PAP Test Versus Colposcopy for Cervical Cancer Screening in HIV-Seropositive Women: A Case-Control Study.

Purpose: The prevalence of pre-invasive lesions (PIL) of cervix in human immunodeficiency virus (HIV)-seropositive women ranges from 12.5 to 69%. Although Papanicolaou (PAP) test is the recommended screening method, it has concerns owing to high false-negative cytology in HIV-infected women and is associated with high attrition rates. The current study aims to compare the role of routine colposcopy with PAP test at initial visit for screening of pre-invasive lesions of cervix in HIV-seropositive women. Methods: A cross-sectional study of 120 HIV-seropositive women aged 25-50 years and screened for PIL of cervix by PAP test and colposcopy simultaneously was conducted. Colposcopy-directed biopsy was taken if SWEDE score was ≥ 5, and the results were compared with PAP report as well as the histopathology findings. Results: Out of the 120 women screened, abnormal colposcopy was found in 22 women (18.3%) out of which 12 (54.54%) were positive for PIL of cervix on biopsy as well. Abnormal PAP test was found in 6 women (5%), and all had abnormal colposcopy and histopathological findings suggestive of PIL as well. There were 6 women with PIL of cervix who would have been missed if only PAP test was to be used as the screening modality. Conclusion: Colposcopy was superior in detection of PIL of cervix in HIV-seropositive women. Therefore, the authors conclude that colposcopy should be incorporated as a primary screening tool for pre-invasive lesions of cervix in HIV-seropositive women.

Daily versus fortnightly oral vitamin D3 in treatment of symptomatic vitamin D deficiency in children aged 1-10 years: An open labelled randomized controlled trial.

OBJECTIVE: Compare the efficacy and safety of daily versus fortnightly oral vitamin D3 in treating symptomatic vitamin D deficiency in children aged 1-10 years. DESIGN: Open labelled randomized controlled trial. PATIENTS: Eighty children with symptomatic vitamin D deficiency were randomized into group daily (D) and group bolus (B) [40 in each group] to receive oral vitamin D3, 4000 IU daily or 60,000 IU fortnightly for 12 weeks respectively. Both groups received daily oral calcium of 500 mg/day. MEASUREMENTS: Serum calcium (Ca), phosphate (P), alkaline phosphatase (ALP), 25-hydroxy cholecalciferol (25(OH)D), parathyroid hormone (PTH) levels, urine calcium: creatinine ratio and radiological score were assessed at baseline, 4 weeks and 12 weeks. At the end of 12 weeks, 74 children were available for evaluation of the efficacy and safety of both regimens. RESULTS: Both regimens led to a significant increase in Ca and P levels and a fall in ALP and PTH levels from baseline to 4 and 12 weeks of therapy, with no intergroup difference. At 4- and 12-week assessments, all children in both treatment arms achieved 25(OH)D level in sufficiency range, with no significant difference in their geometric mean. Both regimens were associated with asymptomatic transient hypercalcemia [group D-51.4% vs. group B-34.3%; p -0.14] and hypercalciuria (5.7%) in group D that resolved spontaneously on follow-up. CONCLUSIONS: Daily and fortnightly oral vitamin D3 in similar cumulative doses are efficacious for treating symptomatic vitamin D deficiency in children (1-10 years). Treated children should be monitored for serum 25(OH)D, Ca and urinary calcium creatinine ratio.

Adherence to Dietary Recommendations in Children With Type 1 Diabetes: A Cross- Sectional Study.

OBJECTIVE: Medical nutrition therapy is an essential component of management of type 1 diabetes (T1D). This study evaluated adherence of children with T1D to ISPAD 2018dietary recommendations. METHODS: Dietary assessmentconducted for 75 children with T1D of duration > 1-year. RESULTS: Adherence to the recommendations was observed in 40% of participants. Mean (SD) % calorie intake from carbohydrate, fat and protein was 51.93 (6.08), 32.42 (5.66) and 15.95 (2.45), respectively. 68% participants had an energy deficit of >10% of the estimated average requirement. Children in "Adherent" group had significantly lower energy intake from carbohydrates [50.26 (2.11) % vs. 53.18(7.39) %], saturated fats (<10%) and higher from proteins [16.74 (1.68) % vs. 15.42 (2.75) %] as compared to "Non-adherent" group (p <0.05). The mean (SD) HbA1c (%) was significantly lower in the "Adherent" group [7.5 (0.50) vs 9.17 (1.12)]. CONCLUSION: Diet inlarge proportion of Indian children with T1D doesn't meetthe ISPAD recommendations.

