Sreenivas Vishnubhatla | All India Institute of Medical Sciences, New Delhi (original) (raw)

Papers by Sreenivas Vishnubhatla

AIDS, 2004

The Brazilian HIV/AIDS drug policy has been highly debated and even criticized, particularly at t... more The Brazilian HIV/AIDS drug policy has been highly debated and even criticized, particularly at the time of its implementation by the Government in early 90s. However, after more than a decade of action, the success of the Brazilian response to HIV is evident and recognized worldwide, lying upon a concerted early governmental response, a strong and effective participation of the civil society, a multisectoral mobilization, a balanced prevention and treatment approach and the advocacy of human rights in all strategies, particularly with the policy of wide access to antiretroviral drugs. This policy made highly active anti-retroviral therapy (HAART) universally available since 1996, with logistic and criteria distribution based on regularly updated national guidelines. Approximately 140,000 patients now receive antiretroviral (ARV) treatment through the public health system. As a result there has been a significant fall in morbidity/mortality rates, hospital admissions and costs of treatment, with significant growth in demand for outpatient services and decrease for hospital, home and day-care services. It has also led to improvements in the quality of life for HIV+ individuals and savings in the medical costs, while economic and social related costs also have fallen. The policy of universal access to combined antiretroviral treatment (ART)' in Brazil has been shown to be cost-effective and the financial resources devoted to this initiative represents an economically viable investment. This experience also shows that a well-designed and supported international effort to reduce drug prices and improve health infrastructure could overcome many obstacles in middle-income and limited-resource countries.

International Journal of Laboratory Hematology

Dysregulation of apoptosis has been explored in acute myeloid leukemia (AML); yet, its correlatio... more Dysregulation of apoptosis has been explored in acute myeloid leukemia (AML); yet, its correlation with clinical outcomes in pediatric AML is unknown. This study was aimed to analyze percentage of apoptosis and apoptosis mediated through the intrinsic pathway with clinical outcomes in patients with pediatric AML. This prospective study included pediatric AML patients enrolled from July 2013 to August 2016. Annexin-V (marker of total apoptosis) and caspase-9 expression (marker of intrinsic pathway) was determined in baseline bone marrow (BM) samples by flow cytometery and compared with controls (unaffected BM of solid tumors and peripheral blood [PB] of unaffected siblings). Overall survival (OS) and event-free survival (EFS) were compared using log-rank test. A total of 151 AML patients were enrolled, median age 10 (range: 0.7-18 years). Annexin-V expression in blast cells was significantly high in AML patients as compared to BM of subjects with solid tumors (P = 0.01) and PB of healthy subjects (P = 0.04). Caspase-9 expression in blast cells was not significantly different. Median annexin-V expression was significantly higher in patients with WBC count ≥11 000/mm (P = 0.02), poor-risk cytogenetics (P = 0.02), the absence of RUNX1-RUNX1T1 translocation (P = 0.004), and the absence of NPM1 mutation (P = 0.05). Patients with high annexin-V expression had significantly inferior OS (P = 0.05) in univariate analysis but not in multivariate analysis (P = 0.32). Apoptosis as a whole was found to be activated in baseline BM samples of AML patients. High apoptosis may be associated with high-risk phenotype in this disease.

Mutation research, 2018

Role of mitochondrial DNA variations, particularly in D loop region, remains investigational in a... more Role of mitochondrial DNA variations, particularly in D loop region, remains investigational in acute myeloid leukaemia (AML). Consecutive 151 pediatric AML patients were prospectively enrolled from June 2013 to August 2016, for evaluating pattern of variations in mitochondrial D-loop region and to determine their association, if any, with expression of mitochondrial-encoded genes. For each patient, D-loop region was sequenced on baseline bone marrow, buccal swab and mother's blood sample. Real time PCR was used for relative gene expression of four mitochondrial DNA encoded genes viz. Nicotinamide-adenine-dineucleotide-dehydrogenase subunit 3 (ND3), Cytochrome-B (Cyt-B), Cytochrome c oxidase-I (COX1) and ATP-synthetase F subunit-6 (ATP6). Total 1490 variations were found at 237 positions in D-Loop; 1206 (80.9%) were germline and 284 (19.1%) were somatic. Positions 73-263 were identified as a probable hotspot region. G bases appeared to be most stable nucleotide (least number of ...

