Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.

BACKGROUND: Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level. METHODS: We systematically searched MEDLINE, Embase and Web of Science (1990-2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration-time curve from 0 to 24 h post-dose (AUC0-24) and peak plasma concentration (C max) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC0-24 and C max were assessed with linear mixed-effects models. RESULTS: Of 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means of steady-state AUC0-24 were summarised for isoniazid (18.7 (95% CI 15.5-22.6) h·mg·L-1), rifampicin (34.4 (95% CI 29.4-40.3) h·mg·L-1), pyrazinamide (375.0 (95% CI 339.9-413.7) h·mg·L-1) and ethambutol (8.0 (95% CI 6.4-10.0) h·mg·L-1). Our multivariate models indicated that younger age (especially <2 years) and HIV-positive status were associated with lower AUC0-24 for all first-line anti-TB drugs, while severe malnutrition was associated with lower AUC0-24 for isoniazid and pyrazinamide. N-acetyltransferase 2 rapid acetylators had lower isoniazid AUC0-24 and slow acetylators had higher isoniazid AUC0-24 than intermediate acetylators. Determinants of C max were generally similar to those for AUC0-24. CONCLUSIONS: This study provides the most comprehensive estimates of plasma exposures to first-line anti-TB drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring.

Characterization of a Newly Isolated Probiotic Strain from Oecophylla smaragdina, an Edible Insect Popular Among the Indigenous Communities of Northeast India.

Northeast India is amongst the 34 Biodiversity Hot Spots of the world with large number of unexplored flora and fauna. A total of 74 potential isolates with probiotic properties were isolated from Oecophylla smaragdina, an edible insect used by local tribes as a nutritious medicinal food source out of which, the most potential probiotic candidate was identified as Bacillus sp. PD6 by 16S rRNA sequencing. Cell surface trait analysis shows hydrophobicity and auto-aggregation percentage of 46.2 ± 0.32% and 61.41 ± 0.28% respectively. The cell free extract (CFE) of the isolate shows the presence of essential amino acids viz, lysine, valine, leucine, isoleucine, and threonine indicating its nutritional value. It survives significantly at pH range from 1 to 10 and capable of hydrolyzing bile salt. The CFE shows antagonistic effect against B. cereus ATCC 11778, E. coli ATCC 25922 and L. monocytogenes ATCC BAA751. FTIR spectra of bacterial exo-polysaccharide shows the presence of νC=C-H stretch, νN-H stretch, νC-H stretch, νC-H bending and νC=O stretch bonds. It was found to be non-cytotoxic against primary mouse liver cell line and sheep erythrocytes and also, sensitive against wide range of broad and narrow spectrum antibiotics making it recommendable for human consumption.

Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India.

We studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA), ethionamide (ETH), and cycloserine (CS) in children with multidrug-resistant tuberculosis (MDR-TB) who were being treated according to the Revised National TB Control Programme (RNTCP) guidelines in India. This observational, pharmacokinetic study was conducted in 25 children with MDR-TB at the Sarojini Naidu Medical College, Agra, India, who were being treated with a 24-month daily regimen. Serial blood samples were collected after directly observed administration of drugs. Estimations of plasma LFX, PZA, ETH, and CS were undertaken according to validated methods by high-performance liquid chromatography. Adverse events were noted at 6 months of treatment. The peak concentration (Cmax) of LFX was significantly higher in female than male children (11.5 µg/ml versus 7.3 µg/ml; P = 0.017). Children below 12 years of age had significantly higher ETH exposure (area under the concentration-time curve from 0 to 8 h [AUC0-8]) than those above 12 years of age (17.5 µg/ml · h versus 9.4 µg/ml; P = 0.030). Multiple linear regression analysis showed significant influence of gender on Cmax of ETH and age on Cmax and AUC0-8 of CS. This is the first and only study from India reporting on the pharmacokinetics of LFX, ETH, PZA, and CS in children with MDR-TB treated in the Government of India program. More studies on the safety and pharmacokinetics of second-line anti-TB drugs in children with MDR-TB from different settings are required.

Single-dose liposomal amphotericin B for visceral leishmaniasis in India.

