Genetic variant in TNF-α gene and its plasma level in relation to obstructive sleep apnoea in the Pakistani population.

OBJECTIVE: To assess the link between tumour necrosis factor-alpha -308 guanine/adenine polymorphism and tumour necrosis factor-alpha plasma levels in relation to obstructive sleep apnoea. METHODS: The cross-sectional study was conducted from December 2018 to March 2021 at the sleep clinic of Dow University Hospital, Karachi, on obstructive sleep apnoea patients and healthy controls. Epworth Sleep Scale score was used to determine daytime sleepiness, while full-night polysomnography was carried out for obstructive sleep apnoea confirmation and categorisation according to severity. Blood sample collection was followed by deoxyribonucleic acid extraction and plasma tumour necrosis factor-alpha measurement using enzyme-linked immunosorbent assay. Genotype distribution and allelic frequency were assessed. Data was analysed using SPSS 20. RESULTS: Out of the 225 subjects, with a mean age of 47.68±9.88 years, 132 (58.7%) were males, and 93 (41.3%) were females. Among them, 150 (66.7%) were patients, and 75 (33.3%) were controls. Heterozygous tumour necrosis factor-alpha -308 guanine/adenine genotypes were significantly higher among the patients (p<0.05). Minor allele - 308 adenine showed an association with obstructive sleep apnoea, its severity, higher tumour necrosis factor-alpha levels, neck circumference, excessive daytime sleepiness and the presence of hypertension (p<0.05). CONCLUSIONS: Tumour necrosis factor-alpha -308 adenine allele and higher tumour necrosis factor-alpha levels were found to be linked with obstructive sleep apnoea. The polymorphism also showed an association with hypertension in obstructive sleep apnoea patients.

Effectiveness and Quality of Life with Montelukast in Asthma - A double-blind randomized control trial.

OBJECTIVE: To determine the role of montelukast - a leukotriene receptor antagonist (LTRA) - in improving the quality of life (QOL) and asthma control of adult patients with mild to moderate persistent asthma. METHODS: Randomized, double-blind, placebo-controlled, non-crossover trial was conducted from March 2017 till November 2018 in three hospitals of Karachi and Hyderabad. Adults of age 15 years or more with mild to moderate persistent asthma. Treatment group was administered tablet montelukast 10mg once daily; the other group was given a similar looking placebo; as an adjuvant to the current medication. QOL was assessed with Asthma Quality of Life Questionnaire - Standard (AQLQ-S) before and after the treatment. Asthma control was monitored via Asthma Control Test (ACT). RESULTS: After 4 weeks, the mean ± SD of overall QOL on AQLQ-S improved from 3.74±0.88 to 5.06±0.89 for montelukast group and from 3.58±0.92 to 4.71±0.97 for placebo group (p=0.02). The improvement in sub-domains of symptoms, activity, and emotional functions was not significant; however, the sub-domain "environmental stimuli" significantly improved with 5.06±0.89 for montelukast group and 4.71±0.97 for placebo group (p=0.02). The mean ± SD of ACT, after four weeks, for montelukast group was 18.19±2.91 and for placebo group 17.28±3.36. Only on ACT, Montelukast did not show any statistically insignificant results. CONCLUSION: The role of montelukast in improving QOL of adult patients with mild to moderate persistent asthma is quite beneficial. It improves patient quality of life. It has the ease of once daily oral administration and also eradicates side effects associated with long-term adherence to steroids.

Results of community-based TB and HIV screening among transgender women and male sex workers in Pakistan.

In Pakistan and globally, a large proportion of people with TB who are not receiving treatment are key populations with poor access to diagnosis and care. Transgender women and male sex workers (MSW) are heavily stigmatized and marginalized groups. While HIV rates are well documented among these key populations, little such data exists for TB. We engaged local organizations working with transgender women and MSW communities in Karachi and five urban cities in Sindh Province. People from the communities served as screening facilitators and treatment supporters. Verbal screening was followed by testing with Xpert MTB/RIF and HIV testing was offered. People with TB were supported through treatment. We screened 18,272 transgender women and 24,253 MSW. 8,921 (21.0%) individuals had presumptive TB and 7,472 (83.8%) provided sputum samples. We detected 438 (5.9%) people with positive results including 140 transgender women and 298 MSW. Including people diagnosed clinically, 625 people with TB were identified and 98.1% initiated treatment. Overall, 1.5% of people screened had TB, 1.7% among MSW and 1.1% among transgender women. Of 1,508 people tested for HIV, 243 had HIV infection (HIV+). The rates of TB among HIV+ transgender women (8.8%) were slightly lower than among MSW (10.3%). Previously, few attempts have been made to address TB in transgender women and MSW. Our work shows that these groups carry a significant burden of both TB and HIV in Pakistan and do not regularly access services. Effective interventions should include the engagement of community leaders and peers.

Hyperimmune anti-COVID-19 IVIG (C-IVIG) treatment in severe and critical COVID-19 patients: A phase I/II randomized control trial.

BACKGROUND: Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG) is an unexplored therapy amidst the rapidly evolving spectrum of medical therapies for COVID-19 and is expected to counter the three most life-threatening consequences of COVID-19 including lung injury by the virus, cytokine storm and sepsis. METHODS: A single center, phase I/II, randomized controlled, single-blinded trial was conducted at Dow University of Health Sciences, Karachi, Pakistan. Participants were COVID-19 infected individuals, classified as either severely or critically ill with Acute Respiratory Distress Syndrome (ARDS). Participants were randomized through parallel-group design with sequential assignment in a 4:1 allocation to either intervention group with four C-IVIG dosage arms (0.15, 0.20, 0.25, 0.30 g/kg), or control group receiving standard of care only (n = 10). Primary outcomes were 28-day mortality, patient's clinical status on ordinal scale and Horowitz index (HI), and were analysed in all randomized participants that completed the follow-up period (intention-to-treat population). The trial was registered at clinicaltrials.gov (NCT04521309). FINDINGS: Fifty participants were enrolled in the study from June 19, 2020 to February 3, 2021 with a mean age of 56.54±13.2 years of which 22 patients (44%) had severe and 28 patients (56%) had critical COVID-19. Mortality occurred in ten of 40 participants (25%) in intervention group compared to six of ten (60%) in control group, with relative risk reduction in intervention arm I (RR, 0.333; 95% CI, 0.087-1.272), arm II (RR, 0.5; 95% CI, 0.171-1.463), arm III (RR, 0.167; 95% CI, 0.024-1.145), and arm IV (RR, 0.667; 95% CI, 0.268-1.660). In intervention group, median HI significantly improved to 359 mmHg [interquartile range (IQR) 127-400, P = 0.009)] by outcome day, while the clinical status of intervention group also improved as compared to control group, with around 15 patients (37.5%) being discharged by 7th day with complete recovery. Additionally, resolution of chest X-rays and restoration of biomarkers to normal levels were also seen in intervention groups. No drug-related adverse events were reported during the study. INTERPRETATION: Administration of C-IVIG in severe and critical COVID-19 patients was safe, increased the chance of survival and reduced the risk of disease progression. FUNDING: Higher Education Commission (HEC), Pakistan (Ref no. 20-RRG-134/RGM/R&D/HEC/2020).