaluated the immunogenicity and safety of recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) in Indian adults. In this observer-blind, randomized, placebo-controlled, Phase II study, adults aged 18-45 years were randomized 2:1 to receive CYD-TDV or placebo at 0, 6 and 12 months in sub-cutaneous administration. Immunogenicity was assessed using a 50% plaque reduction neutralization test (PRNT50) at baseline and 28 days after each study injection. 189 participants were enrolled (CYD-TDV [n = 128]; placebo, [n = 61]). At baseline, seropositivity rates for dengue serotypes 1, 2, 3 and 4 ranged from 77.0% to 86.9%. Seropositivity rates for each serotype increased after each CYD-TDV injection with a more pronounced increase after the first injection. In the CYD-TDV group, geometric mean titres (GMTs) were 2.38 to 6.11-fold higher after the third injection compared with baseline but remained similar to baseline in the placebo group. In the CYD-TDV group, the GMTs were 1.66 to 4.95-fold higher and 9.23 to 24.6-fold higher after the third injection compared with baseline in those who were dengue seropositive and dengue seronegative, respectively. Pain was the most commonly reported solicited injection site reaction after the first injection in both the CYD-TDV (6.3%) and placebo groups (4.9%), but occurred less frequently after subsequent injections. No serious adverse events were vaccine-related, no immediate unsolicited adverse events, and no virologically-confirmed cases of dengue, were reported during the study. The immunogenicity and safety of CYD-TDV was satisfactory in both dengue seropositive and seronegative Indian adults.

Clinical and histopathological correlation of duodenal biopsy with IgA anti-tissue transglutaminase titers in children with celiac disease.

BACKGROUND: Data correlating anti-tissue transglutaminase (tTG) antibody titers with severity of duodenal involvement is limited. OBJECTIVE: The aim of this study was to correlate IgA anti-tTG antibody titers with symptoms, anthropometric parameters, and duodenal histopathology. METHODS: Consecutively diagnosed patients of celiac disease as per modified ESPGHAN criteria presenting over a year were enrolled. Demographic data, symptoms, weight-for-age z score (WAZ), height-for-age z score (HAZ), IgA anti-tTG titer, and duodenal histopathology graded as per modified Marsh criteria were recorded. Spearman rank correlation test was used for association between TTG age, WAZ, and HAZ. Receiver operating curve (ROC), sensitivity, specificity, negative predictive value, and positive predictive value were used to obtain anti-tTG cutoff value predictive of Marsh grade 3. RESULTS: One hundred and forty-two patients with celiac disease were evaluated. tTG showed significant correlation with WAZ (r = 0.822, p = <0.001) and HAZ (r = 0.722, p = <0.001) but not with age (r = 0.202, p = 0.066). The median anti-tTG titers rose progressively with higher Marsh grade on histopathology (p = 0.001). The median anti-tTG titer was also significantly higher in patients with classic celiac disease as compared to non-diarrheal celiac disease (144 u/mL vs. 27, p = 0.02). Anti-tTG titer of 62.5 u/mL was strongly predictive of duodenal histology of Marsh grade 3a and higher with sensitivity, specificity, positive predictive value, and negative predictive value of 95.4 %, 98 %, 93.8 %, and 88.3 % respectively. CONCLUSIONS: There is a significant correlation between IgA anti-tTG titers and anthropometric parameters and severity of duodenal histopathology. With further validation, strongly positive titers may be sufficient to predict severity of this disease.

Celiac disease presentation in a tertiary referral centre in India: current scenario.

