Risk factors for physical disability in patients with leprosy disease in Yunnan,China: Evidence from a retrospective observational study

BackgroundLeprosy is potentially debilitating. The risk factors related to physical disabilities associated with leprosy disease in Yunnan, China was not clear.Methodology/Principal findingsWe studied 10644 newly detected leprosy patients from Yunnan, China, from 1990 to 2019. Factors associated with Grade 1 (G1D) and Grade 2 (G2D) physical disabilities or overall physical disabilities (combined G1D and G2D) associated with leprosy were analyzed using multinomial and ordinal logistic regression analyses. The following factors were associated with the development of physical disability in these patients with leprosy: delayed diagnosis [odds ratio (OR): 5.652, 4.399, and 2.275; 95% confidence intervals (CIs): 4.516–7.073, 3.714–5.212, and 2.063–2.509; for ≥ 10, 5–10 y, and 2–5 years, respectively], nerve damage (OR: 3.474 and 2.428; 95% CI: 2.843–4.244, and 1.959–3.008; for 2 and 1 damaged nerves, respectively), WHO classification of PB (OR: 1.759; 95% CI: 1.341–2.307), Ridley-Jopling classification (OR: 1.479, 1.438, 1.522 and 1.239; 95% CI: 1.052–2.079, 1.075–1.923, 1.261–1.838, and 1.072–1.431; for TT, BT, BB, and BL when compared with LL, respectively), advanced age (OR: 1.472 and 2.053; 95% CI: 1.106–1.960 and 1.498–2.814; for 15–59 and over 60 years old, respectively), zero skin lesions (OR: 1.916; 95% CI: 1.522–2.413), leprosy reaction (OR: 1.528; 95% CI: 1.195–1.952), rural occupation (OR: 1.364; 95% CI: 1.128–1.650), Han ethnicity (OR: 1.268; 95% CI: 1.159–1.386), and male sex (OR: 1.128; 95% CI: 1.024–1.243).ConclusionsDelayed diagnosis, nerve damage, no skin lesions, WHO and Ridley-Jopling classifications, leprosy reactions, advanced age, rural occupation, Han ethnicity, and male sex were associated with disability in leprosy patients. Identifying risk factors could help to prevent physical disability.     

Fine needle aspiration cytology of leprous neuritis

OBJECTIVE: To document the cytomorphologic features of leprous neuritis and their correlation with bacterial density. STUDY DESIGN: A partly retrospective, partly prospective study of the fine needle aspiration cytology of enlarged nerves in leprosy. Cytomorphologic features of nerve aspirates from 28 patients were studied. May-Grünwald-Geimsa and Ziehl-Neelsen staining methods were employed. RESULTS: Five cytomorphologic patterns were observed in smears of nerve aspirates in 19 group I patients with concurrent skin and nerve lesions: (1) inflammation composed of epithelioid cell granulomas (5), bacillary index (BI) = 0; (2) epithelioid cell granulomas with necrosis (5), BI = 0-1+; (3) acellular necrosis (5), BI = 0-4+; (4) macrophage granuloma (3), BI = 5-6+; and (5) granulation tissue (1), BI = 1+. In 9 group II patients with pure neuritic leprosy, 3 patterns were seen: (1) epithelioid cell granulomas (5), BI 0-6+; (2) epithelioid granulomas with necrosis (1), BI = 0; and (3) acellular necrosis (3), BI = 0-6+. CONCLUSION: The entire spectrum of leprosy is seen in nerve aspirates. Necrosis is often a prominent feature. Recognition of the range of cytomorphologic patterns and their correlation with BI contribute to accurate calibration of the disease in nerves, resulting in appropriate choice of treatment.     

