Community-Effectiveness of Temephos for Dengue Vector Control: A Systematic Literature Review

The application of the organophosphate larvicide temephos to water storage containers is one of the most commonly employed dengue vector control methods. This systematic literature review is to the knowledge of the authors the first that aims to assess the community-effectiveness of temephos in controlling both vectors and dengue transmission when delivered either as a single intervention or in combination with other interventions. A comprehensive literature search of 6 databases was performed (PubMed, WHOLIS, GIFT, CDSR, EMBASE, Wiley), grey literature and cross references were also screened for relevant studies. Data were extracted and methodological quality of the studies was assessed independently by two reviewers. 27 studies were included in this systematic review (11 single intervention studies and 16 combined intervention studies). All 11 single intervention studies showed consistently that using temephos led to a reduction in entomological indices. Although 11 of the 16 combined intervention studies showed that temephos application together with other chemical vector control methods also reduced entomological indices, this was either not sustained over time or–as in the five remaining studies—failed to reduce the immature stages. The community-effectiveness of temephos was found to be dependent on factors such as quality of delivery, water turnover rate, type of water, and environmental factors such as organic debris, temperature and exposure to sunlight. Timing of temephos deployment and its need for reapplication, along with behavioural factors such as the reluctance of its application to drinking water, and operational aspects such as cost, supplies, time and labour were further limitations identified in this review. In conclusion, when applied as a single intervention, temephos was found to be effective at suppressing entomological indices, however, the same effect has not been observed when temephos was applied in combination with other interventions. There is no evidence to suggest that temephos use is associated with reductions in dengue transmission.     

Dynamic Epidemiological Models for Dengue Transmission: A Systematic Review of Structural Approaches

Dengue is a vector-borne disease recognized as the major arbovirose with four immunologically distant dengue serotypes coexisting in many endemic areas. Several mathematical models have been developed to understand the transmission dynamics of dengue, including the role of cross-reactive antibodies for the four different dengue serotypes. We aimed to review deterministic models of dengue transmission, in order to summarize the evolution of insights for, and provided by, such models, and to identify important characteristics for future model development. We identified relevant publications using PubMed and ISI Web of Knowledge, focusing on mathematical deterministic models of dengue transmission. Model assumptions were systematically extracted from each reviewed model structure, and were linked with their underlying epidemiological concepts. After defining common terms in vector-borne disease modelling, we generally categorised fourty-two published models of interest into single serotype and multiserotype models. The multi-serotype models assumed either vector-host or direct host-to-host transmission (ignoring the vector component). For each approach, we discussed the underlying structural and parameter assumptions, threshold behaviour and the projected impact of interventions. In view of the expected availability of dengue vaccines, modelling approaches will increasingly focus on the effectiveness and cost-effectiveness of vaccination options. For this purpose, the level of representation of the vector and host populations seems pivotal. Since vector-host transmission models would be required for projections of combined vaccination and vector control interventions, we advocate their use as most relevant to advice health policy in the future. The limited understanding of the factors which influence dengue transmission as well as limited data availability remain important concerns when applying dengue models to real-world decision problems.     

Factors Associated with Dengue Shock Syndrome: A Systematic Review and Meta-Analysis

Background

The pathogenesis of dengue shock syndrome (DSS, grade 3 and 4) is not yet completely understood. Several factors are reportedly associated with DSS, a more severe form of dengue infection that reportedly causes 50 times higher mortality compared to that of dengue patients without DSS. However, the results from these reports remain inconclusive. To better understand the epidemiology, clinical manifestation, and pathogenesis of DSS for development of new therapy, we systematically reviewed and performed a meta-analysis of relevant studies that reported factors in both DSS and dengue hemorrhagic fever (DHF, grade 1 and 2) patients.

