CDC's COVID-19 International Vaccine Implementation and Evaluation Program and Lessons from Earlier Vaccine Introductions.

The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions.

A guide to best practice in faculty development for health professions schools: a qualitative analysis.

BACKGROUND: This is a practice guide for the evaluation tool specifically created to objectively evaluate longitudinal faculty development programs (FDP) using the "5×2 -D backward planning faculty development model". It was necessary to create this tool as existing evaluation methods are designed to evaluate linear faculty development models with a specific endpoint. This backward planning approach is a cyclical model without an endpoint, consisting of 5 dynamic steps that are flexible and interchangeable, therefore can be a base for an evaluation tool that is objective and takes into account all the domains of the FDP in contrast to the existing, traditional, linear evaluation tools which focus on individual aspects of the program. The developed tool will target evaluation of longitudinal faculty development programs regardless of how they were planned. METHODOLOGY: Deductive qualitative grounded theory approach was used. Evaluation questions were generated and tailored based on the 5 × 2-D model followed by 2 Delphi rounds to finalize them. Based on the finalized evaluation questions from the results of the Delphi rounds, two online focus group discussions (FGDs) were conducted to deduce the indicators, data sources and data collection method. RESULTS: Based on the suggested additions, the authors added 1 new question to domains B, with a total of 42 modifications, such as wording changes or discarding or merging questions. Some domains received no comments, therefore, were not included in round 2. For each evaluation question, authors generated indicators, data sources and data collection methods during the FGD. CONCLUSION: The methodology used to develop this tool takes into account expert opinions. Comprehensiveness of this tool makes it an ideal evaluation tool during self-evaluation or external quality assurance for longitudinal FDP. After its validation and testing, this practice guide can be used worldwide, along with the provided indicators which can be quantified and used to suit the local context.

Perception of online and face to face microbiology laboratory sessions among medical students and faculty at Arabian Gulf University: a mixed method study.

BACKGROUND: The COVID-19 pandemic has impacted all spheres of society including medical education and healthcare systems. In response to the pandemic, there has been a transition in medical education practice from traditional forms of teaching to online instruction delivery and virtual learning. Effective clinical microbiology education involves a combination of 'hands-on' practical learning and instructional delivery of scientific knowledge. Microbiology practical laboratories are critical learning environments offering 'hands-on' learning experiences that cannot be replicated through online learning. We conducted a mixed-methods study to understand the perception of online and face-to-face microbiology laboratory sessions among the medical students and microbiology faculty at Arabian Gulf University (AGU). METHODS: The study participants were third and fourth-year undergraduate medical students and faculty involved in delivering microbiology labs at AGU. The questionnaire consisted of questions ranging from perceived learning style to attitude towards online delivery of microbiology curriculum. After the questionnaire administration (google form), focus group discussion (FGD) was conducted for students and microbiology faculty separately. RESULTS: Among 168 students, 50.6% preferred face-to-face lab sessions as compared to 30.4% who preferred online labs, and 51.8% considered online labs to be an essential addition to face-to-face labs. Among the faculty, 85.7% preferred the face-to-face mode of teaching. All the faculty (100%) disagreed that all the microbiology labs teaching should be online. 57.2% considered online labs to be an essential addition to traditional face-to-face labs. Both faculty and students hold that a blended mode of instructional delivery is vital and indispensable for the transfer of skills and knowledge for microbiology students. CONCLUSION: The blended mode of delivering microbiology laboratory sessions in medical school is successful and well-received by both students and faculty. Students take the responsibility for furthering their own learning and understanding of concepts. Instructors have also noticed that blending learning strategies also successfully enhances the development of cognitive skills and problem-solving abilities in students. A review of the microbiology lab curriculum is necessary to identify content areas that can be delivered effectively through online, face-to-face lab sessions, or both, supported with appropriate tools and infrastructure.

Validation of Internal structure of Self-Directed Learning Readiness Scale among Indian Medical Students using factor analysis and the Structural equation Modelling Approach.