High Frequency of Recessive WFS1 Mutations Among Indian Children With Islet Antibody-negative Type 1 Diabetes.

BACKGROUND: While the frequency of islet antibody-negative (idiopathic) type 1 diabetes mellitus (T1DM) is reported to be increased in Indian children, its aetiology has not been studied. We investigated the role of monogenic diabetes in the causation of islet antibody-negative T1DM. METHODS: We conducted a multicenter, prospective, observational study of 169 Indian children (age 1-18 years) with recent-onset T1DM. All were tested for antibodies against GAD65, islet antigen-2, and zinc transporter 8 using validated ELISA. Thirty-four islet antibody-negative children underwent targeted next-generation sequencing for 31 genes implicated in monogenic diabetes using the Illumina platform. All mutations were confirmed by Sanger sequencing. RESULTS: Thirty-five (21%) children were negative for all islet antibodies. Twelve patients (7% of entire cohort, 34% of patients with islet antibody-negative T1DM) were detected to have pathogenic or likely pathogenic genetic variants. The most frequently affected locus was WFS1, with 9 patients (5% of entire cohort, 26% of islet antibody-negative). These included 7 children with homozygous and 1 patient each with a compound heterozygous and heterozygous mutation. Children with Wolfram syndrome 1 (WS) presented with severe insulin-requiring diabetes (including 3 patients with ketoacidosis), but other syndromic manifestations were not detected. In 3 patients, heterozygous mutations in HNF4A, ABCC8, and PTF1A loci were detected. CONCLUSION: Nearly one-quarter of Indian children with islet antibody-negative T1DM had recessive mutations in the WFS1 gene. These patients did not exhibit other features of WS at the time of diagnosis. Testing for monogenic diabetes, especially WS, should be considered in Indian children with antibody-negative T1DM.

Transition of Care of Pediatric Patients with Special Needs to Adult Care Settings: Children with Diabetes Mellitus and Other Endocrine Disorders.

Childhood onset endocrine disorders need long-term medical, psychological and social management. Over time, many illnesses evolve, while others may witness onset of new complications. Thus, the components of the care change as the child grows into adolescence and then adulthood. The transition of children and adolescents with chronic endocrine disorders to adult care continues to be a major challenge. Pediatric and adult healthcare teams should together design a transitional care plan that is developmentally appropriate and responsive to the needs of young adults. The preparation for transition to adult care should begin early in adolescence and involve both the adolescent and his parents. A structured and planned transitional care bridges the gap between pediatric and adult care teams, promote ongoing engagement and build trust with the new healthcare teams. Combined pediatric-adult care transition model for endocrine conditions has yielded high adherence rates and patient satisfaction.

Daily vs. monthly oral vitamin D3 for treatment of symptomatic vitamin D deficiency in infants: a randomized controlled trial.

OBJECTIVES: Compare the efficacy and safety of daily vs. monthly oral vitamin D3 in treating symptomatic vitamin D deficiency in infants. METHODS: 90 infants with symptomatic vitamin D deficiency were randomized into Daily (D) [46 infants] and Bolus (B) [44 infants] groups to receive oral vitamin D3, daily (2000 IU/day) and bolus (60,000 IU/month) for three months respectively. Both groups received daily oral calcium @50 mg/kg/day. Serum calcium (Ca), phosphate (P), alkaline phosphatase (ALP), 25-hydroxy cholecalciferol [25(OH)D], parathyroid hormone (PTH) levels, urine calcium: creatinine ratio and radiological score were assessed at baseline, 4 and 12 weeks. At the end of 12 weeks, 78 infants were available for evaluation of efficacy and safety of both regimens. RESULTS: Both regimens led to a statistically significant increase in Ca and P levels and fall in ALP and PTH levels from baseline to 4 and 12 weeks of therapy, with no inter-group difference. Infants in group D had statistically significant higher mean 25(OH)D levels as compared to group B at 4 weeks (group D 130.89 ± 43.43 nmol/L, group B - 108.25 ± 32.40 nmol/L; p - 0.012) and 12 weeks (group D - 193.69 ± 32.47 nmol/L, group B - 153.85 ± 33.60 nmol/L; p<0.001). Eight infants [group D - 6/41 (14.6 %); group B - 2/37 (5.4 %), p=0.268] developed mild asymptomatic hypercalcemia without hypercalciuria at 12 weeks that corrected spontaneously within a week. CONCLUSIONS: Both daily and monthly oral vitamin D3 in equivalent doses are efficacious and safe for treating symptomatic vitamin D deficiency in infants.

Viewpoints from the National Consultation on Addressing Acute Malnutrition on Mainstreaming Community-Based Program for Management of Acute Malnutrition in India.

