Immediately modifiable risk factors attributable to colorectal cancer in Malaysia

Background: This study aimed to estimate potential reductions in case incidence of colorectal cancer attributable to the modifiable risk factors such as alcohol consumption, overweight and physical inactivity amongst the Malaysian population. Methods: Gender specific population-attributable fractions (PAFs) for colorectal cancer in Malaysia were estimated for the three selected risk factors (physical inactivity, overweight, and alcohol consumptions). Exposure prevalence were sourced from a large-scale national representative survey. Risk estimates of the relationship between the exposure of interest and colorectal cancer were obtained from published meta-analyses. The overall PAF was then estimated, using the 2013 national cancer incidence data from the Malaysian Cancer Registry. Results: Overall, the mean incidence rate for colorectal cancer in Malaysia from 2008 to 2013 was 21.3 per 100,000 population, with the mean age of 61.6 years (±12.7) and the majority were men (56.6%). Amongst 369 colorectal cancer cases in 2013, 40 cases (20 men, 20 women), 10 cases (9 men, 1 woman) or 20 cases (16 men,4 women) would be prevented, if they had done physical exercises, could reduce their body weight to normal level or avoided alcohol consumption, assuming that these factors are causally related to colorectal cancer. It was estimated that 66 (17.8%;66/369) colorectal cancer cases (42 men, 24 women) who had all these three risk factors for the last 10 years would have been prevented, if they could control these three risk factors through effective preventive measures. Conclusions: Findings suggest that approximately 18% of colorectal cancer cases in Malaysia would be prevented through appropriate preventive measures such as doing regular physical exercises, reducing their body weight to normal level and avoiding alcohol consumption, if these factors are causally related to colorectal cancer. Scaling-up nationwide public health campaigns tailored to increase physical activity, controlling body weight within normal limits and avoid alcohol intake are recommended. Future studies with other site-specific cancers and additional risk factors are needed

Loop-mediated isothermal amplification (LAMP) test for diagnosis of uncomplicated malaria in endemic areas: a meta-analysis of diagnostic test accuracy

Background The global malaria decline has stalled and only a few countries are pushing towards pre-elimination. The aim of the malaria elimination phase is interruption of local transmission of a specified malaria parasite in a defined geographical area. New and improved screening tools and strategies are required for detection and management of very low-density parasitaemia in the field. The objective of this study was to synthesize evidence on the diagnostic accuracy of loop-mediated isothermal amplification (LAMP) test for the detection of malaria parasites among people living in endemic areas. Methods This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy (PRISMA-DTA) guideline. Relevant studies in the health-related electronic databases were searched. According to the criteria set for this study, eligible studies were identified. The quality of included studies was evaluated with the use of a quality assessment checklist. A summary performance estimates such as pooled sensitivity and specificity were stratified by type of LAMP. Bivariate model for data analyses was applied. Summary receiver operating characteristics plots were created to display the results of individual studies in a receiver operating characteristics space. Meta-regression analysis was performed to investigate the sources of heterogeneity among individual studies. Results Twenty-seven studies across 17 endemic countries were identified. The vast majority of studies were with unclear risk of bias in the selection of index test. Overall, the pooled test performances were high for Pan LAMP (sensitivity: 0.95, 95% CI 0.91 to 0.97; specificity: 0.98, 95% CI 0.95 to 0.99), Plasmodium falciparum (Pf) LAMP (sensitivity: 0.96, 95% CI 0.94 to 0.98; specificity: 0.99, 95% CI 0.96 to 1.00) or for Plasmodium vivax (Pv) LAMP from 6 studies (sensitivity: 0.98, 95% CI 0.92 to 0.99; specificity: 0.99, 95% CI 0.72 to 1.00). The area under the curve for Pan LAMP (0.99, 95% CI 0.98-1.00), Pf LAMP (0.99, 95% CI 0.97-0.99) and Pv LAMP was (1.00, 95% CI 0.98-1.00) indicated that the diagnostic performance of these tests were within the excellent accuracy range. Meta-regression analysis showed that sample size had the greatest impact on test performance, among other factors. Conclusions The current findings suggest that LAMP-based assays are appropriate for detecting low-level malaria parasite infections in the field and would become valuable tools for malaria control and elimination programmes. Future well-designed larger sample studies on LAMP assessment in passive and active malaria surveillances that use PCR as the reference standard and provide sufficient data to construct 2 × 2 diagnostic table are needed