BACKGROUND: Some 50% of patients with visceral leishmaniasis (kala-azar) worldwide live in the Indian state of Bihar. Liposomal amphotericin B is an effective treatment when administered in short courses. We wanted to determine whether the efficacy of a single infusion of liposomal amphotericin B was inferior to conventional parenteral therapy, consisting of 15 alternate-day infusions of amphotericin B deoxycholate. METHODS: In this open-label study, we randomly assigned 412 patients in a 3:1 ratio to receive either liposomal amphotericin B (liposomal-therapy group) or amphotericin B deoxycholate (conventional-therapy group). Liposomal amphotericin B (at a dose of 10 mg per kilogram of body weight) was given once, and patients were discharged home 24 hours later. Amphotericin B deoxycholate, which was administered in 15 infusions of 1 mg per kilogram, was given every other day during a 29-day hospitalization. We determined the cure rate 6 months after treatment. RESULTS: A total of 410 patients--304 of 304 patients (100%) in the liposomal-therapy group and 106 of 108 patients (98%) in the conventional-therapy group--had apparent cure responses at day 30. Cure rates at 6 months were similar in the two groups: 95.7% (95% confidence interval [CI], 93.4 to 97.9) in the liposomal-therapy group and 96.3% (95% CI, 92.6 to 99.9) in the conventional-therapy group. Adverse events in the liposomal-therapy group were infusion-related fever or rigors (in 40%) and increased anemia or thrombocytopenia (in 2%); such events in the conventional-therapy group were fever or rigors (in 64%), increased anemia (in 19%), and hypokalemia (in 2%). Nephrotoxicity or hepatotoxicity developed in no more than 1% of patients in each group. CONCLUSIONS: A single infusion of liposomal amphotericin B was not inferior to and was less expensive than conventional therapy with amphotericin B deoxycholate. (ClinicalTrials.gov number, NCT00628719.)

Diagnostic accuracy of pulmonary embolism rule-out criteria: a systematic review and meta-analysis.

STUDY OBJECTIVE: To perform a systematic review and meta-analysis to define the diagnostic performance of pulmonary embolism rule-out criteria (PERC) in deferring the need for D-dimer testing to rule out pulmonary embolism in the emergency department (ED). METHODS: We searched EMBASE, MEDLINE, Scopus, Web of Knowledge, and all the evidence-based medicine reviews that included the Cochrane Database of Systematic Reviews through August 14, 2011, and hand searched references in potentially eligible articles and conference proceedings of major emergency medicine organizations for the previous 2 years. We selected studies that reported diagnostic performance of PERC, reported original research, and were conducted in the ED, with no language restrictions. Two investigators independently identified eligible studies and extracted data. We used contingency tables to calculate sensitivity, specificity, and likelihood ratios. RESULTS: We found 12 qualifying cohorts (studying 13,885 patients with 1,391 pulmonary embolism diagnoses), 10 prospective and 2 retrospective, from 6 countries. Pooled sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios for 10 included studies were 0.97 (95% confidence interval [CI] 0.96 to 0.98), 0.23 (95% CI 0.22 to 0.24), 1.24 (95% CI 1.18 to 1.30), and 0.17 (95% CI 0.13 to 0.23), respectively. Significant heterogeneity was observed in specificity (I(2)=97.2%) and positive likelihood ratio (I(2)=84.2%). CONCLUSION: The existing literature suggests consistently high sensitivity and low but acceptable specificity of the PERC to rule out pulmonary embolism in patients with low pretest probability.

Development of a clinical prediction rule for 30-day cardiac events in emergency department patients with chest pain and possible acute coronary syndrome.

STUDY OBJECTIVE: Evaluation of emergency department (ED) patients with chest pain who are at low risk for acute coronary syndrome is resource intensive and may lead to false-positive test results and unnecessary downstream procedures. We seek to identify patients at low short-term risk for a cardiac event for whom additional ED investigations might be unnecessary. METHODS: We prospectively enrolled patients older than 24 years and with a primary complaint of chest pain from 3 academic EDs. Physicians completed standardized data collection forms before diagnostic testing. The primary adjudicated outcome was acute myocardial infarction, revascularization, or death of cardiac or unknown cause within 30 days. We used recursive partitioning to derive the rule and validated the model with 5,000 bootstrap replications. RESULTS: Of 2,718 patients enrolled, 336 (12%) experienced a cardiac event within 30 days (6% acute myocardial infarction, 10% revascularization, 0.2% death). We developed a rule consisting of the absence of 5 predictors: ischemic ECG changes not known to be old, history of coronary artery disease, pain typical for acute coronary syndrome, initial or 6-hour troponin level greater than the 99th percentile, and age greater than 50 years. Patients aged 40 years or younger required only a single troponin evaluation. The rule was 100% sensitive (95% confidence interval 97.2% to 100.0%) and 20.9% specific (95% confidence interval 16.9% to 24.9%) for a cardiac event within 30 days. CONCLUSION: This clinical prediction rule identifies ED chest pain patients at very low risk for a cardiac event who may be suitable for discharge. A prospective multicenter study is needed to validate the rule and determine its effect on practice.