Methods and Findings

PubMed, EMBASE, Scopus, Google Scholar, Dengue Bulletin, Cochrane Library, Virtual Health Library, and a manual search of reference lists of articles published before September 2010 were used to retrieve relevant studies. A meta-analysis using fixed- or random-effects models was used to calculate pooled odds ratios (OR) or event rate with corresponding 95% confidence intervals. Assessment of heterogeneity and publication bias, meta-regression analysis, subgroup analysis, sensitivity analysis, and analysis of factor-specific relationships were further performed. There were 198 studies constituting 203 data sets that met our eligibility criteria. Our meta-regression analysis showed a sustained reduction of DSS/dengue hemorrhagic fever (DHF) ratio over a period of 40 years in Southeast Asia, especially in Thailand. The meta-analysis revealed that age, female sex, neurological signs, nausea/vomiting, abdominal pain, gastrointestinal bleeding, hemoconcentration, ascites, pleural effusion, hypoalbuminemia, hypoproteinemia, hepatomegaly, levels of alanine transaminase and aspartate transaminase, thrombocytopenia, prothrombin time, activated partial thromboplastin time, fibrinogen level, primary/secondary infection, and dengue virus serotype-2 were significantly associated with DSS when pooling all original relevant studies.

Conclusions

The results improve our knowledge of the pathogenesis of DSS by identifying the association between the epidemiology, clinical signs, and biomarkers involved in DSS.     

A Systematic Review of the Relationship between Blood Loss and Clinical Signs

Introduction

This systematic review examines the relationship between blood loss and clinical signs and explores its use to trigger clinical interventions in the management of obstetric haemorrhage.

Methods

A systematic review of the literature was carried out using a comprehensive search strategy to identify studies presenting data on the relationship of clinical signs & symptoms and blood loss. Methodological quality was assessed using the STROBE checklist and the general guidelines of MOOSE.

Results

30 studies were included and five were performed in women with pregnancy-related haemorrhage (other studies were carried in non-obstetric populations). Heart rate (HR), systolic blood pressure (SBP) and shock index were the parameters most frequently studied. An association between blood loss and HR changes was observed in 22 out of 24 studies, and between blood loss and SBP was observed in 17 out of 23 studies. An association was found in all papers reporting on the relationship of shock index and blood loss. Seven studies have used Receiver Operating Characteristic Curves to determine the accuracy of clinical signs in predicting blood loss. In those studies the AUC ranged from 0.56 to 0.74 for HR, from 0.56 to 0.79 for SBP and from 0.77 to 0.84 for shock index. In some studies, HR, SBP and shock index were associated with increased mortality.

Conclusion

We found a substantial variability in the relationship between blood loss and clinical signs, making it difficult to establish specific cut-off points for clinical signs that could be used as triggers for clinical interventions. However, the shock index can be an accurate indicator of compensatory changes in the cardiovascular system due to blood loss. Considering that most of the evidence included in this systematic review is derived from studies in non-obstetric populations, further research on the use of the shock index in obstetric populations is needed.     

Relationship between C-Reactive Protein Level and Diabetic Retinopathy: A Systematic Review and Meta-Analysis

Objectives

To date, the relationship between C-reactive protein (CRP) level and diabetic retinopathy (DR) remains controversial. Therefore, a systematic review and meta-analysis was used to reveal the potential relationship between CRP level and DR.

Methods

A systematic search of PubMed, Embase.com, and Web of Science was performed to identify all comparative studies that compared the CRP level of two groups (case group and control group). We defined that diabetic patients without retinopathy and /or matched healthy persons constituted the control group, and patients with DR were the case group.

Results

Two cross sectional studies and twenty case control studies including a total of 3679 participants were identified. After pooling the data from all 22 studies, obvious heterogeneity existed between the studies, so a subgroup analysis and sensitivity analysis were performed. Removing the sensitivity studies, the blood CRP levels in the case group were observed to be higher than those in the control group [SMD = 0.22, 95% confidence interval (CI), 0.11–0.34], and the blood CRP levels in the proliferative diabetic retinopathy (PDR) group were also higher than those in the non-proliferative diabetic retinopathy (NPDR) group [SMD = 0.50, 95% CI, 0.30–0.70].

Conclusions

The results from this current meta-analysis indicate that the CRP level might be used as a biomarker to determine the severity of DR.     

