Seroprotection With Three Dose vs Four Dose Schedule for Hepatitis B Vaccination in Children Living With Human Immunodeficiency Virus: Follow-up Data at 36-42 Months From a Randomized Controlled Trial.

OBJECTIVE: To compare the long-term seroprotection (anti-HBs ≥10 IU/L) in children living with HIV (CLHIV) receiving a 3- or 4-dose double-strength (20 µg) recombinant Hepatitis B virus (rHBV) vaccination. METHODS: We present anti-retroviral therapy (ART) clinic based follow-up data collected from January, 2021 to August, 2022, from CLHIV who had received either 3-dose or 4-dose double-strength (20 µg) rHBV vaccination, after 36-42 months and assessed for anti-HBs titres, naïve and memory T-helper lymphocytes, CD4 counts and HIV viral load. Children found unprotected after primary immunization, were administered a single double-strength rHBV vaccine booster dose (20 µg) and seroprotection was reassessed after 4 and 12 weeks. RESULTS: Out of 50 children initially vaccinated, 45 were followed up 36-42 months after primary immunization; median (IQR) anti-HBs titres (IU/L) were 230 (80.5 - 305.7) in the 3-dose group (n=23) and 263.5 (47.1-332.9) in the 4-dose group (n=22) (P=0.33). 19 and 20 children in the 3-dose and 4-dose group, respectively, were seroprotected (P=0.24). Anti-HBs titres at 36-42 months correlated with CD4 counts at baseline, anti-HBs titres at 1 and 6 months after completion of primary immunization and percentage of memory T-helper lymphocytes. All the five children (3-dose group: 4; 4-dose group: 1) who received rHBV vaccine booster dose attained seroprotection one-month later. CONCLUSION: Three-dose double strength rHBV vaccination schedule offers comparable seroprotection to a 4-dose double strength rHBV vaccination schedule in CLHIV receiving ART.

COVID-19 Antibody Response in Patients with Thalassemia.

Background The coronavirus disease 2019 (COVID-19) can severely affect people with comorbidities such as those with diabetes, hypertension, chronic lung disease, cancer, and hemoglobinopathies. Studies assessing the clinical characteristics and immune response to COVID-19 infection in patients with thalassemia are limited. Objectives The primary objective of the study was to study the clinical pattern and the immunoglobulin G (IgG) antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with transfusion-dependent thalassemia (TDT) compared to patients without thalassemia. The secondary objective wasto study the relationship of COVID-19 severity with IgG antibody titers. Setting, Design, and Participants This case-control study was conducted at a tertiary care hospital between January 2021 and August 2022. A total of 30 patients with TDT (mean age: 12.7 years, SD: 4.7) and 30 patients without thalassemia (mean age: 13.9 years, SD: 7) who tested positive for COVID-19 in the preceding six weeks were recruited. Methods Serum samples from the cases and controls were collected after 6, 12, and 24 weeks of COVID-19 infection for IgG antibody estimation using chemiluminescent immunoassay. Outcome variables The primary variable was comparative analysis of antibody levels and clinical profile of COVID-19 in cases and controls. The secondaryvariable was association of the severity of COVID-19 with the antibody titers produced. Results Symptomatic individuals among cases (n=12) were significantly lesser than controls (n=22) (p=0.009). The median IgG titers of cases and controls were comparable at six weeks (p=0.40), but the titers were significantly lower for cases at 12 weeks (p=0.011) and 24 weeks (p=0.006). There was significant fall in titers from 6 to 12 and 24 weeks in both the groups. The titers were not affected by COVID-19 severity and pre-existing comorbidities. Conclusion Patients with TDT manifest with mild or asymptomatic COVID-19 and mount a comparable IgG antibody response to COVID-19 akin to controls. However, this serological response could not sustain over three to six months advocating the need for protection through vaccination.

Predictors of Candidemia during Febrile Episode in Lymphoreticular Malignancy Affecting Paediatric Population.