External validation of the Glasgow-Blatchford Bleeding Score and the Rockall Score in the US setting.

BACKGROUND: The Glasgow-Blatchford Bleeding Score (GBS) and Rockall Score (RS) are clinical decision rules that risk stratify emergency department (ED) patients with upper gastrointestinal bleeding (UGIB). We evaluated GBS and RS to determine the extent to which either score identifies patients with UGIB who could be safely discharged from the ED. METHODS: We reviewed and extracted data from the electronic medical records of consecutive adult patients who presented with signs or symptoms of UGIB (hematemesis and/or melena) to an academic ED from April 1, 2004, to April 1, 2009. The primary outcome was need for intervention (blood transfusion and/or endoscopic/surgical intervention) or death within 30 days. RESULTS: We identified 171 patients with the following characteristics: mean age of 69.9 years (SD, 17.0 years ), 52% women, 20% with a history of liver disease, and 22% with history of gastrointestinal bleeding. Ninety (52.6%, 95% confidence interval, 44.9-60.3) patients had the primary outcome. GBS outperformed pre-endoscopy RS [area under the receiver operating characteristic curve (AUC)=0.79 vs 0.62; P=.0001; absolute difference, 0.17]. The prognostic accuracy of GBS and post-endoscopy RS was similarly high (AUC, 0.79 vs 0.72; P=.26; absolute difference, 0.07). The specificity of GBS and RS was suboptimal at all potential decision thresholds. CONCLUSIONS: Although GBS outperformed pre-endoscopy RS, the prognostic accuracy of GBS and post-endoscopy RS was similarly high. The specificity of GBS and RS was insufficient to recommend use of either score in clinical practice.

Diagnostic accuracy of endobronchial ultrasound-guided transbronchial needle biopsy in mediastinal lymphadenopathy: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of prospectively conducted studies to define diagnostic performance of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNB) in mediastinal and hilar lymphadenopathy. METHODS: A comprehensive search was performed using the Embase, Ovid Medline, Ovid Medline In-Process and Other Non-Indexed Citations, All Evidence Based Medicine Reviews-Cochrane Database of Systematic Reviews, American College of Physicians Journal Club, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials (CCTR), Health Technology Assessment (HTA), and SCOPUS databases, in the second week of November 2010. Studies were selected in 2 phases by 2 reviewers, independently. Data extraction from each study was performed using a standardized data extraction form. Quality assessment of study methodology was done using a checklist that was developed based on a Quality Assessment of Diagnostic Accuracy Studies tool and the nature of the test. Using the 2 × 2 tables, we computed the sensitivity, specificity, and likelihood ratios. RESULTS: The 14 studies included for quantitative data synthesis had a pooled cohort of 1,658 patients, from 8 different countries. The EBUS-TBNB had excellent pooled specificity of 100% (95% CI 0.90-1.00) and a positive likelihood ratio of 5.1 (95% CI 2.7-9.7). The pooled sensitivity was 0.92 (95% CI 0.91-0.93), and the pooled negative likelihood ratio was 0.13 (95% CI 0.09-0.19). The sensitivity of this intervention was not dependent on rapid on-site evaluation use or size of needle used. The pooled diagnostic odds ratio was 62.7 (95% CI 25.7-153.0). Only one major complication was reported, which resulted in early termination of the procedure. CONCLUSIONS: Evidence of moderate quality confirms the high diagnostic performance of EBUS-TBNB for mediastinal and hilar lymphadenopathy, both in malignant and non-malignant conditions. Available evidence also demonstrates the safety of this procedure.