Clinical lymphoma, myeloma & leukemia, Jan 31, 2018

The purpose of our study was to evaluate the clinical, cytogenetic, and molecular features, and s... more The purpose of our study was to evaluate the clinical, cytogenetic, and molecular features, and survival outcomes in patients with acute myeloid leukemia (AML) with myeloid sarcoma (MS) and compare them with patients with AML without MS. This was a retrospective analysis of de novo pediatric AML patients with or without MS diagnosed at our cancer center between June 2003 and June 2016. MS was present in 121 of 570 (21.2%), the most frequent site being the orbit. Patients with MS had a younger median age (6 years vs. 10 years) and presented with higher hemoglobin and platelet but lower white blood cell count compared with patients without MS. Further, t (8; 21) (P < .01), loss of Y chromosome (P < .01), and deletion 9q (P = .03) were significantly higher in patients with AML with MS. Event-free survival (EFS; P = .003) and overall survival (OS; P = .001) were better among patients with AML with MS (median EFS 21.0 months and median OS 37.1 months) compared with those with AML w...

Clinical endocrinology, Jan 2, 2017

Cholecalciferol and/or calcium supplementation might increase skeletal muscle strength and serum ... more Cholecalciferol and/or calcium supplementation might increase skeletal muscle strength and serum testosterone in young adult males. We performed a randomized control trial assessing the effect of cholecalciferol/calcium on skeletal muscle strength and serum testosterone in vitamin D deficient young males. Two-by-two factorial RCT. Two-hundred and twenty-eight young males were block-randomized to (i) double-placebo, (ii) calcium/placebo, (iii) cholecalciferol/placebo and (iv) cholecalciferol/calcium. Doses for cholecalciferol were 60 000 IU/wk for 8 weeks followed by 60 000 IU/fortnightly, and doses for elemental calcium were 500 mg/twice daily for 6 months. A total of 180 subjects completed the study protocol. Their ean age, body mass index and baseline 25(OH)D were 20.2 ± 2.2 years, 23.0 ± 3.6 kg/m2 and 21.5 ± 9.5 nmol/L, respectively. Handgrip (primary outcome), pinch-grip strength, distance walked in 6 minutes, dyspnoea-score, quality of life by Short Form 36, serum 25(OH)D, 1,2...

Seizure, Jan 9, 2017

Investigations such as EEG and brain imaging are often difficult to obtain in primary care settin... more Investigations such as EEG and brain imaging are often difficult to obtain in primary care settings of resource-limited regions impacting millions of epilepsy patients. We wanted to test the hypothesis that classification of chronic epilepsy into focal and generalized based on clinical history and examination alone would be comparable to making such a classification with additional inputs from EEG and brain imaging. Two investigators independently classified consecutive chronic epilepsy patients into focal, generalized and unclassified epilepsy. Investigator 1 made this determination using clinical history and examination alone whereas Investigator II additionally used EEG and brain imaging too. We calculated inter observer agreement between the two investigators and also looked at the predictors of focal and generalized epilepsy. Five hundred and twelve patients were recruited. Inter observer agreement between the two investigators in making the focal versus generalized classificat...

Journal of tropical pediatrics, Jan 3, 2017

We estimated the burden of influenza-related acute respiratory tract infection (ARI) among under-... more We estimated the burden of influenza-related acute respiratory tract infection (ARI) among under-fives in India through meta-analysis. We estimated pooled incidence and proportional positivity of laboratory-diagnosed influenza among under-fives using data from observational studies published from 1 January 1961 to 31 December 2016. Death due to influenza was estimated using a multiplier model. Influenza-associated ARI incidence was estimated as 132 per 1000 child-years (115-149). The patients positive for influenza among ARI in outpatients and inpatients were estimated to be 11.2% (8.8-13.6) and 7.1% (5.5-8.8), respectively. We estimated total influenza cases during 2016 as 16 009 207 (13 942 916-18 082 769) in India. Influenza accounted for 10 913 476 (9 504 666-12 362 310) outpatient visits and 109 431 (83 882-134 980) hospitalizations. A total of 27 825 (21 382-34 408) influenza-associated under-five deaths were estimated in India in 2016. Influenza imposes a substantial burden a...

PloS one, 2017

There is a paucity of health policy relevant data for chronic liver disease from India, impeding ... more There is a paucity of health policy relevant data for chronic liver disease from India, impeding formulation of an interventional strategy to address the issue. A prospective, multicentric study to delineate the etiology and clinical profile of chronic liver disease in India is reported here. A centrally coordinated and monitored web-based data repository was developed (Feb, 2010 to Jan, 2013) and analyzed. Eleven hospitals from different parts of India participated. Data were uploaded into a web based proforma and monitored by a single centre according to a standardized protocol. 1.28% (n = 266621) of all patients (n = 20701383) attending the eleven participating hospitals of India had liver disease. 65807 (24·68%) were diagnosed for the first time (new cases). Of these, 13014 (19·77%, median age 43 years, 73% males) cases of chronic liver disease were finally analyzed. 33.9% presented with decompensated cirrhosis. Alcoholism (34·3% of 4413) was the commonest cause of cirrhosis whi...