甲状腺特异性抗体与乳腺癌相关性研究的系统评价

目的：评价血清中甲状腺特异性抗体的存在对乳腺癌患病风险的影响,为评估乳腺癌的预后及制定治疗方案提供理论依据。方法：计算机检索Medline（1950～2012）、EMBASE（1949-2012）、Pubmed（1946-2012）、Current Contents Connect（1998-2012）和Google Scholar（1992-2012）等英文数据库。收集关于甲状腺特异性抗体与乳腺癌（BreastCancer,Bc）相关性分析的横断面研究或队列研究。按Cochrane系统评价方法,评价所纳入研究的文献质量,有效数据采用RevMan5．2软件进行系统评价。结果：最终纳入6项研究,共计6945例患者。系统评价结果显示：乳腺癌的风险会随血清中甲状腺特异性抗体（包括甲状腺过氧化物酶抗体anti-TP0和甲状腺球蛋白抗体anti—TG）的存在而增加（anti—TP00R2．51．95％CI：1．94—3．25;anti—TG2．67,95％CI：1．65—4．33）。结论：乳腺癌的风险会随血清中甲状腺特异性抗体的存在而增加,甲状腺特异性抗体可能为乳腺癌预后的评估以及治疗原则的制定提供理论基础。     

Case-control Studies on the Relationship between Onchocerciasis and Epilepsy: Systematic Review and Meta-analysis

Objective

A systematic review and meta-analysis of all available case-control studies on the relationship between onchocerciasis and epilepsy. Because age and level of onchocerciasis endemicity in the area of residence are major determinants for infection, an additional analysis was performed, restricted to studies achieving control of these confounding factors.

Data sources

Medical databases, the “African Neurology Database, Institute of Neuroepidemiology and Tropical Neurology, Limoges,” reference lists of relevant articles, commercial search engines, up to May 2012.

Methods

We searched for studies examining infection status with Onchocerca volvulus in persons with epilepsy (PWE) and without epilepsy (PWOE) providing data suitable for the calculation of pooled odds ratios (OR_p) and/or standardized mean differences (SMD) using random-effects models.

Results

Eleven studies providing data of qualitative skin biopsies for diagnosis of onchocerciasis were identified. Combined analysis on the total sample of 876 PWE and 4712 PWOE resulted in an OR_p of 2.49 (95% confidence interval (95%CI): 1.61–3.86, p<0.001). When this analysis was restricted to those studies achieving control for age, residence and sex (367 PWE, 624 PWOE), an OR_p of 1.29 (95% CI: 0.93–1.79; p = 0.139) was found. Presence of nodules for diagnosis of onchocerciasis was analyzed in four studies (225 PWE, 189 PWOE; OR_p 1.74; 95%CI: 0.94–3.20; p<0.076), including two studies of the restricted analysis (106 PWE, 106 PWOE; OR_p 2.81; 95%CI: 1.57–5.00; p<0.001). One study examined quantitative microfilariae counts in patients without preceding microfilaricidal treatment and demonstrated significantly higher counts in PWE than in PWOE.

Interpretation

Our results strengthen the hypothesis that, in onchocerciasis foci, epilepsy and infection with O. volvulus are associated. Analysis of indicators giving information on infection intensity, namely nodule palpation and quantitative microfilaria count in untreated patients, support the hypothesis that intensity of infection with O. volvulus is involved in the etiology of epilepsy.     

The Relationship between Serum Lipids and Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-Analysis

Background

Sudden sensorineural hearing loss (SSNHL) is a relatively common condition that is usually of unknown etiology. A number of individual studies have investigated the association between various serum lipids and SSNHL; however, the findings have been inconsistent. In an attempt to obtain more definitive information on the relationship between serum lipids and SSNHL, we carried out a systematic review and meta-analysis.

Methods

Medline, the Cochrane Library, and EMBASE were searched using the following key words: lipid, cholesterol, triglyceride, fat, serum, blood, sudden hearing loss, hearing loss, hearing disorders. Randomized controlled trials, prospective cohort studies, and retrospective case-control studies involving patients with SSNHL and healthy controls that examined the relationship (reported as odds ratios [OR]) between lipid profiles and SSNHL were included. Primary outcomes were total cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations. Secondary outcomes were triglyceride, high-density lipoprotein cholesterol, and lipoprotein(a) concentrations.

