We read the extremely informative study "Non-Alcoholic Steatohepatitis (NASH) -A Review of a Crowded Clinical Landscape, Driven by a Complex Disease" published by Fraile et al 1 in the prestigious journal "Drug Design, Development and Therapy". We would like to appreciate the remarkable work done by the authors on this thorough review, congratulate them on its successful publication, and make further contributions.This review discussed the potential mono-therapeutic options for Non-alcoholic steatohepatitis (NASH) including drugs such as Saroglitazar (Zydus Cadila), Obeticholic acid (Intercept Pharmaceuticals), Cenicriviroc (Allergan), Aramchol (Galmed Pharmaceuticals), Resmetirom (Madrigal Pharmaceuticals), Dapagliflozin, and Semaglutide (Novo Nordisk). The review further discusses the role of anti-diabetic drugs, co-therapies, and antibodies in the treatment of NASH. 1 Even though this review provided exhaustive details in terms of the potential therapeutic options for NASH, we believe that the review provides incomplete vital details in regards to the clinical trial conducted in the United States to demonstrate the efficacy of Saroglitazar. 2 Fraile et al 1 in this review explained Saroglitazar Magnesium (Lipaglyn) has been approved in India for the treatment of type 2 diabetes (T2D) and dyslipidemia. Furthermore, in 2020 Saroglitazar qualified for NASH treatment in India as a result of the promising results of the Phase 3 clinical trial, EVIDENCES II, conducted on Indian NASH patients. In this trial, the histologic improvements of NASH were assessed by liver biopsy, a gold standard in assessing the prognosis of chronic liver diseases. However, a Phase 2 trial conducted in the United States 2 included NASH patients on the basis of elevated ALT levels, although no definitive ALT levels can be used to predict NASH 3 and normal ALT levels are found in approximately 25% of these patients. 4 Hence, saroglitazar cannot be recommended only on the basis of a particular subset of patients with elevated ALT without histological endpoints.Moreover, in the study conducted by Gawrieh et al, the efficacy of Saroglitazar was demonstrated by reporting a significant decrease in ALT levels after 16 weeks. But, this reduction in ALT was not associated with a proportional decrease in Liver Fat Content or improvement in insulin resistance (as assessed by the HOMA-IR index). 4 To help understand its role better it is important to adopt additional ingenious placebo-controlled trials in biopsy-proven NASH with histological endpoints.
Madam, Since the beginning of 2021, massive vaccination programmes have been initiated, aiming to curb the COVID-19 pandemic, yet certain groups remain vulnerable, especially pregnant women (1).
A recent study has emphasized the implications of COVID-19 in pregnant females; evaluating statistics from various countries, the authors reported maternal mortality to be 22 times higher in pregnant women with COVID-19 diagnosis than those without (2). Compared with those without COVID-19, infected females giving birth showed significantly higher rates of ICU admission, respiratory intubation, mechanical ventilation, and a greater risk of having a preterm birth of fewer than 37 weeks (2). In Pakistan, Covid-19 is speculated to cause multiple complications among unvaccinated pregnant women. When local data was collected and presented at a webinar “Pregnancy in Covid-19 and importance of vaccine” held by a public medical university in association with the American Society of Microbiology, it was highlighted that Covid-19 caused a death rate of 8% in pregnant women. Each year, approximately 14% of pregnant women are susceptible to have medical complications. (3)
These adverse outcomes during pregnancy accentuate the need for vaccination of pregnant individuals. Recent studies have started assessing the outcome of Covid-19 vaccination on the pregnant women population and demonstrated positive results. Blakeway et al reported that women who received at least one dose of COVID-19 vaccine in pregnancy versus unvaccinated females had similar rates of all adverse pregnancy outcomes and concluded that vaccines do not affect perinatal outcomes (4). Guidelines recommending urgent vaccination for pregnant people have also been released, stressing that the benefits of the vaccine supercede any potential risks (1). However, several factors have hindered the process of vaccination of pregnant women such as the exclusion of pregnant women from clinical trials that have caused difficulty in establishing confidence of pregnant women in the vaccines In addition, the prevailing conspiracy theories in Pakistan about vaccination programmes, being a Western agenda to induce sterility in Muslim women has further hindered the success of vaccination programme for pregnant women. (5)
Physicians must implement the past positive findings of vaccination among pregnant women when counseling patients who are pregnant, planning a pregnancy, breastfeeding, or planning to breastfeed, and facilitate them in opting for government authorized vaccines for clinical use. At the same time, pregnant women who wish to wait for more data to make an informed decision must be supported and updated by their doctor regularly.
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Introduction
Adverse childhood experiences (ACEs) are proposed to increase the risk of developing multiple sclerosis (MS) later in life. This systematic review aimed to explore the correlation between ACEs and MS development, age of onset, quality of life in MS patients and MS relapse rates.
Methods
We searched a total of six databases in June 2022 and retrieved the relevant studies. The population included adult (18+) individuals who either had been diagnosed or were at risk for developing MS and also had exposure to ACEs. Our primary outcomes include the risks of MS development, age of MS onset, and MS relapse rate in patients who were exposed to different types of ACEs.
Results
A total of 11 studies were included in our review. A study reported that among 300 women diagnosed with MS, 71 (24%) reported a history of childhood abuse; moreover, with further research, it was concluded that ACEs were associated with the development of MS. Abuse that occurred 2–3 times per week was associated with an 18.81‐fold increased risk of having MS when compared to the unexposed sample. The relapse rate of MS was found to be substantially greater in severe cases of ACEs compared to individuals who did not report any ACEs.
Conclusions
Results support a significant association between ACEs and the development of MS; individuals with a positive history of ACEs develop MS symptoms earlier. Moreover, the severity of ACEs is also linked with increased relapse rates of MS.
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