Novel risk loci for rheumatoid arthritis in Han Chinese and congruence with risk variants in Europeans

Objective To investigate differences in genetic risk factors for rheumatoid arthritis (RA) in Han Chinese as compared with Europeans. Methods A genome-wide association study was conducted in China with 952 patients and 943 controls, and 32 variants were followed up in 2,132 patients and 2,553 controls. A transpopulation meta-analysis with results from a large European RA study was also performed to compare the genetic architecture across the 2 ethnic remote populations. Results Three non-major histocompatibility complex (non-MHC) loci were identified at the genome-wide significance level, the effect sizes of which were larger in anti-citrullinated protein antibody (ACPA)-positive patients than in ACPA-negative patients. These included 2 novel variants, rs12617656, located in an intron of DPP4 (odds ratio [OR] 1.56, P = 1.6 × 10 -21), and rs12379034, located in the coding region of CDK5RAP2 (OR 1.49, P = 1.1 × 10-16), as well as a variant at the known CCR6 locus, rs1854853 (OR 0.71, P = 6.5 × 10-15). The analysis of ACPA-positive patients versus ACPA-negative patients revealed that rs12617656 at the DPP4 locus showed a strong interaction effect with ACPAs (P = 5.3 × 10-18), and such an interaction was also observed for rs7748270 at the MHC locus (P = 5.9 × 10-8). The transpopulation meta-analysis showed genome-wide overlap and enrichment in association signals across the 2 populations, as confirmed by prediction analysis. Conclusion This study has expanded the list of alleles that confer risk of RA, provided new insight into the pathogenesis of RA, and added empirical evidence to the emerging polygenic nature of complex trait variation driven by common genetic variants. Copyright © 2014 by the American College of Rheumatology.

Serum levels of soluble receptor for advanced glycation end products and of S100 proteins are associated with inflammatory, autoantibody, and classical risk markers of joint and vascular damage in rheumatoid arthritis

Introduction: The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptor molecules. High concentrations of three of its putative proinflammatory ligands, S100A8/A9 complex (calprotectin), S100A8, and S100A12, are found in rheumatoid arthritis (RA) serum and synovial fluid. In contrast, soluble RAGE (sRAGE) may prevent proinflammatory effects by acting as a decoy. This study evaluated the serum levels of S100A9, S100A8, S100A12 and sRAGE in RA patients, to determine their relationship to inflammation and joint and vascular damage. Methods: Serum sRAGE, S100A9, S100A8 and S100A12 levels from 138 patients with established RA and 44 healthy controls were measured by ELISA and compared by unpaired t test. In RA patients, associations with disease activity and severity variables were analyzed by simple and multiple linear regressions. Results: Serum S100A9, S100A8 and S100A12 levels were correlated in RA patients. S100A9 levels were associated with body mass index (BMI), and with serum levels of S100A8 and S100A12. S100A8 levels were associated with serum levels of S100A9, presence of anti-citrullinated peptide antibodies (ACPA), and rheumatoid factor (RF). S100A12 levels were associated with presence of ACPA, history of diabetes, and serum S100A9 levels. sRAGE levels were negatively associated with serum levels of C-reactive protein (CRP) and high-density lipoprotein (HDL), history of vasculitis, and the presence of the RAGE 82Ser polymorphism. Conclusions: sRAGE and S100 proteins were associated not just with RA inflammation and autoantibody production, but also with classical vascular risk factors for end-organ damage. Consistent with its role as a RAGE decoy molecule, sRAGE had the opposite effects to S100 proteins in that S100 proteins were associated with autoantibodies and vascular risk, whereas sRAGE was associated with protection against joint and vascular damage. These data suggest that RAGE activity influences co-development of joint and vascular disease in rheumatoid arthritis patients.