BACKGROUND: Nondiarrheal celiac disease (NDCD) is being increasingly reported but data from India is limited. AIM: We undertook this study to compare the clinical spectrum of NDCD with that of diarrheal/classical celiac disease (CCD). METHOD: This facility-based retrospective observational study included consecutive patients diagnosed with celiac disease (CD) (as per modified ESPGHAN criteria) from October 2009 to August 2011. RESULTS: A total of 381 patients were diagnosed with CD during the study period. NDCD was present in 192 (51.8 %). NDCD had higher mean age at presentation (5.8 ± 2.8 vs. 6.9 ± 2.9 years respectively; p = 0.003) and longer duration of symptoms prior to diagnosis (2.9 ± 1.7 years vs. 3.6 ± 2.2 years; p = 0.02) as compared to CCD. In the NDCD group, the most frequent gastrointestinal (GI) symptoms were recurrent abdominal pain [122 (63.5 %)] and abdominal distension [102 (53.1 %)] followed by constipation [48 (25 %)], vomiting [76 (39.6 %)] and recurrent oral ulcers [89 (46.4 %)]. Vomiting and constipation were more frequently seen in NDCD as compared to CCD (p < 0.001 in both). Commonly enumerated extraintestinal manifestations in NDCD included failure to thrive [109 (56.8 %)], isolated short stature [36 (18.8 %)], persistent anemia [83 (43.2 %)] and hepatomegaly/splenomegaly or both [56 (29.2 %)]. Associated comorbidities included autoimmune thyroiditis [11 (5.7 %)], type 1 diabetes mellitus [8 (4.2 %)], bronchial asthma [23 (11.9 %)], idiopathic pulmonary hemosiderosis [4 (2.1 %)], Down's syndrome [3 (1.6 %)], alopecia areata [6 (3.1 %)], polyarthritis [2 (1.0 %)], dermatitis herpetiformis [6 (3.1 %)] and chronic liver disease [6 (3.1 %)]. The number of patients with a Marsh score IIIb and above of duodenal biopsy was significantly more in the CCD group (p < 0.001). CONCLUSIONS: NDCD is not uncommon in India. Long-term follow up is needed to evaluate the impact of the disease and of treatment in these children.

Patterns of diagnosis disclosure and its correlates in HIV-Infected North Indian children.

This facility-based cross-sectional study was conducted to determine the patterns of disclosure of HIV positive serostatus among 145 Indian children aged >5 years. Only 60 (41.4%) children were aware of their HIV-positive status. Disclosure was most frequently done by parents [51/60 (85%)] at a mean age of 9.1 ± 1.4 years. The rate of inaccurate disclosure was high [64/85 (75.3%)]. No information regarding their illness was given to 21/85 (24.7%) children. The most common reason for non-disclosure was that the child is too young [79/85 (92.9%)]. The factors favoring disclosure were increasing duration since diagnosis of HIV infection [odds ratio (OR) = 1.46; 95% confidence interval (CI) 1.11-1.93], non-perinatal mode of transmission (OR = 6.14; 95% CI 2.01-15.80), ART initiation (OR = 3.05; 95% CI 1.33-7.01), school enrolment (OR = 3.52; 95% CI 1.44-7.57) and caregiver educated beyond fifth grade (OR = 2.69; 95% CI 1.21-5.96). Detailed guidelines on disclosure are required focusing on children of school-going age with perinatal infection who are not on ART and with caregivers of low educational status.

Lipodystrophy and metabolic complications of highly active antiretroviral therapy.

OBJECTIVE: To assess the metabolic drug toxicities of first-line, World Health Organization (WHO)-recommended generic highly active antiretroviral therapy (HAART) regimens, to estimate the prevalence of body fat redistribution and to identify associated risk factors. METHODS: Cross-sectional observational study. During 3 month period, 52 HIV infected children (25 on HAART; 27 not on HAART) were assessed. Their sociodemographic, clinical, and immunological data was recorded. Children were examined or the signs of fat redistribution (peripheral lipoatrophy and central lipohypertrophy). Liver function tests, fasting blood sugar, lipid profile, serum amylase, serum lactate, blood pH and bicarbonate levels were done in all patients. RESULTS: Twenty-two patients were on stavudine and three on zidovudine based HAART. None of the patients ever received any protease inhibitor. There were no cases of clinical or immunological failure. Children on HAART had significantly lower weight for age and body mass index but the mean height for age was similar between study groups. Only two cases of peripheral lipoatrophy were observed. Hypercholesterolemia was observed in four children on HAART but none without therapy. Hypertriglyceridemia was observed in three children on HAART and seven without therapy. Four cases of asymptomatic mild hyperlactatemia were observed. No case of any hyperglycemia or liver impairment was observed. CONCLUSION: Metabolic abnormalities and lipodystrophy are emerging complications of HAART in Indian children and needs very close follow up. Future studies with larger sample size and longitudinal model are recommended.

Cystic lymphangiomatous hamartoma masquerading as massive ascites.

We report a 4-year-old boy presenting with a tense massive ascites and large hydrocele. History and physical examination were unremarkable. Routine laboratory studies were normal. Abdominal ultrasonography revealed massive ascites. Contrast CT was suggestive of a large cyst covering the entire peritoneal cavity. At laparotomy, a large cystic tumor was found extending into the scrotum through the left inguinal ring. Histopathologic examination diagnosed the tumor as a cystic lymphangiomatous hemartoma. Although abdominal lymphangiomas are seen in children, but presenting as massive ascites with hydrocele is very rare.

Efficacy of modified WHO feeding protocol for management of severe malnutrition in children: a pilot study from a teaching hospital in New Delhi, India.

