Frequency, management and impact of adverse events on treatment outcomes in patients with multidrug resistant tuberculosis in Balochistan, Pakistan.

Background: Early detection, monitoring, and managing adverse events (AEs) are crucial in optimising treatment for multidrug-resistant tuberculosis (MDR-TB) patients. Objectives: To investigate the incidence, factors, management, and impact of AEs on treatment outcomes in MDR-TB patients. Methods: This study reviewed the medical records of 275 MDR-TB patients at Fatimah Jinnah Institute of Chest Diseases in Quetta, Pakistan. Patient information was collected using a designed data collection form. Mann-Whitney U and Kruskal-Wallis tests examined the difference in AEs occurrences based on patients' characteristics. Multiple binary logistic regression identified factors associated with unsuccessful outcomes, with statistical significance set at a p-value < 0.05. Results: Almost all patients (99.6%) experienced at-least one AE (median = 4/patient, interquartile range:3-6). The most common were GI disturbance (95.3%), arthralgia (80.4%), body pain and headache (61.8%), ototoxicity (61.4%), psychiatric disturbance (44%), hypokalaemia (40.4%), dermatological reactions (26.2%) and hypothyroidism (21.5%). AEs led to treatment modification in 7.3% patients. Educated patients, those with a history of TB treatment, previous use and resistance to any second-line drug had significantly higher number of AEs. A total of 64.0% were declared cured, 3.6% completed treatment, 19.6% died and 12.7.9% were lost to follow-up. Patients' age of 41-60(OR = 9.225) and >60 years(OR = 23.481), baseline body weight of 31-60 kg(OR = 0.180), urban residence(OR = 0.296), and experiencing ototoxicity (OR = 0.258) and hypothyroidism (OR = 0.136) were significantly associated with unsuccessful treatment outcomes. Conclusion: AEs were highly prevalent but did not negatively impact treatment outcomes. Patients at higher risk of developing AEs and unsuccessful outcomes should receive special attention for its early management.

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.

Treatment Outcomes of Extensively Drug-Resistant Tuberculosis in Pakistan: A Countrywide Retrospective Record Review.

Background: The current study is conducted with the aim to the fill the gap of information regarding treatment outcomes and variables associated with unsuccessful outcome among XDR-TB patients from Pakistan. Methods: A total of 404 culture confirmed XDR-TB patients who received treatment between 1st May 2010 and June 30, 2017 at 27 treatment centers all over Pakistan were retrospectively followed until their treatment outcomes were reported. A p-value <0.05 reflected a statistical significant association. Results: The patients had a mean age 32.9 ± 14.1 years. The overall treatment success rate was 40.6% (95% confidence interval [CI]:35.80-45.60%). A total of 155 (38.4%) patients were declared cured, 9 (2.2%) completed treatment, 149 (36.9%) died, 60 (14.9%) failed treatment and 31 (7.7%) were lost to follow up (LTFU). The results of the multivariate binary logistic regression analysis revealed that the patients' age of >60 years (OR = 4.69, 95%CI:1.57-15.57) and receiving high dose isoniazid (OR = 2.36, 95%CI:1.14-4.85) had statistically significant positive association with death, whereas baseline body weight >40 kg (OR = 0.43, 95%CI:0.25-0.73) and sputum culture conversion in the initial two months of treatment (OR = 0.33, 95%CI:0.19-0.58) had statistically significant negative association with death. Moreover, male gender had statistically significant positive association (OR = 1.92, 95%CI:1.04-3.54) with LTFU. Conclusion: The treatment success rate (40.6%) of XDR-TB patients in Pakistan was poor. Providing special attention and enhanced clinical management to patients with identified risk factors for death and LTFU in the current cohort may improve the treatment outcomes.

Effectiveness of Shorter Treatment Regimen in Multidrug-Resistant Tuberculosis Patients in Pakistan: A Multicenter Retrospective Record Review.

In Pakistan, the treatment of multidrug-resistant tuberculosis (MDR-TB) with a shorter treatment regimen (STR), that is, 4-6 months of amikacin, moxifloxacin (Mfx), ethionamide, clofazimine (Cfz), pyrazinamide (Z), ethambutol (E), and high-dose isoniazid, followed by 5 months of Mfx, Cfz, Z, and E, was initiated in 2018. However, there is a lack of information about its effectiveness in Pakistani healthcare settings. Therefore, this retrospective record review of MDR-TB patients treated with STR at eight treatment sites in Pakistan aimed to fill this gap. Data were analyzed using SPSS 23. Multivariate binary logistic regression (MVBLR) analysis was conducted to find factors associated with death and treatment failure, and lost to follow-up (LTFU). A P-value < 0.05 was considered statistically significant. Of 912 MDR-TB patients enrolled at the study sites, only 313 (34.3%) eligible patients were treated with STR and included in the current study. Of them, a total of 250 (79.9%) were cured, 12 (3.8%) completed treated, 31 (9.9%) died, 16 (5.1%) were LTFU, and four (1.3%) were declared as treatment failures. The overall treatment success rate was 83.7%. In MVBLR analysis, patients' age of 41-60 (odds ratio [OR] = 4.9, P-value = 0.020) and > 60 years (OR = 3.6, P-value = 0.035), being underweight (OR = 2.7, P-value = 0.042), and previous TB treatment (OR = 0.4, P-value = 0.042) had statistically significant association with death and treatment failure, whereas patients' age of > 60 years (OR = 5.4, P-value = 0.040) and previous TB treatment (OR = 0.2, P-value = 0.008) had statistically significant association with LTFU. The treatment success rate of STR was encouraging. However, to further improve the treatment outcomes, special attention should be paid to the patients with identified risk factors.