Comparison of awareness and perception of menstrual hygiene between pre and postmenarchal adolescents of North India: A cross-sectional study.

CONTEXT: Menstruation is a normal physiologic phenomenon. Due to lack of awareness regarding menstrual hygiene among adolescent girls in India, majority have unhygienic practices which make them vulnerable to various adverse health and social outcomes. AIMS AND OBJECTIVE: The aim of this study was to compare the awareness and perception of pre- and postmenarchal adolescent girls regarding menstrual hygiene. SETTINGS AND DESIGN: A hospital-based cross-sectional study was conducted by the Department of Obstetrics and Gynaecology and Paediatrics of a Government tertiary care center, Lucknow, Uttar Pradesh for 6 months from 1 July 2019 to 31 December 2019. MATERIAL AND METHODS: The study was undertaken among 120 adolescent girls between 09 and 19 years of age. Premenarchal age group was from 9 to 12 years and postmenarchal was 13-19 years. All the adolescent girls who fulfilled the inclusion criteria were subjected to a pretested prevalidated semi-structured questionnaire assessing their awareness and perceptions regarding menstrual hygiene. RESULT: Of 120 respondents, 43 girls were aware of menstruation prior to attainment of menarche. Mother was the first informant regarding menstruation in the case of 49 (49.65%) girls. A total of 57 girls believed it as a physiological process. 32 (53.3%) girls knew the use of sanitary pads during menstruation. Regarding restrictions practiced, 136 (85%) girls practiced different restrictions during menstruation. CONCLUSION: Adolescent girls, being vulnerable, need to have adequate and correct awareness regarding menstrual hygiene. This will protect them from risk of developing reproductive or sexually transmitted infections (RTI/STI) which is a burden on our society and render many females infertile and cause other adverse health outcomes.

Comparison of Diagnostic Yield of Tuberculosis Loop-Mediated Isothermal Amplification Assay With Cartridge-Based Nucleic Acid Amplification Test, Acid-Fast Bacilli Microscopy, and Mycobacteria Growth Indicator Tube Culture in Children With Pulmonary Tuberculosis.

BACKGROUND: Cartridge-based nucleic acid amplification test (CB-NAAT) has been recommended for diagnosis of tuberculosis (TB) in children, but its wide use is limited by high cost and the need for well-equipped laboratories. This study was conducted in children with pulmonary TB to compare the diagnostic yield of TB-LAMP (loop-mediated isothermal amplification test) with CB-NAAT and other conventional methods. METHODS: Patients ≤ 14 years of age diagnosed with probable pulmonary TB were included in the study. Induced sputum/gastric aspirate was obtained and subjected to acid-fast bacilli (AFB) microscopy, mycobacteria growth indicator tube (MGIT) culture, CB-NAAT, and TB-LAMP. The TB-LAMP assay was performed using 2 different primers, IS6110 and mpb64, for detection of Mycobacterium tuberculosis (MTB). TB-LAMP assays were compared to other assays using appropriate statistical tests. RESULTS: One hundred fourteen subjects were recruited in the study. AFB microscopy, MGIT culture, CB-NAAT, TB-LAMP IS6110, and TB-LAMP mpb64 showed positivity of 32 (28.1%), 59 (51.7%), 66 (57.9%), 75 (65.8%), and 81 (71%), respectively. TB-LAMP IS6110 showed significantly higher MTB detection in comparison to AFB microscopy and MGIT culture (P = .0001 and P = .03, respectively), and showed no significant difference in MTB detection in comparison with CB-NAAT (P = .219). TB-LAMP mpb64 showed significantly higher MTB detection as compared to AFB microscopy, MGIT culture, and CB-NAAT (P = .0001, P = .003, and P = .037, respectively). TB-LAMP mpb64 and IS6110 showed sensitivity of 94.9% (95% confidence interval [CI], 85.9%-98.9%) and 89.8% (95% CI, 79.7%-96.2%), respectively, in reference to MGIT culture. The degree of agreement between TB-LAMP (mpb64 and IS6110) with CB-NAAT showed κ values of 0.718 and 0.834, respectively. CONCLUSIONS: TB-LAMP assay can be a useful alternative test in diagnosis of pulmonary TB in children.