Oocyst ingestion as an important transmission route of Toxoplasma gondii in Brazilian urban children

Toxoplasmosis is a cosmopolitan protozoan infection. Data regarding risk factors for the post-natal acquisition of Toxoplasma gondii infection in childhood are limited. We conducted a serological survey for T. gondii IgG antibodies and associated risk factors in 1,217 children 4-11-yr-old from Salvador, Brazil, using a commercial ELISA kit; antibodies were found in 17.5% of the children. Age (OR = 2.18; 95% CI: 1.50-3.17) and maternal schooling level (OR = 0.62; 95% CI: 0.42-0.92) were negatively associated with infection. A greater number of siblings (OR = 1.53; 95% CI: 1.12-2.09), cat at home (OR = 1.54; 95% CI: 1.06-2.24), house with non-treated piped water (OR = 2.54; 95% CI: 1.22-5.31), and the absence of a flush toilet at home (OR = 1.45; 95% CI: 1.04-2.01) were positively associated with T. gondii infection. Our data suggest that low socioeconomic levels and poor hygiene habits are important factors in favoring T. gondii infection.     

Variables associated with squamous intraepithelial lesions among women with a cytologic diagnosis of atypical squamous cells of undetermined significance.

OBJECTIVE: To identify factors among women with atypical squamous cells of undetermined significance (ASCUS) cytologic diagnosis that are associated with either low grade squamous intraepithelial lesions (LSILs) or high grade squamous intraepithelial lesions (HSILs). STUDY DESIGN: From January 1992 to June 1995, 1,660 women with a diagnosis of ASCUS were followed until the next follow-up appointment after the ASCUS diagnosis. Logistic regression analysis with either LSIL or HSIL at follow-up examination as a dependent variable was done with the following independent variables: patient age, method of follow-up, follow-up time, type of health care coverage and household income. RESULTS: In multivariate analyses, there was a 2.7-fold increase in the odds of LSIL (OR = 2.7, 95% CI = 1.3-5.8) for young women (< or = 25 years), a 2-fold decrease in the odds of LSIL (OR = .5, 95% CI .3-.9) for long time to follow-up (> 18 weeks after ASCUS diagnosis) and an 7.8-fold increase in the odds of LSIL (OR = 7.8, 95% CI = 5.1-11.9) for follow-up by colposcopic biopsy. For the odds of HSIL, there was a 6.8-fold increase (95% CI = 3.2-14.5) for follow-up by colposcopic biopsy as compared to Pap smears and a 3-fold decrease in the odds of HSIL (OR = 3, 95% CI = .1-.7) for high-income women (> $34,857). CONCLUSION: Our findings suggest that among ASCUS patients, younger women and those with shorter follow-up time are more likely to be diagnosed with LSIL. Women with a high income showed a protective association for HSIL. Colposcopic biopsy identified more LSIL and HSIL as compared to repeat Pap smear.     

The Association between NQO1 Pro187Ser Polymorphism and Bladder Cancer Susceptibility: A Meta-Analysis of 15 Studies

Background

NAD(P)H:quinone oxidoreductase 1 (NQO1), an obligate two-electron reductase, plays an important role in reducing reactive quinones to less reactive and less toxic hydroquinones. Genetic variations in NQO1 gene that impede its enzyme function may be considered as putative risk factor for cancer. Numerous studies have been performed to investigate the association between NQO1 Pro187Ser polymorphism and bladder cancer risk; nevertheless, the results remain controversial.

Methods

We indentified eligible publications from PubMed, Embase and CBM databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to access the strength of the associations. False-positive report probability (FPRP) analysis was also performed for all statistically significant findings.

Results

We collected a total of 15 studies including 4298 cases and 4275 controls in the final meta-analysis. Overall, the NQO1 187Ser carriers were associated with an increased bladder cancer risk (homozygous: OR = 1.43, 95% CI = 1.08-1.90; recessive: OR = 1.33, 95% CI = 1.03-1.72; dominant: OR = 1.19, 95% CI = 1.04-1.37, and allele comparing: OR = 1.18, 95% CI = 1.06-1.33). Stratification analyses showed a statistically significant association among Asians (homozygous: OR = 1.82, 95% CI = 1.39-2.38; recessive: OR = 1.52, 95% CI = 1.20-1.93, dominant: OR = 1.40, 95% CI = 1.05-1.88, and allele comparing: OR = 1.35, 95% CI = 1.15-1.58), never smokers (homozygous: OR = 2.30, 95% CI = 1.14-4.65; heterozygous: OR = 2.26, 95% CI = 1.43-3.56; dominant model: OR = 1.59, 95% CI = 1.14-2.21, and allele comparing: OR = 1.72, 95% CI = 1.27-2.33), hospital-based studies (homozygous: OR = 1.46, 95% CI = 1.09-1.94; recessive: OR = 1.32, 95% CI = 1.02-1.69; dominant: OR = 1.28, 95% CI = 1.05-1.56, and allele comparing: OR = 1.24, 95% CI = 1.07-1.43), studies with genotyping performed by PCR-RFLP under all genetic models, and studies with minor allele frequency >0.30 (homozygous: OR = 1.69, 95% CI = 1.25-2.27; recessive: OR = 1.46, 95% CI = 1.10-1.95, and allele comparing: OR = 1.25, 95% CI = 1.04-1.51), respectively.