BACKGROUND: The Self-Directed Learning Readiness Scale (SDLRS) is a tool that helps in the assessment of the readiness of the students to pursue Self-Directed Learning (SDL). There are no documented studies on the validation of internal structure of the SDLRS among Indian medical students. Hence, the objective of this study is to validate the internal structure of SDLRS among Indian medical students using factor analysis and the Structural Equation Modelling (SEM) approach. METHODS: We administered Fisher's 40-item SDLRS to 750 students after receiving the ethics clearance and the author's permission and taking written informed consent from all the study participants (response rate: 92%). The exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and Cronbach's alpha were performed using SPSS version 25 and the Lavaan package of R version 3.1.2. RESULTS: The values of the comparative fit index (CFI), standardised root-mean-square residual (SRMR), and root mean square error of approximation (RMSEA) were ≥ 0.9, ≤ 0.08, and ≤ 0.08, respectively, for a model fit to be acceptable. EFA showed that except for Q2 (loading score: 0.210), Q12 (loading score: 0.384), Q13 (loading score: 0.362), and Q25 (loading score: -0.219), all the items loaded well. After the exclusion of the aforementioned items, the factor loading scores for the items in the self-management, desire for learning, and self-control factors ranged from 0.405 to 0.753 (Cronbach α: 0.775), 0.396 to 0.616 (Cronbach α: 0.730), and 0.427 to 0.556 (Cronbach α: 0.799), respectively. The updated model was used for CFA, which displayed a good model fit. CONCLUSIONS: The resultant model consisting of 36 items is shown to have internal structure validity for Indian version of SDLRS, which can be used to assess medical students.

Development and validation of a structured feedback questionnaire from postgraduates on various elements of postgraduate medical curriculum.

BACKGROUND: Medical Council of India, introduced the Post Graduate (PG) curriculum as 'Competency Based Medical Education' (CBME). Feedback from the end users is a vital step in curriculum evaluation. Therefore, the primary objective of this study was to develop and validate a Structured Feedback Questionnaire (SFQ) for postgraduates, encompassing all the components of the PG-CBME curriculum. METHODS: SFQ was developed with 23 Likert based questions and four open ended questions. Content validation was done by Lawshe method. After getting institutional ethics clearance and informed consent, SFQ was administered to 121 final year PGs (response rate 100%). We performed Principal component analysis (PCA), Structural equation modeling (SEM), Chi squared test (χ2/df); goodness-of-fit index (GFI); adjusted GFI; comparative fit index (CFI) and root mean square error of approximation (RMSEA). Cronbach's alpha was done for estimating the internal consistency. RESULTS: The validation resulted in a three-factor model comprising of "curriculum" (42.1%), "assessment" (28%), and "support" (18.5%). Chi squared test (χ2/df ratio) < 2, CFI (0.78), GFI (0.72) and RMSEA (0.09) indicated superior goodness of fit for the three-factor model for the sample data. All the extracted factors had good internal consistency of ≥0.9. CONCLUSION: We believe that this 23 item SFQ is a valid and reliable tool which can be utilized for curriculum evaluation and thereby formulating recommendations to modify the existing curriculum wherever required, facilitating enriched program outcomes.

HS2ST1-dependent signaling pathways determine breast cancer cell viability, matrix interactions, and invasive behavior.