Diagnostic accuracy of the TIMI risk score in patients with chest pain in the emergency department: a meta-analysis.

BACKGROUND: The Thrombolysis in Myocardial Infarction (TIMI) risk score uses clinical data to predict the short-term risk of acute myocardial infarction, coronary revascularization or death from any cause. It was originally developed for use in patients with unstable angina or non-ST-elevation myocardial infarction. We sought to expand the clinical application of the TIMI risk score by assessing its prognostic accuracy in patients in the emergency department with potential acute coronary syndromes. METHODS: We searched five electronic databases, hand-searched reference lists of included studies and contacted content experts to identify articles for review. We included prospective cohort studies that validated the TIMI risk score in emergency department patients. We performed a meta-regression to determine whether a linear relation exists between TIMI risk score and the cumulative incidence of cardiac events. RESULTS: We included 10 prospective cohort studies (with a total of 17 265 patients) in our systematic review. Data were available for meta-analysis in 8 of the 10 studies. Of patients with a score of zero, 1.8% had a cardiac event within 30 days (sensitivity 97.2%, 95% CI 96.4-97.8; specificity 25.0%, 95% CI 24.3-25.7; positive likelihood ratio 1.30, 95% CI 1.28-1.31; negative likelihood ratio 0.11, 95% CI 0.09-0.15). Meta-regression analysis revealed a strong linear relation between TIMI risk score (p < 0.001) and the cumulative incidence of cardiac events. INTERPRETATION: Although the TIMI risk score is an effective risk stratification tool for patients in the emergency department with potential acute coronary syndromes, it should not be used as the sole means of determining patient disposition.

Prevalence of viral infection detected by PCR and RT-PCR in patients with acute exacerbation of COPD: a systematic review.

BACKGROUND AND OBJECTIVE: Viruses are important aetiological agents of acute exacerbation of COPD (AECOPD). Their reported prevalence varies from region to region. This systematic review calculated the prevalence of respiratory viral infections in AECOPD. METHODS: A systematic search was performed using Medline, and references of relevant articles and conference proceedings were hand searched. Articles for review were selected based on the following criteria: (i) prospective or cross-sectional study, (ii) original research, (iii) viral detection used the highly sensitive techniques of PCR and/or Reverse Transcriptase PCR (RT-PCR), (iv) viral prevalence in AECOPD defined, and (v) full paper available in English. We assessed the study quality and extracted data independently and in duplicate using a pre-defined data extraction form. Weighted mean prevalence (WMP) was calculated and a forest plot was constructed to show the dispersion. RESULTS: Eight studies met the inclusion criteria. The WMP of respiratory viral infection in AECOPD was 34.1% (95% CI: 23.9-44.4). picornavirus was the most commonly detected virus with WMP 17.3% (95% CI: 7.2-27.3), followed by influenza; 7.4% (95% CI: 2.9-12.0), respiratory syncytial virus; 5.3% (95% CI: 1.6-9.0), corona viruses; 3.1% (95% CI: 0.4-5.8), parainfluenza; 2.6% (95% CI: 0.4-4.8), adenovirus; 1.1% (95% CI: -1.1 to 3.3), and human metapneumovirus; 0.7% (95% CI: -0.3 to 1.8). Maximum WMP was observed in studies from Europe followed by the USA, Australia and Asia. Picorna was the most common virus detected in Western countries whereas influenza was most common in Asia. CONCLUSIONS: This systematic review demonstrated that viruses are strongly associated with AECOPD, with the highest detection rates of viruses being in Europe. The geographical epidemiology of viruses may have important therapeutic implications for management of AECOPD.

Ultrasonography for diagnosis of abdominal tuberculosis in HIV infected people.

