Efficacy and safety of chemopreventive agents on colorectal cancer incidence and mortality: Systematic review and network meta-analysis

Background: Various interventions have been tested as primary prevention of colorectal cancers (CRC), but comprehensive evidence comparing them is absent. We examined the effects of various chemopreventive agents (CPAs) on CRC incidence and mortality. Methods: We did a network meta-analysis based on a systematic review of randomized controlled trials (RCTs) that compared at least one CPA (aspirin, antioxidants, folic acid, vitamin B6, vitamin B12, calcium, vitamin D, alone or in combination) to placebo or other CPA in persons without history of CRC. Several databases were searched from inception up to March 2017. Primary outcomes were early and long-term CRC incidence and mortality. Results: Twenty-one RCTs comprising 281,063 participants, 9 RCTS comprising 160,101 participants, and 7 RCTs comprising 24,001 participants were included in the network meta-analysis for early risk of CRC incidence, long-term risk of CRC incidence and mortality, respectively. For early CRC incidence, no CPAs were found to be effective. For long-term CRC incidence and mortality, aspirin was the only intervention that showed protective effects with potential dose-dependent effects (risk ratio [RR], 0.74 [95% CI, 0.57–0.97] for high-dose [=325 mg/day] and RR, 0.81 [95% CI, 0.67–0.98] for very-low-dose [=100 mg/day]). Similar trend was found for mortality (RR, 0.43 [95% CI, 0.23–0.81] for low-dose [>100–325 mg/day] and RR, 0.65 [95% CI, 0.45–0.94] for very-low-dose). However, in net clinical benefit analysis, when combining risk estimates on mortality from CRC, cardiovascular disease, and pooled risk estimates of major gastrointestinal bleeding, low-dose aspirin provided the highest net survival gain (%) of 1.736 [95% CI, 1.010–2.434]. Conclusion: Aspirin at the dose range of 75–325 mg/day is a safe and effective primary prevention for long-term CRC among people at average risk. None of the other CPAs were found to be effective. There may potentially be differential effects among various doses of aspirin that needs further investigation

A call for joint action is urgently required in Middle East countries due to prolonged school closures/banning of girl students: “Seek knowledge, from the cradle to the grave” - Prophet Muhammad (SAWA) on education

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Harnessing the Potential of CRISPR/Cas in Atherosclerosis: Disease Modeling and Therapeutic Applications

Atherosclerosis represents one of the major causes of death globally. The high mortality rates and limitations of current therapeutic modalities have urged researchers to explore potential alternative therapies. The clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system is commonly deployed for investigating the genetic aspects of Atherosclerosis. Besides, advances in CRISPR/Cas system has led to extensive options for researchers to study the pathogenesis of this disease. The recent discovery of Cas9 variants, such as dCas9, Cas9n, and xCas9 have been established for various applications, including single base editing, regulation of gene expression, live-cell imaging, epigenetic modification, and genome landscaping. Meanwhile, other Cas proteins, such as Cas12 and Cas13, are gaining popularity for their applications in nucleic acid detection and single-base DNA/RNA modifications. To date, many studies have utilized the CRISPR/Cas9 system to generate disease models of atherosclerosis and identify potential molecular targets that are associated with atherosclerosis. These studies provided proof-of-concept evidence which have established the feasibility of implementing the CRISPR/Cas system in correcting disease-causing alleles. The CRISPR/Cas system holds great potential to be developed as a targeted treatment for patients who are suffering from atherosclerosis. This review highlights the advances in CRISPR/Cas systems and their applications in establishing pathogenetic and therapeutic role of specific genes in atherosclerosis.</jats:p

Association of HLA-B*5801 allele and allopurinol-induced stevens johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis

Background: Despite some studies suggesting a possible association between human leukocyte antigen, HLA-B*5801 and allopurinol induced Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), the evidence of association and its magnitude remain inconclusive. This study aims to systematically review and meta-analyze the association between HLA-B*5801 allele and allopurinol-induced SJS/TEN.Methods: A comprehensive search was performed in databases including MEDLINE, Pre-MEDLINE, Cochrane Library, EMBASE, International Pharmaceutical Abstracts (IPA), CINAHL, PsychInfo, the WHO International, Clinical Trial Registry, and ClinicalTrial.gov from their inceptions to June 2011. Only studies investigating association between HLA-B*5801 with allopurinol-induced SJS/TEN were included. All studies were extracted by two independent authors. The primary analysis was the carrier frequency of HLA-B*5801 comparison between allopurinol-induced SJS/TEN cases and each comparative group. The pooled odds ratios were calculated using a random effect model.Results: A total of 4 studies with 55 SJS/TEN cases and 678 matched-controls (allopurinol-tolerant control) was identified, while 5 studies with 69 SJS/TEN cases and 3378 population-controls (general population) were found. SJS/TEN cases were found to be significantly associated with HLA-B*5801 allele in both groups of studies with matched-control (OR 96.60, 95%CI 24.49-381.00, p < 0.001) and population-control (OR 79.28, 95%CI 41.51-151.35, p < 0.001). Subgroup analysis for Asian and Non-Asian population yielded similar findings.Conclusion: We found a strong and significant association between HLA-B*5801 and allopurinol-induced SJS/TEN. Therefore, HLA-B*5801 allele screening may be considered in patients who will be treated with allopurinol

Impact of pharmacist’s interventions on cost of drug therapy in intensive care unit. Pharmacy

Pharmacist participation in patient care team has been shown to reduce incidence of adverse drug events, and overall drug costs. However, impact of pharmacist participation in the multidisciplinary intensive care team on cost saving and cost avoidance has little been studied in Thailand.Objective: To describe the characteristics of the interventions and to determine pharmacist’s interventions led to change in cost saving and cost avoidance in intensive care unit (ICU). Methods: A Prospective, standard care-controlled study design was used to compare cost saving and cost avoidance of patients receiving care from patient care team (including a clinical pharmacist) versus standard care (no pharmacist on team). All patients admitted to the medical intensive care unit 1 and 2 during the same period were included in the study. The outcome measures were overall drug cost and length of ICU stay. Interventions made by the pharmacist in the study group were documented. The analyses of acceptance and cost saving and/or cost avoidance were also performed. Results: A total of 65 patients were admitted to either ICU 1 or 2 during the 5 week- study period. The pharmacist participated in patient care and made total of 127 interventions for the ICU-1 team. Ninety-eight percent of the interventions were accepted and implemented by physicians. The difference of overall drug cost per patient between two groups was 182.01 USD (1,076.37 USD in study group and 1,258.38 USD in control group, p=0.138). The average length of ICU stay for the intervention group and the control group was not significantly different (7.16 days vs. 6.18 days, p=0.995). The 125 accepted interventions were evaluated for cost saving and cost avoidance. Pharmacist’s interventions yielded a total of 1,971.43 USD from drug cost saving and 294.62 USD from adverse drug event cost avoidance. The net cost saved and avoided from pharmacist interventions was 2,266.05 USD. Interventions involving antibiotic use accounted for the largest economic impact (1,958.61 USD). Conclusions: Although the statistical was not significant, having a pharmacist participated in ICU patient care team tend to reduced overall drug cost, cost saving, and cost avoidance. The largest cost impact and intervention requirement involved antibiotic use

Economic Evaluation of Pharmacist-Managed Warfarin Therapy: A Review of Studies

Recent studies have shown that the pharmacist-participated warfarin therapy management (PPWTM) can significantly prevent bleeding events when it is compared with the usual care. Though some studies have shown economic value of PWTM, however, no review has been conducted to summarize them. The objective of this review was to identify relevant studies and summarize economic evidence of PPWTM, when compared with the usual care. The databases including MEDLINE, EMBASE, and Cochrane were systematically searched from their inception to August 31, 2015. The inclusion criteria were studies which: (1) used warfarin as an anticoagulant, (2) evaluated both cost and effectiveness outcomes (e.g., incremental cost-effectiveness ratio), (3) had a control group, and (4) had an anticoagulant clinic with PPWTM as an intervention. Studies which were not original articles were excluded. The quality of each included study was assessed by three tools including one proposed by Drummond et al. (2005), Quality of Health Economic Studies, and Consolidated Health Economic Evaluation Reporting Standards. Out of 494 articles found from the databases, four articles met the inclusion criteria and they were included in the final analysis. All four studies evaluated cost-effectiveness of two or more warfarin therapy strategies by using Markov cohort simulation technique. The studies included have shown that the frequent monitoring was provided by the healthcare professionals including pharmacists whereas comparators show usual care patterns with less time being spent on monitoring or care provided by physicians alone. All studies concluded that the intervention of PPWTM was cost-effective