Conclusions

Despite some limitations, our meta-analysis provides sufficient evidence that NQO1 Pro187Ser polymorphism may contribute to bladder cancer risk. These findings need further validation in well-designed prospective studies with larger sample size and different ethnicities, especially for Asians.     

Interrupted aortic arch: an epidemiologic study

BACKGROUND: Interruption of the aortic arch (IAA) is a rare but severe anomaly associated with major intracardiac defects and with multisystem noncardiac malformations, recently linked to chromosome deletion of 22q11.2. METHODS: The Baltimore-Washington Infant Study (1981-1989), a population-based epidemiologic study of cardiovascular malformations, evaluated 53 infants with IAA in comparison with 3,572 controls. Risk factors for the anatomic subtypes were evaluated in 14 cases of IAA type A and 32 cases of IAA type B, but no molecular genetic tests were available. The distribution of associated cardiac defects was similar for both types. RESULTS: DiGeorge syndrome (DGS) occurred more frequently in IAA type B. Case-control comparisons demonstrated that infants in both groups were growth retarded at birth. A family history of noncardiac defects occurred only in IAA type B cases and included relatives with cleft lip and/or cleft palate. Candidate risk factors were associated only in type B cases and differed for those with (n = 10) and for those without (n = 19) DGS: a family history of noncardiac defects (odds ratio [OR] = 7.2, 95% confidence interval [CI] = 1.5-39.2) and maternal use of aspirin during the critical period (OR = 4.8, 95% CI = 1.3-25.4) occurred with DGS, while previous stillbirth (OR = 9.4, 95% CI = 1.3-53.1), bleeding during pregnancy (OR = 3.7, 95% CI = 1.4-11.4), and maternal exposure to arts/crafts paints (OR = 4.8, 95% CI = 1.3-17.4) were associated in those without DGS. CONCLUSIONS: These findings confirm the heterogeneity of IAA and of the type B subtype. Risk factors specific for cases with DGS may open a window to further investigations of the etiology of IAA and of the associated molecular genetic abnormalities.     

Examining ERBB2 as a candidate gene for susceptibility to leprosy (Hansen’s disease) in Brazil

Leprosy remains prevalent in Brazil. ErbB2 is a receptor for leprosy bacilli entering Schwann cells, which mediates Mycobacterium leprae-induced demyelination and the ERBB2 gene lies within a leprosy susceptibility locus on chromosome 17q11-q21. To determine whether polymorphisms at the ERBB2 locus contribute to this linkage peak, three haplotype tagging single nucleotide polymorphisms (tag-SNPs) (rs2517956, rs2952156, rs1058808) were genotyped in 72 families (208 cases; 372 individuals) from the state of Pará (PA). All three tag-SNPs were associated with leprosy per se [best SNP rs2517959 odds ratio (OR) = 2.22; 95% confidence interval (CI) 1.37-3.59; p = 0.001]. Lepromatous (LL) (OR = 3.25; 95% CI 1.37-7.70; p = 0.007) and tuberculoid (TT) (OR = 1.79; 95% CI 1.04-3.05; p = 0.034) leprosy both contributed to the association, which is consistent with the previous linkage to chromosome 17q11-q21 in the population from PA and supports the functional role of ErbB2 in disease pathogenesis. To attempt to replicate these findings, six SNPs (rs2517955, rs2517956, rs1810132, rs2952156, rs1801200, rs1058808) were genotyped in a population-based sample of 570 leprosy cases and 370 controls from the state of Rio Grande do Norte (RN) and the results were analysed using logistic regression analysis. However, none of the associations were replicated in the RN sample, whether analysed for leprosy per se, LL leprosy, TT leprosy, erythema nodosum leprosum or reversal reaction conditions. The role of polymorphisms at ERBB2 in controlling susceptibility to leprosy in Brazil therefore remains unclear.     