BACKGROUND & OBJECTIVES: There is an increasing incidence of abdominal tuberculosis with the advent of HIV infection. This study was aimed at determining the pattern of presentation of abdominal tuberculosis on ultrasonography (USG) in HIV positive patients. METHODS: This retrospective study was carried at the ART Centre, Sir Sunderlal Hospital, Banaras Hindu University, Varanasi, between March 2005 to July 2007. HIV positive patients (n=2453) with prolonged fever, abdominal pain/distension, altered bowel habits and diarrhoea underwent ultrasonography for tuberculosis of abdomen. The different ultrasonological findings in abdominal tuberculosis were noted. CD4 counts of these patients were also recorded. RESULTS: Of the total 2453 patients, 244 showed findings suggestive of abdominal tuberculosis. Lymphadenopathy with predominantly hypoechoic/necrotic echotexture was seen in 158/244 (64.8%) patients. Splenomegaly was seen in 68 patients with 61 of them (89.7%) showing multiple hypoechoic lesions in the parenchyma. 53 of 244 (21.7%) showed extensive abdominal involvement. Liver enlargement was seen as a part of extensive abdominal involvement. A total of 203 patients completed antitubercular treatment, of which 198 (97.5%) showed resolution of lesions in USG. CD4 counts in patients with extensive abdominal involvement were lowest compared to CD4 count in patients with others USG findings. INTERPRETATION & CONCLUSION: Ultrasonological findings like lymphadenopathy (>or=1.5 cm) with hypoechoeic/necrotic echotexture, hypoechoic splenic lesions and extensive abdominal involvement in HIV infected patients may be suggestive of abdominal tuberculosis.

High incidence of zidovudine induced anaemia in HIV infected patients in eastern India.

BACKGROUND & OBJECTIVES: Zidovudine (ZDV) is the preferred nucleoside reverse transcriptase inhibitor in the first line antiretroviral regimen in India. It is known to be associated with life threatening toxicity like anaemia. This study was aimed at determining the prevalence of ZDV induced anaemia in HIV infected patients initiated on ZDV containing antiretroviral therapy regimen and also to find out the correlates, if any, for causing ZDV induced anaemia. METHODS: This retrospective study was carried in ART Centre, Sir Sunderlal Hospital, Banaras Hindu University, Varanasi between March 2005 to December 2007. HIV infected patients registered at ART Centre were treated according to guidelines of National AIDS Control Organization (NACO). Patients (n=1256) with haemoglobin (Hb)>8 g/dl were prescribed ZDV based antiretroviral therapy regimens. Patients developing anaemia (<8 g/dl) with other causes of anaemia excluded were recorded. Correlation of baseline characteristics (age, gender, haemoglobin levels, weight, CD(4) counts and WHO clinical stage) with risk of developing anaemia was also calculated. RESULTS: Two hundred three (16.2%) patients on ZDV regimen developed anaemia (<8 g%); 7.9 per cent (n=100) of these developed severe anaemia (<6.5 g%). Females were more prone to develop anaemia (P=0.026). Age, weight, WHO clinical stage and CD4 counts had no relation to development of anaemia. INTERPRETATION & CONCLUSION: High incidence of ZDV induced anaemia seen in this study indicates regular monitoring of patients, particularly women on ZDV based antiretroviral regimens.

Recurrent Peumonia in an Infant With an Esophageal Lung.

Esophageal lung is a rare variety of communicating bronchopulmonary foregut malformation with anomaolous communication between an isolated portion of respiratory tissue and esophagus. Children present in early life with recurrent cough and pneumonia. Majority of the reported cases are associated with other anomalies like tracheoesophageal fistula. We report a case of a 7-month-old girl with right sided esophageal lung who was misdiagnosed as dextrocardia with right sided pneumonitis.

Short-course paromomycin treatment of visceral leishmaniasis in India: 14-day vs 21-day treatment.

BACKGROUND: Treatment of visceral leishmaniasis (VL) is far from satisfactory. There is an urgent need for a therapy that is efficacious, safe, affordable, and of short duration. METHODS: A randomized open-label study was conducted to assess the efficacy and safety of 2 regimens of paromomycin administered intramuscularly. Group A received 11 mg/kg/day for 14 days (n = 217) and group B received 11 mg/kg/day for 21 days (n = 112) for the treatment of VL in India. RESULTS: Mild grade injection site pain was the most common adverse event. There was no nephrotoxicity, but 4 patients in group A had to discontinue treatment because of grade 3 elevation of hepatic enzymes. Initial cure was observed in 91.2% and 96.4% of patients in group A and group B, respectively. Definitive cure at 6 months of follow up was seen in 82% of patients in group A and 92% of patients in group B by intention-to-treat analysis and in 84.3% of patients in group A and 92.8% of patients in group B by per protocol analysis. CONCLUSIONS: Although the cure rate in the group of patients who received the 14-day regimen was not optimal, the results with respect to initial cure were encouraging. Further studies that combine a short course of paromomycin with treatment with another antileishmanial agent are warranted. ( ClinicalTrials.gov identifier: NCT00629031).