Limited studies on candidemia in malignancy in the paediatric population from developing countries show a high incidence, high morbidity and a unique epidemiology as compared to developed nations. Our prospective observational study aimed to explore the prevalence of invasive candidiasis, especially candidemia, in febrile paediatric patients with lymphoreticular malignancy. A sample size of 49 children, with 100 recorded febrile episodes was studied. The relevance of candida colonization and mannan antigen detection as indicators of impending candidemia was evaluated. Genotypic identification of the yeast isolates was followed by sequence analysis using the NCBI-BLAST program, and the generation of the phylogenetic tree using MEGA 6.0 software. We observed a 5% prevalence of candidemia among febrile paediatric patients with lymphoreticular malignancy, predominantly caused by non-albicans candida. Colonization at multiple anatomical sites decreased from day 1 to day 8 of febrile episodes. Significant candida colonization (colonization index ≥0.5) was seen in a larger proportion of candidemia patients on day 1 and day 4 (p < 0.001) displaying a definite association between the two. The receiver operator characteristic (ROC) curve analysis for mannan antigen level revealed a cut-off of ≥104.667 pg/mL, suitable for predicting candidemia with a sensitivity of 100%, specificity of 92% and area under ROC value of 0.958 (95% CI: 0.915-1; p < 0.001). A phylogenetic tree with three population groups, clade 1, 2 and 3, consisting of Candida auris (1), Candida tropicalis (2) and Candida parapsilosis (2), respectively, was generated. The diagnosis of candidemia based on mannan antigen detection gives early results and has high negative predictive values. It can be combined with other biomarkers to increase sensitivity, specificity and positive predictive value.

Chemotherapy-Induced Oxidative Stress in Pediatric Acute Lymphoblastic Leukemia.

Introduction Plasma antioxidant capacity in children receiving chemotherapy decreases due to the effect of the disease and chemotherapy. Increased oxidative stress (OS) predisposes to an increased risk for chemotherapy-related toxicity and febrile neutropenic episodes. Materials and methods We conducted this case-control study in the hematology-oncology unit of the department of pediatrics of a tertiary hospital in Delhi, India, from November 2017 to March 2019 to compare OS between children with acute lymphoblastic leukemia (ALL) and healthy controls. We estimated the trends in OS as measured by the plasma total antioxidant capacity (TAC) and thiobarbituric acid reactive substance (TBARS) levels at baseline and at the completion of induction I (four weeks), induction II (eight weeks), and induction IIA-consolidation (16 weeks) phases of chemotherapy in children with ALL. We also assessed the change in OS during different phases of initial treatment and studied the association between OS and the hematological toxicity of chemotherapy (determined by the need for blood component therapy and the number of febrile neutropenic episodes) and serum cobalamin and folate levels. Results OS was significantly higher in children with ALL at diagnosis (n=23) compared to controls (n=19). The median (interquartile range (IQR)) TAC levels (mM) were significantly lower (1.21 (1.05-1.26) versus 1.28 (1.26-1.32), P=0.006), and TBARS levels (nmol/mL) were significantly higher (312.0 (216.6-398.0) versus 58.5 (46.2-67.2), P<0.001) in children with ALL at diagnosis compared to controls. OS was highest at the end of the induction I phase (four weeks) despite the patients being in clinical and hematological remission. OS at the completion of intensive chemotherapy (16 weeks) was higher than at diagnosis. A significant correlation was found between serum folate levels and TAC levels at baseline (P=0.03). Serum cobalamin levels, the need for blood component therapy, and the number of febrile neutropenic episodes did not have any association with OS. Conclusion Children with ALL had significantly higher OS compared to controls, indicating that underlying disease affects the oxidative balance unfavorably. Chemotherapy itself increases oxidative stress.

Correlation of T-regulatory Cells and Iron Status in ß-Thalassemia Major Patients.

Background The increased risk of infections in transfusion-dependent ß-thalassemia major (TDT) patients is mainly due to underlying immune dysfunction; however, its cause is largely unidentified. There is sufficient evidence to suggest immune changes due to iron deficiency; however, similar studies demonstrating the effects of iron excess on immune cells in these cases are limited. Aim and objectives To analyze the correlation between T-regulatory cells and iron stores in ß-thalassemia major patients. Methods In this study, 20 ß-thalassemia major cases and 20 healthy controls were studied for complete hemogram, iron profile, and flow cytometric immunophenotyping for CD3+, CD4+, CD8+, and T-regulatory cells markers (CD4+CD25+ and CD4+CD25+FOXP3+). Result Significantly higher levels of serum iron, ferritin, transferrin saturation, and CD4+ cell percentage were observed in cases than in controls. In 70% of cases with serum ferritin cut-off levels of less than 1000 µg/L, the T-regulatory cell marker CD4+CD25+ and serum ferritin revealed a significant moderate positive correlation (p=0.031, r=0.627). These same 70% cases also demonstrated a moderately significant positive correlation between serum iron and absolute lymphocyte count (r=0.529, p=0.042). Conclusion The results suggest that serum ferritin in excess amounts can increase T-regulatory cells, which may further alter the immune status of TDT patients; however, the absence of such a correlation in cases with serum ferritin of more than 1000 µg/L remains unanswered. It is important to understand immune system alterations as this will help provide new modalities for managing thalassemia patients in the form of immunoregulatory therapies.

Higher baseline natural killer cell counts are associated with a lower 8-day blast count and lower day 33 minimal residual disease in children with pediatric B-acute lymphoblastic leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Despite advancements in treatment, a significant proportion of children relapse. Recently, immunotherapy has gained momentum and is becoming popular, especially for relapsed and refractory cases. NK cells are an important part of tumor immunity and are involved in the direct killing of tumor cells. Their role in B-ALL has not been explored. Therefore, this study was conducted to correlate the number of NK cells with standard prognostic parameters in B-ALL. METHODS: 25 subjects with newly diagnosed B-ALL between 0-14 years were recruited for the study from Pediatric OPD or emergency of the hospital. Along with a complete hemogram and peripheral smear examination, immunophenotyping by flow cytometry was done at the time of diagnosis for NK cell enumeration. The number of NK cells was correlated with standard prognostic parameters using the spearman correlation coefficient. RESULTS: Baseline NK cell percentage demonstrated a significant negative correlation with Prednisone poor day 8 blast response (P value = 0.02, r value = -0.44) and positive MRD (P value = 0.01, r value = -0.49) at day 33. A negative correlation was also noticed between NK cell percentage and unfavorable cytogenetics (hypodiploidy), although it was not significant (P value = 0.06, r value = -0.38). The number of NK cells did not correlate with age, gender and WBC count. Therefore, evaluating NK cells at diagnosis may serve as a simple and useful parameter for prognostication and risk stratification. CONCLUSION: It may be assumed that a higher percentage of NK cells is associated with improved outcomes and probably a better prognosis. NK numbers may serve as an early independent parameter predicting prognosis and survival in children with B-ALL, thus helping to decide individual therapeutic regimens.

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.

Shared care for children with cancer in India through social and healthcare partnerships during the COVID-19 pandemic.

BACKGROUND: The COVID pandemic posed a challenge for the tertiary centers to continue treatment. Some tertiary centers were designated as COVID-only hospitals, making it difficult for existing childhood cancer patients to continue their treatment at those centres. The need for shared care in childhood cancer was perceived by Cankids and its partnering childhood cancer-treating centers in North and East India. AIM: We aim to show how Cankids upscaled its shared care model to ensure that COVID designated hospitals connected with other hospitals who have to continue to provide care to childhood cancer patients in the pandemic and thus ensured the continuation of treatment for these patients. METHODS AND RESULT: The need assessment of the beneficiaries was done in discussion with the hospital of origin and destination hospital. The need for shared care was also discussed with the families and consent was taken before shifting their children. Cankids with the help of advisors identified cases of high risk that need immediate attention, proactive regular monitoring, and help in care planning with the perspective and recommendation of the multiple providers. The shared care unit came forward with reasonable and discounted packages for treatment. There was a total of five hospitals requiring shared care, and 55 children were supported from April to November 2020. The median age was 8 years and their hospital of origin are in Bihar, Uttar Pradesh, West Bengal, and Delhi. The expenditure on the treatment of the 55 patients was INR 61 61 636 ($ 84 843), with a median of INR 41765 (IQR 19491-174 129) on each patient. Total 291 trips for the transport were arranged and all the patients combined stayed 174 days at Cankids accommodation facility. CONCLUSION: The shared care helped the patients access standard treatment and reduce the financial burden.

Methotrexate-Induced Leukocytoclastic Vasculitis.