Results

A total of 6 case-control studies were included in this systematic review/meta-analysis. The total number of participants ranged from 30 to 250 in the case group and from 43 to 271 in the control group. Meta-analysis revealed no significant difference in total cholesterol levels between the case and control groups (pooled OR = 1.79, 95% confidence interval [CI] = 0.98 to 3.26, P = 0.057). Likewise, meta-analysis revealed no significant difference in LDL-C concentrations between the case and control groups (pooled OR = 1.15, 95% CI = 0.64 to 2.07, P = 0.639). Since there were an insufficient number of studies reporting data for the secondary outcomes, meta-analysis was not possible.

Conclusions

Our results do not provide evidence for serum lipids being associated with SSNHL, nor do they definitively rule out such an association. Additional studies are needed to ascertain the relationship, or lack thereof, between serum lipids and SSNHL.     

The Relationship between Anti-merozoite Antibodies and Incidence of Plasmodium falciparum Malaria: A Systematic Review and Meta-analysis

Background

One of the criteria to objectively prioritize merozoite antigens for malaria vaccine development is the demonstration that naturally acquired antibodies are associated with protection from malaria. However, published evidence of the protective effect of these antibodies is conflicting.

Methods and Findings

We performed a systematic review with meta-analysis of prospective cohort studies examining the association between anti-merozoite immunoglobin (Ig) G responses and incidence of Plasmodium falciparum malaria. Two independent researchers searched six databases and identified 33 studies that met predefined inclusion and quality criteria, including a rigorous definition of symptomatic malaria. We found that only five studies were performed outside sub-Saharan Africa and that there was a deficiency in studies investigating antibodies to leading vaccine candidates merozoite surface protein (MSP)-1₄₂ and erythrocyte binding antigen (EBA)-175. Meta-analyses of most-studied antigens were conducted to obtain summary estimates of the association between antibodies and incidence of P. falciparum malaria. The largest effect was observed with IgG to MSP-3 C terminus and MSP-1₁₉ (responders versus nonresponders, 54%, 95% confidence interval [CI] [33%–68%] and 18% [4%–30%] relative reduction in risk, respectively) and there was evidence of a dose-response relationship. A tendency towards protective risk ratios (RR<1) was also observed for individual study estimates for apical membrane antigen (AMA)-1 and glutamate-rich protein (GLURP)-R0. Pooled estimates showed limited evidence of a protective effect for antibodies to MSP-1 N-terminal regions or MSP-1-EGF (epidermal growth factor-like modules). There was no significant evidence for the protective effect for MSP-2 (responders versus nonresponders pooled RR, MSP-2_FC27 0.82, 95% CI 0.62–1.08, p = 0.16 and MSP-2_3D7 0.92, 95% CI 0.75–1.13, p = 0.43). Heterogeneity, in terms of clinical and methodological diversity between studies, was an important issue in the meta-analysis of IgG responses to merozoite antigens.

Conclusions

These findings are valuable for advancing vaccine development by providing evidence supporting merozoite antigens as targets of protective immunity in humans, and to help identify antigens that confer protection from malaria. Further prospective cohort studies that include a larger number of lead antigens and populations outside Africa are greatly needed to ensure generalizability of results. The reporting of results needs to be standardized to maximize comparability of studies. We therefore propose a set of guidelines to facilitate the uniform reporting of malaria immuno-epidemiology observational studies. Please see later in the article for the Editors'' Summary     

Relevance of Non-communicable Comorbidities for the Development of the Severe Forms of Dengue: A Systematic Literature Review