Critical risk factors affecting the implementation of PPP waste-to-energy projects in China

Since 2003, Mainland China has been promoting the public–private partnership (PPP) procurement model in the waste-to-energy incineration sector to reduce the waste burying rate and improve environmental quality. Five critical risk factors (CRFs) that affect the construction and operation of waste-to-energy incineration projects have been identified from real-life risk events of 14 PPP waste-to-energy incineration plants through content analysis. These risk factors are insufficient waste supply, disposal of non-licensed waste, environmental risk, payment risk, and lack of supporting infrastructure. A recently completed PPP waste-to-energy incineration plant, the Shanghai Tianma project, was investigated to learn from the effective management of CRFs. First-hand data about the Shanghai Tianma project was collected, with a focus on project negotiation and concession agreement. Lessons learned about risk management were acquired. This paper presents a detailed study of the contractual structure, risk sharing scheme, risk response measures to CRFs, and project transfer of a PPP project. The study results will provide governments with management implications to prepare equitable concession agreements and benefit private investors by effectively mitigating and managing risks in future PPP waste-to-energy incineration projects.

Limited utility of exercise stress testing in the evaluation of suspected acute coronary syndrome in patients aged less than 40 years with intermediate risk features

Objective National guidelines for management of intermediate risk patients with suspected acute coronary syndrome, in whom AMI has been excluded, advocate provocative testing to final risk stratify these patients into low risk (negative testing) or high risk (positive testing suggestive of unstable angina). Adults less than 40 years have a low pretest probability of acute coronary syndrome. The utility of exercise stress testing in young adults with chest pain suspected of acute coronary syndrome who have National Heart Foundation intermediate risk features was evaluated Methods A retrospective analysis of exercise stress testing performed on patients less than 40 years was evaluated. Patients were enrolled on a chest pain pathway and had negative serial ECGs and cardiac biomarkers before exercise stress testing to rule-out acute coronary syndrome. Chart review was completed on patients with positive stress tests. Results The 3987 patients with suspected intermediate risk acute coronary syndrome underwent exercise stress testing. One thousand and twenty-seven (25.8%) were aged less than 40 years (age 33.3 ± 4.8 years). Four of these 1027 patients had a positive exercise stress test (0.4% incidence of positive exercise stress testing). Of those, three patients had subsequent non-invasive functional testing that yielded a negative result. One patient declined further investigations. Assuming this was a true positive exercise stress test, the incidence of true positive exercise stress testing would have been 0.097% (95% confidence interval: 0.079–0.115%) (one of 1027 patients). Conclusions Routine exercise stress testing has limited value in the risk stratification of adults less than 40 years with suspected intermediate risk of acute coronary syndrome

Spatiotemporal transmission dynamics of hemorrhagic fever with renal syndrome in China, 2005-2012

Background Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by many serotypes of hantaviruses. In China, HFRS has been recognized as a severe public health problem with 90% of the total reported cases in the world. This study describes the spatiotemporal dynamics of HFRS cases in China and identifies the regions, time, and populations at highest risk, which could help the planning and implementation of key preventative measures. Methods Data on all reported HFRS cases at the county level from January 2005 to December 2012 were collected from Chinese Center for Disease Control and Prevention. Geographic Information System-based spatiotemporal analyses including Local Indicators of Spatial Association and Kulldorff's space-time scan statistic were performed to detect local high-risk space-time clusters of HFRS in China. In addition, cases from high-risk and low-risk counties were compared to identify significant demographic differences. Results A total of 100,868 cases were reported during 2005–2012 in mainland China. There were significant variations in the spatiotemporal dynamics of HFRS. HFRS cases occurred most frequently in June, November, and December. There was a significant positive spatial autocorrelation of HFRS incidence during the study periods, with Moran's I values ranging from 0.46 to 0.56 (P<0.05). Several distinct HFRS cluster areas were identified, mainly concentrated in northeastern, central, and eastern of China. Compared with cases from low-risk areas, a higher proportion of cases were younger, non-farmer, and floating residents in high-risk counties. Conclusions This study identified significant space-time clusters of HFRS in China during 2005–2012 indicating that preventative strategies for HFRS should be particularly focused on the northeastern, central, and eastern of China to achieve the most cost-effective outcomes.