Effect of neosporosis on productive and reproductive performance of dairy cattle in Costa Rica

A cross-sectional study was conducted to assess the effect of neosporosis on productive and reproductive parameters in dairy cows. Cows (n=2743) from 94 farms located in the most important dairy areas in Costa Rica were used in the study. The size of the herds ranged from 32 to 379 females (mean=110, median=125). An indirect ELISA was used to determine the serostatus of the cows towards Neospora caninum. The effect of neosporosis on milk production was analysed by a mixed linear model. In addition, the effects on calving interval (days) and calving to conception interval (days) were analysed by survival analysis. The risk of abortion in relation to N. caninum serostatus was assessed by logistic regression, with herd as a random effect. Overall, 1185 of 2743 cows (43.3%) were seropositive for Neospora. Eighty-nine of 94 (94.7%) farms were classified as Neospora-seropositive. It was estimated that cows seronegative to Neospora produced an additional 84.7L of milk (P=0.6). Serostatus did not have a significant effect on the length of the calving interval in the Cox proportional hazard survival analysis (Hazard ratio=1.2, 95% CI: 0.9, 1.4). The logistic regression model had a weak positive association between serostatus and abortion (OR 1.7, 95% CI: 0.8, 3.9), but did not show a strong association between serostatus and the number of services per conception (OR=0.95, 95% CI: 0.7, 1.3). In conclusion, there were no significant effects of Neospora serostatus on production and reproductive performance in this study.     

Placental Cadmium Levels Are Associated with Increased Preeclampsia Risk

Environmental exposure to heavy metals is a potentially modifiable risk factor for preeclampsia (PE). Toxicologically, there are known interactions between the toxic metal cadmium (Cd) and essential metals such as selenium (Se) and zinc (Zn), as these metals can protect against the toxicity of Cd. As they relate to preeclampsia, the interaction between Cd and these essential metals is unknown. The aims of the present study were to measure placental levels of Cd, Se, and Zn in a cohort of 172 pregnant women from across the southeast US and to examine associations of metals levels with the odds of PE in a nested case-control design. Logistic regressions were performed to assess odds ratios (OR) for PE with exposure to Cd controlling for confounders, as well as interactive models with Se or Zn. The mean placental Cd level was 3.6 ng/g, ranging from 0.52 to 14.5 ng/g. There was an increased odds ratio for PE in relationship to placental levels of Cd (OR = 1.5; 95% CI: 1.1–2.2). The Cd-associated OR for PE increased when analyzed in relationship to lower placental Se levels (OR = 2.0; 95% CI: 1.1–3.5) and decreased with higher placental Se levels (OR = 0.98; 95% CI: 0.5–1.9). Similarly, under conditions of lower placental Zn, the Cd-associated OR for PE was elevated (OR = 1.8; 95% CI: 0.8–3.9), whereas with higher placental Zn it was reduced (OR = 1.3; 95% CI: 0.8–2.0). Data from this pilot study suggest that essential metals may play an important role in reducing the odds of Cd-associated preeclampsia and that replication in a larger cohort is warranted.     

Maternal age and non‐chromosomal birth defects,Atlanta—1968–2000: Teenager or thirty‐something,who is at risk?