Patients with dengue fever and comorbidities seem to be at higher risk of developing complications and/or severe dengue compared to healthier individuals. This study systematically reviews the evidence related to comorbidities and dengue. A systematic literature review was performed in five databases (EMBASE, PUBMED, Global Health, SciELO, Cochrane) and grey literature for full-text articles since its inceptions until October 10, 2015. A total of 230 articles were retrieved. Sixteen studies were analysed after applying all inclusion and exclusion criteria. Seven case control studies and nine retrospective cohort studies showed that comorbidities may contribute to severe dengue, especially 1) cardiovascular disease, 2) stroke, 3) diabetes, 4) respiratory disease and 5) renal disease, as well as old age. However, due to heterogeneity in studies, the real estimate effect of comorbidities as modifiers of dengue severity could not be established. Further research in regions with high prevalence of dengue infection would contribute to a better understanding of the relevance of comorbidities in severe dengue, especially with a standardised protocol, for outcomes, specific comorbidities, study design—best using prospective designs—and sample sizes.     

Parameters for the Mathematical Modelling of Clostridium difficile Acquisition and Transmission: A Systematic Review

Introduction

Mathematical modelling of Clostridium difficile infection dynamics could contribute to the optimisation of strategies for its prevention and control. The objective of this systematic review was to summarise the available literature specifically identifying the quantitative parameters required for a compartmental mathematical model of Clostridium difficile transmission.

Methods

Six electronic healthcare databases were searched and all screening, data extraction and study quality assessments were undertaken in duplicate. Results were synthesised using a narrative approach.

Results

Fifty-four studies met the inclusion criteria. Reproduction numbers for hospital based epidemics were described in two studies with a range from 0.55 to 7. Two studies provided consistent data on incubation periods. For 62% of cases, symptoms occurred in less than 4 weeks (3-28 days) after infection. Evidence on contact patterns was identified in four studies but with limited data reported for populating a mathematical model. Two studies, including one without clinically apparent donor-recipient pairs, provided information on serial intervals for household or ward contacts, showing transmission intervals of <1 week in ward based contacts compared to up to 2 months for household contacts. Eight studies reported recovery rates of between 75% - 100% for patients who had been treated with either metronidazole or vancomycin. Forty-nine studies gave recurrence rates of between 3% and 49% but were limited by varying definitions of recurrence. No study was found which specifically reported force of infection or net reproduction numbers.

Conclusions

There is currently scant literature overtly citing estimates of the parameters required to inform the quantitative modelling of Clostridium difficile transmission. Further high quality studies to investigate transmission parameters are required, including through review of published epidemiological studies where these quantitative estimates may not have been explicitly estimated, but that nonetheless contain the relevant data to allow their calculation. [Systematic review reference: CRD42012003081]     

Epidemiological Trends of Dengue Disease in Colombia (2000-2011): A Systematic Review

A systematic literature review was conducted to describe the epidemiology of dengue disease in Colombia. Searches of published literature in epidemiological studies of dengue disease encompassing the terms “dengue”, “epidemiology,” and “Colombia” were conducted. Studies in English or Spanish published between 1 January 2000 and 23 February 2012 were included. The searches identified 225 relevant citations, 30 of which fulfilled the inclusion criteria defined in the review protocol. The epidemiology of dengue disease in Colombia was characterized by a stable “baseline” annual number of dengue fever cases, with major outbreaks in 2001–2003 and 2010. The geographical spread of dengue disease cases showed a steady increase, with most of the country affected by the 2010 outbreak. The majority of dengue disease recorded during the review period was among those <15 years of age. Gaps identified in epidemiological knowledge regarding dengue disease in Colombia may provide several avenues for future research, namely studies of asymptomatic dengue virus infection, primary versus secondary infections, and under-reporting of the disease. Improved understanding of the factors that determine disease expression and enable improvement in disease control and management is also important.     

Tourniquet Test for Dengue Diagnosis: Systematic Review and Meta-analysis of Diagnostic Test Accuracy

BackgroundDengue fever is a ubiquitous arboviral infection in tropical and sub-tropical regions, whose incidence has increased over recent decades. In the absence of a rapid point of care test, the clinical diagnosis of dengue is complex. The World Health Organisation has outlined diagnostic criteria for making the diagnosis of dengue infection, which includes the use of the tourniquet test (TT).PurposeTo assess the quality of the evidence supporting the use of the TT and perform a diagnostic accuracy meta-analysis comparing the TT to antibody response measured by ELISA.ConclusionThe tourniquet test is widely used in resource poor settings despite currently available evidence demonstrating only a marginal benefit in making a diagnosis of dengue infection alone.RegistrationThe protocol for this systematic review was registered at PROSPERO: CRD42015020323.     