Prevalence and risk factors for foot and ankle musculoskeletal disorders experienced by nurses

Background Nurses are at high risk of musculoskeletal disorders (MSDs). Although the prevalence of MSDs of the lower back, upper limbs, neck and shoulders have been reported previously in nursing, few studies have evaluated MSDs of the foot and ankle. This study evaluated the prevalence of foot and ankle MSDs in nurses and their relation to individual and workplace risk factors. Methods A self-administered survey incorporating the Nordic Musculoskeletal Questionnaire (NMQ) was distributed, over a nine-week period, to all eligible nurses (n = 416) working in a paediatric hospital in Brisbane, Australia. The prevalence of MSDs for each of the NMQ body regions was determined. Bivariate and multivariable logistic regression analyses were conducted to examine the relationships between activity-limiting foot/ankle MSDs and risk factors related to the individual (age, body mass index, number of existing foot conditions, smoking history, general physical health [SF36 Physical Component Scale], footwear features) or the workplace (level of nursing position, work location, average hours worked, hours worked in previous week, time since last break from work). Results A 73% response rate was achieved with 304 nurses completing surveys, of whom 276 were females (91%). Mean age of the nurses was 37 years (±10), younger than the state average of 43 years. Foot/ankle MSDs were the most prevalent conditions experienced by nurses during the preceding seven days (43.8%, 95% CI 38.2-49.4%), the second most prevalent MSDs to impair physical activity (16.7%, 95% CI 13.0-21.3%), and the third most prevalent MSD, after lower-back and neck problems, during the preceding 12 months (55.3%, 95% CI 49.6-60.7%). Of the nurse and work characteristics investigated, obesity, poor general physical health, existing foot conditions and working in the intensive care unit emerged as statistically significant (p < 0.05) independent risk factors for activity-limiting foot/ankle MSDs. Conclusions Foot/ankle MSDs are common in paediatric hospital nurses and resulted in physical activity limitations in one out of every six nurses. We recommend targeted education programs regarding the prevention, self-management and treatment strategies for foot/ankle MSDs. Further research is needed into the impact of work location and extended shift durations on foot/ankle MSDs.

Mobile medical applications for melanoma risk assessment: False assurance or valuable tool?

With the smartphone revolution, consumer-focused mobile medical applications (apps) have flooded the market without restriction. We searched the market for commercially available apps on all mobile platforms that could provide automated risk analysis of the most serious skin cancer, melanoma. We tested 5 relevant apps against 15 images of previously excised skin lesions and compared the apps' risk grades to the known histopathologic diagnosis of the lesions. Two of the apps did not identify any of the melanomas. The remaining 3 apps obtained 80% sensitivity for melanoma risk identification; specificities for the 5 apps ranged from 20%-100%. Each app provided its own grading and recommendation scale and included a disclaimer recommending regular dermatologist evaluation regardless of the analysis outcome. The results indicate that autonomous lesion analysis is not yet ready for use as a triage tool. More concerning is the lack of restrictions and regulations for these applications.

Adjustment of apnea-hypopnea index with severity of obstruction events enhances detection of sleep apnea patients with the highest risk of severe health consequences

Introduction Presently, the severity of obstructive sleep apnea (OSA) is estimated based on the apnea-hypopnea index (AHI). Unfortunately, AHI does not provide information on the severity of individual obstruction events. Previously, the severity of individual obstruction events has been suggested to be related to the outcome of the disease. In this study, we incorporate this information into AHI and test whether this novel approach would aid in discriminating patients with the highest risk. We hypothesize that the introduced adjusted AHI parameter provides a valuable supplement to AHI in the diagnosis of the severity of OSA. Methods This hypothesis was tested by means of retrospective follow-up (mean ± sd follow-up time 198.2 ± 24.7 months) of 1,068 men originally referred to night polygraphy due to suspected OSA. After exclusion of the 264 patients using CPAP, the remaining 804 patients were divided into normal (AHI < 5) and OSA (AHI ≥ 5) categories based on conventional AHI and adjusted AHI. For a more detailed analysis, the patients were divided into normal, mild, moderate, and severe OSA categories based on conventional AHI and adjusted AHI. Subsequently, the mortality and cardiovascular morbidity in these groups were determined. Results Use of the severity of individual obstruction events for adjustment of AHI led to a significant rearrangement of patients between severity categories. Due to this rearrangement, the number of deceased patients diagnosed to have OSA was increased when adjusted AHI was used as the diagnostic index. Importantly, risk ratios of all-cause mortality and cardiovascular morbidity were higher in moderate and severe OSA groups formed based on the adjusted AHI parameter than in those formed based on conventional AHI. Conclusions The adjusted AHI parameter was found to give valuable supplementary information to AHI and to potentially improve the recognition of OSA patients with the highest risk of mortality or cardiovascular morbidity.