Erythematous tender cutaneous lesions developed in a 10-year-old child of acute leukemia receiving oral methotrexate and 6-mercaptopurine during maintenance phase of chemotherapy. She was also found to have coagulopathy and transaminitis. Differential clinical diagnosis included infectious processes, pyoderma gangrenosum, connective tissue disorders like rheumatoid neutrophilic dermatitis, and drug-induced side effects. Oral methotrexate was withheld following which the lesions subsided. Skin biopsy revealed a diagnosis of leukocytoclastic vasculitis. Cutaneous vasculitis is a rare side effect of methotrexate and its possibility should be considered in any patient who develops skin lesions while being receiving chemotherapy.

Oxidative Stress in Cerebrospinal Fluid During Treatment in Childhood Acute Lymphoblastic Leukemia.

Introduction Central nervous system (CNS) treatment using intrathecal chemotherapy and cranial radiation to enable long-term disease-free survival from childhood acute lymphoblastic leukemia (ALL) comes at the cost of neurotoxic side effects and long-term sequelae. We investigated oxidative stress as a possible mechanism of chemotherapy-induced neurotoxicity in children with ALL. Materials and methods In this case-control study, we estimated the cerebrospinal fluid (CSF) levels of 8-hydroxy-deoxyguanosine (8-OH-dG), a DNA damage product, in children with B-cell ALL and control children. CSF samples were collected at diagnosis, at end of Induction 1, Induction 2, and Induction 2A - consolidation phase. CSF 8-OH-dG levels were compared in children with and without neurotoxicity. Results Children with ALL (n=23) at diagnosis had significantly higher median (interquartile range, IQR) CSF 8-OH-dG levels (ng/mL) compared to controls (n=19) [1.97 (1.59-2.56) Vs 0.65 (0.59-0.82), P<0.001]. CSF 8-OH-dG levels at the end of four weeks, eight weeks, and 16 weeks of chemotherapy were [3.96 (2.85-5.44) ng/mL], 1.00 (0.89-1.09), and 3.73 (2.80-4.39) ng/mL, respectively. Out of 23 children with ALL, 12 developed neurotoxicity; the CSF levels of 8-OH-dG in them were only marginally higher compared to those who did not develop neurotoxicity. The CSF 8-OH-dG levels did not show a significant correlation with the number of doses of methotrexate or vincristine received. Conclusion Chemotherapy increases the CNS oxidative stress as measured by CSF 8-OH-dG levels, with the levels being proportional to the intensity of chemotherapy. Children with neurotoxicity had only marginally higher CSF 8-OH-dG levels as compared to children without neurotoxicity.

Procalcitonin Clearance, CD64, and HLA-DR as Predictors of Outcome in Febrile Neutropenic Children With Lymphoreticular Malignancies.

BACKGROUND: Febrile neutropenia (FN) is a dreaded complication of cancer chemotherapy. There has been a lot of improvement in supportive care in FN that has drastically reduced the infection-related mortality in these patients. The focus now is on reducing infection-related morbidity, healthcare costs and optimizing the quality of life of the child as well as their family during these episodes. In this study, biomarkers were studied as predictors of outcome so that outcome can be predicted earlier, and treatment modified accordingly. OBJECTIVE: To measure procalcitonin levels (at baseline and day 3), procalcitonin clearance, neutrophil CD64 expression levels (at baseline) and monocyte HLA-DR expression levels (at baseline), and their correlation with outcome. SETTING: Tertiary care hospital. STUDY TYPE: Cross-sectional observational study. POPULATION/PARTICIPANTS: Sixty-five episodes of FN in children below 12 years with lymphoreticular malignancies. Children receiving antibacterial and/or antifungal treatment within the last 7 days were excluded from the study. METHODS: The subjects recruited into the study had undergone complete clinical and laboratory evaluation as per hospital protocol. Procalcitonin (day 0 and 3), neutrophil CD64 expression, and monocytic HLA-DR expression levels were measured in these patients. RESULTS: Sixty-five episodes of FN were studied in children with lymphoreticular malignancy. It was found that procalcitonin and HLA-DR are very good markers of outcome, whereas CD64 although a good marker, was inferior to procalcitonin and HLA-DR in predicting outcome. Procalcitonin clearance was found to be superior to single value of procalcitonin. Furthermore, procalcitonin on day 3 was found to be a better predictor of outcome compared with its baseline value. Also, it was found that procalcitonin and HLA-DR had a significant correlation with baseline C-reactive protein levels. CONCLUSIONS: On the basis of the findings of the study we suggest that serial monitoring of procalcitonin levels be used in febrile neutropenic children with cancer. Procalcitonin levels on day 3 alone can be offered in resource poor setting. The role of HLA-DR and CD64 also seems promising and needs to be further explored in larger multicentric studies.