Heparan sulfate proteoglycans (HSPGs) act as signaling co-receptors by interaction of their sulfated glycosaminoglycan chains with numerous signaling molecules. In breast cancer, the function of heparan sulfate 2-O-sulfotransferase (HS2ST1), the enzyme mediating 2-O-sulfation of HS, is largely unknown. Hence, a comparative study on the functional consequences of HS2ST1 overexpression and siRNA knockdown was performed in the breast cancer cell lines MCF-7 and MDA-MB-231. HS2ST1 overexpression inhibited Matrigel invasion, while its knockdown reversed the phenotype. Likewise, cell motility and adhesion to fibronectin and laminin were affected by altered HS2ST1 expression. Phosphokinase array screening revealed a general decrease in signaling via multiple pathways. Fluorescent ligand binding studies revealed altered binding of fibroblast growth factor 2 (FGF-2) to HS2ST1-expressing cells compared with control cells. HS2ST1-overexpressing cells showed reduced MAPK signaling responses to FGF-2, and altered expression of epidermal growth factor receptor (EGFR), E-cadherin, Wnt-7a, and Tcf4. The increased viability of HS2ST1-depleted cells was reduced to control levels by pharmacological MAPK pathway inhibition. Moreover, MAPK inhibitors generated a phenocopy of the HS2ST1-dependent delay in scratch wound repair. In conclusion, HS2ST1 modulation of breast cancer cell invasiveness is a compound effect of altered E-cadherin and EGFR expression, leading to altered signaling via MAPK and additional pathways.

Prevalence of vitamin D deficiency in childhood acute lymphoblastic leukemia and its association with adverse outcomes during induction phase of treatment.

Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Vitamin D inadequacy is now an internationally recognized health problem. Some relation has been observed between Vitamin D insufficiency and poor outcome in ALL though evidence is limited. Methods: A prospective observational study was done including children (1-15 years) with newly diagnosed ALL. Vitamin D estimation was performed at baseline and at end of induction chemotherapy. Results: Ninety-three patients were recruited in the study. Majority of them belonged to lower socio-economic status (75.3%), and were from rural background (89.2%). Vitamin D deficiency was found in 84.95% of the study population. Seventy-five children (80.6%) completed induction, 9 (9.7%) abandoned treatment and 9 (9.7%) died during induction. Vitamin D levels were significantly low in children with ALL who died (P = 0.016), who had complications (P = 0.002), females (P = 0.036), and those with high risk ALL (P = 0.001). There was a significant drop in the Vitamin D levels (P < 0.001) from pre to post induction phase of chemotherapy. Conclusion: Vitamin D deficiency is prevalent in patients with ALL and is also associated with adverse outcome in these children. Further studies are needed on possible benefits of vitamin D supplementation for preventing complications during treatment of ALL.

How does cognitive function measured by the reaction time and critical flicker fusion frequency correlate with the academic performance of students?

BACKGROUND: The reaction time (RT) is "the time taken for the appearance of rapid voluntary reaction by an individual following a stimulus, either auditory or visual" and the Critical Flickering Fusion Frequency (CFFF) is "the rate at which successively presented light stimuli appear to be steady and continuous". RT and CFFF are commonly used for the assessment of cognitive functions that are known to influence academic performance. However, data about the exact correlation between these are scarce, particularly in India. This research aimed to study the association between visual RT (VRT), auditory RT (ART) and CFFF and their impact on the academic performance of undergraduate students. METHODS: This cross-sectional study was conducted on 700 students of Faculty of Medicine and Dentistry at a private medical university in South India, during the period from 2015 to 2017. The VRT, ART and CFFF were evaluated, and the best out of three subsequent attempts was recorded. The mean score (in percentage) of the three best marks out of the five internal assessments for the course during each academic year was considered for analysis. The association between the different cognitive tests and the average academic performance was analysed. RESULTS: Female students had faster VRT (n = 345, mean = 243.97, SD = 83.87) than male students (n = 273, mean = 274.86, SD = 96.97) (p = 0.001). VRT and ART had a moderate negative correlation with academic performance (for ART, r = - 0.42, p < 0.001; for VRT; r = - 0.40, p < 0.001). CFFF had a very weak positive correlation with academic performance (r = 0.19, p = 0.01). The only independent predictors of academic performance were RT and gender (Adjusted R2 = 0.11). CONCLUSION: Although there is a correlation between CFFF and cognitive function, our study showed only a weak correlation between CFFF and academic performance. Female students had faster RTs, and gender was an independent predictor of academic performance. Rather, students with faster RTs appear to have an advantage in academic performance.