OBJECTIVE: This investigation explored the association between maternal age and non-chromosomal birth defects to assess any increased risk associated with maternal age. METHODS: Birth defect cases were ascertained by the Metropolitan Atlanta Congenital Defects Program (MACDP), denominator information was obtained using birth certificate data. Infants with any chromosomal diagnosis were excluded. Effect estimates were calculated using 5-year maternal age categories with 25-29 years as the referent. Multiple logistic regression was used to adjust for maternal race, parity, infant sex, and birth year. RESULTS: A total of 1,050,616 singleton infants, born after > or = 20 weeks gestation in the five counties of metropolitan Atlanta from 1968 through 2000 who did not have a chromosomal abnormality and whose mother was 14 to 40 years old, were included in the analyses, 32,816 of them were identified with birth defects by the MACDP. Young maternal age (14-19 years) was associated with anencephaly (OR = 1.81, 95% CI = 1.30-2.52), hydrocephaly without neural tube defect (OR = 1.56, 95% CI = 1.23-1.96), all ear defects (OR = 1.28, 95% CI = 1.10-1.49), cleft lip (OR = 1.88, 95% CI = 1.30-2.73), female genital defects (OR = 1.57, 95% CI = 1.12-2.19), hydronephrosis (OR = 1.42, 95% CI = 1.11-1.82), polydactyly (OR = 1.29, 95% CI = 1.09-1.52), omphalocele (OR = 2.08, 95% CI = 1.39-3.12), and gastroschisis (OR = 7.18, 95% CI = 4.39-11.75). Advanced maternal age (35-40 years) was associated with all heart defects (OR = 1.12, 95% CI = 1.03-1.22), tricuspid atresia (OR = 1.24, 95% CI = 1.02-1.50), right outflow tract defects (OR = 1.28, 95% CI = 1.10-1.49), hypospadias 2nd degree or higher (OR = 1.85, 95% CI = 1.33-2.58), male genital defects excluding hypospadias (OR = 1.25, 95% CI = 1.08-1.45) and craniosynostosis (OR = 1.65, 95% CI = 1.18-2.30). CONCLUSIONS: Young and advanced maternal ages are associated with different types of birth defects. Underlying causes for these associations are not clear.     

Human TLR1 deficiency is associated with impaired mycobacterial signaling and protection from leprosy reversal reaction

Toll-like receptors (TLRs) are important regulators of the innate immune response to pathogens, including Mycobacterium leprae, which is recognized by TLR1/2 heterodimers. We previously identified a transmembrane domain polymorphism, TLR1_T1805G, that encodes an isoleucine to serine substitution and is associated with impaired signaling. We hypothesized that this TLR1 SNP regulates the innate immune response and susceptibility to leprosy. In HEK293 cells transfected with the 1805T or 1805G variant and stimulated with extracts of M. leprae, NF-kappaB activity was impaired in cells with the 1805G polymorphism. We next stimulated PBMCs from individuals with different genotypes for this SNP and found that 1805GG individuals had significantly reduced cytokine responses to both whole irradiated M. leprae and cell wall extracts. To investigate whether TLR1 variation is associated with clinical presentations of leprosy or leprosy immune reactions, we examined 933 Nepalese leprosy patients, including 238 with reversal reaction (RR), an immune reaction characterized by a Th1 T cell cytokine response. We found that the 1805G allele was associated with protection from RR with an odds ratio (OR) of 0.51 (95% CI 0.29-0.87, p = 0.01). Individuals with 1805 genotypes GG or TG also had a reduced risk of RR in comparison to genotype TT with an OR of 0.55 (95% CI 0.31-0.97, p = 0.04). To our knowledge, this is the first association of TLR1 with a Th1-mediated immune response. Our findings suggest that TLR1 deficiency influences adaptive immunity during leprosy infection to affect clinical manifestations such as nerve damage and disability.     

miR-196a2 C allele is a low-penetrant risk factor for cancer development

Published data on the association between miR-196a2 T/C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 21 studies including 10,441 cases and 12,353 controls were involved in this meta-analysis. Overall, significantly elevated cancer risk was associated with miR-196a2 C allele when all studies were pooled into the meta-analysis (TC vs. TT: OR=1.23, 95% CI=1.11-1.36; CC vs. TT: OR=1.30, 95% CI=1.14-1.48; dominant model: OR=1.25, 95% CI=1.13-1.38). In the subgroup analysis by ethnicity, significantly increased risks were found in Asains (TC vs. TT: OR=1.24, 95% CI=1.10-1.40; CC vs. TT: OR=1.31, 95% CI=1.13-1.52; dominant model: OR=1.26, 95% CI=1.12-1.41) but with bordline statistical significance in Caucasians (TC vs. TT: OR=1.15, 95% CI=1.00-1.31). In the subgroup analysis by cancer type, statistically significantly increased risks were found for breast cancer (TC vs. TT: OR=1.15, 95% CI=1.01-1.31; CC vs. TT: OR=1.30, 95% CI=1.01-1.68; dominant model: OR=1.22, 95% CI=1.00-1.50; and recessive model: OR=1.11, 95% CI=1.01-1.23) and lung cancer (CC vs. TT: OR=1.30, 95% CI=1.10-1.54; and recessive model: OR=1.18, 95% CI=1.02-1.36). When stratified by study design, statistically significantly elevated risk was found in hospital-based studies (TC vs. TT: OR=1.30, 95% CI=1.13-1.49; CC vs. TT: OR=1.37, 95% CI=1.14-1.66; dominant model: OR=1.32, 95% CI=1.15-1.53) and population-based studies (CC vs. TT: OR=1.19, 95% CI=1.06-1.35; dominant model: OR=1.13, 95% CI=1.01-1.25). Despite some limitations, this meta-analysis suggests that the miR-196a2 C allele is a low-penetrant risk factor for cancer development.     

