HEALTH RELATED QUALITY OF LIFE ASSESSMENT USING ST. GEORGE'S RESPIRATORY QUESTIONNAIRE IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS ON COMBINED INHALED CORTICOSTEROIDS AND BRONCHODILATORS

Objective: Chronic diseases like COPD have significant effects on patient's health-related quality of life (HRQoL). HRQoL measures additional indices as compared to objective measurements like spirometry. Our aim is to assess and compare the disease-specific quality of life in Chronic Obstructive Pulmonary Disease patients using St. George's Respiratory Questionnaire (SGRQ-C) receiving Salmeterol/Fluticasone (SF), Formoterol/Budesonide (FB), Formoterol/Fluticasone (FF).Methods: A prospective, open-label, randomized, parallel group study conducted at a tertiary care teaching hospital in South India. A 6-months follow-up of 90 patients with severe and very severe COPD randomized to receive Salmeterol/Fluticasone, Formoterol/Budesonide, and Formoterol/Fluticasone in appropriate doses according to their global initiative for chronic obstructive lung disease (GOLD) severity. After spirometry, St. George's Respiratory Questionnaire (SGRQ-C) was administered at baseline and after 180 d to assess improvement in lung function and HRQoL. Statistical analysis used: Data analyzed using SPSS version: 13.0. General linear repeated measures using the post-hoc Bonferroni method assessed significance between treatment groups.Results: Significant decrease (P<0.05) in each SGRQ-C domains and total scores as well as improvement in FEV1 (P<0.05) was observed in all study subjects. The mean SGRQ-C total score for the group I subjects (SF) at the initial visit was 86.69 and the scores reduced to 58.78 at final visit (i.e. after using SF for 6 mo). This reduction was highly significant statistically (t=10.989, p=0.000) at 95% CI. The mean SGRQ-C total scores for group II subjects (FB) at initial visit were 85.85 and the scores reduced to 67.98 at the final visit. This reduction was highly significant statistically (t=9.669, p=0.000) at 95% CI. The mean SGRQ-C total scores for group III subjects (FF) at initial visit were 83.96 and the scores reduced to 70.37 at final visit (after 6 mo). This reduction was highly significant statistically (t=12.285, p=0.000) at 95% CI.Conclusion: Maximum improvement in HRQoL (P<0.05) was noted in patients receiving Salmeterol/Fluticasone with respect to SGRQ-C (activity, impact and total) scores and FEV1. This improvement with SF was due to its greater effect in patients with severe and very severe chronic obstructive pulmonary disease. There was a significant improvement in QoL with SF as compared to FB and FF in severe and very severe COPD patients. Subsequently, the three combined inhaled corticosteroids and bronchodilators showed similar improvements in lung functions and Health related quality of life throughout the study.Â

Amphotericin B Nano-Assemblies Circumvent Intrinsic Toxicity and Ensure Superior Protection in Experimental Visceral Leishmaniasis with Feeble Toxic Manifestation

In spite of its high effectiveness in the treatment of both leishmaniasis as well as a range of fungal infections, the free form of the polyene antibiotic amphotericin B (AmB) does not entertain the status of the most preferred drug of choice in clinical settings. The high intrinsic toxicity of the principal drug could be considered the main impedance in the frequent medicinal use of this otherwise very effective antimicrobial agent. Taking into consideration this fact, the pharma industry has introduced many novel dosage forms of AmB to alleviate its toxicity issues. However, the limited production, high cost, requirement for a strict cold chain, and need for parenteral administration are some of the limitations that explicitly compel professionals to look for the development of an alternate dosage form of this important drug. Considering the fact that the nano-size dimensions of drug formulation play an important role in increasing the efficacy of the core drug, we employed a green method for the development of nano-assemblies of AmB (AmB-NA). The as-synthesized AmB-NA manifests desirable pharmacokinetics in the treated animals. The possible mechanistic insight suggested that as-synthesized AmB-NA induces necrosis-mediated cell death and severe mitochondrial dysfunction in L. donovani promastigotes by triggering depolarization of mitochondrial membrane potential. In vivo studies demonstrate a noticeable decline in parasite burden in the spleen, liver, and bone marrow of the experimental BALB/c mice host. In addition to successfully suppressing the Leishmania donovani, the as-formed AmB-NA formulation also modulates the host immune system with predominant Th1 polarization, a key immune defender that facilitates the killing of the intracellular parasite

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old