Impact of financial support and focussed group counselling on treatment abandonment in children with acute lymphoblastic leukaemia. Experience over 22 years from North India.

OBJECTIVES: Efforts are being made worldwide to prevent abandonment in children with leukaemia. The study aimed to determine changes in treatment refusal, treatment abandonment rates, and its reasons in response to financial support and focussed group counselling. METHODS: A retrospective cohort study conducted at paediatric haematology-oncology unit, King George's Medical University, Lucknow among children <18 years admitted with acute lymphoblastic leukaemia from 1995 to 2017. Study divided into three periods: Phase 1 (1995-March 2003): Basic support, Phase 2 (April 2003-June 2009): Financial support and Phase 3 (July 2009-2017): Financial, social support with group counselling. Phase 3- subdivided into 3a: group counselling and 3b: intensified group counselling. RESULTS: Number of children registered for treatment during phase 1, 2, 3a, 3b: 176, 200, 360, and 305. Treatment refusal decreased significantly over time: 21% vs 14.5% vs 12.5% vs 5.9% (P < 0.001), especially during phase 3b. Although no change was found in treatment abandonment during phase 2, abandonment significantly reduced in phase 3a (20.3%) as compared with phase 1 (30.2%), with the proportion of children abandoning, due to financial constraints, declining. Abandonment further reduced in phase 3b vs phase 3a (11.1% vs 20.3%) (P = 0.001). After adjusting for other variables, abandonment was found to decrease independently in phase3 (a, b) as compared with phase 1 (P1 = 0.017, P2 = 0.007). CONCLUSIONS: Although helpful, financial assistance unaccompanied by counselling may be insufficient to bring a radical change. Hence, parental counselling, emphasising on treatment adherence and the aftermaths of treatment abandonment, is indispensable for preventing abandonment in semi-literate populations.

Demographics and Outcome of Philadelphia-positive ALL in a Pediatric Population in North India: a Single-center Experience.

Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) in children had a worse outcome before the use of tyrosine kinase inhibitors. We have evaluated the demographics and outcome of Ph+ ALL patients treated with imatinib without blood marrow transplantation. Of the 206 children with ALL registered for treatment, the demographic data of 15 Ph+ ALL patients were compared with the remaining Ph- patients. Imatinib (340 mg/m) was started on day 5 (D5) of induction in Ph+ patients, and their overall survival was compared with Ph- high-risk patients treated on similar protocols. Statistical analysis was carried out by the Fisher exact test and the t test. The Kaplan-Meier test was used for survival analysis. Philadelphia positivity noted in 15/206 (7.28%) ALL patients was higher than reported earlier. Median initial total leukocyte count and central nervous system positivity were significantly higher in Ph+ patients. Myeloid markers, CD13 and CD33, were also positive in 33.3% Ph+ patients. D15 and D35 marrow showed remissions in a larger proportion of Ph+ ALL, as compared with Ph- patients, but chemotherapy interruptions and neutropenic deaths were significantly higher after starting imatinib, as compared with Philadelphia high-risk patients. Overall survival was similar in Ph+ and Ph- high-risk ALL patients. Ph+ ALL, noted in 7.28%, presented with high initial white blood cell counts, high central nervous system positivity, poor steroid response, and higher induction deaths, as compared with high-risk Ph- ALL, and raised the question about the appropriate dose and time of introduction of imatinib to prevent toxicity.

Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease.

BACKGROUND & AIMS: The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn's disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. METHODS: We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P < 5.0 × 10-8 in meta-analysis with a nominal evidence (P < .05) in each scan were considered to have genome-wide significance. RESULTS: We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P < 1.6 × 10-6): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B,PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. CONCLUSIONS: We performed a genome-wide association study of African Americans with IBD and identified loci associated with UC in only this population; we also replicated IBD, CD, and UC loci identified in European populations. The detection of variants associated with IBD risk in only people of African descent demonstrates the importance of studying the genetics of IBD and other complex diseases in populations beyond those of European ancestry.