Serum and Urinary Hepcidin for Diagnosing Iron-deficiency Anemia in Under-5 Children.

Bone marrow iron estimation remains the gold standard for diagnosing iron-deficiency anemia (IDA); serum ferritin, total iron-binding capacity, and transferrin saturation are routinely used as surrogate markers of IDA. However, these tests are marred by problems like poor specificity and sensitivity. Recently, hepcidin, a protein hormone synthesized in the liver and excreted in urine, has been shown to be related to iron status. We estimated the serum and urinary hepcidin levels in healthy children 6 to 60 months of age with (n=30) and without IDA (n=30). The mean (SD) serum hepcidin levels in children with IDA were significantly lower than those in children without IDA (3.03 [1.06] vs. 4.78 [3.94] ng/mL; P=0.02). The mean (SD) urinary hepcidin levels were also significantly lower in children with IDA than those in children without IDA (2.29 [0.53] vs. 2.79 [0.75] ng/mL; P=0.004). Performance of urinary and serum hepcidin compared with serum ferritin (<12 µg/L) for diagnosing IDA in terms of area under the receiver operating characteristic curve was 0.704 (P=0.007) and 0.59 (P=0.22), respectively. Serum hepcidin is not useful for diagnosing IDA in under-5 children. In contrast, urinary hepcidin holds promise as a noninvasive diagnostic tool for IDA in under-5 children.

Glucose Homeostasis Markers in Beta-Thalassemia.

BACKGROUND: Glycosylated hemoglobin (HbA1c) has been a well-recognized marker of glucose homeostasis among thalassemics. Recently some studies have proposed the role of fructosamine as a better marker as compared with HbA1c. Hence, the study was carried out to find out which marker holds promise among Indian beta-thalassemic children. METHODS: In this case-control study, 60 diagnosed cases of beta-thalassemia major and equal number of normal controls who were ≥8 years of age were enrolled. HbA1c, fructosamine, and fasting insulin levels were measured in all. Oral glucose tolerance test was done as a gold standard and the measured parameters were compared. RESULTS: HbA1c was significantly higher in cases (7.10% [±0.47%]) than in controls (5.15% [±0.19%]) (P<0.001). Thalassemics with abnormal glucose tolerance had higher HbA1c level (7.34% [±0.57%]) than those with normal glucose tolerance (7.05% [±0.43%]) (P=0.05). Insulin resistance was noticed among thalassemics with abnormal glucose tolerance as compared with their normal counterparts (P=0.04). No significant difference was found in fructosamine levels between cases (239.80 [±31.80] µmol/L) and controls (234.10 [±21.34] µmol/L) (P=0.25) or between thalassemics with abnormal glucose tolerance (243.92 [±21.94] µmol/L) and their normal counterparts (238.77 [±33.93] µmol/L) (P=0.62). CONCLUSIONS: The use of HbA1c as a diagnostic marker for diabetes in hemolytic anemias has to be done with caution as its baseline values are higher in them. Despite this finding, HbA1c continues to be a good marker for worsening glucose homeostasis in thalassemics as higher values were found in thalassemics with abnormal glucose tolerance compared with their normal counterparts. The present study did not find any relationship of fructosamine levels with impaired glucose tolerance in beta-thalassemia.

Glucose Homeostasis and Effect of Chelation on ß Cell Function in Children With ß-Thalassemia Major.