High burden of acute malnutrition among children less than 5 years is a major public health problem in India. A "Two-days National Consultation on Addressing Acute Malnutrition" was organized to gather experiences and evidence from 13 states of India on prevention and management of acute malnutrition among children and documenting viewpoints from experts and government counterparts on the same. The consultation centered around five key themes of addressing acute malnutrition; 1) capacity building, 2) strengthening screening, 3) nutritional care of wasting, 4) tracking progress, and 5) scale-up. The paper highlights the experiences and key recommendations around the above key themes. It emerged that there is a need to further accelerate the efforts toward strengthening existing platforms and services to address acute malnutrition among children. Regular trainings of the frontline workers, increased convergence, regular monitoring, and continued service delivery during the pandemic should be undertaken for better outcomes.

Hearts don't lie: Cardiac tuberculosis diagnosed on fine-needle aspiration cytology.

Cardiac involvement in tuberculosis is relatively rare when compared to other organs and often involves the pericardium leading to constrictive pericarditis. Myocardial tuberculoma is exceedingly rare and only seldom cases have yet been reported. Our report is of a case diagnosed on fine-needle aspiration cytology.

Short-Term Adverse Drug Reactions to Antiretroviral Therapy in Children with HIV: A Cohort Study.

OBJECTIVES: To carry out an active surveillance for adverse drug reactions (ADRs) in children with HIV infection newly initiated on antiretroviral therapy (ART), determine risk factors for their occurrence, and assess their influence on adherence to ART. METHODS: All children newly initiated on ART from 1st March 2014 to 30th June 2019 at a tertiary care children's hospital in New Delhi, were actively monitored for ADRs to ART for a period of 6 mo after ART initiation. The frequency, spectrum, and severity of ADRs, their influence on adherence, and risk factors for their occurrence were analyzed. RESULTS: Among the 174 enrolled children, ADRs were observed in 78 (44.8%) children during the first 6 mo after ART initiation. Total numbers of episodes of ADR observed were 108 (0.62 episodes of ADR/child). Sixty percent of events were of grade 1 severity, 19.4% events were of grade 2 and 3 each, while 1 (0.9%) event was of grade 4 severity. Adherence to ART was adversely affected in 21.8% of ADRs. Gastrointestinal symptoms (49.1%) were most frequent among all the events observed. Zidovudine, lopinavir/ritonavir, efavirenz and nevirapine based regimes were significantly associated with hematological, gastrointestinal, neurological, and dermatological ADRs, respectively. Children with immunological suppression were at a higher risk of developing ADRs as compared to those without it [RR 1.9 (95% CI (1.1-3.2)]. CONCLUSIONS: ADRs to ART are very frequent; most of them are mild and self-limiting. However, they can adversely impact adherence to ART. Anticipatory guidance, ongoing monitoring, and provision of symptomatic treatment will help tide over most ADRs and reduce their adverse impact upon ART adherence.

Insulin Resistance in children on Sodium Valproate - A hospital based cross-sectional study in Indian children.

Our objective was to compare the point prevalence of insulin resistance (IR) in children taking sodium valproate (VPA) and phenytoin sodium (PS) monotherapy for >1 year. 150 children, aged 6-18 years, were categorized (50 each) into - group A (VPA), group B (PS) and group C (healthy controls age-sex matched with group A). Groups were compared for metabolic complications and risk factors assessed. The point prevalence of IR and non-alcoholic fatty liver disease was significantly higher in children on VPA (12% and 34% respectively) than on PS and healthy controls, regardless of age, sex, pubertal and nutritional status. The presence of central obesity, acanthosis, hypertension, dyslipidaemia was significantly associated with IR but none showed an independent association on multivariate analysis. Therapy with VPA makes children susceptible to metabolic complications. Close monitoring will facilitate early detection and timely intervention.

Point Prevalence of Peripheral Neuropathy in Children and Adolescents with Type 1 Diabetes Mellitus.