Association of a disintegrin and metalloprotease 33 (ADAM33) gene polymorphisms with the risk of COPD: An updated meta-analysis of 2,644 cases and 4,804 controls

A series of observational studies have been made to investigate the association of the ADAM33 gene polymorphisms with the risk of COPD, but their results were conflicting. Therefore, we performed an updated meta-analysis to quantitatively summarize the associations of ADAM33 gene polymorphisms with the risk of COPD. Thirteen case–control studies referring to nine SNPs were identified: V4 (rs2787094), T+1 (rs2280089), T2 (rs2280090), T1 (rs2280091), S2 (rs528557), S1 (rs3918396), Q−1 (rs612709), F+1 (rs511898) and ST+5 (rs597980). A dominant model (AA+Aa vs. aa), recessive model (AA vs. Aa+aa), additive model (AA vs. aa) and allelic model (A vs. a) were used to evaluate the association of ADAM33 polymorphism with the risk of COPD. The results indicated that significant associations were found for ADAM33 T1, T2, S1, Q−1, F+1 and ST+5 polymorphisms associated with the risk of COPD in different populations. However, no significant associations were found for V4, T+1 and S2 polymorphisms with the risk of COPD in all genetic models, even in the subgroup analysis by ethnicity. This meta-analysis provided evidence that the ADAM33 T1, T2, S1, Q−1, F+1 and ST+5 six locus polymorphisms association with the risk of COPD. Furthermore, T2, Q−1 and ST+5 indicated an association with the risk of COPD in the European populations, whereas T1, T2, S1, F+1 and Q−1 indicated an association with the risk of COPD in the Asian populations.

Occupational injury risk among Australian paramedics: An analysis of national data

Objective To identify the occupational risks for Australian paramedics, by describing the rate of injuries and fatalities and comparing those rates with other reports. Design and participants Retrospective descriptive study using data provided by Safe Work Australia for the period 2000–2010. The subjects were paramedics who had been injured in the course of their duties and for whom a claim had been made for workers compensation payments. Main outcome measures Rates of injury calculated from the data provided. Results The risk of serious injury among Australian paramedics was found to be more than seven times higher than the Australian national average. The fatality rate for paramedics was about six times higher than the national average. On average, every 2 years during the study period, one paramedic died and 30 were seriously injured in vehicle crashes. Ten Australian paramedics were seriously injured each year as a result of an assault. The injury rate for paramedics was more than two times higher than the rate for police officers. Conclusions The high rate of occupational injuries and fatalities among paramedics is a serious public health issue. The risk of injury in Australia is similar to that in the United States. While it may be anticipated that injury rates would be higher as a result of the nature of the work and environment of paramedics, further research is necessary to identify and validate the strategies required to minimise the rates of occupational injury for paramedics.

Increased risk of emergency hospital admissions for children with renal diseases during heatwaves in Brisbane, Australia

Background Heatwaves have a significant impact on population health including both morbidity and mortality. In this study we examined the association between heatwaves and emergency hospital admissions (EHAs) for renal diseases in children (aged 0–14 years) in Brisbane, Australia. Methods Daily data on EHAs for renal diseases in children and exposure to temperature and air pollution were obtained for Brisbane city from January 1, 1996 to December 31, 2005. A time-stratified case-crossover design was used to compare the risks for renal diseases between heatwave and non-heatwave periods. Results There were 1565 EHAs for renal diseases in children during the study period. Heatwaves exhibited a significant impact on EHAs for renal diseases in children after adjusting for confounding factors (odds ratio: 3.6; 95% confidence interval: 1.4–9.5). The risk estimates differed with lags and the use of different heatwave definitions. Conclusions There was a significant increase in EHAs for renal diseases in children during heatwaves in Brisbane, a subtropical city where people are well accustomed to warm weather. This finding may have significant implications for pediatric renal care, particularly in subtropical and tropical regions.

Current research: Neurocognitive risk assessment

The current research began from the starting point that what we are grappling with when we are dealing with violent extremists by and large is essentially ‘normal people’. What follows in this third major section of this research paper is the theoretical and conceptual search for making researchable the following question: ‘How do you assess someone who is normal?’

