Neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia: Experience from a tertiary care center in India.

BACKGROUND: Data of neurocognitive deficits in survivors of acute lymphoblastic leukemia (ALL) is scarce from low middle-income countries (LMICs), and is influenced by biological and cultural variations. The objective of this study was to assess the prevalence and spectrum of neurocognitive deficits in a cohort of survivors from India. PROCEDURE: Seventy survivors of childhood ALL were evaluated for neurocognitive deficits by the Indian adaptation of Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IVINDIA ). The prevalence of neurocognitive deficits was calculated based on the full-scale intelligence quotient (FSIQ), and scores in discrete domains like verbal comprehension, perceptual reasoning, working memory, and processing speed were calculated and compared to demographics, treatment, and sociocultural factors. RESULTS: The mean (SD) current age and time since diagnosis was 10.5 (±3.2) years and 5 (±2.8) years, respectively. The mean FSIQ was 86.1 ± 20.5, with significant neurocognitive deficit (FSIQ <90) being prevalent in 50% (95% CI: 38%-62%) of the cohort. The proportion of survivors with deficits in individual domains of verbal comprehension, perceptual reasoning, working memory, and processing speed were 49%, 50%, 47%, and 44%, respectively. The odds of having neurocognitive deficits were higher when a child belonged to lower socioeconomic strata (OR 5.7, p = .004), parents with lower education attainment (OR 4.3, p = .041), and whose birth order was higher (OR 20.1, p = .005). Age at diagnosis/assessment, chemotherapy received, or dose of radiotherapy did not have a direct impact on neurocognition. CONCLUSIONS AND RELEVANCE: Rates of neurocognitive deficits are higher in survivors in LMICs, with socioeconomic variables contributing more than the direct neurotoxic effects of treatment.

Single-phase Split-bolus Dual Energy Computed Tomography Angiography for Evaluation of Hemoptysis: A Novel Application.

PURPOSE: The purpose of this study was to assess feasibility and overall utility of single-phase split-bolus dual energy computed tomography (DECT) angiography (DECTA) for evaluation of hemoptysis, and to establish an injection protocol for evaluation of hemoptysis, by comparing 2 contrast injection protocols. MATERIALS AND METHODS: Using dual-source (80 and 140 kV), 2×128-slice equipment, DECTA was performed using 400 mg iodine/mL, 50 to 80 mL iodinated contrast in 257 patients (189 male individuals, 68 female individuals, age range: 15 to 76 y) presenting with hemoptysis. Initially, 50 patients were randomized into 2 groups for 2 different injection protocols (A and B). Images were assessed quantitative and qualitatively. Later, 207 patients were randomized using protocol B, which was technically simpler, and single-CT acquisition, for simultaneous opacification of systemic and pulmonary vessels. RESULTS: Injection protocol A resulted in higher vessel attenuation, both in the aorta and in the pulmonary artery and its segmental branches; however, the difference was not statistically significant. No significant difference was noted in signal-to-noise ratio, contrast-to-noise ratio, as well as subjective image quality parameters. Overall optimal opacification of both systemic and pulmonary arteries was achieved in 247/257 patients. A total of 308 abnormal bronchial arteries were noted. A total of 392 nonbronchial systemic arteries were noted, the majority arising from posterior intercostals and subclavian artery branches. The pulmonary source of hemoptysis was identified in 9 patients (3 pulmonary thromboembolisms, 5 pulmonary artery pseudoaneurysms, and 1 pulmonary venous ectasia). CONCLUSION: Combined DECTA is a novel technique that enables simultaneous evaluation of both systemic and pulmonary vascular cause of hemoptysis in a single acquisition with small contrast dose. Both injection protocols "A" and "B" were equally efficacious in simultaneous opacification of both the aorta and pulmonary arteries. To the best of our knowledge, such a protocol has never been described for hemoptysis evaluation.

Clinicomicrobiological profile of endophthalmitis: A 10 year experience in a Tertiary Care Center in North India.