Pacemaker Dependency after Cardiac Surgery: A Systematic Review of Current Evidence

Background

Severe postoperative conduction disturbances requiring permanent pacemaker implantation frequently occur following cardiac surgery. Little is known about the long-term pacing requirements and risk factors for pacemaker dependency in this population.

Methods

We performed a systematic review of the literature addressing rates and predictors of pacemaker dependency in patients requiring permanent pacemaker implantation after cardiac surgery. Using a comprehensive search of the Medline, Web of Science and EMBASE databases, studies were selected for review based on predetermined inclusion and exclusion criteria.

Results

A total of 8 studies addressing the endpoint of pacemaker-dependency were identified, while 3 studies were found that addressed the recovery of atrioventricular (AV) conduction endpoint. There were 10 unique studies with a total of 780 patients. Mean follow-up ranged from 6–72 months. Pacemaker dependency rates ranged from 32%-91% and recovery of AV conduction ranged from 16%-42%. There was significant heterogeneity with respect to the definition of pacemaker dependency. Several patient and procedure-specific variables were found to be independently associated with pacemaker dependency, but these were not consistent between studies.

Conclusions

Pacemaker dependency following cardiac surgery occurs with variable frequency. While individual studies have identified various perioperative risk factors for pacemaker dependency and non-resolution of AV conduction disease, results have been inconsistent. Well-conducted studies using a uniform definition of pacemaker dependency might identify patients who will benefit most from early permanent pacemaker implantation after cardiac surgery.     

Assessing Social Networks in Patients with Psychotic Disorders: A Systematic Review of Instruments

Background

Evidence suggests that social networks of patients with psychotic disorders influence symptoms, quality of life and treatment outcomes. It is therefore important to assess social networks for which appropriate and preferably established instruments should be used.

Aims

To identify instruments assessing social networks in studies of patients with psychotic disorders and explore their properties.

Method

A systematic search of electronic databases was conducted to identify studies that used a measure of social networks in patients with psychotic disorders.

Results

Eight instruments were identified, all of which had been developed before 1991. They have been used in 65 studies (total N of patients = 8,522). They assess one or more aspects of social networks such as their size, structure, dimensionality and quality. Most instruments have various shortcomings, including questionable inter-rater and test-retest reliability.

Conclusions

The assessment of social networks in patients with psychotic disorders is characterized by a variety of approaches which may reflect the complexity of the construct. Further research on social networks in patients with psychotic disorders would benefit from advanced and more precise instruments using comparable definitions of and timescales for social networks across studies.     

The Effects of Vector Movement and Distribution in a Mathematical Model of Dengue Transmission

Background

Mathematical models have been used to study the dynamics of infectious disease outbreaks and predict the effectiveness of potential mass vaccination campaigns. However, models depend on simplifying assumptions to be tractable, and the consequences of making such assumptions need to be studied. Two assumptions usually incorporated by mathematical models of vector-borne disease transmission is homogeneous mixing among the hosts and vectors and homogeneous distribution of the vectors.

Methodology/Principal Findings

We explored the effects of mosquito movement and distribution in an individual-based model of dengue transmission in which humans and mosquitoes are explicitly represented in a spatial environment. We found that the limited flight range of the vector in the model greatly reduced its ability to transmit dengue among humans. A model that does not assume a limited flight range could yield similar attack rates when transmissibility of dengue was reduced by 39%. A model in which mosquitoes are distributed uniformly across locations behaves similarly to one in which the number of mosquitoes per location is drawn from an exponential distribution with a slightly higher mean number of mosquitoes per location. When the models with different assumptions were calibrated to have similar human infection attack rates, mass vaccination had nearly identical effects.