Risk factors for posttraumatic stress disorder following an industrial disaster in a residential area: A note on the origin of observed gender differences

Background: Studies indicate that differences in trait anxiety and trauma-related distress may mediate the gender differences observed in posttraumatic stress disorder (PTSD).Objective: We examined the contributions of gender, trait anxiety, and trauma-related distress to the development of PTSD after an industrial disaster.Methods: Three months after a massive explosion in a fireworks factory in Kolding, Denmark, in November 2004, residents in the surrounding area were asked to complete the Harvard Trauma Questionnaire, the General Health Questionnaire, and a questionaire designed for the present study. Using multivariable logistic regression with PTSD as the dependent variable, we examined 4 explanatory models: (1) gender; (2) gender and trait anxiety; (3) gender, trait anxiety, and perceived danger; and (4) gender, trait anxiety, perceived danger, perceived hostility, feeling isolated, depersonalization, and behavioral self-blame.Results: Fifty-one percent (N = 516; 265 women and 251 men) of the area residents participated in the study. The female-to-male ratio of PTSD was 2.4:1. Women experienced significantly more trait anxiety (P < 0.001), feelings of isolation (P < 0.005), and behavioral self-blame (P = 0.018), and less perceived danger (P = 0.034) than did men. In multivariable logistic regression analysis, gender alone predicted 3.7% of the variance in PTSD status (odds ratio [OR] = 2.40; 95% CI, 1.35-4.27; P < 0.005); however, in all other models, gender was not significant. The final model comprised trait anxiety (OR = 1.20; 95% CI, 1.11-1.30; P < 0.001), perceived danger (OR = 4.62; 95% Cl, 2.24-9.50; P < 0.001), perceived hostility (OR = 5.21; 95% CI, 1.93-14.09; P < 0.001), feeling isolated (OR = 3.34; 95% CI, 1.55-7.16; P < 0.002), depersonalization (OR = 2.49; 95% CI, 1.42-4.37; P < 0.001), and behavioral self-blame (OR = 0.46; 95% CI, 0.24-0.86; P = 0.015), explaining 48.9% of the variance in PTSD severity.Conclusion: This cross-sectional study found that gender was no longer associated with PTSD status when trait anxiety, perceived danger and hostility, feeling isolated, depersonalization, and behavioral selfblame were taken into account.     

Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms in cancer: a meta-analysis

Toll-like receptor 4 (TLR4) is critical in the recognition of Gram-negative bacteria serving as a key immune system effector. Recently, a number of case-control studies were conducted to investigate the association between TLR4 gene polymorphism and cancer risk, especially Asp299Gly and Thr399Ile polymorphisms. However, published data were still conflicting. In this paper, we summarized 9463 cancer cases and 10,825 controls from 22 studies and attempted to assess the susceptibility of TLR4 gene polymorphism to cancers by a synthetical meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. Our results suggested that Asp299Gly represented a risk factor on cancers in digestive system (G allele versus A allele, OR=1.64, 95% CI: 1.02-2.64; GA+GG versus AA, OR=1.64, 95% CI: 1.00-2.71) but tend to have a protective effect on prostate cancer (GG versus AA, OR=0.37, 95% CI: 0.14-0.98; GG versus GA+AA, OR=0.37, 95% CI: 0.14-0.98). Thr399Ile polymorphism was significantly associated with an elevated cancer risk in overall analysis (T allele versus C allele, OR=1.72, 95% CI: 1.27-2.33; TC versus CC, OR=1.63, 95% CI: 1.18-2.26; TT+TC versus CC, OR=1.70, 95% CI: 1.24-2.34) and especially in gastrointestinal subgroup (T allele versus C allele, OR=2.01, 95% CI: 1.40-2.89; TC versus CC, OR=1.86, 95% CI: 1.26-2.74; TT+TC versus CC, OR=1.97, 95% CI: 1.35-2.88). Further prospective researches with larger numbers of worldwide participants are warranted to draw comprehensive and true conclusions.     