Polish journal of radiology, 2017

To evaluate the role of diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC)... more To evaluate the role of diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) values at 3 Tesla in characterizing sinonasal masses. After ethical clearance, 79 treatment naive patients with head and neck masses underwent magnetic resonance imaging (MRI), including DWI at 3 Tesla using the following b values - 0, 500 and 1000 s/mm(2). Thirty-one patients were found to have sinonasal tumours and were subsequently analysed. Image analysis consisted of a morphological evaluation of conventional MR images, qualitative evaluation of DW trace images and quantitative assessment of mean ADC values. Receiver operating characteristic (ROC) curve was drawn to determine a cut-off ADC value for the differentiation between benign and malignant masses. Sinonasal masses showed an overlapping growth pattern on conventional imaging, irrespective of their biological nature. The mean ADC value of benign lesions was 1.948±0.459×10(-3) mm(2)/s, while that of malignant lesions was 1.046...

JAMA Oncology, 2017

IMPORTANCE Although oral metronomic chemotherapy is often used in progressive pediatric solid mal... more IMPORTANCE Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence. OBJECTIVES To compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy. DESIGN, SETTING, AND PARTICIPANTS A double-blinded, placebo-controlled randomized clinical trial was conducted from October 1, 2013, through December 31, 2015, at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options. INTERVENTIONS One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide, whereas the other arm received placebo. Disease status was assessed at baseline, 9 weeks, 18 weeks, and 27 weeks or at clinical progression. MAIN OUTCOMES AND MEASURES The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months, and PFS duration and overall survival (OS) were secondary end points. RESULTS A total of 108 of the 123 patients screened were enrolled, with 52 randomized to the placebo group (median age, 15 years; 40 male [76.9%]) and 56 to the metronomic chemotherapy group (median age, 13 years; 42 male [75.0%]). At a median follow-up of 2.9 months, 100% of the patients had disease progression by 6 months in the placebo group vs 96.4% in the metronomic chemotherapy group (P = .24). Median PFS and OS in the 2 groups was similar (hazard ratio [HR], 0.69; 95% CI, 0.47-1.03 [P = .07] for PFS; and HR, 0.74; 95% CI, 0.50-1.09 [P = .13] for OS). In post hoc subgroup analysis, cohorts receiving more than 3 cycles (HR for PFS, 0.46; 95% CI, 0.23-0.93; P = .03) and those without a bone sarcoma (ie, neither primitive neuroectodermal tumor nor osteosarcoma) (HR for PFS, 0.39; 95% CI, 0.18-0.81; P = .01) appeared to benefit from metronomic chemotherapy. CONCLUSIONS AND RELEVANCE Metronomic chemotherapy does not improve 6-month PFS, compared with placebo, among pediatric patients with extracranial progressive solid malignant tumors. However, patients without bone sarcoma and those able to tolerate therapy for more than 3 cycles (9 weeks) benefit. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01858571

Leukemia & lymphoma, Jul 6, 2016

Clinical stage alone is used for risk stratification in treatment of pediatric advanced Hodgkin l... more Clinical stage alone is used for risk stratification in treatment of pediatric advanced Hodgkin lymphoma (HL). To identify other risk factors, we collected data from three tertiary centers on 186 patients with advanced stage (IIB-IV) consecutively treated with Adriamycin, bleomycin, vinblastine, Dacarbazine (ABVD) chemotherapy ± radiotherapy. Freedom from treatment failure (FFTF) and overall survival (OS) were end points. With median follow-up period of 57.9 months (range: 1-151 months), five-year FFTF and OS was 84.8% (95% CI 78.6-89.3%) and 95.3% (95% CI 90.78-97.6%), respectively. We identified stage-4 [HR-3.6(1.25, 9.97); p = .017], high total leukocyte count (>15,000/mm(3)) [HR-2.6(1.3,8.1); p = .008] and lymphopenia (lymphocyte count ≤8%) [HR-4.9(1.7,14.1); p = .002] predictive of inferior FFTF. Patients with none or one of these risk factors had significantly better five-year FFTF (91.9%) as compared to those with risk factors (two risk factor [74.7%; p = .001]; 3,4 risk f...