Folate deficiency in north Indian children undergoing maintenance chemotherapy for acute lymphoblastic leukemia-Implications and outcome.

BACKGROUND: Treatment-related toxicity and mortality are not uncommon during maintenance chemotherapy for childhood acute lymphoblastic leukemia (ALL), especially in the low- and middle-income countries (LMIC). Undernutrition and micronutrient deficiencies are commonly seen in children from LMICs undergoing treatment for ALL. The present study examines the prevalence and clinical implications of folate deficiency in north Indian children with ALL during the maintenance phase of treatment in view of prolonged antifolate treatment and high population prevalence of folate deficiency. PROCEDURES: Pre-cycle folate levels/deficiency as well as weight for age z-score and serum albumin level were determined and correlated with complications of treatment and mortality encountered during the maintenance phase of treatment. RESULTS: Twenty-nine of 52 children enrolled in the study had folate deficiency at some point during maintenance chemotherapy. Neutropenia (18 of 29 vs. 4 of 23; P = 0.002), thrombocytopenia (17 of 29 vs. 4 of 23; P = 0.005), febrile neutropenia (17 of 29 vs. 4 of 23; P = 0.005), and need for chemotherapy dose reduction (20 of 29 vs. 7 of 21; P = 0.01) were more common in folate-deficient children. Maintenance deaths were higher (8 of 29 vs. 1 of 23; P = 0.03) and survival lower (P = 0.02) in deficient children. In multivariate analysis, hypoalbuminemia (P = 0.02) and folate deficiency (P = 0.01) were associated with febrile neutropenia, and folate deficiency with maintenance deaths (P = 0.03). CONCLUSIONS: Folate deficiency was associated with treatment-related complications and adverse outcome in our patients. The risks and benefits of folate supplementation in deficient children during maintenance chemotherapy need to be explored with properly designed randomized studies in similar settings.

Use of Reticulocyte Hemoglobin Content in the Assessment of Iron Deficiency in Children With Inflammatory Bowel Disease.

BACKGROUND: Iron deficiency and anemia affect up to 50% to 75% of patients with inflammatory bowel disease (IBD). Iron deficiency in IBD may be difficult to diagnose because of the effect of inflammation on iron status biomarkers. Thus, there is a need for better methods to accurately determine iron status in IBD. OBJECTIVE: The aim of the study was to investigate the association of inflammation with hemoglobin content of reticulocytes (CHr) and the utility of CHr in comparison to standard iron biomarkers. METHODS: We conducted a cross-sectional study of children with IBD. Iron biomarkers (CHr, ferritin, soluble transferrin receptor [sTfR], hepcidin, hemoglobin) were measured along with systemic biomarkers of inflammation (C-reactive protein, α1-acid glycoprotein]. Spearman correlations were used to evaluate the relation of inflammation and iron biomarkers. The criterion standard for iron deficiency was defined as inflammation-corrected ferritin <15 µg/L or sTfR >8.3 mg/L. Receiver operating characteristic curves were used to estimate the prognostic values of all iron biomarkers to identify patients with iron deficiency. RESULTS: We analyzed data in 62 children ages 5 to 18 years. Sixty-nine percent of our subjects had Crohn disease and 31% had ulcerative colitis, of which 42% were girls and 53% African American. The prevalence of anemia was 32%, of iron deficiency was 52% using ferritin <15 µg/L or sTfR >8.3 mg/L, 39% using red blood cell distribution width of >14.5%, 26% using body iron stores of <0 mg/kg body weight, 25% using CHr of <28 pg, and 11% using mean corpuscular volume of <75 fL/cell. The prevalence of elevated CRP or AGP was 48%. After correcting ferritin and sTfR levels for inflammation, the prevalence of iron deficiency was 68%. CHr was correlated with C-reactive protein (rs -0.44, P < 0.001) and α1-acid glycoprotein (rs -0.37, P < 0.05). The optimal prognostic value for inflammation-adjusted CHr to predict iron deficiency was 34 pg (area under the receiver operating characteristic of 0.70), with 88% sensitivity and 30% specificity. CONCLUSIONS: Iron deficiency and anemia are common in this pediatric IBD cohort. All explored iron biomarkers, including CHr, were affected by inflammation and should be adjusted. A single iron biomarker is unlikely to best predict iron deficiency in pediatric IBD. Iron intervention studies are needed to examine the response of iron biomarkers to iron supplementation in the setting of inflammation.

