Treatment outcome of multi-drug resistant tuberculosis in a tertiary care hospital in Karachi

Objective: To assess the outcomes of pulmonary multidrug-resistant tuberculosis (MDR-TB) patients treated at Ojha Institute of Chest Diseases (OICD), a reference hospital for TB in Karachi, Pakistan. Methods: Clinical study for the period 1996-2006, with follow-up until June 2007 was performed. All the culture and sensitivity proven cases of MDR pulmonary TB were initially admitted for 3-6 months till the sputum converted negative. Treatment regimen was decided on individual basis, and included 4-6 drugs. Supervised treatment was given to all patients during the hospitalization. After discharge from the hospital, patients were followed at monthly interval at the outpatient department of OICD for 18 months total. Results: Five hundred and seventy nine adult patients (59.93% male) with mean age of 32.44 ± 12.63 years were studied. All patients had a history of treatment with first line anti-tuberculosis drugs. Treatment was successful in 227 (39.2%). The mortality rate was 27(4.6%) during hospitalization. During admission 83(14.3%) left treatment and 239 (41.2%) were lost to follow-up during treatment. Treatment failure was observed in three patients. Conclusion: The treatment success rate in this study is satisfactory but high default rate is a challenge in the management of MDR tuberculosis (JPMA 59:694; 2009)

Primary drug resistance against Mycobacterium tuberculosis in Karachi

OBJECTIVE: To evaluate the primary drug resistance of new culture positive cases of pulmonary tuberculosis in Karachi. METHODS: All new suspected pulmonary tuberculosis patients were recruited initially. They were instructed to produce three-sputum samples for smear examination and on one of the specimen\u27s culture was applied. Bronchoscopy and bronchial wash was done in patients who were not expectorating. Bronchial wash was then applied for both smear and culture for Mycobacterium tuberculosis. RESULTS: Out of 79 cases recruited initially, 52 were able to produce sputum while bronchoscopy was performed in the remaining. AFB direct smear was positive in 32/52 sputum and 12/27 bronchial wash samples. Later, 02 sputums and 04 bronchial washes became culture positive which were initially smear negative. All cultures were of Mycobacterium tuberculosis species. These fifty culture positive cases were then included in the final analysis. Pyrazinamide was the most sensitive drug i.e. 49 isolates (98%). The resistance pattern is as follows: Streptomycin 13(26%), Isoniazid 08 (16%), Ethambutol 08 (16%), Rifampicin 04 (08%) and Pyrazinamide one (02%). Multi-Drug Resistant tuberculosis was observed in 02 (04%) patients. CONCLUSION: In this small study, the high prevalence of primary resistance against streptomycin, INH and Ethambutol raises an urgent need of a proper nationwide survey to evaluate the true picture of primary resistance

Drug Resistance Pattern in Multidrug Resistance Pulmonary Tuberculosis Patients

Objective: To evaluate accuracy of modified Kenneth Jones scoring criteria (MKJSC) as a screening tool to diagnose tuberculous meningitis in children. Study Design: Cross-sectional study. Place and Duration of Study: Paediatric Medicine, Unit-I, Bahawal Victoria Hospital, Bahawalpur, from May 2006 to March 2007. Methodology: A total of 100 children admitted through emergency in Paediatric Medicine, Unit-I, were included who were having fever and features suggestive of central nervous system (CNS) infection. Lumbar puncture was done in all patients after written consent. Findings of lumbar puncture were taken as gold standard for the diagnosis of TBM. MKJSC was applied on each patient and accuracy determined against the gold standard. Results: Out of 100 children, 47 were diagnosed as TBM on the basis of CSF results. All children had scored 0-7 or above according to MKJSC. A score 1-2, 3-4, 5-6 and 7 or more was obtained in 23, 25, 30 and 22 children respectively. Children who had scored 5 or more received ATT. Accuracy of MKJSC was calculated to be 91%. Conclusion: MKJSC is a simple and accurate tool to improve tuberculous meningitis case detection rate in children