Tamoxifen for hepatocellular carcinoma

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the benefits and harms of tamoxifen in people with hepatocellular carcinoma, irrespective of sex, administered dose, type of formulation, and duration of treatment

Is Plasmodium vivax a severe malaria?: a systematic review and meta-analysis

Background: Plasmodium vivax is one of the major species of malaria infecting humans. Although emphasis on P. falciparum is appropriate, the burden of vivax malaria should be given due attention. This study aimed to synthesize the evidence on severe malaria in P. vivax infection compared with that in P. falciparum infection. Methods/Principal Findings: We searched relevant studies in electronic databases. The main outcomes required for inclusion in the review were mortality, severe malaria (SM) and severe anaemia (SA). The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Overall, 26 studies were included. The main meta-analysis was restricted to the high quality studies. Eight studies (n = 27490) compared the incidence of SM between P. vivax infection and P. falciparum mono-infection; a comparable incidence was found in infants (OR: 0.45, 95% CI:0.04-5.68, I2:98%), under 5 year age group (OR: 2.06, 95% CI: 0.83-5.1, I2:83%), the 5-15 year-age group (OR: 0.6, 95% CI: 0.31-1.16, I2:81%) and adults (OR: 0.83, 95% CI: 0.67-1.03, I2:25%). Six studies reported the incidences of SA in P. vivax infection and P. falciparum mono-infection; a comparable incidence of SA was found among infants (OR: 3.47, 95%:0.64-18.94, I2: 92%), the 5-15 year-age group (OR:0.71, 95% CI: 0.06-8.57, I2:82%). This was significantly lower in adults (OR:0.75, 95% CI: 0.62-0.92, I2:0%). Five studies (n = 71079) compared the mortality rate between vivax malaria and falciparum malaria. A lower rate of mortality was found in infants with vivax malaria (OR:0.61, 95% CI:0.5-0.76, I2:0%), while this was comparable in the 5-15 year- age group (OR: 0.43, 95% CI:0.06-2.91, I2:84%) and the children of unspecified-age group (OR: 0.77, 95% CI:0.59-1.01, I2:0%). Conclusion: Overall, the present analysis identified that the incidence of SM in patients infected with P. vivax was considerable, indicating that P. vivax is a major cause of SM. Awareness of the clinical manifestations of vivax malaria should prompt early detection. Subsequent treatment and monitoring of complications can be life-saving

Efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region: a network meta-analysis

Background: The WHO recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria. Hence, monitoring the efficacy of antimalarial drugs is a key component of malaria control and elimination. The published randomized trials that assessed comparisons of ACTs for treating uncomplicated falciparum malaria reported conflicting results in treatment efficacy. A network meta-analysis is an extension of pairwise meta-analysis that can synthesize evidence simultaneously from both direct and indirect treatment comparisons. The objective was to synthesize evidence on the comparative efficacy of antimalarial drugs for treatment of uncomplicated falciparum malaria in Asian region. Methods: Relevant randomized trials that assessed efficacy of antimalarial drugs for patients having uncomplicated falciparum malaria in Asian region were searched in health-related databases. We evaluated the methodological quality of the included studies with the Cochrane risk of bias tool. Main outcome was treatment success at day 28 as determined by the absence of parasiteamia. We performed network meta-analysis of the interventions in the trials, and assessed the overall quality of evidence using the GRADE approach. Results: Seventeen randomized trials (n = 5043) were included in this network meta-analysis study. A network geometry was formed with 14 antimalarial treatment options such as artemetherlumefantrine (AL), artemisinin-piperaquine, artesunate-amodiaquine, artesunate-mefloquine (ASMQ), artesunate-chloroquine, artesunate-mefloquine home treatment, artesunate-mefloquine 2-day course, artesunate plus sulfadoxine-pyrimethamine, chloroquine, dihydroartemisinin-piperaquine (DHP), dihydroartemisinin-piperaquine home treatment, dihydroartemisinin-piperaquine 4-day course, dihydroartemisinin-piperaquine and added artesunate, sulfadoxine-pyrimethamine. A maximum number of trials included was DHP compared to ASMQ (n = 5). In general, DHP had better efficacy than AL at day 28 (DHP vs AL: OR 2.5, 95%CI:1.08–5.8). There is low certainty evidence due to limited number of studies and small trials. Discussion/ Conclusions: The findings suggest the superiority of DHP (3–day course) to AL and other comparator ACTs are with the overall low/very low quality of evidence judgements. Moreover, one drug regimen is better than another is only if current drug-resistance patterns are at play. For example, the AL might be better than DHP in areas where both artemisinin and piperaquine resistance patterns are prevalent. For substantiation, well-designed larger trials from endemic countries are needed. In the light of benefit versus harm concept, future analysis with safety information is recommended