Conclusions/Significance

Small changes in assumptions in a mathematical model of dengue transmission can greatly change its behavior, but estimates of the effectiveness of mass dengue vaccination are robust to some simplifying assumptions typically made in mathematical models of vector-borne disease.     

Systematic Review and Meta-Analysis of the Relationship between EPHX1 Polymorphisms and Colorectal Cancer Risk

Background

Microsomal epoxide hydrolase (EPHX1) plays an important role in both the activation and detoxification of PAHs, which are carcinogens found in cooked meat and tobacco smoking. Polymorphisms at exons 3 and 4 of the EPHX1 gene have been reported to be associated with variations in EPHX1 activity. The aim of this study is to quantitatively summarize the relationship between EPHX1 polymorphisms and colorectal cancer (CRC) risk.

Methods

Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before June 2012. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for EPHX1 Tyr113His (rs1051740) and His139Arg (rs2234922) polymorphisms and CRC were calculated in a fixed-effects model and a random-effects model when appropriate.

Results

This meta-analysis yielded 14 case-control studies, which included 13 studies for Tyr113His (6395 cases and 7893 controls) and 13 studies for His139Arg polymorphisms (5375 cases and 6962 controls). Overall, the pooled results indicated that EPHX1 Tyr113His polymorphism was not associated with CRC risk; while the His139Arg polymorphism was significantly associated with decreased CRC risk (Arg/His vs. His/His, OR = 0.90, 95%CI = 0.83–0.98; dominant model, OR = 0.92, 95%CI = 0.85–0.99). The statistically significant association between EPHX1 His139Arg polymorphism and CRC was observed among Caucasians and population-based case-control studies. This association showed little heterogeneity and remained consistently strong when analyses were limited to studies in which genotype frequencies were in Hardy–Weinberg equilibrium, or limited to studies with matched controls. When cumulative meta-analyses of the two associations were conducted by studies’ publication time, the results were persistent and robust.

Conclusion

This meta-analysis suggests that EPHX1 Tyr113His polymorphism may be not associated with CRC development; while the EPHX1 His139Arg polymorphism may have a potential protective effect on CRC.     

Relationship between Sponsorship and Failure Rate of Dental Implants: A Systematic Approach

Background

The number of dental implant treatments increases annually. Dental implants are manufactured by competing companies. Systematic reviews and meta-analysis have shown a clear association between pharmaceutical industry funding of clinical trials and pro-industry results. So far, the impact of industry sponsorship on the outcomes and conclusions of dental implant clinical trials has never been explored. The aim of the present study was to examine financial sponsorship of dental implant trials, and to evaluate whether research funding sources may affect the annual failure rate.

Methods and Findings

A systematic approach was used to identify systematic reviews published between January 1993 and December 2008 that specifically deal with the length of survival of dental implants. Primary articles were extracted from these reviews. The failure rate of the dental implants included in the trials was calculated. Data on publication year, Impact Factor, prosthetic design, periodontal status reporting, number of dental implants included in the trials, methodological quality of the studies, presence of a statistical advisor, and financial sponsorship were extracted by two independent reviewers (kappa  = 0.90; CI_95% [0.77–1.00]). Univariate quasi-Poisson regression models and multivariate analysis were used to identify variables that were significantly associated with failure rates. Five systematic reviews were identified from which 41 analyzable trials were extracted. The mean annual failure rate estimate was 1.09%.(CI_95% [0.84–1.42]). The funding source was not reported in 63% of the trials (26/41). Sixty-six percent of the trials were considered as having a risk of bias (27/41). Given study age, both industry associated (OR = 0.21; CI_95% [0.12–0.38]) and unknown funding source trials (OR = 0.33; (CI_95% [0.21–0.51]) had a lower annual failure rates compared with non-industry associated trials. A conflict of interest statement was disclosed in 2 trials.

Conclusions

When controlling for other factors, the probability of annual failure for industry associated trials is significantly lower compared with non-industry associated trials. This bias may have significant implications on tooth extraction decision making, research on tooth preservation, and governmental health care policies.