OBJECTIVE: To assess the prevalence of impaired glucose tolerance in ß-thalassemia major and correlate it with chelation therapy. MATERIALS AND METHODS: Sixty-seven subjects with ß-thalassemia major, aged 1 to 20 years, were enrolled in our prospective cohort. Clinical details were recorded. Baseline oral glucose tolerance test, serum insulin, C peptide, and insulin resistance were measured. The biochemical profile was repeated after 6 months. RESULTS: The mean age of subjects was 7.43±4.48 years. Eight (11.9%) subjects had impaired fasting glucose, 7 (10.4%) had impaired glucose tolerance, and 1 (1.4%) subject had diabetes at baseline. Subjects with abnormal glucose profile had longer disease duration (95% confidence interval [CI] of difference=-6.64 to -0.68; P=0.019) and higher fasting blood glucose (95% CI of difference=-32.1 to -10.5; P=0.001) and serum ferritin (95% CI of difference=-219.8 to -3.4; P=0.001) than normoglycemic subjects. Insulin resistance and serum ferritin showed significant increase at 6 months (P<0.001 and P=0.001, respectively). Patients on deferiprone alone significantly improved glucose homeostasis on follow-up than those on desferrioxamine or combination therapy of desferrioxamine and deferiprone (P<0.05). CONCLUSIONS: Prolonged disease duration and higher serum ferritin adversely affects glucose homeostasis in thalassemic children. Deferiprone was the most effective chelator to improve glucose homeostasis in chronically transfused thalassemics.

Comparative Efficacy and Safety of Oral Iron Chelators and their Novel Combination in Children with Thalassemia.

OBJECTIVE: To compare the efficacy and safety of oral iron chelators (Deferiprone and Deferasirox) when used singly and in combination in multi-transfused children with thalassemia. DESIGN: Prospective comparative study. SETTING: Thalassemia Center of a medical college affiliated hospital. PARTICIPANTS AND INTERVENTION: 49 multi-transfused children with thalassemia with a mean (SD) age 11.6 (6.21) y received daily chelation therapy with either deferiprone alone (75 mg/kg/day in 3 divided doses), deferasirox alone (30 mg/kg/day single dose) or their daily combination (same dose as monotherapy) for 12 months. OUTCOME MEASURES: Serum ferritin levels at the start of study, after 6 months and after 12 months. MRI T2* of liver and heart initially and after 6 months of follow up. 24-hour urinary iron excretion values at the outset and after 12 months of chelation therapy. At every visit for blood transfusion, all patients were clinically assessed for any adverse effects; liver and renal functions were monitored 6-monthly. RESULTS: After 12 months of respective chelation therapy, serum ferritin values decreased from a mean of 3140.5 ng/mL to 2910.0 ng/mL in deferiprone alone group, 3859.2 ng/mL to 3417.4 ng/mL in deferasirox alone group and from 3696.5 ng/mL to 2572.1 ng/mL in the combination group. The combination therapy was more efficacious in causing fall in serum ferritin levels compared to deferiprone and deferasirox monotherapy (P= 0.035 and 0.040, respectively). Results of MRI T2 were equivocal. Combined drug usage produced maximum negative iron balance in the body by maximally increasing the iron excretion in urine from 61.1 umol/day to 343.3 umol/day (P = 0.002). No significant adverse reactions were noticed in either the monotherapy or the combination group. CONCLUSION: Oral combination therapy of deferiprone and deferasirox appears to be an efficacious and safe modality to reduce serum ferritin in multi-transfused children with thalassemia.

Systematic review and meta-analysis of randomized controlled trials on the role of mometasone in adenoid hypertrophy in children.