Signal detection to identify serious adverse events (neuropsychiatric events) in travelers taking mefloquine for chemoprophylaxis of malaria

Background: For all medications, there is a trade-off between benefits and potential for harm. It is important for patient safety to detect drug-event combinations and analyze by appropriate statistical methods. Mefloquine is used as chemoprophylaxis for travelers going to regions with known chloroquine-resistant Plasmodium falciparum malaria. As such, there is a concern about serious adverse events associated with mefloquine chemoprophylaxis. The objective of the present study was to assess whether any signal would be detected for the serious adverse events of mefloquine, based on data in clinicoepidemiological studies. Materials and methods: We extracted data on adverse events related to mefloquine chemoprophylaxis from the two published datasets. Disproportionality reporting of adverse events such as neuropsychiatric events and other adverse events was presented in the 2 × 2 contingency table. Reporting odds ratio and corresponding 95% confidence interval [CI] data-mining algorithm was applied for the signal detection. The safety signals are considered significant when the ROR estimates and the lower limits of the corresponding 95% CI are ≥2. Results: Two datasets addressing adverse events of mefloquine chemoprophylaxis (one from a published article and one from a Cochrane systematic review) were included for analyses. Reporting odds ratio 1.58, 95% CI: 1.49–1.68 based on published data in the selected article, and 1.195, 95% CI: 0.94–1.44 based on data in the selected Cochrane review. Overall, in both datasets, the reporting odds ratio values of lower 95% CI were less than 2. Conclusion: Based on available data, findings suggested that signals for serious adverse events pertinent to neuropsychiatric event were not detected for mefloquine. Further studies are needed to substantiate this

Loop-mediated isothermal amplification (LAMP) test in the detection of uncomplicated malaria in pregnancy: a meta-analysis of diagnostic accuracy

Background: Due to relatively low malaria parasitaemia in pregnancy, an appropriate field test that can adequately detect infections in pregnant women presenting with illness or for malaria screening during antenatal care is crucially important. The objective was to evaluate the diagnostic accuracy of loop-mediated isothermal amplification (LAMP) for the detection of uncomplicated malaria in pregnancy. Methods: This was a meta-analysis of diagnostic accuracy. Relevant studies that assessed the diagnostic performance of LAMP for the detection of malaria in pregnancy were searched in health-related electronic databases including PubMed, Ovid, and Google Scholar. The methodological quality of the studies included was evaluated using the QUADAS-2 tool. Results: Of the 372 studies identified, eight studies involving 2999 pregnant women in five endemic countries that assessed the accuracy of LAMP were identified. With three types of PCR as reference tests, the pooled sensitivity of LAMP was 91% (95%CI 67–98%) and pooled specificity was 99% (95%CI 83–100%, 4 studies), and the negative likelihood ratio was 9% (2–40%). Caution is needed in the interpretation as there was substantial between-study heterogeneity (I2: 80%), and a low probability that a person without infection is tested negative. With microscopy as a reference, the pooled sensitivity of LAMP was 95% (95%CI 26–100%) and pooled specificity was 100% (95%CI 94–100%, 4 studies). There was a wide range of sensitivity and substantial between-study heterogeneity (I2: 83.5–98.4%). To investigate the source of heterogeneity, a meta-regression analysis was performed with covariates. Of these potential confounding factors, reference test (p: 0.03) and study design (p:0.03) had affected the diagnostic accuracy of LAMP in malaria in pregnancy. Overall, there was a low certainty of the evidence in accuracy estimates. Conclusion: The findings suggest that LAMP is more sensitive than traditional tests used at facilities, but the utility of detecting and treating these low-density infections is not well understood. Due to the limited number of studies with bias in their methodological quality, variation in the study design, and different types of reference tests further research is likely to change the estimate. Well-conceived large prospective studies with blinding of the index test results are recommenced