Clinical Profile and Outcome of Influenza A/H1N1 in Pediatric Oncology Patients During the 2015 Outbreak: A Single Center Experience from Northern India.

BACKGROUND: Owing to their immunocompromised status, childhood cancer patients on chemotherapy are at a greater risk for Influenza infection and its associated complications. There is limited data available on the clinical profile and outcome of Influenza A/H1N1 in this subset of patients. METHODS: A retrospective study was performed of Influenza A/H1N1 cases diagnosed between January 2015 to December 2015 in the in-patients of Pediatric Oncology unit of a tertiary care hospital from Northern India. RESULTS: In total, 16 children were diagnosed with laboratory confirmed H1N1. Most frequent symptoms were fever and cough. Oseltamivir was administered to all patients. Complications encountered were delay/interruption of antineoplastic therapy (9), need for respiratory support (5), and air leaks (1). Prolonged viral shedding was encountered in 50% of patients who were retested for H1N1 in their throat swabs. There were 2 deaths, 1 in a child of Acute Lymphoblastic Leukemia on induction therapy and another in a child with anaplastic Wilms tumor. CONCLUSIONS: Childhood cancer patients infected with Influenza A/H1N1 are at risk of serious illness and higher mortality. Delay of anticancer treatment is a concern in these infected children. Prompt initiation of antivirals and an optimum duration of treatment are warranted to reduce the morbidity and mortality.

Folic acid, one-carbon metabolism & childhood cancer.

Folate has been studied in relation to many diseases, especially cancer. Although it has been postulated to exert a dual effect on development of cancer, its role remains to be clearly defined. Its effect on cancer is the result of gene-nutrient interaction between the genes in folate metabolic pathway and dietary folate availability; mutations in genes of folate metabolism have been shown to alter individual susceptibility to certain childhood cancers as well as response to cancer chemotherapy. Although mandatory fortification of food items with folate has been initiated in some countries, many countries are yet to adopt this due to concerns about undesired adverse effects of high folate levels on health, especially cancer. However, initial reports suggest that folate fortification has led to reduction in incidence of certain childhood cancers such as neuroblastoma, wilms tumour and leukaemias. Despite studies showing folate depletion during antifolate chemotherapy and higher toxicity of chemotherapy in folate-depleted individuals, folate supplementation during cancer chemotherapy is not routinely recommended. Studies investigating the precise effect of folate supplementation during chemotherapy on both short- and long-term outcomes of cancer are needed to arrive at a consensus guideline.

Comparative evaluation of pan-fungal real-time PCR, galactomannan and (1-3)-ß-D-glucan assay for invasive fungal infection in paediatric cancer patients.

Limited specific data and investigations are available for the diagnosis of Invasive Fungal Infection (IFI) in paediatrics cancer patients. Three non-invasive tests; Platelia Aspergillus EIA for galactomannan (GM), ß-D-glucan (BDG) assay and pan-fungal real-time PCR for fungal DNA in blood were evaluated. One hundred twenty-five paediatrics cancer patients at the high risk of IFI were enrolled. Single blood and serum samples were evaluated by all the three methods. Patients were classified into 10 proven, 52 probable and 63 no IFI cases in accordance with EORTC MSG 2008 revised guidelines. The sensitivity, specificity, PPV and NPV of all the three tests in proven, probable and no IFIs cases were analysed singly and in combination. The sensitivity, specificity, PPV and NPV of GM, BDG and pan-fungal real-time PCR were: 87%, 61%, 81%, 69.5% for GM, 88%, 59.5%, 81%, 71.4% for BDG and 89%, 69.2%, 85%, 67.5% for PCR (95% CI). Among different combinations, best combination was found to be GM and PCR with sensitivity, specificity, PPV and NPV of 98.2%, 89.3%, 97.1% and 90% respectively. Single samples must be evaluated by combination of tests.