Six-Minute Walk Test Performance in Healthy Adult Pakistani Volunteers

Objective: To determine the six-minute walking distance (6MWD) for healthy Pakistanis, identify factors affecting 6MWD, compare published equations with the local data and derive an equation. Study Design: Cross-sectional study. Place and Duration of Study: Two medical institutes of Karachi, from January to May 2011. Methodology: Subjects between 15 and 65 years were prospectively enrolled after screening. A standardized 6MWT was administered. SpO2, HR, BP and dyspnoea scores were determined pre- and post-test. Results: Two hundred and eleven (71%) men and 85 (29%) women participated. Mean 6MWD was 469.88 ± 101.24 m: men walked 502.35 ± 92.21 m and women walked 389.28 ± 74.29 m. On univariate analysis, gender, height, weight and age showed a significant relationship with the 6MWD. Gender and age were identified as independent factors in multiple regression analysis, and together explained 33% of the variance. The gender-specific prediction equations were: 6MWD (m) for men = 164.08 + (78.06*1) - (1.90*age in years) + (1.95*height in cms) 6MWD (m) for women = 164.08 - (1.90*age in years) + (1.95*height in cms). Conclusion: 6MWDs among the volunteer subjects were shorter than predicted by reference equations in literature. Height, gender and weight combined explained 33% of the variance. The moderate over-estimation of the 6MWD in Pakistani subject. The proposed equation gives predicted (mean) 6MWDs for adult Pakistani naïve to the test when employing standardized protocol

Interplay of chemo attractant peptides (cathelicidin and chemerin) with vitamin-D in patients with pulmonary tuberculosis

Aim: Both Cathelicidin and Chemerin are chemoattractant proteins and possess antimicrobial activity.Sufficient level of Vitamin D is important for optimum response of Cathelicidin for its antimycobacterial activity. Studies on the role of these antimicrobial peptides and their relationship withVitamin D level are limited in tuberculosis. The aim of this study was to investigate an associationof Vitamin D with antimicrobial peptide (Cathelicidin) and an adipokine (Chemerin) in patients with pulmonary tuberculosis (TB). Methods: In a case control study we estimated level of Vitamin D, Chemerin, Cathelicidin and TNFα in pulmonary TB patients (n=22) and healthy endemic controls (n=17) using sandwich ELISA methodology. The study was conducted at Aga Khan University Karachi during 2011. Results: TB group had higher proportion of subjects above median level of Cathelicidin (median test; p=0.034) and fewer number of subjects with Chemerin (median test; p=0.001).Pairwise comparison also showed significant differences between average ranks of Vitamin D vs.Cathelicidin (p\u3c0.0001), Chemerin vs. Cathelicidin (p=0.04) and Vitamin D vs.TNFα(p\u3c0.0001). Cathelicidin was identified as most discriminatory marker between TB disease and healthy group(ROC,AUC 0.780; p=0.007). Conclusion: Our results highlight the role of Cathelicidin as a potential biomarker of active TB disease. The role of Cathelicidin and Chemerin as plausible biomarkers requires further studies in both inflammatory and non inflammatory condition

National registry of interstitial lung disease from Pakistan

Introduction: Interstitial lung disease (ILD) is a heterogeneous group of over 200 parenchymal lung diseases with a myriad of etiologies. Interstitial lung disease registries from around the world show varying prevalence and incidence of these diseases. The aim of this study was to determine the epidemiology and characteristics of ILD in Pakistan.Methods: This web-based registry, which is the first multicenter registry of ILD from Pakistan, recruited patients from 10 centers of five major cities between January 2016 and March 2019.Results: A total of 744 patients were enrolled in the registry. The five most frequent ILDs were idiopathic pulmonary fibrosis (IPF) 34.4%, hypersensitivity pneumonitis (HP) - 17.7%, idiopathic nonspecific interstitial pneumonitis (iNSIP) - 16.8%, connective tissue disease-associated ILD (CTD-ILD) - 16.3%, and sarcoidosis - 9.1%.Conclusion: Idiopathic pulmonary fibrosis is the most prevalent ILD in Pakistan, followed by HP and iNSIP. An ongoing prospective registry with longitudinal follow-up will help us further elaborate on the clinical characteristics, treatment, and survival outcome of patients with ILD