OBJECTIVE: To assess the point prevalence of peripheral neuropathy (PN) in children with type 1 diabetes mellitus (T1DM) and to determine their predictors. METHODS: In this cross-sectional study, children aged 8-18 y with T1DM on insulin therapy for > 2 y and free from acute complications were enrolled. All participants were evaluated for symptoms of PN with diabetic neuropathy symptom (DNS) score and underwent a detailed neurological examination. Assessment of nerve dysfunction was done using nerve conduction studies (NCS). The disease-related factors that increase the risk of PN were determined. RESULTS: Fifty children (52% boys) were enrolled with mean age of 12.2 ± 2.8 y and duration of diabetes 5.1 ± 2.1 y. No subject had clinical evidence or DNS score suggestive of PN. Twenty-eight (56%) children demonstrated subclinical neuropathy on NCS. Proportion of children with pure motor, pure sensory, and mixed motor-sensory neuropathy was 40%, 2%, and 14%, respectively. The peroneal nerve was the most common motor nerve affected. Poor glycemic control (HbA1c > 9%) and longer duration of diabetes (> 5 y) were significantly associated with the risk of PN (p value < 0.05). CONCLUSION: A large proportion of children with T1DM have subclinical PN. Poor glycemic control and longer duration of diabetes are risk factors for nerve dysfunction. Neurophysiological studies should be performed in these children to facilitate early detection.

Clinical Profile of COVID-19 Illness in Children-Experience from a Tertiary Care Hospital.

OBJECTIVE: To detail clinical profile and outcome in children infected with SARS-CoV-2. METHODS: This retrospective study was undertaken at a tertiary care pediatric teaching hospital in Northern India. The data on clinical characteristics and outcome of children (< 18 y) with COVID-19 illness from April 2020-October 2020 were reviewed and analyzed. RESULTS: A total of 2919 children with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) illness were tested for novel COVID-19 virus in the flu emergency (n = 1744), severe acute respiratory infection (SARI) ward (n = 825), and non-COVID area (n = 350) of the hospital. 8.73% (255/2919) children tested positive for SARS-CoV-2 infection. Of the 255 positive cases, 144 (56.47%) were managed on an outpatient basis and 100 (59 boys) required admission in COVID ward. The mortality rate of patients with SARS-CoV-2 was 11.4% (29/255). Majority of children admitted with COVID-19 had severe to critical illness due to the presence of malnutrition and underlying comorbidities. CONCLUSIONS: Children of all age groups were susceptible to COVID-19 illness with a slight male preponderance. Amongst infected, two-third were asymptomatic or had mild symptoms that required outpatient management and home isolation. The adverse outcomes were more commonly seen in infants and children > 10 y of age with malnutrition and comorbid illness.

Indian Academy of Pediatrics Revised (2021) Guidelines on Prevention and Treatment of Vitamin D Deficiency and Rickets.

JUSTIFICATION: The emerging literature on prevalence of vitamin D deficiency in India, prevention and treatment strategies of rickets, and extra-skeletal benefits of vitamin D suggest the need for revising the existing guidelines for prevention and treatment of vitamin D deficiency in India. OBJECTIVES: To review the emerging literature on vitamin D prevalence and need for universal vitamin D supplementation. To suggest optimum vitamin D therapy for treatment of asymptomatic and symptomatic vitamin D deficiency, and rickets. To evaluate the extra-skeletal health benefits of vitamin D in children. PROCESS: A National consultative committee was formed that comprised of clinicians, epidemiologists, endocrinologists, and nutritionists. The Committee conducted deliberations on different aspects of vitamin D deficiency and rickets through ten online meetings between March and September, 2021. A draft guideline was formulated, which was reviewed and approved by all Committee members. RECOMMENDATIONS: The group reiterates the serum 25-hydroxy vitamin D cutoffs proposed for vitamin D deficiency, insufficiency, and sufficiency as <12 ng/mL, 12-20 ng/mL and >20 ng/mL, respectively. Vitamin D toxicity is defined as serum 25OHD >100 ng/mL with hypercalcemia and/or hypercalciuria. Vitamin D supplementation in doses of 400 IU/day is recommended during infancy; however, the estimated average requirement in older children and adolescents (400-600 IU/day, respectively) should be met from diet and natural sources like sunlight. Rickets and vitamin D deficiency should be treated with oral cholecalciferol, preferably in a daily dosing schedule (2000 IU below 1 year of age and 3000 IU in older children) for 12 weeks. If compliance to daily dosing cannot be ensured, intermittent regimens may be prescribed for children above 6 months of age. Universal vitamin D supplementation is not recommended in childhood pneumonia, diarrhea, tuberculosis, HIV and non-infectious conditions like asthma, atopic dermatitis, and developmental disorders. Serum 25-hydroxy vitamin D level of >20 ng/mL should be maintained in children with conditions at high-risk for vitamin deficiency, like nephrotic syndrome, chronic liver disease, chronic renal failure, and intake of anticonvulsants or glucocorticoids.

Prevalence and management of vitamin D deficiency in children with newly diagnosed coeliac disease: cohort study.

