Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of spinal motor neurons and poses significant adverse outcome in affected population. Survival motor neuron 1 (SMN1) protein encoded by SMN1 gene located on 5q is critical for survival and functioning of motor neurons. Almost identical gene SMN2, present on the same chromosome, produces a small truncated protein (SMN2) because of skipping of exon 7 from translation due to translation silent C6U substitution in exon 7 of SMN2 pre-mRNA transcript. Only 10% of the SMN2 mRNAs produce full length SMN2 protein by including exon 7 in healthy individuals. A large deletion or sometimes a point mutation in SMN1 gene is responsible for SMA. In this case the number of copies of SMN2 genes in an individual determines the severity of disease (the more the number of copies the less severe the disease). Nusinersen (ISIS 396443) binds to intron splicing silencer-N1 (ISS-N1; a site present ten nucleotides down to the junction of exon 7 and intron 7), modulating the splicing of SMN2 pre-mRNA transcript to increase the inclusion of exon 7, thereby increasing the production of full length SMN2 protein. Major evidence of its efficacy came from a sham controlled phase 3 clinical study ENDEAR. The study was stopped early based on significantly favorable results in interim analysis and all the patients were transitioned to receive nusinersen in an ongoing open-label, phase 3 study, SHINE, which will evaluate the long-term efficacy, safety and tolerability of the drug. Nusinersen is globally the first drug approved (by the US FDA) for treatment of SMA in children and adults.
Background Helicobacter pylori infection has been associated with insulin resistance and non-alcoholic fatty liver disease (NAFLD). This study was done to evaluate the effect of H. pylori-eradication therapy (HPET) in patients with NAFLD compared to standard management therapy (SMT). Methods Eighty NAFLD patients with H. pylori co-infection were randomized into SMT (diet and exercise, n = 36) and HPET (SMT plus amoxicillin, clarithromycin, and pantoprazole, n = 44) groups. The controlled attenuation parameter (CAP), anthropometric parameters, liver enzymes, lipid profile, and glycemic parameters including homeostasis model assessment-insulin resistance (HOMA-IR) were measured and compared between two groups at the baseline and 24 weeks. Results Sixty-four participants (SMT group [n = 28] and HPET group [n = 36]) were included in a modified intention-to-treat analysis. Both the SMT group and the HPET group had a significant reduction in CAP scores at 24 weeks (P = 0.002 and P < 0.001, respectively), but the change between the groups was insignificant (P = 0.213). Successful eradication of H. pylori occurred in 68% of the HPET group and led to greater improvement in HOMA-IR at 24 weeks compared to SMT or non-responder patients (P = 0.007). The liver enzymes reduced significantly at 24 weeks in both groups, but the changes between the groups were similar. The lipid parameters remained unchanged within the groups and between the groups at 24 weeks. A significant increase in the levels of reduced glutathione was noted in the HPET group, but the change between the two groups was not statistically different. Conclusions HPET was found to be comparable to SMT alone in reducing hepatic steatosis and liver enzymes at 24 weeks in NAFLD patients. However, successful eradication of H. pylori led to greater improvement in HOMA-IR (Trial registration CTRI/2017/05/008608).
Background and Objective Interferon-β, as with several other anti-viral agents, has been investigated as a treatment option for COVID-19 as a repurposed drug. The present study is a systematic review and meta-analysis of interferon-β to determine its efficacy among moderate-to-severe COVID-19 patients. Methods A systematic literature search was done using relevant terms for ‘COVID-19’ and ‘interferon-β’. Randomised controlled trials (RCT) evaluating the efficacy of interferon-β in COVID-19 were included. Data were extracted for outcome measures, namely mortality, time to clinical improvement and length of hospital stay. Random effects meta-analysis was performed using RevMan V.5.4.1 to calculate overall effect estimate as odds ratio/hazard ratio for categorical variables and mean difference for continuous variable. Result Eight RCTs were eligible for qualitative synthesis and seven for meta-analysis. The overall effect estimate (odds ratio [OR] 0.59; 95 % CI 0.91, 1.12) and (mean difference [MD] − 1.41; 95 % CI − 2.84, 0.02) indicated no statistically significant difference between effect of IFN-β and that of control on mortality and length of hospital stay, respectively. However, the overall effect estimate (hazard ratio [HR] 1.95; 95 % CI 1.36, 2.79) denoted a favourable effect of INF-β on reducing the time to clinical improvement in moderate-to-severe COVID-19 patients. Conclusion Addition of interferon-β to standard of care resulted in significant reduction in time to clinical improvement but no significant benefit in terms of reduction in mortality and length of hospital stay in moderate-to-severe cases of COVID-19.
Introduction Several drugs have been explored for the antiviral action against COVID-19 disease but none of them has been approved barring few such as Remdesivir which got emergency use authorization from USFDA. Interferon are attractive agents due to their broad anti-viral and immunological properties. Interferon alpha-2b has been recently investigated for this purpose. This study presents a systematic review of all the clinical studies involving Interferon alpha-2b to determine its efficacy and safety. Methods A systematic review of literature was done using relevant terms for ‘COVID-19” and “Interferon alpha”. The studies evaluating the effect of Interferon alpha were identified and included in the study for qualitative analysis. Result and Discussion All four clinical studies have shown that Interferon alpha 2b has efficacy as antiviral agent as shown by different clinical and laboratory parameters. It has also found to be safe and free of any major side effects. Conclusion Interferon alpha 2b is an effective antiviral agent with potential to be use in COVID-19. This drug has already been given restricted use authorization in India.
Olanzapine (atypical antipsychotics) should also be kept in the list of suspected drugs causing blepharospasm in psychotic patients on treatment although further similar evidences from observational studies and/or reports are needed to establish the causal relationship.
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