A comparison of neoadjuvant therapies for gastroesophageal and gastric cancer on tumour resection rate: A network meta-analysis

Background: Gastric cancer is one of the most common malignancies around the world, and a variety of neoadjuvant chemotherapies with different drug combinations are available for the treatment. R0 resection refers to a microscopically negative margin on resection, where no gross or microscopic tumour remains in the primary tumour. We aimed to find evidence on the relative effectiveness of neoadjuvant therapies for patients with advanced gastroesophageal and gastric cancer on the R0 resection rate. Methods: Relevant randomised controlled trials were searched using appropriate keywords in health-related databases. We performed network meta-analysis within a frequentist framework. The endpoint assessed was the R0 resection rate. We assessed consistency and transitivity assumptions that are necessary for network meta-analysis. This study only used data from published studies. The need for consent from participants was waived by the Ethics Review Committee of the International Medical University in Malaysia. Results: Six randomised controlled trials involving 1700 patients were identified. A network plot was formed with five neoadjuvant regimens [DLX (pyrimidine analogue + platinum compounds + chemoradiotherapy), DELX (pyrimidine analogue + epipodophylllotoxins/etoposide + platinum compounds + chemoradiotherapy), ADL (anthracycline + pyrimidine analogue + platinum compounds), ADM (anthracycline+ pyrimidine analogue + anti-folate compounds) and LTX (platinum compounds + taxane + chemoradiotherapy)] and surgery alone for management of patients with advanced gastroesophageal and gastric cancer. Assumptions required for a network meta-analysis such as consistency ((global test: Chi2 (1): 3.71; p:0.054)), and the transitivity in accord to the characteristics of interventions considered in this review were not violated. In the network comparison, surgery alone has a lower R0 resection rate compared with LTX (OR 0.2, 95%CI:0.01, 0.38) or DLX (OR 0.48, 95%CI: 0.29, 0.79). LTX has higher resection rate compared with DLX (OR 2.47, 95%CI: 1.08 to 5.63), DELX (OR 106.0, 95%CI: 25.29 to 444.21), ADM (OR 5.41, 95%CI: 1.56 to 18.78) or ADL (OR 3.12, 95%CI: 1.27 to 7.67). There were wide or very wide CIs in many of these comparisons. Overall certainty of the evidence was low or very low. Further research in this field is very likely to have an important impact on our confidence in the R0 resection rates between LTX versus other neoadjuvant chemotherapy is likely to change the estimate. Conclusions: Findings suggest that overall quality of evidence on the relative effectiveness of neoadjuvant chemotherapies was low to very low level. Therefore, we are very uncertain about the true effect of neoadjuvant therapies in the R0 resection rate in patients with gastroesophageal and gastric cancer. Future well-designed large trials are needed. To recruit large samples in this field, multicountry trials are recommended. Future trials also need to assess treatment-related adverse events, and patients-centered outcomes such as health‐related quality of life

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

Community engagement in health services research on elimination of lymphatic filariasis: A systematic review

This study aimed to contextualize the extent, nature, and quality of community engagement in health services research on eliminating lymphatic filariasis in low-and middle-income countries of Southeast Asia and Pacific Region. We performed a systematic review, and the results were reported according to the PRISMA-S checklist. Relevant studies were searched in health-related electronic databases, and selected according to the inclusion criteria. Sixteen studies with various study designs were identified. The majority (68%) were conducted in India. Lay people, community leaders, and volunteers were the most common groups of community members (12/16,75%). Overall, the majority (13/16, 81%) were at the ‘moderate level’ of engagement in research context mainly by ‘collaboration’ in ‘developing methodology’ ‘collaboration’ in data collection and ‘collaboration’ for ‘dissemination of findings. The common barriers to the community engagement were lack of involvement of participating bodies and technology-related issues. In conclusion, the insufficient description of the community engagement process in the studies limits a deeper understanding and analysis of the issue. Future well-designed prospective studies with attention to the description of mechanisms of engagement, facilitating the whole process and reporting the community level outcome are recommended

Risk factors for human leptospirosis following flooding: a meta-analysis of observational studies

Leptospirosis is probably the most widespread zoonotic disease in the world especially in tropical countries. There has been an increase in individual studies, which assessed the frequency of leptospirosis in flood conditions. Some studies showed contact with floods was significantly associated with the occurrence of leptospirosis while other studies reported differently. The objective of this meta-analysis was to synthesize the evidence on the risk factors which are associated with human leptospirosis following flooding. We set up the inclusion criteria and searched for the original studies, addressing leptospirosis in human with related to flood in health-related electronic databases including PubMed, Embase, Ovid Medline, google scholar and Scopus sources. We used the terms 'leptospirosis', 'flood', 'risk factor' and terms from the categories were connected with "OR" within each category and by "AND" between categories. The initial search yielded 557 citations. After the title and abstract screening, 49 full-text papers were reviewed and a final of 18 observational studies met the pre-specified inclusion criteria. Overall, the pooled estimates of 14 studies showed that the contact with flooding was a significant factor for the occurrence of leptospirosis (pooled OR: 2.19, 95%CI: 1.48-3.24, I2:86%). On stratification, the strength of association was greater in the case-control studies (pooled OR: 4.01, 95%CI: 1.26-12.72, I2:82%) than other designs (pooled OR:1.77,95%CI:1.18-2.65, I2:87%). Three factors such as 'being male'(pooled OR:2.06, 95%CI:1.29-2.83), the exposure to livestock animals (pooled OR: 1.95, 95%CI:1.26-2.64), the lacerated wound (pooled OR:4.35, 95%CI:3.07-5.64) were the risk factors significantly associated with the incidence of leptospirosis following flooding in the absence of within-study heterogeneity (I2: 0%). We acknowledge study limitations such as publication bias and type 2 statistical errors. We recommended flood control and other environmental modifications that are expected to reduce the risk of leptospiral infection, and a multi-sectoral effort to this aspect would have long-term benefits