Variables predictive of outcome in patients with acute hypercapneic respiratory failure treated with noninvasive ventilatio

OBJECTIVE: To assess results with NIV in acute hypercapneic respiratory failure and to identify outcome predictors. METHODS: This was a retrospective observational study on consecutive patients presenting with acute type II respiratory failure and meeting criteria for NIV use over a 5 year period. Patients presenting with haemodynamic instability, inability to protect their airway, malignant arrhythmias and recent oesophageal surgery were excluded. Univariate and Multivariate regression analysis was used to determine the impact on survival. A p value of \u3c 0.05 was considered statistically significant. Software used was SPSS 14. RESULTS: Total numbers of patients included were 119; 52.9% were males. Mean age was 63.4 +/- 11.9 years. Overall Survival to discharge rate was 76.5%, intubation rate was 12.6% and mean length of stay was 11.4 +/- 10.9 days. Statistically significant improvements were observed in the pH and PaCO2 at 24 hours and 48 hours compared to baseline (7.28 v/s 7.37, p \u3c 0.001; 74.2 v/s 65, p \u3c 0.001). On multivariate regression analysis, sepsis at admission predicted mortality (adjusted Odds ratio 26.4; 95% CI 2.3, 304, p \u3c 0.009). A serum HCO3 \u3e 35 Meq/L (adjusted Odds ratio 0.9; 95% CI 0.83, 0.98, p \u3c 0.015) identified those less at risk for intubation. CONCLUSION: NIV was found to be both safe and effective in the management of acute hypercapneic respiratory failure. Sepsis and serum HCO3 at admission identified patients having poor outcomes

A randomized, double-blind, placebo-controlled trial of oral montelukast in acute asthma exacerbation.

Background: Leukotriene receptor antagonists (LTRAs) are well established in the management of outpatient asthma. However, there is very little information as to their role in acute asthma exacerbations. We hypothesized that LTRAs may accelerate lung function recovery when given in an acute exacerbation. Methods: A randomized, double blind, placebo-controlled trial was conducted at the Aga Khan University Hospital to assess the efficacy of oral montelukast on patients of 16 years of age and above who were hospitalized with acute asthma exacerbation. The patients were given either montelukast or placebo along with standard therapy throughout the hospital stay for acute asthma. Improvements in lung function and duration of hospital stay were monitored. Results: 100 patients were randomized; their mean age was 52 years (SD +/− 18.50). The majority were females (79%) and non-smokers (89%). The mean hospital stay was 3.70 ± 1.93 days with 80% of patients discharged in 3 days. There was no significant difference in clinical symptoms, PEF over the course of hospital stay (p = 0.20 at day 2 and p = 0.47 at day 3) and discharge (p = 0.15), FEV1 at discharge (p = 0.29) or length of hospital stay (p = 0.90) between the two groups. No serious adverse effects were noted during the course of the study. Conclusion: Our study suggests that there is no benefit of addition of oral montelukast over conventional treatment in the management of acute asthma attack

Quantifying risks and interventions that have affected the burden of diarrhoea among children younger than 5 years : an analysis of the Global Burden of Disease Study 2017