The Indian journal of medical research, 2016

Mutations in fms-like tyrosine kinase 3 (FLT3) receptor have significant role in assessing outcom... more Mutations in fms-like tyrosine kinase 3 (FLT3) receptor have significant role in assessing outcome in patients with acute myeloid leukaemia (AML). Data for FLT3 surface expression in relation to FLT3 internal tandem duplication (ITD) status and outcome are not available from India. The objective of the current study was to investigate adult patients with AML for FLT3 expression and FLT3 ITD mutation, and their association with long-term outcome. Total 51 consecutive de novo AML patients aged 18-60 yr were enrolled in the study. FLT3 ITD was detected by polymerase chain reaction (PCR); flowcytometry and qPCR (Taqman probe chemistry) were used for assessment of FLT3 protein and transcript, respectively. Kaplan Meier curves were obtained for survival analysis followed by log rank test. FLT3 ITD was present in eight (16%) patients. Complete remission was achieved in 33 (64.6%) patients. At 57.3 months, event free survival (EFS) was 26.9±6.3 per cent, disease free survival (DFS) 52.0±9.2...

The Indian journal of medical research, 2016

Acute respiratory distress syndrome (ARDS) is a common disorder in critically ill patients and is... more Acute respiratory distress syndrome (ARDS) is a common disorder in critically ill patients and is associated with high mortality. There is a paucity of literature on this condition from developing countries. This prospective observational study was designed to find out the aetiology, outcomes and predictors of mortality in ARDS. Sixty four consecutive patients who satisfied American-European Consensus Conference (AECC) definition of ARDS from medical Intensive Care Unit (ICU) of a tertiary care centre in New Delhi, India, were enrolled in the study. Demographic, biochemical and ventilatory variables were recorded for each patient. Baseline measurements of serum interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α), procalcitonin (PCT) and high sensitivity C-reactive protein (hsCRP) were performed. Common causes of ARDS included pneumonia [44/64 (68.7%)], malaria [9/64 (14.1%)] and sepsis [8/64 (12.5%]. Eight of the 64 (12.5%) patients had ARDS due to viral pneumonia. The 2...

Leukemia & lymphoma, Oct 4, 2016

In chronic lymphocytic leukemia (CLL), the geographical bias in immunoglobulin heavy-chain variab... more In chronic lymphocytic leukemia (CLL), the geographical bias in immunoglobulin heavy-chain variable (IGHV) gene usage lead us to analyze IGHV gene usage and B-cell receptor stereotypy in 195 patients from India. IGHV3, IGHV4, and IGHV1 families were the most frequently used. 20.5% sequences had stereotyped BCR and were clustered in 12 pre-defined and 6 novel subsets. Unmutated IGHV was significantly associated with reduced time to first treatment (p < 0.033) and poor overall survival (OS; p = 0.01). We observed a significant difference in OS between IGHV1, IGHV3, and IGHV4 family cases (p = 0.045) in early stage patients. Regarding subfamily usage, only IGHV1-69 expression was found to have statistically significant poor outcome (p = 0.017). Our results from the analysis of various molecular and clinical features suggest that the expression of specific IGHV gene influences the outcome in early stage CLL, and hence its assessment may be added to the clinical leukemia laboratory ar...

The Indian Journal of Medical Research

Subsequent to the publication of the article 1 highlighting the role of acute viral hepatitis as ... more Subsequent to the publication of the article 1 highlighting the role of acute viral hepatitis as a confounding factor in antituberculosis (anti-TB) treatment induced hepatotoxicity, we extended the study with a similar study design at the All India Institute of Medical Sciences hospital, New Delhi. We enrolled patients (January 2007 to March 2009) with features suggestive of drug-induced hepatitis (DIh) while on anti-TB treatment. The definition of anti-TB DIH as also management of DIh patients was as described previously 1 .

PloS one, 2015

Pulmonary tuberculosis still remains a major communicable disease worldwide. In 2013, 9 million p... more Pulmonary tuberculosis still remains a major communicable disease worldwide. In 2013, 9 million people developed TB and 1.5 million people died from the disease. India constitutes 24% of the total TB burden. Early detection of TB cases is the key to successful treatment and reduction of disease transmission. Xpert MTB/RIF, an automated cartridge-based molecular technique detects Mycobacterium tuberculosis and rifampicin resistance within two hours has been endorsed by WHO for rapid diagnosis of TB. Our study is the first study from India with a large sample size to evaluate the performance of Xpert MTB/RIF assay in PTB samples. The test showed an overall sensitivity and specificity of 95.7% (430/449) and 99.3% (984/990) respectively. In smear negative-culture positive cases, the test had a sensitivity of 77.7%. The sensitivity and specificity for detecting rifampicin resistance was 94.5% and 97.7% respectively with respect to culture as reference standard. However, after resolving t...