Missing in space: An evaluation of imputation methods for missing data in spatial analysis of risk factors for type II diabetes

Background Spatial analysis is increasingly important for identifying modifiable geographic risk factors for disease. However, spatial health data from surveys are often incomplete, ranging from missing data for only a few variables, to missing data for many variables. For spatial analyses of health outcomes, selection of an appropriate imputation method is critical in order to produce the most accurate inferences. Methods We present a cross-validation approach to select between three imputation methods for health survey data with correlated lifestyle covariates, using as a case study, type II diabetes mellitus (DM II) risk across 71 Queensland Local Government Areas (LGAs). We compare the accuracy of mean imputation to imputation using multivariate normal and conditional autoregressive prior distributions. Results Choice of imputation method depends upon the application and is not necessarily the most complex method. Mean imputation was selected as the most accurate method in this application. Conclusions Selecting an appropriate imputation method for health survey data, after accounting for spatial correlation and correlation between covariates, allows more complete analysis of geographic risk factors for disease with more confidence in the results to inform public policy decision-making.

The Queensland high risk foot form (QHRFF): Is it a reliable and valid clinical research tool for foot disease?

Background Foot disease complications, such as foot ulcers and infection, contribute to considerable morbidity and mortality. These complications are typically precipitated by “high-risk factors”, such as peripheral neuropathy and peripheral arterial disease. High-risk factors are more prevalent in specific “at risk” populations such as diabetes, kidney disease and cardiovascular disease. To the best of the authors’ knowledge a tool capturing multiple high-risk factors and foot disease complications in multiple at risk populations has yet to be tested. This study aimed to develop and test the validity and reliability of a Queensland High Risk Foot Form (QHRFF) tool. Methods The study was conducted in two phases. Phase one developed a QHRFF using an existing diabetes foot disease tool, literature searches, stakeholder groups and expert panel. Phase two tested the QHRFF for validity and reliability. Four clinicians, representing different levels of expertise, were recruited to test validity and reliability. Three cohorts of patients were recruited; one tested criterion measure reliability (n = 32), another tested criterion validity and inter-rater reliability (n = 43), and another tested intra-rater reliability (n = 19). Validity was determined using sensitivity, specificity and positive predictive values (PPV). Reliability was determined using Kappa, weighted Kappa and intra-class correlation (ICC) statistics. Results A QHRFF tool containing 46 items across seven domains was developed. Criterion measure reliability of at least moderate categories of agreement (Kappa > 0.4; ICC > 0.75) was seen in 91% (29 of 32) tested items. Criterion validity of at least moderate categories (PPV > 0.7) was seen in 83% (60 of 72) tested items. Inter- and intra-rater reliability of at least moderate categories (Kappa > 0.4; ICC > 0.75) was seen in 88% (84 of 96) and 87% (20 of 23) tested items respectively. Conclusions The QHRFF had acceptable validity and reliability across the majority of items; particularly items identifying relevant co-morbidities, high-risk factors and foot disease complications. Recommendations have been made to improve or remove identified weaker items for future QHRFF versions. Overall, the QHRFF possesses suitable practicality, validity and reliability to assess and capture relevant foot disease items across multiple at risk populations.

Exposure risk assessment and evaluation of the best management practice for controlling pesticide runoff from paddy fields. Part 2: Model simulation for the herbicide pretilachlor

BACKGROUND: Monitoring studies revealed high concentrations of pesticides in the drainage canal of paddy fields. It is important to have a way to predict these concentrations in different management scenarios as an assessment tool. A simulation model for predicting the pesticide concentration in a paddy block (PCPF-B) was evaluated and then used to assess the effect of water management practices for controlling pesticide runoff from paddy fields. RESULTS: The PCPF-B model achieved an acceptable performance. The model was applied to a constrained probabilistic approach using the Monte Carlo technique to evaluate the best management practices for reducing runoff of pretilachlor into the canal. The probabilistic model predictions using actual data of pesticide use and hydrological data in the canal showed that the water holding period (WHP) and the excess water storage depth (EWSD) effectively reduced the loss and concentration of pretilachlor from paddy fields to the drainage canal. The WHP also reduced the timespan of pesticide exposure in the drainage canal. CONCLUSIONS: It is recommended that: (1) the WHP be applied for as long as possible, but for at least 7 days, depending on the pesticide and field conditions; (2) an EWSD greater than 2 cm be maintained to store substantial rainfall in order to prevent paddy runoff, especially during the WHP.