AIM: To assess the efficacy of modified World Health Organization (WHO) feeding protocol for severe malnutrition. SETTING: Prospective observational study conducted in the nutritional rehabilitation center of a tertiary care teaching hospital of New Delhi, India over four months period from August to November 2007. METHODS: 25 children with severe malnutrition (age 6 months to 5 years) were recruited. All children were treated according to Indian Academy of Pediatrics modified WHO guidelines. Daily weight gain and improvement in the clinical status was assessed. Children were followed up at day 15, day 30 and day 45 after discharge or when a new problem emerged. RESULTS: Weight-for-age z score (WAZ) at admission was -4.82+/-0.96, weight-for-height z score (WHZ) was -5.0+/-0.7, height-for-age z-score (HAZ) was -2.55+/-1.65. All children had diarrhea on admission, two had pneumonia in addition, and one each had otitis, sepsis and hepatitis in addition to diarrhea. The mean duration of admission was 8.32+/-2.87 days. At discharge the mean WAZ was -4.15+/-0.92 and mean WHZ, -3.91+/-0.61 (p value highly significant). Follow up at day 15, 30 and 45 showed significant improvement in WAZ and WHZ. CONCLUSIONS: Following modified WHO guidelines is feasible, efficacious and cost effective in resource-limited settings. Early discharge of patients is possible with no complications or mortality.

Caspofungin.

Caspofungin is a new antifungal drug meant for intravenous use. It has been shown to be comparable to other antifungal agents such as amphotericin B and fluconazole for empirical therapy in febrile neutropenic patients, oropharyngeal/esophageal candidiasis and invasive aspergillosis. Its efficacy has also been documented in children in small uncontrolled trials. The biggest assets of caspofungin are its excellent tolerability/safety profile and minimal drug interactions.

Use of VSL[sharp]3 in the treatment of rotavirus diarrhea in children: preliminary results.

UNLABELLED: We conducted a double-blind randomized placebo-controlled study to evaluate efficacy and tolerability of VSL[sharp]3 (CD Pharma India) in the treatment of acute rotavirus diarrhea in children. The patients were randomly assigned to receive 4 days of oral treatment with VSL[sharp]3 probiotic mixture or placebo in addition to usual care for diarrhea. RESULTS: Out of 230 rotavirus-positive acute diarrhea children, 224 children completed the study, (113 in the drug group and 111 in the placebo group). At recruitment on Day 1, there were no significant differences between the 2 groups in terms of frequency of vomiting, mean loose stool frequency, stool consistency, and mean frequency of oral rehydration salts (ORS) and intravenous fluids administered. On Day 2, a lower mean stool frequency and improved stool consistency was noted in the drug group, which achieved statistical significance. This was also reflected in the lower volume of ORS administration in the drug group. Even on Day 3, mean loose stool frequency and frequency of ORS use and frequency of intravenous fluid use was significantly lower in the drug group. The differences in the frequency of loose stools persisted till 8 hours of Day 4. After this, as the placebo group also showed spontaneous improvement the difference between the 2 groups in terms of the overall stools frequency became comparable. However, the overall ORS requirement continued to be significantly lower in the drug group even on Day 4. The overall recovery rates were significantly better in the drug group compared with placebo. No side effects were noted with the use of the probiotic mixture. Use of probiotic mixture VSL[sharp]3 in acute rotavirus diarrhea resulted in earlier recovery and reduced frequency of ORS administration reflecting decreased stool volume losses during diarrhea.

Chemotherapy induced nail changes.

Anticancer chemotherapy is associated with a variety of nail changes. We present two children who developed different nail changes, while receiving almost similar antineoplastic drugs.

Celiac disease in a child with beta-thalassemia major: a need for improved screening and awareness.

Growth failure is one of the most common problems in children with thalassemia with multiple etiologies. We present a case of celiac disease, an underdiagnosed cause of growth failure in a child with beta-thalassemia major. A 10-year-old boy on a hypertransfusion regimen was referred for early onset growth failure. Serology for hepatitis B, hepatitis C, and HIV was negative. Serum zinc levels were normal. Thyroid function tests and growth hormone secretion, evaluated with clonidine stimulation test were normal. Malabsorption syndrome was suspected, even in the absence of gastrointestinal symptoms. Tissue transglutaminase were highly raised >300 IU/mL (normal values <15 U/L). Characteristic mucosal lesions on jejunal biopsy confirmed the diagnosis of celiac disease. Institution of a gluten-free diet resulted in rapid gain in weight and improvement in height velocity.