Outcome of extraocular retinoblastoma in a resource limited center from low middle income country.

Retinoblastoma (RB) is the most common ocular malignancy in children, and is managed by multimodal treatment. There is a paucity of data regarding the clinical profile and outcome of children with extraocular retinoblastoma from Low Middle Income Countries (LMIC) including India. Case records of children with newly diagnosed extraocular RB from January 2013 to August 2016 treated at our unit were analysed for clinical profile, treatment, and outcome. Over the 44 month study period, 91 children were diagnosed with RB, out of which 41 had extraocular disease. While 26 children had extraocular spread limited to orbit (IRSS stage III), 15 had a distant spread to brain (IRSS stage IV). Median lag period for diagnosis was eight months. Treatment abandonment rates were 38.5% and 46.6% in International Retinoblastoma Staging System (IRSS) stage III and IV respectively. With a median follow up of 31.5 months, the projected overall survival for IRSS III at one, two, and three years was 87.5%, 55.6%, and 39.7%. All patients with stage IV disease died after a median follow up duration of three months. High treatment abandonment rates and limited availability of resources lead to suboptimal survival in children with extraocular RB from LMIC. Initiatives aimed at improving early diagnosis, so that the disease is detected in the intraocular stage, are critical to improve the survival in children with RB.

Characterization of genetic loci that affect susceptibility to inflammatory bowel diseases in African Americans.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) has familial aggregation in African Americans (AAs), but little is known about the molecular genetic susceptibility. Mapping studies using the Immunochip genotyping array expand the number of susceptibility loci for IBD in Caucasians to 163, but the contribution of the 163 loci and European admixture to IBD risk in AAs is unclear. We performed a genetic mapping study using the Immunochip to determine whether IBD susceptibility loci in Caucasians also affect risk in AAs and identify new associated loci. METHODS: We recruited AAs with IBD and without IBD (controls) from 34 IBD centers in the United States; additional controls were collected from 4 other Immunochip studies. Association and admixture loci were mapped for 1088 patients with Crohn's disease, 361 with ulcerative colitis, 62 with IBD type unknown, and 1797 controls; 130,241 autosomal single-nucleotide polymorphisms (SNPs) were analyzed. RESULTS: The strongest associations were observed between ulcerative colitis and HLA rs9271366 (P = 7.5 × 10(-6)), Crohn's disease and 5p13.1 rs4286721 (P = 3.5 × 10(-6)), and IBD and KAT2A rs730086 (P = 2.3 × 10(-6)). Additional suggestive associations (P < 4.2 × 10(-5)) were observed between Crohn's disease and IBD and African-specific SNPs in STAT5A and STAT3; between IBD and SNPs in IL23R, IL12B, and C2orf43; and between ulcerative colitis and SNPs near HDAC11 and near LINC00994. The latter 3 loci have not been previously associated with IBD, but require replication. Established Caucasian associations were replicated in AAs (P < 3.1 × 10(-4)) at NOD2, IL23R, 5p15.3, and IKZF3. Significant admixture (P < 3.9 × 10(-4)) was observed for 17q12-17q21.31 (IZKF3 through STAT3), 10q11.23-10q21.2, 15q22.2-15q23, and 16p12.2-16p12.1. Network analyses showed significant enrichment (false discovery rate <1 × 10(-5)) in genes that encode members of the JAK-STAT, cytokine, and chemokine signaling pathways, as well those involved in pathogenesis of measles. CONCLUSIONS: In a genetic analysis of 3308 AA IBD cases and controls, we found that many variants associated with IBD in Caucasians also showed association evidence with these diseases in AAs; we also found evidence for variants and loci not previously associated with IBD. The complex genetic factors that determine risk for or protection against IBD in different populations require further study.

