Prevalence of myocardial infarction among patients with chest pain and cocaine use: A systematic review and meta-analysis.

BACKGROUND: Cocaine abuse is a public health burden. Cocaine is known to cause vasospasm and acute myocardial infarction (AMI). The prevalence of AMI in patients presenting with chest pain and concurrent cocaine use (CPCC) varies among studies. We performed a systemic review and meta-analysis to assess the current literature for the prevalence of AMI in patients with CPCC. METHODS: We performed a literature search of PubMed, EMBASE, and Scopus from its beginning to May 18, 2020 and updated this search on February 18, 2021. Full-text studies that assessed the primary outcome (AMI) specifically among patients with CPCC who presented to the emergency department (ED) were included. We excluded studies that were not in English, did not take place in the ED, and case reports, which only reported positive cases and not incidence of AMI. Random effect meta-analysis was performed to assess the prevalence of primary outcome and to examine correlations between risk factors and AMI. Heterogeneity was assessed by I-square value. We also performed subgroup analysis to identify potential sources of heterogeneity. RESULTS: We identified 2178 studies and screened 102 full-text studies to include 16 studies (3269 patients) in our final analysis. The pooled prevalence of AMI was 4.7% (95% CI 0.8-23), I-square of 84%. However, rates among studies of low risk patients were lower (1.1% 95% CI 0.2-5) compared to studies of mixed risk patients (7.7%, 95% 5-11). A meta-regression was used to look at correlation between risk factors and AMI and found that AMI was positively correlated in patients with a history of CAD (correlation coefficient [Corr. Coeff.] 5.6, 96% CI 2.3-8.7), HTN (Corr. Coeff. 2.9, 95% CI 0.9-4.9), DM (Corr. Coeff. 8.0, 95% CI 2.4-14), HLD (Corr. Coeff. 5.9, 95% CI 2.4, 9). Sources of potential heterogeneity included patients' risk as defined by the authors, study designs, publication year, and study sample size. CONCLUSION: The overall prevalence of AMI and death among patients with cocaine-associated chest pain was relatively low, although high risk patients were still associated with high prevalence of AMI. Clinicians should consider risk-stratify these patients and treat them accordingly.

Cyclosporine laden tailored microemulsion-gel depot for effective treatment of psoriasis: In vitro and in vivo studies.

Psoriasis is a widespread chronic disease affecting 1-3 % of total population. In major cases (>80 %), it is treated by topical application of corticosteroids. However, the topical route is very challenging due to physico-chemical nature of diseased stratum corneum and so no single treatment works for every patient. The oral route showed severe side effects due to systemic immunosuppression, which can be avoided by topical route. The aim of the research work was to investigate cyclosporine loaded microemulsion based gel for effective cyclosporine permeation and retention in the skin tissue for psoriasis treatment. The pseudo ternary phase diagram at three Smix ratios (2:1, 1:1, and 1:2; Tween 80: isopropyl alcohol) were constructed using isopropyl myristate as oil phase. The Smix at 2:1 ratio showed large microemulsion area. The transmission electron microscope images showed spherical non-aggregated oil globules with the size < 50 nm. The selected microemulsion (Cy-2-ME12O55SM) was incorporated in Carbopol 940 gel for topical application. The ex vivo diffusion study showed improved permeation (>24 h) with microemulsion-gel in comparison to cyclosporine suspension. The microemulsion-gel was non-irritating on the rabbit skin. In drug retention studies, microemulsion-gel showed high drug retention (trapping, 38.92 %) in the skin tissue, which was due to destabilization of microemulsion after penetration in the skin layer causing precipitation of cyclosporine. The depot effect due to cyclosporine precipitates could be helpful for sustained effect of cyclosporine for the effective treatment of psoriasis.

Targeting the Bcl-2.

PURPOSE OF REVIEW: Members of the Bcl-2 family of proteins are critical components in regulating the intrinsic apoptotic pathway. Bcl-2 protein overexpression is associated with drug resistance and poor clinical outcome in cancer patients. Preclinical and clinical evaluations demonstrate that downregulation of Bcl-2 restores the intrinsic apoptotic pathways with antitumor effects. Thus, Bcl-2 is aggressively pursued as a therapeutic target in cancer with several new drugs undergoing clinical investigations. In this manuscript, we will review clinical information on some of the novel compounds specifically designed to target the Bcl-2 gene product(s). RECENT FINDINGS: Extensive clinical evaluations using a Bcl-2-specific antisense have resulted in an overall disappointing experience. But new small molecule inhibitors of the Bcl-2 hold promise with high target affinity, ease of administration and improved toxicity profile. Early stage clinical trials of these agents are revealing promising results alone as well as in combination with existing anticancer therapeutics. Encouraging results from some of these clinical investigations are summarized in this review. SUMMARY: Downregulation of Bcl-2 and restoration of a critical apoptotic pathway in cancer cells remains an important strategy. Novel Bcl-2 inhibitors have started to deliver the therapeutic promise of this target-specific quest.