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Background and objectives: India, the country with the largest market availability of antimicrobial fixed-dose combinations (FDCs), banned certain antimicrobial FDCs in September 2018. Our objective was to examine the impact of Government ban on the sales of antimicrobial FDCs. Methods: The sales patterns of 14 of the 26 banned antimicrobial FDCs were analyzed using monthly private sector drug sales data from IQVIA (a comprehensive and nationally representative drug sales database) between January 2018 and December 2019. We carried out descriptive analyses to evaluate the trend in sales over time for banned and non-banned antimicrobial FDCs using cumulative sales volumes. Results: Overall, the cumulative sales volume of banned antimicrobial FDCs declined by 75% between January and September 2018 and the same months of 2019, although some banned FDCs continued to be available in significant volumes. The effectiveness of the ban was offset by several pathways. First, the sales of combinations containing moieties belonging to the same drug-classes as the antimicrobials in the banned FDCs increased after the ban. Second, while certain formulations of particular combinations were banned, the sales of other non-banned formulation of these combinations increased. Third, in some cases, products containing new non-antimicrobial components added to the banned combinations remained available. Interpretation and conclusions: While sales of the banned antimicrobial FDCs decreased in 2019, we identified several mechanisms that counterbalanced the ban, including implementation failure, rising sales of congeners, and products with additional non-antimicrobial components. [ABSTRACT FROM AUTHOR]

Vitiligo is an autoimmune depigmenting skin disease characterised by loss of melanocytes wherein oxidative stress is proposed to be the initial triggering factor with subsequent immune dysregulation. This study aimed to evaluate the relationship, if any, between the generation of reactive oxygen species (ROS), markers of oxidative damage and circulating cytokines in patients with active vitiligo. The generation of ROS in erythrocytes and neutrophils was significantly higher in patients with active vitiligo than healthy controls. Alongside, markers of oxidative stress-mediated damage namely lipid peroxidation, DNA damage and protein carbonylation were evaluated. Patients with active vitiligo demonstrated increased lipid and DNA damage but minimal protein damage. There was a significant decline in the free radical scavenging capacity of active vitiligo cases. A positive correlation existed between baseline levels of ROS and lipid peroxidation as also DNA damage. Patients with active vitiligo demonstrated an increase in several proinflammatory (IL-6, TNF-α, IL-1β, IFN-γ and IL-8) and some anti-inflammatory/immunoregulatory (IL-5 and IL-10) cytokines. Importantly, the levels of IFN-γ and IL-10 consistently correlated with the generation of ROS, markers of damage and their free radical scavenging capacity. Taken together, patients with active vitiligo demonstrated an enhanced generation of ROS in erythrocytes and neutrophils which mediated lipid peroxidation, DNA damage and coupled with a decline in their antioxidant capacity created a pro-oxidant milieu that favoured tissue damage and potential generation of neoantigens, accounting for disease progression. [ABSTRACT FROM PUBLISHER]

Objectives: Levodopa-induced dyskinesia (LID) is one of the most disabling complications of long-term pharmacotherapy of Parkinson's disease (PD). The objective of our study was to examine the clinical profile and determinants of severity of LID in Indian PD patients on levodopa therapy. Methods: Retrospective analysis of records of PD patients with LID was performed. All patients were on levodopa and carbidopa combination. Records of subjects with complete information about disease profile, drug intake, and dyskinesia were analyzed. Characterization of LID was based on responses to part IV of unified Parkinson's disease rating scale (UPDRS). Results: Records of 42 patients (M : F = 4.6 : 1) were analyzed. The median Hoehn and Yahr (H&Y) stage was 2.5 while median duration of levodopa therapy was 6.16 years (range: 1.91-14.58). Early morning dystonia was reported by 97.6% of the patients. Patients treated with ≤2 concomitant PD medication reported a significantly lower median UPDRS IV A score compared to patients treated with <2 number of concomitant drugs. A trend toward a lower UPDRS IV A score was associated with use of dopamine agonists (DA). Patients with H&Y score ≤3 had a significantly higher median total UPDRS IV A score than patients with H&Y score <3. Discussion: Early morning dystonia might be more common among Indian patients of LID. Use of a higher number of concomitant PD medications alongside levodopa is associated with a reduced severity of dyskinesia, even on prolonged use. Levodopa-induced dyskinesia is not only a drug-related phenomenon but the stage of PD itself also affects the dyskinesia severity. [ABSTRACT FROM AUTHOR]