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

Detection of asymptomatic malaria in Asian countries: a meta-analysis of diagnostic accuracy

Background Achieving malaria elimination requires the targeting of the human reservoir of infection, including those patients with asymptomatic infection. The objective was to synthesise evidence on the accuracy of the rapid-onsite diagnostic tests (RDTs) and microscopy for the detection of asymptomatic malaria as part of the surveillance activities in Asian countries. Methods This was a meta-analysis of diagnostic test accuracy. Relevant studies that evaluated the diagnostic performance of RDTs and microscopy for detection of asymptomatic malaria were searched in health-related electronic databases. The methodological quality of the studies included was assessed using the QUADAS-2 tool. Results Ten studies assessing RDT and/or microscopy were identified. The diagnostic accuracies in all these studies were verified by PCR. Overall, the pooled sensitivities of RDT, as well as microscopy for detection of any malaria parasites in asymptomatic participants, were low, while their pooled specificities were almost ideal. For the detection of Plasmodium falciparum, pooled sensitivity by RDT (59%, 95%CI:16–91%) or microscopy (55%, 95%CI: 25–82%) were almost comparable. For detection of Plasmodium vivax, pooled sensitivity of RDT (51%, 95% CI:7–94%) had also the comparable accuracy of microscopy (54%, 95%CI,11–92%). Of note are the wide range of sensitivity and specificity. Conclusion The findings of this meta-analysis suggest that RDTs and microscopy have limited sensitivity and are inappropriate for the detection of asymptomatic Plasmodium infections. Other methods including a combination of PCR-based strategies, Loop-Mediated Isothermal Amplification (LAMP) technique must be considered to target these infections, in order to achieve malaria elimination. However, more data is needed for the wide acceptance and feasibility of these approaches. Studies to explore the role of asymptomatic and sub-patent infections in the transmission of malaria are of critical importance and are recommended

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

An association between IL-10 promoter polymorphisms and diabetic nephropathy: a meta-analysis of case-control studies

Background: This study aimed to synthesize evidence on the association between IL-10 gene (−819 C/T, −1082 A/G, −592 A/C) polymorphisms and the risk of developing diabetic nephropathy. Methods: A systematic literature search was done in health-related electronic databases. The search was limited to studies published in English until September 2017. We also checked the references of retrieved articles and relevant reviews for any additional studies. The methodological quality of the studies included in this review was assessed using the 'Scales for Quality Assessment'. The I 2 test was used to quantify between-study heterogeneity. A value of I 2 > 50% indicated substantial heterogeneity. For the pooled analysis, summary odds ratio (OR) and its 95% confidence interval (CI) in random effect model were used. Results: Eight case-control studies (1192 cases with diabetic nephropathy and 2399 controls) met the inclusion criteria. Three groups of people namely Africans, Asians and Caucasians were included in this review. There were significant protective effects of SNP -819 C/T in overall population (OR 0.32, 95% CI 0.26–0.4) and − 1082 A/G SNP in the Asian population (OR 0.64, 95% CI 0.47–0.86) on diabetic nephropathy in the recessive model. There was no significant effect of −592 A/C on diabetic nephropathy. Conclusion: The findings suggest the protective effects of −1082A/G and -819G/A polymorphisms on the risk of developing diabetic nephropathy in type 2 diabetes mellitus, especially in the Asian population. Well- designed, prospective studies with sufficient number of participants are recommended to substantiate these findings

Pairwise meta-analysis for the Ro resection rate.

Pairwise meta-analysis for the Ro resection rate.</p

Community engagement in health services research on elimination of lymphatic filariasis: A systematic review

This study aimed to contextualize the extent, nature, and quality of community engagement in health services research on eliminating lymphatic filariasis in low-and middle-income countries of Southeast Asia and Pacific Region. We performed a systematic review, and the results were reported according to the PRISMA-S checklist. Relevant studies were searched in health-related electronic databases, and selected according to the inclusion criteria. Sixteen studies with various study designs were identified. The majority (68%) were conducted in India. Lay people, community leaders, and volunteers were the most common groups of community members (12/16,75%). Overall, the majority (13/16, 81%) were at the ‘moderate level’ of engagement in research context mainly by ‘collaboration’ in ‘developing methodology’ ‘collaboration’ in data collection and ‘collaboration’ for ‘dissemination of findings. The common barriers to the community engagement were lack of involvement of participating bodies and technology-related issues. In conclusion, the insufficient description of the community engagement process in the studies limits a deeper understanding and analysis of the issue. Future well-designed prospective studies with attention to the description of mechanisms of engagement, facilitating the whole process and reporting the community level outcome are recommended