Genotype 3b of human parvovirus B19 detected from hospitalized children with solid malignancies in a North Indian tertiary care hospital.

Human parvovirus B19 (B19V) infection is known to cause serious consequences in immuno-compromized individuals. The present cross sectional study was designed to estimate the prevalence and genotype distribution of B19V in children receiving chemotherapy for solid malignancies at a tertiary care hospital in North India during October 2013 to May 2015. Serum samples from all the patients were tested for anti-B19V IgM and IgG antibodies and for B19V-DNA as soon as received. Samples testing positive for B19V-DNA were subjected to viral load estimation and to genotype determination by sequencing. Total 96 children were enrolled of which 9 (9.3%), 32 (33.3%), and 25 (26%) tested positive for anti-B19V IgM, anti-B19V IgG, and B19V-DNA, respectively. The viral load of B19V-DNA positive children ranged from 5.5 × 10(2) to 3.5 × 10(12) copies/ml. Accordingly children were divided into three groups: group I, with acute infection (n = 25); group II, previously exposed (n = 27), and group III, negative for B19V infection or with inappropriate antibody response (n = 44). B19V positivity was significantly associated (P-value < 0.0001) with a history of blood transfusion in the past 6 months, severe anemia (hemoglobin levels <6 gm%) and thrombocytopenia (platelets <150,000/cu.mm.). Sequence analysis of 21 of 25 DNA positive samples showed that all of them were Genotype 3b that clustered into three groups. All the sequences within each cluster were identical. The nucleotide identity of the sequences suggests a nosocomial outbreak of B19V during the study period. Children on chemotherapy for solid tumors should be routinely screened for B19V infection by both serology and PCR. J. Med. Virol. 88:1922-1929, 2016. © 2016 Wiley Periodicals, Inc.

Pilot Study Evaluating Efficacy of 2 Regimens for Hypovitaminosis D Repletion in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: Vitamin D is critical for skeletal health; hypovitaminosis D is common in pediatric inflammatory bowel disease (IBD), yet optimal repletion therapy is not well studied. We aimed to conduct a pilot trial comparing the efficacy of 2 vitamin D regimens of weekly dosing for the repletion of hypovitaminosis D in pediatric IBD. METHODS: Subjects identified from our IBD clinic with 25-hydroxyvitamin D (25[OH]D) concentrations <30 ng/mL were randomized to 10,000 (n = 18) or 5000 (n = 14) IU of oral vitamin D3/10 kg body weight per week for 6 weeks. Serum 25(OH)D, Ca, and parathyroid hormone concentrations were measured at baseline, week 8, and week 12. RESULTS: In the higher dosing group, serum 25(OH)D increased from 23.7 ±â€Š8.5 ng/mL at baseline to 49.2 ±â€Š13.6 ng/mL at 8 weeks; P < 0.001. In the lower dosing group, serum 25(OH)D increased from 24.0 ±â€Š7.0 ng/mL at baseline to 41.5 ±â€Š9.6 ng/mL at 8 weeks; P < 0.001. At 12 weeks, serum 25(OH)D concentrations were 35.1 ±â€Š8.4 and 30.8 ±â€Š4.2 ng/mL for the higher and lower dose regimens, respectively. Mean serum Ca and parathyroid hormone concentrations did not significantly change during the study. No patient exhibited hypercalcemia, and no serious adverse events occurred. CONCLUSIONS: Both treatment arms were safe and effective at normalizing vitamin D nutriture in pediatric IBD. Although significant repletion of 25(OH)D concentration was achieved in both dosing groups at 8 weeks, this effect was lost by the 12-week follow-up. Maintenance vitamin D therapy following initial repletion is likely required to maintain long-term normalized vitamin D status.