Malaria and soil-transmitted intestinal helminth co-infection and its effect on anemia: a meta-analysis

This study aimed to synthesize available evidence on the extent of malaria and soil-transmitted intestinal helminth (STH) co-infections in people living in endemic countries and to explore the effect of interactions between malaria and STHs on anemia. We searched relevant studies in electronic databases up to March 2013. Studies comparing malaria and STH co-infected patients with those not co-infected were included and the effect estimates were pooled using a random-effects model. We identified 30 studies for meta-analyses of which 17 were cross-sectional design. The majority of included studies (80%) were carried out in African countries. Among pregnant women, those infected with hookworm were found to have higher association with malaria infection compared with those without (summary OR: 1.36; 95% CI: 1.17-1.59; I2: 0%). Among non-pregnant adults, the summary OR of the association between anemia and the combined malaria and STH was 2.91 (1.38-6.14). The summary OR of the association between anemia and malaria alone was 1.53 (0.97-2.42), while the association between anemia and STH alone was 0.28 (0.04-1.95). There is no good evidence to support a different effect of malaria and STH on anemia. A subgroup analysis showed a higher risk of malaria infection in the primigravidae (summary OR: 1.61; 95% CI: 1.3-1.99; I2: 0%). In conclusion, the malaria-STH co-infection was variable with complex outcomes on anemi

Molecular characterization of a cDNA encoding an excretory–secretory antigen from Toxocara canis second stage larvae and its application to the immunodiagnosis of human toxocariasis

The cDNA encoding an excretory–secretory antigen from the second stage larvae of Toxocara canis has been characterized. Sequence analysis revealed an open reading frame encoding a protein of 226 amino acid residues (Mr=24 398). Sequence database searches showed similarities to regions corresponding to epidermal growth factor-like and lectin-like domains of the core proteins of vertebrate chondroitin sulfate proteoglycans, which are major components of the extracellular matrix. The T. canis core protein was expressed as a fusion protein with thioredoxin A using an Escherichia coli expression system, and then affinity purified on a metal affinity resin in the presence of 8 M urea. When the purified recombinant T. canis protein was used as an antigen, immunoblot analysis revealed the protein specifically reacted with sera from toxocariasis patients. The antigenic protein did not react with sera from patients with Brugia malayi infection, dirofilariasis, or ascariasis. In some cases of anisakiasis, cross-reactions were observed; however, the cross-reacting bands disappeared when anisakiasis sera preabsorbed with Anisakis antigen were used, indicating that the recombinant T. canis protein is very promising for use as an immunodiagnostic antigen for human toxocariasis

Drinking water is a significant predictor of Blastocystis infection among rural Malaysian primary schoolchildren

Blastocystis infection has a worldwide distribution especially among the disadvantaged population and immunocompromised subjects. This study was carried out to determine the prevalence and the association of Blastocystis infection with the socio-economic characteristics among 300 primary schoolchildren, living in rural communities in Lipis and Raub districts of Pahang state, Malaysia. Stool samples were collected and examined for the presence of Blastocystis using direct smear microscopy after in vitro cultivation in Jones' medium. The overall prevalence of Blastocystis infection was found to be as high as 25·7%. The prevalence was significantly higher among children with gastrointestinal symptoms as compared to asymptomatic children (x2=4·246; P=0·039). Univariate and multivariate analyses showed that absence of a piped water supply (OR=3·13; 95% CI=1·78, 5·46; P<0·001) and low levels of mothers’ education (OR=3·41; 95% CI=1·62, 7·18; P<0·01) were the significant predictors of Blastocystis infection. In conclusion, Blastocystis is prevalent among rural children and the important factors that determine the infection were the sources of drinking water and mothers' educational level. Interventions with provision of clean water supply and health education especially to mothers are required