Treatment Outcomes of Childhood Tuberculosis in Three Districts of Balochistan, Pakistan: Findings from a Retrospective Cohort Study.

BACKGROUND: This study aimed to evaluate treatment outcomes and factors associated unsuccessful outcomes among pediatric tuberculosis (TB) patients (age ≤14 years). METHODS: This was a retrospective cohort study conducted at three districts (Quetta, Zhob and Killa Abdullah) of Balochistan, Pakistan. All childhood TB patients enrolled for treatment at Bolan Medical Complex Hospital (BMCH) Quetta and District Headquarter Hospitals of Zhob and Killa Abdullah from 1 January 2016 to 31 December 2018 were included in the study and followed until their treatment outcomes were reported. Data were collected through a purpose developed standardized data collection form and analyzed by using SPSS 20. A p-value <0.05 was considered statistically significant. RESULTS: Out of 5152 TB patients enrolled at the study sites, 2184 (42.4%) were children. Among them, 1941 childhood TB patients had complete medical record were included in the study. Majority of the study participants were <5 years old (66.6%) and had pulmonary TB (PTB; 65%). A total of 45 (2.3%) patients were cured, 1680 (86.6%) completed treatment, 195 (10%) lost to follow-up, 15 (0.8%) died, 5 (0.3%) failed treatment and 1 (0.1%) was not evaluated for outcomes. In multivariate binary logistic regression analysis, treatment at BMCH Quetta (OR = 25.671, p-value < 0.001), rural residence (OR = 3.126, p-value < 0.001) and extra-PTB (OR = 1.619, p-value = 0.004) emerged as risk factors for unsuccessful outcomes. CONCLUSION: The study sites collectively reached the World Health Organization's target of treatment success (>85%). Lost to follow-up was the major reason for unsuccessful outcomes. Special attention to patients with identified risk factors for unsuccessful outcomes may improve outcomes further.

Inhaler Use Technique in Chronic Obstructive Pulmonary Disease Patients: Errors, Practices and Barriers.

Background Inhaled medications are the main therapeutic treatment of chronic obstructive pulmonary disease (COPD) and inhaler technique remained important that can increase medication efficacy, reducing dose and side effects. Poor inhaler technique is multi-factorial and the quality of inhaler technique has not previously assessed in Pakistan. We conducted a study to examine a range of competing factors that impact COPD patient willingness, practices, and preference in using their inhalers. Methods A cross-sectional of 765 patients with COPD were interviewed and assessed by qualitative questionnaires. Objective inhalation technique and steps assessment was performed; satisfaction, preferences, perception, and practice of different types of inhaler devices were evaluated at a single cross-sectional visit at the study enrolment. Results The study included 765 participants of mean age 58.7 years (SD ±7.8); 32% males and 68% females. Almost all of the females were exposed to biomass fuel smoke exposure (99%) and pipe (Huka) smokers 53%, while most male participants were cigarette smokers (92%). Only 6.3% of participants were able to perform correct steps of inhaler use, and few educated patients completed 7-steps. 66% of patients were using dry powder inhalers (DPI) inhaler devices and mostly performed the steps 1, 2, and 4 (98%) correctly, while 44% who were using metered-dose inhalers (MDI) completed only steps 2 and 4 correctly (88%). The majority of participants reported the particular inhaler devices was prescribed by the visiting consultants (54%). Interestingly, they were using two inhalers together (47%) relieving symptoms of dyspnea (83%) and cough (73%). The inhaler use technique was demonstrated to most of the patients by the pharmacy salesman (38.4%), while 15.8% reported that their doctors taught them the inhaler technique. 54.2% reported reason for poor adherence to inhaler use as they understand it might not work lately and 75.2% were not aware of any side effects associated with the regular use of an inhaler. Conclusions Poor inhaler technique is highly prevalent and the associated errors did not appear to be dependent on device type. Most of the participants had not receive proper training about the correct use and were not involved in decision making about the choice of inhaler device.