PURPOSE: To determine the clinicomicrobiological profile of infectious agents and their antibiotic susceptibility in different type of endophthalmitis. METHODS: A retrospective review of clinical and microbiological records from January 2001 to December 2010, was performed in 1110 patients diagnosed with different type of endophthalmitis (postoperative, posttraumatic, endogenous and post keratitis) to record the demographic details, clinical presentations; microbiological agents isolated with their antimicrobial sensitivity pattern. Antimicrobial susceptibility testing for various culture positive isolates (bacterial/fungal) was performed by the disc diffusion technique. RESULTS: Out of the 1110 intra-ocular specimens processed, 384 (34.6%) were positive for bacteria. S epidermidis was the most predominant isolate accounting for 42.7% of all bacteria obtained, followed by Pseudomonas aeruginosa (24.5%). Besides Pseudomonas, Acinetobacter spp. were the next common gram negative bacilli detected (8.3%) followed by Klebsiella, E. coli, Enterobacter and Alkaligenes in 2.6%, 0.8%, 0.8% and 0.5% cases respectively. The predominant fungal species were Aspergillus spp., in 36.1%, followed by Fusarium spp. in 26.4% cases. Overall susceptibility pattern in our study showed that gram positive bacteria were most susceptible to glycopeptides like vancomycin (80-100%) and fluoroquinolones (87-91%). The sensitivity pattern of gram negative organisms like Pseudomonas and Klebsiella towards fluoroquinolones ranged between 61% - 82%. CONCLUSION: S epidermidis was the most common bacteria isolated in postoperative and posttraumatic endophthalmitis, Pseudomonas aeruginosa was the most common bacterial isolated in posttraumatic endophthalmitisAmongst fungi Aspergillus was the most common organism.

Correlation of chest computed tomography findings with dyspnea and lung functions in post-tubercular sequelae.

AIMS: To study the correlation between dyspnea, radiological findings, and pulmonary function tests (PFTs) in patients with sequelae of pulmonary tuberculosis (TB). MATERIALS AND METHODS: Clinical history, chest computed tomography (CT), and PFT of patients with post-TB sequelae were recorded. Dyspnea was graded according to the Modified Medical Research Council (mMRC) scale. CT scans were analyzed for fibrosis, cavitation, bronchiectasis, consolidation, nodules, and aspergilloma. Semi-quantitative analysis was done for these abnormalities. Scores were added to obtain a total morphological score (TMS). The lungs were also divided into three zones and scores added to obtain the total lung score (TLS). Spirometry was done for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1/FVC. RESULTS: Dyspnea was present in 58/101 patients. A total of 22/58 patients had mMRC Grade 1, and 17/58 patients had Grades 2 and 3 dyspnea each. There was a significant difference in median fibrosis, bronchiectasis, nodules (P < 0.01) scores, TMS, and TLS (P < 0.0001) between dyspnea and nondyspnea groups. Significant correlations were obtained between grades of dyspnea and fibrosis (r = 0.34, P = 0.006), bronchiectasis (r = 0.35, P = 0.004), nodule (r = 0.24, P = 0.016) scores, TMS (r = 0.398, P = 0.000), and TLS (r = 0.35, P = 0.0003). PFTs were impaired in 78/101 (77.2%) patients. Restrictive defect was most common in 39.6% followed by mixed in 34.7%. There was a negative but statistically insignificant trend between PFT and fibrosis, bronchiectasis, nodule scores, TMS, and TLS. However, there were significant differences in median fibrosis, cavitation, and bronchiectasis scores in patients with normal, mild to moderate, and severe respiratory defects. No difference was seen in TMS and TLS according to the severity of the respiratory defect. CONCLUSION: Both fibrosis and bronchiectasis correlated with dyspnea and with PFT. However, this correlation was not linear. The overall extent of radiological abnormalities correlated only with dyspnea but not with PFT.

Association of birth of girls with postnatal depression and exclusive breastfeeding: an observational study.

OBJECTIVES AND HYPOTHESIS: To examine the influence of gender of the baby on exclusive breastfeeding and incidence of postnatal depression (PND). We hypothesise that in a society with a male gender bias there may be more PND and less exclusive breastfeeding of the girl child. DESIGN: Prospective study. SETTING: The study was conducted in an urban, tertiary hospital in Delhi. PARTICIPANTS: Mothers delivering normally with their babies roomed-in.1537 eligible women participated in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: Exclusive breastfeeding within the first 48 h of life and score on the Edinburgh Postnatal Depression Scale (EPDS) were recorded. RESULTS: 3466 babies were born in the hospital. There were 792 girls for every 1000 boys. Among primiparous women, the sex ratio was 901 girls per 1000 boys. For second babies, the sex ratio was 737:1000. If the first child was a girl the birth ratio fell to 632. 1026 mothers were exclusively breastfeeding. Exclusive breastfeeding of boys was significantly higher (70.8% vs 61.5%, p<0.001). The EPDS score was significantly higher with the birth of girls (EPDS 6.0±3.39 vs 5.4±2.87, p<0.01). Women with an EPDS score >11 were less likely to exclusively breastfeed (p<0.01). CONCLUSIONS: The results point to a pro-male gender bias evidenced by a low sex ratio at birth, higher EPDS score in mothers of girls and less breastfeeding of female children.

