Mpox, formerly known as monkeypox, has re-emerged as a significant global health concern, particularly during the widespread outbreak of 2022. As an orthopoxvirus related to the eradicated smallpox virus, mpox has been primarily managed with smallpox vaccines and treatments, including the antiviral agent Tecovirimat. This systematic review aims to evaluate the effectiveness and safety of Tecovirimat in treating mpox, focusing on its use during the 2022 outbreak, especially among high-risk populations, including men who have sex with men and people living with HIV. We conducted a comprehensive search across databases, such as Embase, PubMed, and Web of Science, up to August 30, 2024. The selection involved a two-stage review process utilizing the Nested Knowledge platform, which helped streamline the screening and data extraction. We included studies that focused on the clinical efficacy and safety of Tecovirimat in human patients with confirmed mpox infections. Our analysis mainly synthesized data narratively due to the heterogeneity of study designs and outcomes. Fifteen studies met the inclusion criteria, providing data on 1031 mpox cases. The preliminary analysis of the PALM 007 RCT indicated that tecovirimat did not significantly outperform placebo in lesion resolution for all patients. Lesions healed faster than expected, regardless of tecovirimat or placebo treatment. A lower mortality rate of 1.7% among those enrolled in the PALM 007 RCT was observed, compared to the general mpox mortality rate of 3.6% or higher in the DRC. Observational studies revealed that early administration of Tecovirimat, especially within the first week of symptom onset, significantly improves symptom resolution, reduces the severity of the disease, and decreases the likelihood of hospitalization and complications in observational studies. However, the impact on viral clearance was inconsistent, and some studies suggested limited efficacy in severely immunocompromised patients. Regarding safety, Tecovirimat was generally well-tolerated as indicated by the RCT; however, mild adverse effects such as fatigue, headache, and nausea were commonly reported among observational studies. Serious adverse events were rare but included elevated liver enzymes and psychiatric symptoms, particularly in patients with pre-existing conditions. Tecovirimat demonstrates some potential benefits in treating mpox, particularly when administered early. The PALM 007 RCT failed to meet the efficacy point. Tecovirimat is generally well-tolerated with a favorable safety profile, although monitoring is advisable for those with existing liver or renal conditions. Despite promising results, further large-scale randomized controlled trials are needed to fully ascertain the drug's effectiveness across diverse populations and to explore its impact on viral clearance and transmission dynamics.
The objective of this study was to describe preliminary experience with moclobemide in the treatment of depressive disorders in the University outpatient clinic in Malaysia. Twenty patients who satisfied DSM III R criteria for depressive disorders and scored more than 16 on the Hamilton Rating Depression Score at the initial interview were recruited into this open study. The primary diagnosis of 4 patients was later ascertained to be panic disorder(2), schizophrenia(1) and social phobia(1). Patients rated themselves as improved by first follow up (7-14 days), and rated their depression as very mild to mild by the third follow up visit (ie at a mean of 46 days). Side effects were minimal and compliance good.
Study site: outpatient psychiatric clinic at the General Hospital, Kuala
Lumpur.
The introduction and success of imatinib mesylate (IM) has become a paradigm shift in chronic myeloid leukemia (CML) treatment. However, the high efficacy of IM has been hampered by the issue of clinical resistance that might due to pharmacogenetic variability. In the current study, the contribution of three common single nucleotide polymorphisms (SNPs) of ABCB1 (T1236C, G2677T/A and C3435T) and two SNPs of ABCG2 (G34A and C421A) genes in mediating resistance and/or good response among 215 CML patients on IM therapy were investigated. Among these patients, the frequency distribution of ABCG2 421 CC, CA and AA genotypes were significantly different between IM good response and resistant groups (P=0.01). Resistance was significantly associated with patients who had homozygous ABCB1 1236 CC genotype with OR 2.79 (95%CI: 1.217-6.374, P=0.01). For ABCB1 G2677T/A polymorphism, a better complete cytogenetic remission was observed for patients with variant TT/AT/AA genotype, compared to other genotype groups (OR=0.48, 95%CI: 0.239-0.957, P=0.03). Haplotype analysis revealed that ABCB1 haplotypes (C1236G2677C3435) was statistically linked to higher risk to IM resistance (25.8% vs. 17.4%, P=0.04), while ABCG2 diplotype A34A421 was significantly correlated with IM good response (9.1% vs. 3.9%, P=0.03). In addition, genotypic variant in ABCG2 421C>A was associated with a major molecular response (MMR) (OR=2.20, 95%CI: 1.273-3.811, P=0.004), whereas ABCB1 2677G>T/A variant was associated with a significantly lower molecular response (OR=0.49, 95%CI: 0.248-0.974, P=0.04). However, there was no significant correlation of these SNPs with IM intolerance and IM induced hepatotoxicity. Our results suggest the usefulness of genotyping of these single nucleotide polymorphisms in predicting IM response among CML patients.