Visceral Leishmaniasis-Optimum Treatment Options in Children.

Visceral leishmaniasis affects 200-400 thousands people annually worldwide. For last few decades, there has been a steady decline in the response to pentavalent antimonial (Sb), the drug that has been used for treating visceral leishmaniasis for almost a century. Oral miltefosine and amphotericin B are alternative drugs being been used in the treatment of leishmaniasis in children. Liposomal amphotericin B has the advantage over conventional amphotericin B is that higher doses can be given with fewer adverse effects. Liposomal amphotericin B in combination with other drugs is the preferred treatment option globally especially in Indian subcontinent. Combination therapy with multiple drugs should undergo larger clinical trials in children as these will shorten the duration of therapy, improve compliance and decrease both toxicity and drug resistance.

Clinical and pulmonary functions profiling of patients with chronic obstructive pulmonary disease experiencing frequent acute exacerbations.

PURPOSE: The present study aimed at clinical and pulmonary functions profiling of patients with chronic obstructive pulmonary disease (COPD) to anticipate future exacerbations. METHODS: The study included 80 COPD patients; 40 patients had ≥2 acute exacerbations during preceding 1 year (frequent exacerbation [FECOPD] group) and 40 patients had <2 acute exacerbations during preceding 1 year (infrequent exacerbation [I-FECOPD] group). Clinical profile, sputum microbiology, blood gas analysis, spirometric indices, and diffusion capacity (transfer test) variables were assessed. Groups' comparison was performed using an independent t-test for numeric scale parameters and Chi-square test for nominal parameters. Pearson's and Spearman's correlation coefficients were derived for numeric scale parameters and numeric nominal parameters, respectively. Multinomial logistic regression analysis was done using SPSS software. RESULTS: FECOPD group contained younger patients than in I-FECOPD group although the difference was not statistically significant. There was no significant difference between two groups regarding smoking pack-years and duration of illness. FECOPD group had significantly more expectoration score and Modified Medical Research Council dyspnea scores. Cough score and wheeze score did not differ significantly between two groups. More patients in FECOPD group (12/40 vs. 4/40) had lower airway bacterial colonization. Arterial blood gas parameters were more deranged in FECOPD group. Spirometric indices (forced expiratory volume during 1st s) as well as transfer test (both diffusing capacity for carbon monoxide and transfer coefficient of the lung values) were significantly reduced in FECOPD group. CONCLUSIONS: The patients in FECOPD group had clinical, spirometric, and transfer test profiling suggestive of a severe COPD phenotype, the recognition will help in predicting future exacerbations and a better management.

Tuberculosis Burden among Household Pediatric Contacts of Adult Tuberculosis Patients.

OBJECTIVES: To find out the prevalence of latent tuberculosis (TB) infection and TB disease among pediatric household contacts of adult drug resistant (MDR) and drug susceptible (DS) TB patients and to identify the risk factors for occurrence of TB infection in the contacts. METHODS: Pediatric household contacts (less than 15 y age) of adult TB patients (both MDR and DS) were included in the study. They were categorized as latent TB infection (LTBI), TB disease and TB exposed based on the results of tuberculin skin testing (TST), clinical examination and chest X-ray. Various factors (age, gender, socioeconomic status, BCG immunization etc.) were evaluated to assess their association with TB transmission. RESULTS: A total of 271 household contacts were included in the study. Prevalence of LTBI was 20.3% (31% in MDR TB group and 14% in DS TB group); difference was significant (p value = 0.0018). TB disease was seen in 3 subjects in DS group while none in MDR group developed TB disease. Lower socioeconomic status was significantly associated with risk of TB infection in MDR group (p value =0.0027). In DS TB group, male gender, BCG non-immunization was significantly associated with risk of developing TB (p value 0.0068 and 0.0167 respectively). CONCLUSIONS: Prevalence of latent TB infection was found to be high in household pediatric contacts especially in contacts of MDR TB patients. Risk factors identified for occurrence of TB included lower socioeconomic status, BCG non-immunization and male gender. The study focuses on the importance of contact screening and the need for its implementation in TB control programs.