Poor glycemic control among diabetics is a risk factor for TB occurrence. The result shows metformin use is a protective agent against TB infection in diabetics. Hence, incorporation of metformin into standard clinical care would offer a therapeutic option for the prevention of TB.
Saving lives and flattening the curve are the foremost priorities during the ongoing pandemic spread of SARS-CoV-2. Developing cutting-edge technology and collating available evidence would support frontline health teams. Nutritional adequacy improves general health and immunity to prevent and assuage infections. This review aims to outline the potential role of probiotics in fighting the COVID-19 by covering recent evidence on the association between microbiota, probiotics, and COVID-19, the role of probiotics as an immune-modulator and antiviral agent. The high basic reproduction number (R0) of SARS-CoV-2, absence of conclusive remedies, and the pleiotropic effect of probiotics in fighting influenza and other coronaviruses together favour probiotics supplements. However, further support from preclinical and clinical studies and reviews outlining the role of probiotics in COVID-19 are critical. Results are awaited from many ongoing clinical trials investigating the benefits of probiotics in COVID-19.
Vitamin D deficiency (VDD) partly explains geographical differences in COVID-19 susceptibility, severity, and mortality. VDD among African-Americans, diabetics, hypertensive, and aged populations possibly explain the higher death rate, aggravated by cocooning. Vitamin D is pleiotropic, mediating bone metabolism, calcium homeostasis, and immune functions, whereas VDD is associated with inflammatory reactions and immune dysfunction, predisposing individuals to severe infections. Vitamin D modulates innate and adaptive immunity via the expression of genes that code antimicrobial peptides (AMPs). And the expression of cluster of differentiation (CD)14, the co-receptor for epidermal toll-like receptor (TLR)4. AMPs stimulate TLR2 in macrophages, increasing the conversion of vitamin D into its active form by cytochrome P450 27B1. Antiviral properties of vitamin D-induced AMPs can shift the polarization of the adaptive immune response from helper T cells (Th)1 to the more regulatory Th2 responses that suppress immune over-reactivity by preventing cytokine storm, which is already demonstrated during the Spanish flu episode. Vitamin D induces antiviral effects by both direct and indirect mechanisms via AMPs, immunomodulation, the interplay between major cellular and viral elements, induction of autophagy and apoptosis, variation of genetic and epigenetic factors. The crosstalk between vitamin D and intracellular signaling pathways may operate as a primary regulatory action on viral gene transcription. VDD may increase the likelihood of infection with enveloped viruses, including retrovirus, hepatitis, and dengue. Global data correlates severe VDD with COVID-19 associated coagulopathy, disrupted immune response and mortality, reduced platelet count, and prolonged prothrombin time, suggesting benefits from supplementation. KEY TEACHING POINTS Vitamin D induces antiviral effects by direct and indirect mechanisms via AMPs, immunomodulation, induction of autophagy, etc. Epidemiology of VDD partly explains geographical differences in COVID-19 susceptibility, severity, and mortality. Global data correlates severe VDD with COVID-19 associated coagulopathy, disrupted immune response and mortality, reduced platelet count, and prolonged prothrombin time, together suggesting benefits from supplementation. Many clinical trials are underway globally to delineate the role of vitamin D in both prevention and treatment of COVID-19.
The Food and Drug Administration (FDA) safety review revealed that the use of fluoroquinolones (FQs) is linked with disabling and potentially permanent serious adverse effects. These adverse effects compromise the tendons, muscles, joints, nerves, and central nervous system of the human body. The purpose of the study was to investigate the incidence and risk factors for adverse drug reactions (ADRs) caused by FQs in comparison with other antibiotics used. A retrospective cohort study was conducted over seven months in Kasturba Medical College Hospital, Manipal, India. Patients who were prescribed with FQs were selected as the study cohort (SC; n = 482), and those without FQs were the reference cohort (RC; n = 318). The results showed that 8.5% (41) of patients developed ADRs in the SC, whereas 4.1% (13) of patients developed ADRs in the RC. With oral and parenteral routes of administration, almost a similar number of ADRs were observed. Levofloxacin caused the highest number of ADRs reported, especially with the 750-mg dose. Based on a multiple logistic regression model, FQ use (odds ratio (OR): 2.27; 95% confidence interval (CI): 1.18–4.39; p = 0.015) and concomitant steroid use (OR: 3.19; 95% CI: 1.31–7.79; p = 0.011) were identified as independent risk factors for the development of ADRs among antibiotics users, whereas age was found to be protective (OR: 0.98; 95% CI: 0.97–1.00; p = 0.047). The study found a higher incidence of ADRs related to FQs compared to other antibiotics. The study concludes a harmful association between FQ use and the development of ADRs. Moreover, FQs are not safe compared to other antibiotics. Hence, the use of FQs should be limited to the conditions where no other alternatives are available.