Prenatal loud music and noise: differential impact on physiological arousal, hippocampal synaptogenesis and spatial behavior in one day-old chicks.

Prenatal auditory stimulation in chicks with species-specific sound and music at 65 dB facilitates spatial orientation and learning and is associated with significant morphological and biochemical changes in the hippocampus and brainstem auditory nuclei. Increased noradrenaline level due to physiological arousal is suggested as a possible mediator for the observed beneficial effects following patterned and rhythmic sound exposure. However, studies regarding the effects of prenatal high decibel sound (110 dB; music and noise) exposure on the plasma noradrenaline level, synaptic protein expression in the hippocampus and spatial behavior of neonatal chicks remained unexplored. Here, we report that high decibel music stimulation moderately increases plasma noradrenaline level and positively modulates spatial orientation, learning and memory of one day-old chicks. In contrast, noise at the same sound pressure level results in excessive increase of plasma noradrenaline level and impairs the spatial behavior. Further, to assess the changes at the molecular level, we have quantified the expression of functional synapse markers: synaptophysin and PSD-95 in the hippocampus. Compared to the controls, both proteins show significantly increased expressions in the music stimulated group but decrease in expressions in the noise group. We propose that the differential increase of plasma noradrenaline level and altered expression of synaptic proteins in the hippocampus are responsible for the observed behavioral consequences following prenatal 110 dB music and noise stimulation.

Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment.

BACKGROUND: For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. METHODS: In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. FINDINGS: A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar. INTERPRETATION: Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. TRIAL REGISTRATION: CTRI/2011/12/002260.

The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment.

BACKGROUND: Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV) and tuberculosis (TB) co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART) when co-administered with rifampicin-containing antituberculosis treatment (ATT) and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. METHODS: 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. RESULTS: 97 out of 114 (85.1%) patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83) at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD) Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10), 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08), 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10) respectively and 3.04 µg/ml (in cases). CONCLUSIONS: Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in antiretroviral effectiveness. Larger sample sized studies and longer follow-up are required to identify populations of individuals where the reduction in nevirapine concentration may result in lower ART response or shorter response duration.

Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study.

PURPOSE: We designed this study to evaluate efficacy of modified gemcitabine and oxaliplatin (mGEMOX) over best supportive care (BSC) or fluorouracil (FU) and folinic acid (FA) in unresectable gall bladder cancer (GBC). PATIENTS AND METHODS: Patients with unresectable GBC were enrolled for single center randomized study. Arm A, BSC; arm B, FU 425 mg/m(2) and FA 20 mg/m(2) intravenous (IV) bolus weekly for 30 weeks (FUFA); arm C, gemcitabine 900 mg/m(2) and oxaliplatin 80 mg/m(2) IV infusion on days 1 and 8 every 3 weeks for maximum of six cycles. Eighty-one patients were randomly assigned, arms A (n = 27), B (n = 28), and C (n = 26). RESULTS: Complete response plus partial response in the three groups was 0 (0%), four (14.3%), and eight (30.8%) respectively (P < .001). Two patients in the mGEMOX arm and one patient in the FUFA arm underwent curative resection after chemotherapy. One patient in the mGEMOX arm had complete pathologic response. Median overall survival (OS) was 4.5, 4.6, and 9.5 months for the BSC, FUFA, and mGEMOX arms (P = .039), respectively. Progression-free survival (PFS) was 2.8, 3.5, and 8.5 months for the three groups (P < .001). There was no difference in grade 3/4 toxicities in the chemotherapy arms except transaminitis, which was more prevalent in mGEMOX arm (P = .04). Two patients in the FUFA arm and 10 patients in the mGEMOX arm had grade 3 or 4 myelosuppression. Two patients in the mGEMOX group had neutropenic fever that resolved with antibiotics. CONCLUSION: This randomized controlled trial confirmed the efficacy of chemotherapy (mGEMOX) compared with BSC and FUFA in improving OS and PFS in unresectable GBC.