Prevalence of tuberculosis, HIV/AIDS, and hepatitis; in a prison of Balochistan: a cross-sectional survey.

BACKGROUND: Human Immunodeficiency Virus (HIV), Hepatitis, and Tuberculosis (TB) are three primary communicable infections have the likely potential to cause severe morbidity in prison settings. The prison has the most favorable environment for the transmission of infections. We conducted this survey to determine the prevalence and feasibility of rapid diagnostic tests in an active screening of these infectious diseases in prison. METHODS: This cross-sectional survey conducted in central Jail Gaddani, one of the largest prisons in the Balochistan province of Pakistan. All prisoners, jail staffs, and staff's family members participated. Informed consent obtained from each participant before the screening. Van equipped with digital X-ray linked with Computer-Aided Detection for TB (CAD4TB) software used for testing. Sputum samples tested on Xpert for MTB/RIF assay and blood specimens collected for HIV and hepatitis serology. Diagnosed TB patients enrolled for treatment at Basic Management Unit (BMU), reactive on hepatitis Rapid Diagnostic Tools (RDTs) were referred for further testing and management, while HIV reactive referred to Anti Retro Viral (ARV) center for Anti Retro Viral Treatment (ART). RESULTS: A total of 567 participants offered screening, 63% (356) prisoners, 23% (129) staff's family members, and 14% (82) jail staffs. Among tested 10.3% (58/562) were hepatitis seropositive (Hepatitis-C 41 [7.29%] Hepatitis-B, 16 [2.84%] Hepatitis B&C both, 01 [0.17%]). In reactive participants, 49 were prisoners, 08 were jail staffs, and 01 was the staff's family member. HIV seropositive was 4% (24/566), and all were prisoners. Almost 99% (565/567) screened by digital X-ray, 172 (30%) were with abnormal CAD4TB suggestion (score > 50), out of them sputum of 26% (148) tested on Xpert, and 2% (03) found Mycobacterium tuberculosis Positive (MTB+). A total of five TB patients were detected; out of two were diagnosed clinically. Co-morbidities observed in 15 patients, (01 TB/HIV co-infected, 12 HIV/HCV, 01 HIV/HBV, and 01 HBV/HCV). CONCLUSION: The high frequency of infectious diseases in prison is alarming. For limiting the transmission of infections among prison and community, immediate steps are needed to be taken for improvement of prisons condition by application of recommended screening protocols at the time of the first entry of prisoners in prisons.

Evaluation of treatment outcomes and factors associated with unsuccessful outcomes in multidrug resistant tuberculosis patients in Baluchistan province of Pakistan.

BACKGROUND: Evaluating treatment outcomes of a cohort of patients is an effective way for analyzing the effectiveness of a program. Information regarding drug resistance pattern, detailed management, treatment outcomes and factors associated with unsuccessful outcomes in multidrug resistant (MDR-TB) patients is missing from Baluchistan province of Pakistan. METHODS: This study was carried out at Programmatic Management of Drug Resistant TB unit at Fatimah Jinnah General and Chest Hospital Quetta. All eligible 186 MDR-TB patients enrolled at the study site from January 1, 2012 to April 30, 2016 were retrospectively followed until the treatment outcomes were reported. Data was abstracted through a standardized data collection form and analysed by SPSS 20. Multivariate binary logistic regression (MVBLR) analysis was used to evaluate factors associated with i) death and treatment failure and ii) lost to follow up. A p-value of <0.05 was considered statistically significant. RESULTS: The study participants were resistant to a median of four drugs (range 2-8) with majority being resistant to any second-line anti-TB drug (SLD) (55.5%). Among SLD, resistance was highest for ofloxacin (52.2%). The study site had an overall treatment success rate of 71.6%. A total of 129 (69.4%) patients were cured, four (2.2%) completed treatment, 37 died (19.9%), 14 (7.5%) were lost to follow up and two (1.1%) were declared treatment failures. In MVBLR analysis, patients' age of >40 years (OR = 4.249, p-value = 0.001) had statistically significant positive and baseline body weight of >40 kg (OR = 0.256, p-value = 0.002) had statistically significant negative association with death and treatment failure. No factor had statistical significant association with lost to follow up. CONCLUSION: Overall treatment success rate was promising but did not achieve the target success rate (>75%) set by World Health Organization. It can be further improved by paying special attention and providing enhanced management to the patients with risk factors for unsuccessful outcomes.

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

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 < 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 < 0.001; 74.2 v/s 65, p < 0.001). On multivariate regression analysis, sepsis at admission predicted mortality (adjusted Odds ratio 26.4; 95% CI 2.3, 304, p < 0.009). A serum HCO3 > 35 Meq/L (adjusted Odds ratio 0.9; 95% CI 0.83, 0.98, p < 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.