AIDS, 2004

The Brazilian HIV/AIDS drug policy has been highly debated and even criticized, particularly at t... more The Brazilian HIV/AIDS drug policy has been highly debated and even criticized, particularly at the time of its implementation by the Government in early 90s. However, after more than a decade of action, the success of the Brazilian response to HIV is evident and recognized worldwide, lying upon a concerted early governmental response, a strong and effective participation of the civil society, a multisectoral mobilization, a balanced prevention and treatment approach and the advocacy of human rights in all strategies, particularly with the policy of wide access to antiretroviral drugs. This policy made highly active anti-retroviral therapy (HAART) universally available since 1996, with logistic and criteria distribution based on regularly updated national guidelines. Approximately 140,000 patients now receive antiretroviral (ARV) treatment through the public health system. As a result there has been a significant fall in morbidity/mortality rates, hospital admissions and costs of treatment, with significant growth in demand for outpatient services and decrease for hospital, home and day-care services. It has also led to improvements in the quality of life for HIV+ individuals and savings in the medical costs, while economic and social related costs also have fallen. The policy of universal access to combined antiretroviral treatment (ART)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; in Brazil has been shown to be cost-effective and the financial resources devoted to this initiative represents an economically viable investment. This experience also shows that a well-designed and supported international effort to reduce drug prices and improve health infrastructure could overcome many obstacles in middle-income and limited-resource countries.

International Journal of Laboratory Hematology

Dysregulation of apoptosis has been explored in acute myeloid leukemia (AML); yet, its correlatio... more Dysregulation of apoptosis has been explored in acute myeloid leukemia (AML); yet, its correlation with clinical outcomes in pediatric AML is unknown. This study was aimed to analyze percentage of apoptosis and apoptosis mediated through the intrinsic pathway with clinical outcomes in patients with pediatric AML. This prospective study included pediatric AML patients enrolled from July 2013 to August 2016. Annexin-V (marker of total apoptosis) and caspase-9 expression (marker of intrinsic pathway) was determined in baseline bone marrow (BM) samples by flow cytometery and compared with controls (unaffected BM of solid tumors and peripheral blood [PB] of unaffected siblings). Overall survival (OS) and event-free survival (EFS) were compared using log-rank test. A total of 151 AML patients were enrolled, median age 10 (range: 0.7-18 years). Annexin-V expression in blast cells was significantly high in AML patients as compared to BM of subjects with solid tumors (P = 0.01) and PB of healthy subjects (P = 0.04). Caspase-9 expression in blast cells was not significantly different. Median annexin-V expression was significantly higher in patients with WBC count ≥11 000/mm (P = 0.02), poor-risk cytogenetics (P = 0.02), the absence of RUNX1-RUNX1T1 translocation (P = 0.004), and the absence of NPM1 mutation (P = 0.05). Patients with high annexin-V expression had significantly inferior OS (P = 0.05) in univariate analysis but not in multivariate analysis (P = 0.32). Apoptosis as a whole was found to be activated in baseline BM samples of AML patients. High apoptosis may be associated with high-risk phenotype in this disease.

Mutation research, 2018

Role of mitochondrial DNA variations, particularly in D loop region, remains investigational in a... more Role of mitochondrial DNA variations, particularly in D loop region, remains investigational in acute myeloid leukaemia (AML). Consecutive 151 pediatric AML patients were prospectively enrolled from June 2013 to August 2016, for evaluating pattern of variations in mitochondrial D-loop region and to determine their association, if any, with expression of mitochondrial-encoded genes. For each patient, D-loop region was sequenced on baseline bone marrow, buccal swab and mother's blood sample. Real time PCR was used for relative gene expression of four mitochondrial DNA encoded genes viz. Nicotinamide-adenine-dineucleotide-dehydrogenase subunit 3 (ND3), Cytochrome-B (Cyt-B), Cytochrome c oxidase-I (COX1) and ATP-synthetase F subunit-6 (ATP6). Total 1490 variations were found at 237 positions in D-Loop; 1206 (80.9%) were germline and 284 (19.1%) were somatic. Positions 73-263 were identified as a probable hotspot region. G bases appeared to be most stable nucleotide (least number of ...

Clinical lymphoma, myeloma & leukemia, Jan 31, 2018

The purpose of our study was to evaluate the clinical, cytogenetic, and molecular features, and s... more The purpose of our study was to evaluate the clinical, cytogenetic, and molecular features, and survival outcomes in patients with acute myeloid leukemia (AML) with myeloid sarcoma (MS) and compare them with patients with AML without MS. This was a retrospective analysis of de novo pediatric AML patients with or without MS diagnosed at our cancer center between June 2003 and June 2016. MS was present in 121 of 570 (21.2%), the most frequent site being the orbit. Patients with MS had a younger median age (6 years vs. 10 years) and presented with higher hemoglobin and platelet but lower white blood cell count compared with patients without MS. Further, t (8; 21) (P < .01), loss of Y chromosome (P < .01), and deletion 9q (P = .03) were significantly higher in patients with AML with MS. Event-free survival (EFS; P = .003) and overall survival (OS; P = .001) were better among patients with AML with MS (median EFS 21.0 months and median OS 37.1 months) compared with those with AML w...

Clinical endocrinology, Jan 2, 2017

Cholecalciferol and/or calcium supplementation might increase skeletal muscle strength and serum ... more Cholecalciferol and/or calcium supplementation might increase skeletal muscle strength and serum testosterone in young adult males. We performed a randomized control trial assessing the effect of cholecalciferol/calcium on skeletal muscle strength and serum testosterone in vitamin D deficient young males. Two-by-two factorial RCT. Two-hundred and twenty-eight young males were block-randomized to (i) double-placebo, (ii) calcium/placebo, (iii) cholecalciferol/placebo and (iv) cholecalciferol/calcium. Doses for cholecalciferol were 60 000 IU/wk for 8 weeks followed by 60 000 IU/fortnightly, and doses for elemental calcium were 500 mg/twice daily for 6 months. A total of 180 subjects completed the study protocol. Their ean age, body mass index and baseline 25(OH)D were 20.2 ± 2.2 years, 23.0 ± 3.6 kg/m2 and 21.5 ± 9.5 nmol/L, respectively. Handgrip (primary outcome), pinch-grip strength, distance walked in 6 minutes, dyspnoea-score, quality of life by Short Form 36, serum 25(OH)D, 1,2...

Seizure, Jan 9, 2017

Investigations such as EEG and brain imaging are often difficult to obtain in primary care settin... more Investigations such as EEG and brain imaging are often difficult to obtain in primary care settings of resource-limited regions impacting millions of epilepsy patients. We wanted to test the hypothesis that classification of chronic epilepsy into focal and generalized based on clinical history and examination alone would be comparable to making such a classification with additional inputs from EEG and brain imaging. Two investigators independently classified consecutive chronic epilepsy patients into focal, generalized and unclassified epilepsy. Investigator 1 made this determination using clinical history and examination alone whereas Investigator II additionally used EEG and brain imaging too. We calculated inter observer agreement between the two investigators and also looked at the predictors of focal and generalized epilepsy. Five hundred and twelve patients were recruited. Inter observer agreement between the two investigators in making the focal versus generalized classificat...

Journal of tropical pediatrics, Jan 3, 2017

We estimated the burden of influenza-related acute respiratory tract infection (ARI) among under-... more We estimated the burden of influenza-related acute respiratory tract infection (ARI) among under-fives in India through meta-analysis. We estimated pooled incidence and proportional positivity of laboratory-diagnosed influenza among under-fives using data from observational studies published from 1 January 1961 to 31 December 2016. Death due to influenza was estimated using a multiplier model. Influenza-associated ARI incidence was estimated as 132 per 1000 child-years (115-149). The patients positive for influenza among ARI in outpatients and inpatients were estimated to be 11.2% (8.8-13.6) and 7.1% (5.5-8.8), respectively. We estimated total influenza cases during 2016 as 16 009 207 (13 942 916-18 082 769) in India. Influenza accounted for 10 913 476 (9 504 666-12 362 310) outpatient visits and 109 431 (83 882-134 980) hospitalizations. A total of 27 825 (21 382-34 408) influenza-associated under-five deaths were estimated in India in 2016. Influenza imposes a substantial burden a...

PloS one, 2017

There is a paucity of health policy relevant data for chronic liver disease from India, impeding ... more There is a paucity of health policy relevant data for chronic liver disease from India, impeding formulation of an interventional strategy to address the issue. A prospective, multicentric study to delineate the etiology and clinical profile of chronic liver disease in India is reported here. A centrally coordinated and monitored web-based data repository was developed (Feb, 2010 to Jan, 2013) and analyzed. Eleven hospitals from different parts of India participated. Data were uploaded into a web based proforma and monitored by a single centre according to a standardized protocol. 1.28% (n = 266621) of all patients (n = 20701383) attending the eleven participating hospitals of India had liver disease. 65807 (24·68%) were diagnosed for the first time (new cases). Of these, 13014 (19·77%, median age 43 years, 73% males) cases of chronic liver disease were finally analyzed. 33.9% presented with decompensated cirrhosis. Alcoholism (34·3% of 4413) was the commonest cause of cirrhosis whi...

Polish journal of radiology, 2017

To evaluate the role of diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC)... more To evaluate the role of diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) values at 3 Tesla in characterizing sinonasal masses. After ethical clearance, 79 treatment naive patients with head and neck masses underwent magnetic resonance imaging (MRI), including DWI at 3 Tesla using the following b values - 0, 500 and 1000 s/mm(2). Thirty-one patients were found to have sinonasal tumours and were subsequently analysed. Image analysis consisted of a morphological evaluation of conventional MR images, qualitative evaluation of DW trace images and quantitative assessment of mean ADC values. Receiver operating characteristic (ROC) curve was drawn to determine a cut-off ADC value for the differentiation between benign and malignant masses. Sinonasal masses showed an overlapping growth pattern on conventional imaging, irrespective of their biological nature. The mean ADC value of benign lesions was 1.948±0.459×10(-3) mm(2)/s, while that of malignant lesions was 1.046...

JAMA Oncology, 2017

IMPORTANCE Although oral metronomic chemotherapy is often used in progressive pediatric solid mal... more IMPORTANCE Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence. OBJECTIVES To compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy. DESIGN, SETTING, AND PARTICIPANTS A double-blinded, placebo-controlled randomized clinical trial was conducted from October 1, 2013, through December 31, 2015, at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options. INTERVENTIONS One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide, whereas the other arm received placebo. Disease status was assessed at baseline, 9 weeks, 18 weeks, and 27 weeks or at clinical progression. MAIN OUTCOMES AND MEASURES The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months, and PFS duration and overall survival (OS) were secondary end points. RESULTS A total of 108 of the 123 patients screened were enrolled, with 52 randomized to the placebo group (median age, 15 years; 40 male [76.9%]) and 56 to the metronomic chemotherapy group (median age, 13 years; 42 male [75.0%]). At a median follow-up of 2.9 months, 100% of the patients had disease progression by 6 months in the placebo group vs 96.4% in the metronomic chemotherapy group (P = .24). Median PFS and OS in the 2 groups was similar (hazard ratio [HR], 0.69; 95% CI, 0.47-1.03 [P = .07] for PFS; and HR, 0.74; 95% CI, 0.50-1.09 [P = .13] for OS). In post hoc subgroup analysis, cohorts receiving more than 3 cycles (HR for PFS, 0.46; 95% CI, 0.23-0.93; P = .03) and those without a bone sarcoma (ie, neither primitive neuroectodermal tumor nor osteosarcoma) (HR for PFS, 0.39; 95% CI, 0.18-0.81; P = .01) appeared to benefit from metronomic chemotherapy. CONCLUSIONS AND RELEVANCE Metronomic chemotherapy does not improve 6-month PFS, compared with placebo, among pediatric patients with extracranial progressive solid malignant tumors. However, patients without bone sarcoma and those able to tolerate therapy for more than 3 cycles (9 weeks) benefit. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01858571

Leukemia & lymphoma, Jul 6, 2016

Clinical stage alone is used for risk stratification in treatment of pediatric advanced Hodgkin l... more Clinical stage alone is used for risk stratification in treatment of pediatric advanced Hodgkin lymphoma (HL). To identify other risk factors, we collected data from three tertiary centers on 186 patients with advanced stage (IIB-IV) consecutively treated with Adriamycin, bleomycin, vinblastine, Dacarbazine (ABVD) chemotherapy ± radiotherapy. Freedom from treatment failure (FFTF) and overall survival (OS) were end points. With median follow-up period of 57.9 months (range: 1-151 months), five-year FFTF and OS was 84.8% (95% CI 78.6-89.3%) and 95.3% (95% CI 90.78-97.6%), respectively. We identified stage-4 [HR-3.6(1.25, 9.97); p = .017], high total leukocyte count (>15,000/mm(3)) [HR-2.6(1.3,8.1); p = .008] and lymphopenia (lymphocyte count ≤8%) [HR-4.9(1.7,14.1); p = .002] predictive of inferior FFTF. Patients with none or one of these risk factors had significantly better five-year FFTF (91.9%) as compared to those with risk factors (two risk factor [74.7%; p = .001]; 3,4 risk f...