Pharmacogenomics is the branch of pharmacology which deals with the influence of genetic variation on drug response in patients by correlating gene expression or single-nucleotide polymorphisms with a drug's efficacy or toxicity. It aims to develop rational means to optimize drug therapy, with respect to the patients genotype, to ensure maximum efficacy with minimal adverse effects. Such approaches promise the advent of personalized medicine, in which drugs and drug combinations are optimized for each individual's unique genetic makeup. Pharmacogenomics is the whole genome application of pharmacogenetics, which examines the single gene interactions with drugs.KeywordsPharmacogenetics; Single nucleotide polymorphisms; Genomics; Genotype
BackgroundAntimicrobial resistance is a global health emergency, and one of the contributing factors is overuse and misuse of antibiotics. India is one of the world’s largest consumers of antibiotics, and inappropriate use is potentially widespread. This study aimed to use standardised patients (SPs) to measure over-the-counter antibiotic dispensing in one region.MethodsThree adults from the local community in Udupi, India, were recruited and trained as SPs. Three conditions, in both adults and children, were considered: diarrhoea, upper respiratory tract infection and acute fever. Adult SPs were used as proxies for the paediatric cases.ResultsA total of 1522 SP interactions were successfully completed from 279 pharmacies. The proportion of SP interactions resulting in the provision of an antibiotic was 4.34% (95% CI 3.04% to 6.08%) for adult SPs and 2.89% (95% CI 1.8% to 4.4%) for child SPs. In the model, referral to another provider was associated with an OR 0.38 (95% CI 0.18 to 0.79), the number of questions asked was associated with an OR 1.54 (95% CI 1.30 to 1.84) and an SP–pharmacist interaction lasting longer than 3 min was associated with an OR 3.03 (95% CI 1.11 to 8.27) as compared with an interaction lasting less than 1 min.ConclusionOver-the-counter antibiotic dispensing rate was low in Udupi district and substantially lower than previously published SP studies in other regions of India. Dispensing was lowest when pharmacies referred to a doctor, and higher when pharmacies asked more questions or spent more time with clients.
BackgroundPatient education (PE) is as important as medical and surgical interventions in the management of diabetic foot ulcer (DFU). Patient information leaflets (PILs) are globally accepted patient counseling aids.ObjectivesThis study aimed at developing PILs for DFU patients and investigating its validation.MethodsThe PILs were prepared based on different model leaflets available from various online resources, including “Patient UK”. The PILs readability was evaluated by Flesch/ Flesch-Kincaid readability (FRE/FK-GL) method before user-testing (n = 34 DFU patients) by quasi-experimental methods in patients with DFU. Additionally, user-opinion on legibility and content of the PIL was also determined. Baker Able Leaflet Design (BALD) method was employed to assess the layout and design characteristics of the PIL.ResultsThe best FRE score achieved was 73.9 and the FK-GL score was 6.1. The mean BALD assessment score for English and Kannada versions of PIL were 27 and 26, respectively. The ICC of the test-retest reliability of user-testing and user-opinion questionnaires in both English and Kannada ranged from 0.91 to 0.96. The overall user-testing knowledge-based mean score significantly improved from 43.4 to 69.7 (P < 0.05). Overall, 82.4% of patients reported overall user-opinion on legibility and content of the PIL as good.ConclusionsThe developed PILs met the criteria of fairly easy readability and good layout design. The user-opinion of the majority of patients reported the PIL content, legibility, and design as good. The Pictogram-based PILs (P-PILs) was found to be an effective PE tool in DFU patients.
Rifampin (RF) is metabolized in the liver into an active metabolite 25-desacetylrifampin and excreted almost equally via biliary and renal routes. Various influx and efflux transporters influence RF disposition during hepatic uptake and biliary excretion. Evidence has also shown that Vitamin D deficiency (VDD) and Vitamin D receptor (VDR) polymorphisms are associated with tuberculosis (TB). Hence, genetic polymorphisms of metabolizing enzymes, drug transporters and/or their transcriptional regulators and VDR and its pathway regulators may affect the pharmacokinetics of RF. In this narrative review, we aim to identify literature that has explored the influence of single nucleotide polymorphisms (SNPs) of genes encoding drug transporters and their transcriptional regulators (SLCO1B1, ABCB1, PXR and CAR), metabolizing enzymes (CES1, CES2 and AADAC) and VDR and its pathway regulators (VDR, CYP27B1 and CYP24A1) on plasma RF concentrations in TB patients on antitubercular therapy. Available reports to date have shown that there is a lack of any association of ABCB1, PXR, CAR, CES1 and AADAC genetic variants with plasma concentrations of RF. Further evidence is required from a more comprehensive exploration of the association of SLCO1B1, CES2 and Vitamin D pathway gene variants with RF pharmacokinetics in distinct ethnic groups and a larger population to reach conclusive information.
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