BACKGROUND: Coeliac disease (CD) causes deficiency of various micronutrients including vitamin D, and there are no specific guidelines for treatment. AIMS: To determine the prevalence of vitamin D deficiency in children newly diagnosed with CD and the role of oral high-dose vitamin D in its treatment. METHODS: Calcium intake, sun exposure and biochemical and radiological parameters related to vitamin D deficiency were compared between 60 children aged 0-18 years diagnosed with CD and 60 healthy age- and sex-matched controls. The cases with serum 25(OH)D (<20 ng/ml) were given oral vitamin D (60,000 IU/week) and calcium (500 mg/day) for 12 weeks, along with a gluten-free diet (GFD); they were re-evaluated within a week of completion. The primary outcome measure was the serum 25(OH)D level, and secondary measures included serum calcium, phosphorus, alkaline phosphatase, parathormone and clinical and/or radiological rickets. RESULTS: The prevalence of vitamin D deficiency (25(OH)D <20 ng/ml) was significantly greater in the cases (n=38, 63.3%) than in the controls (n=27, 45.0%). Upon treatment, all 38 cases with vitamin D deficiency showed a significant rise in 25(OH)D levels along with normalisation of other biochemical abnormalities. Two children had 25(OH)D levels >100 ng/ml with no other feature suggestive of vitamin D toxicity. CONCLUSIONS: Vitamin D deficiency is more prevalent in children with CD. Administration of oral high-dose vitamin D for 12 weeks along with a GFD leads to a robust response, indicating rapid mucosal recovery. The vitamin D dosage recommended for malabsorption states may be excessive in CD.Abbreviations: ALP: alkaline phosphatase; CaBP: calcium-binding proteins; CD: coeliac disease; GFD: gluten-free diet; PTH: parathormone; RU: reproducibility units; 25(OH)D: 25 hydroxy vitamin D.

Pubertal Development and its Determinants in Adolescents With Transfusion-Dependent Thalassemia.

OBJECTIVES: To assess pubertal development and its determinants in adolescents with transfusion-dependent thalassemia (TDT). METHODS: In this cross-sectional study from a tertiary teaching hospital in Delhi, records of adolescents aged 17-19 years with TDT on regular transfusion at thalassemia day-care centre were reviewed. Pubertal development and its determinants were assessed. RESULTS: Records of 58 (33 male) adolescents with TDT were reviewed. Among them, 42 (72.4%) had normal/delayed onset with spontaneous progression of puberty, while 16 (27.6%) had pubertal arrest/failure and received hormonal replacement therapy (HRT). Short stature was observed in all adolescents on HRT. Amongst other endocrinopathies, only hypoparathyroidism was found to be significantly higher in the HRT group. On multivariate analysis, serum ferritin (OR-1.005, 95% CI 1.002, 1.009) was observed to be the only significant determinant of pubertal arrest/failure. CONCLUSIONS: A significant proportion of adolescents with TDT continue to have pubertal arrest/failure. High systemic iron load is the key determinant for this.

Brief Report: Subclinical Kidney Dysfunction in HIV-Infected Children: A Cross-Sectional Study.

OBJECTIVE: Most of the kidney dysfunction in HIV-positive children receiving antiretroviral therapy (ART) is attributed to tenofovir. There is a paucity of data on kidney dysfunction in tenofovir-naive children. The primary objective was to know the point prevalence of albuminuria and ß2-microglobulinuria in HIV-infected children aged 3-18 years receiving ART. Albuminuria and ß2-microglobulinuria were used as surrogates for glomerular and tubular dysfunction, respectively. The secondary objective was to determine their predictors. DESIGN: Cross-sectional study-design. METHODS: One hundred consecutive HIV-positive children (3-18 years) on ART were included. Spot urine sample was analyzed for urinary creatinine, total protein, microalbumin, and ß2-microglobulin. Albuminuria was defined as albumin to creatinine ratio of >30 mg/g; proteinuria as urine dipstick ≥trace or spot urine protein to creatinine ratio (uPCR) of ≥0.2. ß2-microglobulinuria was defined as ß2-microglobulin levels of >350 µg/L. RESULTS: There were 71 boys and 29 girls. Most of the children had WHO clinical stage I and were getting zidovudine-based regimen. Only 7 children were getting tenofovir. estimated Glomerular Filtration Rate and serum creatinine were normal in all children. Approximately half (48%) had renal dysfunction in the form of glomerular dysfunction (26%), tubular dysfunction (27%), or both (5%). Age at diagnosis was significantly associated with ß2-microglobulinuria (P = 0.044). None of the selected variables were associated with albuminuria. CONCLUSIONS: HIV-associated glomerular and tubular dysfunction is common in children receiving ART other than tenofovir. The standard guidelines should consider including routine urinary biomarker monitoring in children on ART.