A Phase-IV Non-interventional Study to Assess Virological Effectiveness, Safety, and Tolerability of DTG-based Antiretroviral Therapy in HIV-1 Infected Indian Persons Living with HIV.

BACKGROUND: Dolutegravir (DTG) is a novel yet preferential first- and -second-line treatment for persons living with HIV (PLH). Owing to its recent introduction, DTG-based regimens have not undergone a comprehensive, systematic evaluation regarding their real-world utilization and safety profile among a sizeable Indian population. OBJECTIVE: This study aimed to assess the 24 week immunovirological outcomes, anthropometric and metabolic changes, tolerability, and adverse events (AEs) of DTG-based antiretroviral (ART) regimens. METHODS: A single-centre phase-IV non-interventional observational study involving 322 ART naïve and treatment-experienced PLH initiating DTG-based-regimens until October 2022 were followed up for outcomes at 24 weeks. RESULTS: At 24 weeks, all PLH (n = 113) in the naïve group, all PLH (n = 67) in the first-line substitution group, 93.9% PLH (n = 46) in the first-line failure group, and 95.7% PLH (n = 89) in the second-line substitution group were virologically suppressed to plasma HIV-RNA <1000 copies/mL. Virological suppression rates to plasma HIV-RNA <200 copies/mL and <50 copies/mL were consistent among PLH who received DTG as first- or second-line ART. The mean-unadjusted weight gain observed was 3.5 kg (SE: 0.330), and it was significantly higher in PLH with poorer health at baseline (either HIV-RNA ≥ 1000 copies/ml or CD4 cell count <350 cells/µL). Overall, 27.3% PLH (n = 88) gained ≥10% of their baseline body weight, corresponding to 3.7% incidence (n = 12) of treatment-emergent clinical obesity. DTG had an overall lipid-neutral effect, with an advantageous effect being observed in PLH switching from non-nucleoside analogue reverse-transcriptase inhibitors (NNRTI) or ritonavir-boosted protease inhibitors (b/PI), especially in dyslipidemic pre-treated PLH (median change in total cholesterol: 28.5 mg/dL and triglycerides: 51 mg/dL), possibly emanating from the withdrawal of the offending ART. The incidence of DTG-specific AEs, including CNS AEs, was low. Two PLH developed proximal myopathy and one developed transaminitis, warranting DTG discontinuation. Asymptomatic serum-CPK elevation and drug-induced transaminitis were seen in 25.2% (n = 27) and 3.2% (n = 10) PLH, respectively. No apparent negative effects on renal function were detected. CONCLUSION: Our results from a large Indian cohort indicate a favourable virological and metabolic response, with good tolerance of DTG-based ART at 24 weeks.

Impact of Levodopa in Lung Functions in Patients with Parkinson Disease.

BACKGROUND: Parkinson's disease (PD) is the second-most common neurodegenerative disorder known primarily by its motor symptomatology. These motor manifestations are also hypothesised to affect the respiratory muscular function of PD patients contributing to restrictive pattern of ventilatory dysfunction. Previous reports attempting to detect these abnormalities through spirometric assessments have been inconclusive. Attempts at reversal of the restrictive abnormalities by levodopa therapy too, have yielded conflicting results. OBJECTIVES: This study aims to classify spirometric abnormalities in asymptomatic PD patients after levopopa withdrawal and document changes after levodopa replacement. METHODS: Thirty-six non-smoker PD patients without pre-existing respiratory abnormalities were enrolled. Their standard spirometric values- FEV1, FVC and FEV1/FVC, were noted before and after their morning levodopa dose. RESULTS: Nineteen patients had abnormal PFT values at baseline - 14 restrictive and 5 obstructive defects. Fourteen patients showed improvement in their pulmonary performances after dopamine administration with 6 showing complete reversibility. Statistically significant improvement in the post-levodopa FVC values was seen in patients with restrictive disorder (P value=0.04) but not for obstructive disorders. DISCUSSIONS: This pilot study characterised that 39% of PD patients had restrictive ventilatory defects prior to morning dopamine administration. Of these, 40% showed improvement after levodopa administration. CONCLUSION: Restrictive defects are common in PD patients which are evident on routine spirometric screening. These defects are reversible on levodopa administration.

Lack of efficacy of pre bronchoscopy inhaled salbutamol on symptoms and lung functions in patients with pre-existing airway obstruction.

BACKGROUND: Fiberoptic bronchoscopy (FOB) may exaggerate symptoms and lung functions in patients with pre-existing airway obstruction. Interventions which can alleviate or minimize this procedure-related bronchospasm, especially in this high-risk group are, therefore, required. METHODS: A double-blinded randomized controlled trial was conducted to evaluate the efficacy of 400 µg of inhaled salbutamol on patients with spirometric evidence of airflow obstruction planned for FOB. Patient's dyspnea, procedure tolerability, and change in spirometry were assessed before and after the procedure. RESULTS: A total of 50 patients were enrolled (78% males), with a mean (standard deviation) age of 49.8 (6.2) years. There was a significant fall in % predicted FEV1 within each group compared to their respective pre-bronchoscopy values. However, no significant difference in the % predicted or absolute FEV1 level was observed between the two groups. Similarly, although both groups experienced increased dyspnea immediately following FOB, this difference was not significant between the two groups either on the Borg or visual analog scale scales. Pre-FOB anxiety levels and the tolerability of the procedure as assessed by the bronchoscopist were similar in both groups. CONCLUSION: FOB in patients with pre-existing airway obstruction aggravates cough and dyspnea, with a concomitant decline in FEV1 and FVC. The administration of pre-FOB inhaled salbutamol does not have any significant beneficial effect on procedure-related outcomes.

Lingual hematoma causing upper airway obstruction: an unusual manifestation of dengue fever.

The spectrum of dengue infection varies from dengue fever to more severe forms such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). In DHF bleeding may be overt (external) or internal. At time bleeding can occur at unusual sites. We report one such case of DHF in which bleeding occurred within the tongue manifesting as an intra-lingual hematoma, causing significant upper airway obstruction.

Impact of chronic obstructive pulmonary disease on respiratory status and quality of life in newly diagnosed patients with lung cancer.

OBJECTIVE AND BACKGROUND: A significant proportion of patients with lung cancer have associated COPD, which is considered an independent risk factor and cause of morbidity and mortality. However, the effect of COPD on respiratory status and quality of life in lung cancer has not been evaluated. METHODS: Newly diagnosed patients with lung cancer were assessed at diagnosis before starting treatment, for detailed respiratory status, spirometry and World Health Organization-Bref Quality of Life questionnaire in Hindi (WHOQOL-Bref Hindi). RESULTS: One hundred and sixty patients were studied. Spirometry was abnormal in 92.7% patients, 42% had COPD, and the majority (88.6%) had advanced disease (stage III and IV). Patients scored poorly in all QOL domains, with social domain faring worst. Karnofsky Performance status (KPS) correlated significantly with all QOL domains. No significant differences were found in clinical profile, KPS, or QOL scores between patients with and without COPD. Chest pain and dyspnoea severity (assessed by Medical Research Council) grading and visual analogue scale correlated with physical QOL domain. CONCLUSION: Patients with lung cancer have a poor QOL that is affected by the severity of respiratory profile and KPS. The presence of COPD does not significantly affect QOL in lung cancer patients.