Background Many countries have shown marked declines in diarrhoea! disease mortality among children younger than 5 years. With this analysis, we provide updated results on diarrhoeal disease mortality among children younger than 5 years from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) and use the study's comparative risk assessment to quantify trends and effects of risk factors, interventions, and broader sociodemographic development on mortality changes in 195 countries and territories from 1990 to 2017. Methods This analysis for GBD 2017 had three main components. Diarrhoea mortality was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive, Bayesian, ensemble modelling tool; and the attribution of risk factors and interventions for diarrhoea were modelled in a counterfactual framework that combines modelled population-level prevalence of the exposure to each risk or intervention with the relative risk of diarrhoea given exposure to that factor. We assessed the relative and absolute change in diarrhoea mortality rate between 1990 and 2017, and used the change in risk factor exposure and sociodemographic status to explain differences in the trends of diarrhoea mortality among children younger than 5 years. Findings Diarrhoea was responsible for an estimated 533 768 deaths (95% uncertainty interval 477 162-593 145) among children younger than 5 years globally in 2017, a rate of 78.4 deaths (70.1-87.1) per 100 000 children. The diarrhoea mortality rate ranged between countries by over 685 deaths per 100 000 children. Diarrhoea mortality per 100 000 globally decreased by 69.6% (63.1-74.6) between 1990 and 2017. Among the risk factors considered in this study, those responsible for the largest declines in the diarrhoea mortality rate were reduction in exposure to unsafe sanitation (13.3% decrease, 11.2-15.5), childhood wasting (9.9% decrease, 9.6-10.2), and low use of oral rehydration solution (6.9% decrease, 4-8-8-4). Interpretation Diarrhoea mortality has declined substantially since 1990, although there are variations by country. Improvements in sociodemographic indicators might explain some of these trends, but changes in exposure to risk factors-particularly unsafe sanitation, childhood growth failure, and low use of oral rehydration solution-appear to be related to the relative and absolute rates of decline in diarrhoea mortality. Although the most effective interventions might vary by country or region, identifying and scaling up the interventions aimed at preventing and protecting against diarrhoea that have already reduced diarrhoea mortality could further avert many thousands of deaths due to this illness

Quantifying risks and interventions that have affected the burden of lower respiratory infections among children younger than 5 years : an analysis for the Global Burden of Disease Study 2017

Background Despite large reductions in under-5 lower respiratory infection (LRI) mortality in many locations, the pace of progress for LRIs has generally lagged behind that of other childhood infectious diseases. To better inform programmes and policies focused on preventing and treating LRIs, we assessed the contributions and patterns of risk factor attribution, intervention coverage, and sociodemographic development in 195 countries and territories by drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) LRI estimates. Methods We used four strategies to model LRI burden: the mortality due to LRIs was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive ensemble modelling tool; the incidence of LRIs was modelled using population representative surveys, health-care utilisation data, and scientific literature in a compartmental meta-regression tool; the attribution of risk factors for LRI mortality was modelled in a counterfactual framework; and trends in LRI mortality were analysed applying changes in exposure to risk factors over time. In GBD, infectious disease mortality, including that due to LRI, is among HIV-negative individuals. We categorised locations based on their burden in 1990 to make comparisons in the changing burden between 1990 and 2017 and evaluate the relative percent change in mortality rate, incidence, and risk factor exposure to explain differences in the health loss associated with LRIs among children younger than 5 years. Findings In 2017, LRIs caused 808 920 deaths (95% uncertainty interval 747 286-873 591) in children younger than 5 years. Since 1990, there has been a substantial decrease in the number of deaths (from 2 337 538 to 808 920 deaths; 65.4% decrease, 61.5-68.5) and in mortality rate (from 362.7 deaths [3304-392.0] per 100 000 children to 118.9 deaths [109.8-128.3] per 100 000 children; 67.2% decrease, 63.5-70.1). LRI incidence dedined globally (32.4% decrease, 27.2-37.5). The percent change in under-5 mortality rate and incidence has varied across locations. Among the risk factors assessed in this study, those responsible for the greatest decrease in under-5 LRI mortality between 1990 and 2017 were increased coverage of vaccination against Haemophilus influenza type b (11.4% decrease, 0.0-24.5), increased pneumococcal vaccine coverage (6.3% decrease, 6.1-6.3), and reductions in household air pollution (8.4%, 6 8-9.2). Interpretation Our findings show that there have been substantial but uneven declines in LRI mortality among countries between 1990 and 2017. Although improvements in indicators of sociodemographic development could explain some of these trends, changes in exposure to modifiable risk factors are related to the rates of decline in LRI mortality. No single intervention would universally accelerate reductions in health loss associated with LRIs in all settings, but emphasising the most dominant risk factors, particularly in countries with high case fatality, can contribute to the reduction of preventable deaths