OBJECTIVES: Mometasone has been reported to improve the symptoms of nasal obstruction in children with adenoidal hypertrophy. This systematic review and meta-analysis were conducted to evaluate the role of mometasone on different nasal symptoms, otitis media with effusion, adenoid size, and quality of life in children with adenoidal hypertrophy. METHODS: A comprehensive search of MEDLINE, EMBASE, CINAHL and COCHRANE Collaboration databases was undertaken. We identified all the randomized controlled trials (RCTs) in children with adenoidal hypertrophy that compared the effects of mometasone nasal spray and normal saline nasal spray on different outcomes. The deadline of the search was April 2015. The search was supplemented by hand searching of cross-references in the studies and reviews and by contacting the authors of various studies. Only English language RCTs were considered for the systematic review. The primary outcomes were improvement in symptoms of nasal obstruction, mouth breathing, rhinorrhea, snoring, cough, and total nasal symptoms. The secondary outcomes were improvement in otitis media with effusion, quality of life, and size of adenoid. Quality assessment of RCTs was performed using SIGN 50 and Cochrane risk of bias tools. Risk ratio (RR), weighted mean differences (WMD) and their 95% confidence intervals (CI) were calculated for dichotomous and continuous data, respectively. Random effects model was used for the analyses. Heterogeneity was measured by using the I(2) statistics and p value <0.05. RESULTS: Our search generated 87 citations, of which eight RCTs met the inclusion criteria. The methodological quality of all the RCTs was poor. There was no significant difference between mometasone and control groups for the patient's characteristic and grades of different nasal symptoms, otitis media with effusion, obstructive sleep apnea, and quality of life at the basal level. There was also no significant difference in the number of patients with different symptoms at the basal level. After the administration of mometasone, there were significant improvements in grades of nasal obstruction, 0.8±0.5 versus 2.0±0.6, WMD -1.16 [-2.09, -0.23], snoring 0.3±0.4 versus 1.6±0.6, WMD -1.07 [-2.09, -0.05], total nasal symptoms 2.9±1.3 versus 6.9±1.5, WMD -4.09 [-6.64, -1.53], obstructive sleep apnea, 0.6±0.3 versus 1.4±0.4, WMD -0.95 [-1.74, -0.16], as well as the percentage of patients with nasal obstruction, snoring, obstructive sleep apnea, compared to control. There was tendency of improvement in rhinorrhea, and cough with mometasone. Compared to control, mometasone nasal spray significantly improved adenoid size or adenoid/choana ratio 50.9±8.8 versus 74.2±12.6, WMD -21.2 [-34.0, -8.4], change in adenoid/choana obstruction from the basal level (p=0.01), and percentage of patients with adenoid hypertrophy, 26% versus 92%, RR 0.29 [0.18, 0.48]. There was improvement in otitis media with effusion, 40% versus 72%, pure tone audiometry 5.2±11 versus 11.6±11dB, WMD -6.40dB [-12.65, -0.15], and quality of life with mometasone. Subgroup analyses showed that RCTs that followed blinding showed significantly less response compared to RCTs that did not follow it for most of the outcomes. CONCLUSIONS: Mometasone caused improvements in outcomes of nasal obstruction, snoring, total nasal symptoms, pure tune audiometry, otitis media with effusion, adenoid size, and quality of life. The data is based on meta-analysis of RCTs of poor methodological quality. A high methodological quality, placebo controlled RCT of different doses and duration of administration of mometasone is required to evaluate its clear efficacy and safety in children with adenoid hypertrophy.

Assessment of quality of life during treatment of pediatric oncology patients.

BACKGROUND: The objective of this study was to assess health-related quality of life (HRQOL) of pediatric cancer patients and their parents in North India. MATERIALS AND METHODS: Seventy-five cancer children were assessed for HRQOL, using Lansky play performance scale and health utility index-2 (HUI-2). Fifty-seven patients were followed-up after 4 months after therapy and reassessed. Their parents were also assessed using World Health Organisation (WHO) QOL BREF. Seventy five controls were also assessed and compared. RESULTS: Lansky and HUI-2 scores of patients, as well as WHO QOL BREF of parents were significantly poor in cancer patients when compared to controls. There was significant improvement after therapy in patients with lymphomas and miscellaneous tumors. Pain and self-care were found to be maximally affected domains on HUI-2. CONCLUSIONS: Large prospective multicenter studies may be undertaken and hence that need based interventions can be planned.

Congenital tuberculosis: a rare manifestation of a common disease.

Congenital tuberculosis is difficult to diagnose unless there is a high index of suspicion. A 2-month-old infant boy presented with a history of fever since birth and failure to thrive. Chest radiograph demonstrated right upper lobe collapse/consolidation and an ultrasonogram of the abdomen showed multiple hypo-echoic hepatic and splenic lesions, and multiple retroperitoneal nodes. Fine needle aspiration of a cervical lymph node detected acid-fast bacilli (AFB). The mother's chest radiograph demonstrated features of pulmonary tuberculosis. Placental histology detected AFB. The combined clinical and laboratory features in both mother and infant supports the diagnosis of congenital tuberculosis.