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

Care maps are an effective tool for optimizing quality of care of infectious diseases in a resource-constrained short-stay ambulatory care setting

Care maps (CMs), which are innovative, comprehensive, educational, and simple medical tools, were developed for 6 common diseases, including heart failure, stroke, hyperglycemia, urinary tract infection, dengue infection, and upper gastrointestinal bleeding, were implemented in a short-stay ambulatory ward. This study aimed to investigate the effectiveness of and level of clinician satisfaction with CMs in an ambulatory care setting. A retrospective chart review study comparing the quality of care between before and after CM implementation was conducted. The medical records of patients who were admitted to a short-stay ambulatory ward in a tertiary referral center were reviewed. Demographic data, severity of disease, quality of care, length of stay (LOS), admission cost, and CM user satisfaction were collected and recorded. The medical records of 1116 patients were evaluated. Of those, 589 and 527 patients were from before (non-CM group) and after CM (CM group) implementation, respectively. There were no significant differences between groups for age, gender, or disease-specific severity the median (interquartile range) total and essential quality scores were significantly higher in the CM group than in the non-CM group [total quality score 85.3 (75.0–92.9) vs 61.1 (50.0–75.0); P < .001, and essential quality scores 90.0 (75.0–100.0) vs 60.0 (40.6–80.0); P < .0001, respectively]. All aspects of quality of care were significantly improved between before and after CM implementation. Overall median LOS was significantly decreased from 3.8 (2.5–5.7) to 3.0 (2.0–4.9) days, but there was no significant decrease for admission cost. However, CMs were able to significantly reduce both LOS and admission cost in the infectious disease-related subgroup. Most CM users reported satisfaction with CMs. CMs were shown to be an effective tool for improving the quality of care in patients with ambulatory infectious diseases. In that patient subgroup, LOS and admission cost were both significantly reduced compared to pre-CM implementation

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

Accuracy and the factors influencing the accuracy of death certificates completed by first-year general practitioners in Thailand

Background Although death certificates (DCs) provide valuable health information which may help to guide local health policies and priorities, there is little information concerning their validity in Thailand. First-year general practitioners (GPs) have a major role in DC completion, especially in provincial general hospitals. The aim of this study was to evaluate the accuracy and factors influencing the accuracy of DCs completed by first-year GPs in Thailand, compared with the cause of death (COD) derived from medical records by experts. Methods This retrospective study was conducted at 14 provincial general hospitals in Thailand during the June 2011 to May 2012 study period. Medical records and DCs completed by first-year GPs who graduated from 16 Thai medical schools were sampled. The cause of death recorded on the DCs was compared with the medical conditions and histories derived from patient medical records. A cross-sectional survey of the 210 GPs who completed the DCs reviewed in this study was also conducted. Respondent GPs’ demographic characteristics, factors associated with COD, and COD coding system were evaluated. Results Five hundred and sixty-three medical records and corresponding DCs were included. Of those, 36.9% of DCs were found to be correct. Common mistakes included incorrect sequence of events leading to death (32.4%), and mode of death use (26.2%). Of the 210 GPs, 155 questionnaires were completed and returned. The mean time spent on recording COD and completing DCs in the medical school curriculum was 2.1 ± 0.9 h and only 27.7% of participants had experience in completing DCs by themselves during medical school. Mean medical school GPA was significantly higher in the correctly completed DC GPs group than in the incorrectly completed DC GPs group (3.3 ± 0.4 vs. 3.2 ± 0.3; p = 0.03). However, no significant difference was found for other factors associated with COD between groups. Conclusions This is the first study documenting gaps and disparities in DC accuracy, and factors influencing completion of DCs among first-year GPs in Thailand, based on a clinical assessment of medical records. GPs made errors on 63.1% of DCs. This finding suggests that proven education, system-related support, and additional training interventions specific to DC completion are required

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

Sajesh K Veettil,1 Peerawat Jinatongthai,2,3 Surakit Nathisuwan,4 Nattawat Teerawattanapong,2,3 Siew Mooi Ching,5,6 Kean Ghee Lim,7 Surasak Saokaew,3,8&ndash;10 Pochamana Phisalprapa,11 Christopher M Reid,12,13 Nathorn Chaiyakunapruk3,9,14,15 1Department of Pharmacy Practice, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia; 2Division of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand; 3School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia; 4Clinical Pharmacy Division, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; 5Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia; 6Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, Malaysia; 7Clinical School, Department of Surgery, International Medical University, Seremban, Malaysia; 8Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand; 9Center of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand; 10Unit of Excellence on Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand; 11Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 12School of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia; 13School of Public Health, Curtin University, Perth WA, Australia; 14School of Pharmacy, University of Wisconsin, Madison, WI, USA; 15Asian Centre for Evidence Synthesis in Population, Implementation and Clinical Outcomes (PICO), Health and Well-being Cluster, Global Asia in the 21st Century (GA21) Platform, Monash University Malaysia, Subang Jaya, Malaysia 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&ndash;0.97] for high-dose [&ge;325 mg/day] and RR, 0.81 [95% CI, 0.67&ndash;0.98] for very-low-dose [&le;100 mg/day]). Similar trend was found for mortality (RR, 0.43 [95% CI, 0.23&ndash;0.81] for low-dose [&gt;100&ndash;325 mg/day] and RR, 0.65 [95% CI, 0.45&ndash;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&ndash;2.434].Conclusion: Aspirin at the dose range of 75&ndash;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. Keywords: colorectal cancer, primary chemoprevention, chemopreventive agents, aspirin, network meta-analysis, net clinical benefit analysi

Effects of chemopreventive agents on the incidence of recurrent colorectal adenomas: a systematic review with network meta-analysis of randomized controlled trials

Sajesh K Veettil,1 Nattawat Teerawattanapong,2 Siew Mooi Ching,3,4 Kean Ghee Lim,5 Surasak Saokaew,6&ndash;9 Pochamana Phisalprapa,10 Nathorn Chaiyakunapruk7,8,11,12 1School of Pharmacy/School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia; 2Division of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand; 3Department of Family Medicine, Faculty of Medicine and Health Sciences, 4Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, 5Clinical School, Department of&nbsp;Surgery, International Medical University, Seremban, Negeri Sembilan, 6Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Phayao, 7School of Pharmacy, Monash University Malaysia, Selangor, Malaysia; 8Centre of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand; 9Unit of Excellence on Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao, Thailand; 10Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 11School of Pharmacy, University of Wisconsin, Madison, USA; 12Health and Well-being Cluster, Global Asia Platform in the 21st Century (GA21) Platform, Monash University Malaysia, Selangor, Malaysia Background: Protective effects of several chemopreventive agents (CPAs) against colorectal adenomas have been well documented in randomized controlled trials (RCTs); however, there is uncertainty regarding which agents are the most effective.Methods: We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. We performed both pairwise analysis and network meta-analysis (NMA) of RCTs to compare the effects of CPAs on the recurrence of colorectal adenomas (primary outcome). Using NMA, we ranked CPAs based on efficacy.Results: We identified 20 eligible RCTs enrolling 12,625 participants with a history of colorectal cancer or adenomas who were randomly assigned to receive either a placebo or one of 12 interventions. NMA using all trials demonstrated that celecoxib 800&nbsp;mg/day (relative risk [RR] 0.61, 95% confidence interval [CI] 0.45&ndash;0.83), celecoxib 400&nbsp;mg/day (RR 0.70, 95% CI 0.55&ndash;0.87), low-dose aspirin (RR 0.75, 95% CI 0.59&ndash;0.96) and calcium (RR 0.81, 95% CI 0.69&ndash;0.96) were significantly associated with a reduction in the recurrence of any adenomas. NMA results were consistent with those from pairwise meta-analysis. The evidence indicated a high (celecoxib), moderate (low-dose aspirin) and low (calcium) Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality. NMA ranking showed that celecoxib 800&nbsp;mg/day and celecoxib 400&nbsp;mg/day were the best CPAs, followed by low-dose aspirin and calcium. Considering advanced adenoma recurrence, only celecoxib 800&nbsp;mg/day and celecoxib 400&nbsp;mg/day were demonstrated to have a protective effect (RR 0.37, 95% CI&nbsp;0.27&ndash;0.52 vs RR 0.48, 95% CI 0.38&ndash;0.60, respectively).Conclusion: The available evidence from NMA suggests that celecoxib is more effective in reducing the risk of recurrence of colorectal adenomas, followed by low-dose aspirin and calcium. Since cyclooxygenase-2 (COX-2) inhibitors (eg, celecoxib) are associated with important cardiovascular events and gastrointestinal harms, more attention is warranted toward CPAs with a favorable benefit-to-risk ratio, such as low-dose aspirin and calcium. Keywords: colorectal adenomas, chemoprevention, systematic review, meta-analysis, network meta-analysis, randomized controlled trial

Cardiometabolic risk factors in Thai individuals with prediabetes treated in a high-risk, prevention clinic - unexpected relationship between HDL cholesterol and glycaemia in men

BACKGROUND: Relationships between cardiometabolic risk and glycaemia have been rarely studied in people under clinical evaluation and treatment for cardiometabolic risk and with prediabetes. We investigated relationships between glycaemia and cardiometabolic risk factors in clinic participants with prediabetes. METHODS: This was a cross-sectional analysis of data collected at a centre in Thailand. Clinic attendees were at high-risk of diabetes or cardiovascular disease, with HbA1c 39-<48 mmol/mol or fasting plasma glucose (FPG) 5.6-<7.0 mmol/L. The relationships between glycaemia and cardiometabolic risk factors were explored. RESULTS: Of 357 participants, two or more insulin resistance-related metabolic disturbances were present in 84%; 61% took a statin and 75% an antihypertensive agent. Independently of age, gender, adiposity, medication use, possible NAFLD and gender-glycaemia interaction, neither FPG nor HbA1c were associated with variation in any other cardiometabolic risk factors. HDL cholesterol decreased with HbA1c in women (female*HbA1c interaction, p=0.03) but, unexpectedly, increased with FPG in men (male*FPG interaction, p=0.02). CONCLUSION: Overall, in Thai people treated for high-cardiometabolic risk and with prediabetes defined by FPG and/or HbA1c, neither FPG nor HbA1c were associated with other cardiometabolic risk factors. However, according to gender, HDL cholesterol showed the expected relationship with glycaemia in women but the reverse in men