The Indian journal of medical research, 2016

Mutations in fms-like tyrosine kinase 3 (FLT3) receptor have significant role in assessing outcom... more Mutations in fms-like tyrosine kinase 3 (FLT3) receptor have significant role in assessing outcome in patients with acute myeloid leukaemia (AML). Data for FLT3 surface expression in relation to FLT3 internal tandem duplication (ITD) status and outcome are not available from India. The objective of the current study was to investigate adult patients with AML for FLT3 expression and FLT3 ITD mutation, and their association with long-term outcome. Total 51 consecutive de novo AML patients aged 18-60 yr were enrolled in the study. FLT3 ITD was detected by polymerase chain reaction (PCR); flowcytometry and qPCR (Taqman probe chemistry) were used for assessment of FLT3 protein and transcript, respectively. Kaplan Meier curves were obtained for survival analysis followed by log rank test. FLT3 ITD was present in eight (16%) patients. Complete remission was achieved in 33 (64.6%) patients. At 57.3 months, event free survival (EFS) was 26.9±6.3 per cent, disease free survival (DFS) 52.0±9.2...

The Indian journal of medical research, 2016

Acute respiratory distress syndrome (ARDS) is a common disorder in critically ill patients and is... more Acute respiratory distress syndrome (ARDS) is a common disorder in critically ill patients and is associated with high mortality. There is a paucity of literature on this condition from developing countries. This prospective observational study was designed to find out the aetiology, outcomes and predictors of mortality in ARDS. Sixty four consecutive patients who satisfied American-European Consensus Conference (AECC) definition of ARDS from medical Intensive Care Unit (ICU) of a tertiary care centre in New Delhi, India, were enrolled in the study. Demographic, biochemical and ventilatory variables were recorded for each patient. Baseline measurements of serum interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α), procalcitonin (PCT) and high sensitivity C-reactive protein (hsCRP) were performed. Common causes of ARDS included pneumonia [44/64 (68.7%)], malaria [9/64 (14.1%)] and sepsis [8/64 (12.5%]. Eight of the 64 (12.5%) patients had ARDS due to viral pneumonia. The 2...

Leukemia & lymphoma, Oct 4, 2016

In chronic lymphocytic leukemia (CLL), the geographical bias in immunoglobulin heavy-chain variab... more In chronic lymphocytic leukemia (CLL), the geographical bias in immunoglobulin heavy-chain variable (IGHV) gene usage lead us to analyze IGHV gene usage and B-cell receptor stereotypy in 195 patients from India. IGHV3, IGHV4, and IGHV1 families were the most frequently used. 20.5% sequences had stereotyped BCR and were clustered in 12 pre-defined and 6 novel subsets. Unmutated IGHV was significantly associated with reduced time to first treatment (p < 0.033) and poor overall survival (OS; p = 0.01). We observed a significant difference in OS between IGHV1, IGHV3, and IGHV4 family cases (p = 0.045) in early stage patients. Regarding subfamily usage, only IGHV1-69 expression was found to have statistically significant poor outcome (p = 0.017). Our results from the analysis of various molecular and clinical features suggest that the expression of specific IGHV gene influences the outcome in early stage CLL, and hence its assessment may be added to the clinical leukemia laboratory ar...

The Indian Journal of Medical Research

Subsequent to the publication of the article 1 highlighting the role of acute viral hepatitis as ... more Subsequent to the publication of the article 1 highlighting the role of acute viral hepatitis as a confounding factor in antituberculosis (anti-TB) treatment induced hepatotoxicity, we extended the study with a similar study design at the All India Institute of Medical Sciences hospital, New Delhi. We enrolled patients (January 2007 to March 2009) with features suggestive of drug-induced hepatitis (DIh) while on anti-TB treatment. The definition of anti-TB DIH as also management of DIh patients was as described previously 1 .

PloS one, 2015

Pulmonary tuberculosis still remains a major communicable disease worldwide. In 2013, 9 million p... more Pulmonary tuberculosis still remains a major communicable disease worldwide. In 2013, 9 million people developed TB and 1.5 million people died from the disease. India constitutes 24% of the total TB burden. Early detection of TB cases is the key to successful treatment and reduction of disease transmission. Xpert MTB/RIF, an automated cartridge-based molecular technique detects Mycobacterium tuberculosis and rifampicin resistance within two hours has been endorsed by WHO for rapid diagnosis of TB. Our study is the first study from India with a large sample size to evaluate the performance of Xpert MTB/RIF assay in PTB samples. The test showed an overall sensitivity and specificity of 95.7% (430/449) and 99.3% (984/990) respectively. In smear negative-culture positive cases, the test had a sensitivity of 77.7%. The sensitivity and specificity for detecting rifampicin resistance was 94.5% and 97.7% respectively with respect to culture as reference standard. However, after resolving t...