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

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

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

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

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability