METHODS: We performed a MEDLINE search via OVID with the Medical Subject Headings (MeSH) terms "Colorectal Neoplasms"[Mesh] and "Malaysia"[Mesh], and PubMed with the key words "colorectal cancer" and "Malaysia" from 1990 to 2015 for studies reporting any clinical, societal, and economical findings associated with colorectal cancer in Malaysia. Incidence and mortality data were retrieved from population-based cancer registries/databases.
RESULTS: In Malaysia, colorectal cancer is the second most common cancer in males and the third most common cancer in females. The economic burden of colorectal cancer is substantial and is likely to increase over time in Malaysia owing to the current trend in colorectal cancer incidence. In Malaysia, most patients with colorectal cancer have been diagnosed at a late stage, with the 5-year relative survival by stage being lower than that in developed Asian countries. Public awareness of the rising incidence of colorectal cancer and the participation rates for colorectal cancer screening are low.
CONCLUSION: The efficiency of different screening approaches must be assessed, and an organized national screening program should be developed in a phased manner. It is essential to maintain a balanced investment in awareness programs targeting general population and primary care providers, focused on increasing the knowledge on symptoms and risk factors of colorectal cancer, awareness on benefits of screening, and promotion of healthy life styles to prevent this important disease.
METHODS: The antinociceptive potential of orally administered PECN (100, 250, 500 mg/kg) was studied using the abdominal constriction-, hot plate- and formalin-induced paw licking-test in mice (n = 6). The effect of PECN on locomotor activity was also evaluated using the rota rod assay. The role of opioid receptors was determined by pre-challenging 500 mg/kg PECN (p.o.) with antagonist of opioid receptor subtypes, namely β-funaltrexamine (β-FNA; 10 mg/kg; a μ-opioid antagonist), naltrindole (NALT; 1 mg/kg; a δ-opioid antagonist) or nor-binaltorphimine (nor-BNI; 1 mg/kg; a κ-opioid antagonist) followed by subjection to the abdominal constriction test. In addition, the role of L-arg/NO/cGMP pathway was determined by prechallenging 500 mg/kg PECN (p.o.) with L-arg (20 mg/kg; a NO precursor), 1H-[1, 2, 4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 2 mg/kg; a specific soluble guanylyl cyclase inhibitor), or the combinations thereof (L-arg + ODQ) for 5 mins before subjection to the abdominal constriction test. PECN was also subjected to phytoconstituents analyses.
RESULTS: PECN significantly (p 0.05) affect the locomotor activity of treated mice. The antinociceptive activity of PECN was significantly (p 0.05) affected by ODQ. HPLC analysis revealed the presence of at least cinnamic acid in PECN.
CONCLUSION: PECN exerted antinocicpetive activity at peripheral and central levels possibly via the activation of non-selective opioid receptors and modulation of the NO-mediated/cGMP-independent pathway partly via the synergistic action of phenolic compounds.
METHOD: A cross-sectional study was conducted among patients aged >18 years attending Klinik Kesihatan Putrajaya Presint 9 with a high risk of contracting COVID-19 recruited via systematic random sampling. Data were collected using a self-administered questionnaire. A multiple logistic regression analysis was performed to identify the associated factors.
RESULTS: The response rate for this study was 97.4% (N=489). The median patient age was 55 years. Approximately 51.7% were men, and 90.4% were Malays. Approximately 81.2% were willing to receive a COVID-19 booster vaccine. The patients who perceived COVID-19 as a serious illness (Adjusted Odd Ratio, AOR=2.414), those who perceived COVID-19 booster vaccines as beneficial (AOR=7.796), those who disagreed that COVID-19 booster vaccines have many side effects (AOR=3.266), those who had no doubt about the content of COVID-19 vaccines (AOR=2.649) and those who were employed (AOR=2.559) and retired (AOR=2.937) were more likely to be willing to receive a booster vaccine than those who were unemployed and those who did not have close friends or family members who contracted severe COVID-19 (AOR=2.006).
CONCLUSION: The majority of the participants were willing to receive a COVID-19 booster vaccine. Healthcare authorities should take initiatives to design targeted public intervention programmes to increase the willingness for COVID-19 booster vaccination.
METHODS: A cross-sectional study was carried out using a systematic random sampling method in hypertensive patients who attended two government primary care clinics in Sarawak. The STOP-Bang questionnaire was used to screen for OSA, and social-demographic data was captured with a questionnaire. Multiple logistic regressions were used to examine the determinants of the OSA.
RESULTS: A total of 410 patients were enrolled in this study. The mean age of study population patients was 56.4 years, with more than half being female. The mean blood pressure was 136/82. The prevalence of probable OSA among patients with hypertension was 54.4%. According to multiple logistic regression analyses, smoking (odds ratio [OR] 14.37, 95% confidence interval [CI] 3.335-61.947), retirees (OR 3.20, 95% CI 1.675-6.113), and being Chinese (OR 2.21, 95% CI 1.262-3.863) had a significant positive association with probable OSA.
CONCLUSIONS: Because of the high prevalence of probable OSA among patients with hypertension, primary care physicians should be more vigilant in identifying hypertensive patients with OSA risk. Early detection and intervention would reduce disease complications and healthcare costs.
METHODS: The study comprised a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials (RCTs). We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. Primary outcome measures were the incidences of any recurrent adenomas and of advanced adenomas. Meta-analytic estimates were calculated with the random-effects model and random errors were evaluated with trial sequential analyses (TSAs).
RESULTS: Five randomized trials (2234 patients with a history of adenomas) were included. Two of the 5 trials showed either unclear or high risks of bias in most criteria. Meta-analysis of good quality RCTs suggest a moderate protective effect of calcium supplementation on recurrence of adenomas (relative risk [RR], 0.88 [95% CI 0.79-0.99]); however, its effects on advanced adenomas did not show statistical significance (RR, 1.02 [95% CI 0.67-1.55]). Subgroup analyses demonstrated a greater protective effect on recurrence of adenomas with elemental calcium dose ≥1600 mg/day (RR, 0.74 [95% CI 0.56-0.97]) compared to ≤1200 mg/day (RR, 0.84 [95% CI 0.73-0.97]). No major serious adverse events were associated with the use of calcium, but there was an increase in the incidence of hypercalcemia (P = .0095). TSA indicated a lack of firm evidence for a beneficial effect. Concerns with directness and imprecision rated down the quality of the evidence to "low."
CONCLUSION: The available good quality RCTs suggests a possible beneficial effect of calcium supplementation on the recurrence of adenomas; however, TSA indicated that the accumulated evidence is still inconclusive. Using GRADE-methodology, we conclude that the quality of evidence is low. Large well-designed randomized trials with low risk of bias are needed.
Methods: We performed a meta-analysis based on a systematic review of randomized controlled trials (RCTs) comparing celecoxib at various doses (400 mg once daily, 200 mg twice daily, and 400 mg twice daily) vs placebo in persons with history of colorectal adenomas. Several databases were searched from inception up to April 2018. Long-term follow-ups of RCTs were also included to evaluate posttreatment effect. Primary outcome was the incidence of recurrent colorectal adenomas. Various safety outcomes were evaluated, especially cardiovascular (CV) events. Risk-benefit integrated analyses were also performed.
Results: A total of three RCTs (4,420 patients) and three post-trial studies (2,159 patients) were included in the analysis. Use of celecoxib at any dose for 1-3 years significantly reduced the incidence of recurrent advanced adenomas (risk ratio, 0.42 [95% CI, 0.34-0.53]) and any adenomas (0.67 [95% CI, 0.62-0.72]) compared with placebo. Subgroup analysis on different dosing suggested a greater effect with 400 mg twice daily. However, celecoxib 400 mg twice daily significantly increased the risk of serious adverse (1.2 [95% CI, 1.0-1.5]) and CV events (3.42 [95% CI, 1.56-7.46]), while celecoxib at 400 mg/day, especially with once daily dosing, did not increase CV risk (1.01 [95% CI, 0.70-1.46]). Analysis of post-trial studies indicated that the treatment effect disappeared (1.15 [95% CI, 0.88-1.49]) after discontinuing celecoxib for >2 years.
Conclusion: Celecoxib 400 mg once daily dosing could potentially be considered as a viable chemopreventive option in patients with high risk of adenomas but with low CV risk. Long-term trials on celecoxib at a dose of ≤400 mg either once or twice daily are warranted.
METHODS: We will acquire eligible studies through a systematic search of MEDLINE, EMBASE, the Cochrane Central Registry of Controlled Trials, CINAHL plus, IPA and clinicaltrials.gov website. The Cochrane Risk of Bias Tool will be used to assess the quality of included studies. The primary outcomes are the incidence of CRC, the incidence/recurrence of any adenoma or change in polyp burden (number or size). Quantitative synthesis or meta-analysis will be considered. We will also construct a network meta-analysis (NMA) to improve precision of the comparisons among chemo-preventive interventions by combining direct and indirect evidence. The probability of each treatment being the best and/or safest, the number-needed-to-treat [NNT; 95% credible interval (CrIs)], and the number-needed-to-harm (NNH; 95% CrIs) will be calculated to provide measures of treatment efficacy. The GRADE approach will be used to rate the quality of evidence of estimates derived from NMA.
RESULTS: This protocol has been registered (registration number: CRD42015025849) with the PROSPERO (International Prospective Register of Systematic Reviews). The procedures of this systematic review and NMA will be conducted in accordance with the PRISMA-compliant guideline. The results of this systematic review and NMA will be submitted to a peer-reviewed journal for publication.
CONCLUSIONS: To the best of our knowledge, this study will be the first NMA to identify the comparative effectiveness of interventions for the prevention of CRC. The results of our study will update evidence for chemoprevention of CRC, identify key areas for future research, and provide a framework for conducting large systematic reviews involving indirect comparisons.
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 mg/day (relative risk [RR] 0.61, 95% confidence interval [CI] 0.45-0.83), celecoxib 400 mg/day (RR 0.70, 95% CI 0.55-0.87), low-dose aspirin (RR 0.75, 95% CI 0.59-0.96) and calcium (RR 0.81, 95% CI 0.69-0.96) 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 mg/day and celecoxib 400 mg/day were the best CPAs, followed by low-dose aspirin and calcium. Considering advanced adenoma recurrence, only celecoxib 800 mg/day and celecoxib 400 mg/day were demonstrated to have a protective effect (RR 0.37, 95% CI 0.27-0.52 vs RR 0.48, 95% CI 0.38-0.60, 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.
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.
METHODS: Our objective was to update and systematically evaluate the evidence for aspirin and other NSAIDs on the incidence of recurrent colorectal adenomas taking into consideration the risks of random error and to appraise the quality of evidence using GRADE (The Grading of Recommendations, Assessment, Development and Evaluation) approach. Retrieved trials were evaluated using Cochrane risk of bias instrument. Meta-analytic estimates were calculated with random-effects model and random errors were evaluated with trial sequential analysis (TSA).
RESULTS: In patients with a previous history of colorectal cancer or adenomas, low-dose aspirin (80-160 mg/day) compared to placebo taken for 2 to 4 years reduces the risk of recurrent colorectal adenomas (relative risk (RR), 0.80 [95% CI (confidence interval), 0.70-0.92]). TSA indicated a firm evidence for this beneficial effect. The evidence indicated moderate GRADE quality. Low-dose aspirin also reduces the recurrence of advanced adenomas (RR, 0.66 [95% CI, 0.44-0.99]); however, TSA indicated lack of firm evidence for a beneficial effect. High-dose aspirin (300-325 mg/day) did not statistically reduce the recurrent adenomas (RR, 0.90 [95% CI, 0.68-1.18]). Cyclooxygenase-2 (COX-2) inhibitors (e.g. celecoxib 400 mg/day) were associated with a significant decrease in the recurrence of both adenomas (RR, 0.66 [95% CI, 0.59-0.72]) and advanced adenomas (RR, 0.45 [95% CI, 0.33-0.57]); however, this association did not persist and there was a trend of an increased risk of recurrent adenomas observed 2 years after the withdrawal.
CONCLUSION: Our findings confirm the beneficial effect of low-dose aspirin on recurrence of any adenomas; however, effect on advanced adenomas was inconclusive. COX-2 inhibitors seem to be more effective in preventing recurrence of adenomas; however, there was a trend of an increased risk of recurrence of adenomas observed after discontinuing regular use.
METHOD: Two hundred sixty eight serum specimens collected from patients that were diagnosed for dengue fever were confirmed for dengue virus serotyping by real-time polymerase chain reaction. Clinical, laboratory and demographic data were extracted from the hospital database to identify patients with confirmed leptospirosis infection among the dengue patients. Thus, frequency of co-infection was calculated and association of the dataset with dengue-leptospirosis co-infection was statistically determined.
RESULTS: The frequency of dengue co-infection with leptospirosis was 4.1%. Male has higher preponderance of developing the co-infection and end result of shock as clinical symptom is more likely present among co-infected cases. It is also noteworthy that, DENV 1 is the common dengue serotype among all cases identified as dengue-leptospirosis co-infection in this study.
CONCLUSION: The increasing incidence of leptospirosis among dengue infected patients has posed the need to precisely identify the presence of co-infection for the betterment of treatment without mistakenly ruling out either one of them. Thus, anticipating the possible clinical symptoms and laboratory results of dengue-leptospirosis co-infection is essential.
METHODOLOGY AND PRINCIPAL FINDINGS: A total of 120 retrospective dengue serum specimens were subjected to serotyping and genotyping by Taqman Real-Time RT-PCR, sequencing and phylogenetic analysis. Subsequently, the dengue serotype and genotype data were statistically analyzed for 101 of 120 corresponding patients' clinical manifestations to generate a descriptive relation between the genetic components and clinical outcomes of dengue infected patients. During the study period, predominant dengue serotype and genotype were found to be DENV 1 genotype I. Additionally, non-severe clinical manifestations were commonly observed in patients infected with DENV 1 and DENV 3. Meanwhile, patients with DENV 2 infection showed significant warning signs and developed severe dengue (p = 0.007). Cases infected with DENV 2 were also commonly presented with persistent vomiting (p = 0.010), epigastric pain (p = 0.018), plasma leakage (p = 0.004) and shock (p = 0.038). Moreover, myalgia and arthralgia were highly prevalent among DENV 3 infection (p = 0.015; p = 0.014). The comparison of genotype-specific clinical manifestations showed that DENV 2 Cosmopolitan was significantly common among severe dengue patients. An association was also found between genotype I of DENV 3 and myalgia. In a similar vein, genotype III of DENV 3 was significantly common among patients with arthralgia.
CONCLUSION: The current data contended that different dengue serotype and genotype had caused distinct clinical characteristics in infected patients.