Mutation in the ITPA gene predicts intolerance to azathioprine

Inosine triphosphate pyrophosphatase (ITPase) deficiency occurs with polymorphic frequencies in Caucasians and results in the benign accumulation of the inosine nucleotide ITP. In 62 patients treated with azathioprine for inflammatory bowel disease, the ITPA 94C>A deficiency-associated allele was significantly associated with adverse drug reactions (OR 4.2, 95% CI 1.6-11.5, p = 0.0034). Significant associations were found for flu-like symptoms (OR 4.7, 95% CI 1.2-18.1, p = 0.0308), rash (OR 10.3, 95% CI 4.7-62.9, p = 0.0213) and pancreatitis (OR 6.2, CI 1.1-32.6, p = 0.0485). Polymorphism in the ITPA gene thus predicts AZA intolerance. Alternative immunosuppressive drugs, particularly 6-thioguanine, should be considered for AZA-intolerant patients with ITPase deficiency.     

Association between CTLA-4 exon-1 +49A/G polymorphism and systemic lupus erythematosus: an updated analysis

The results of studies on association between CTLA-4 exon-1 +49A/G (rs231775) polymorphism and susceptibility to systemic lupus erythematosus are controversial. To derive a more precise estimation of the relationship between the CTLA-4 exon-1 +49A/G polymorphism and SLE, a meta-analysis of 18 published case-control studies was performed. 18 studies meeting our inclusion criteria comprising 1806 SLE cases and 2,490 controls were included. The effect summary odds ratio (OR) and 95 % confidence intervals were obtained. Publication bias was tested by funnel plot, Egger's test and heterogeneity was assessed. The combined results showed that there were significant differences in genotype distribution between SLE cases and control on the basis of all studies, GG versus AA (OR = 1.53, 95 % CI: 1.12-2.10), GG versus GA/AA (OR = 1.30, 95 % CI: 1.04-1.64), GG versus GA (OR = 1.27, 95 % CI: 1.03-1.55). When stratifying for the race, the phenomenon was found that SLE cases had a significantly higher frequency of GG/GA versus AA (OR = 1.58, 95 % CI: 1.23-2.03), GG versus AA (OR = 1.89, 95 % CI: 1.23-2.91), GG versus GA/AA(OR = 1.39, 95 % CI: 1.03-1.89), GA versus AA(OR = 1.38, 95 % CI: 1.06-1.80) and G versus A(OR = 1.34, 95 % CI: 1.07-1.67) than control in Asians. Our meta-analysis results suggest that CTLA-4 exon-1 +49A/G polymorphism might be a risk factor for SLE susceptibility, at least in Asians. The large sample and well-designed study based on different ethnic groups should be considered in future associated studies to clarify the association of CTLA-4 exon-1 +49A/G polymorphism with SLE susceptibility.     

Factors Associated with Fatal Occupational Accidents among Mexican Workers: A National Analysis

Objective

To identify the factors associated with fatal occupational injuries in Mexico in 2012 among workers affiliated with the Mexican Social Security Institute.

Methods

Analysis of secondary data using information from the National Occupational Risk Information System, with the consequence of the occupational injury (fatal versus non-fatal) as the response variable. The analysis included 406,222 non-fatal and 1,140 fatal injuries from 2012. The factors associated with the lethality of the injury were identified using a logistic regression model with the Firth approach.

Results

Being male (OR=5.86; CI95%: 4.22-8.14), age (OR=1.04; CI95%: 1.03-1.06), employed in the position for 1 to 10 years (versus less than 1 year) (OR=1.37; CI95%: 1.15-1.63), working as a facilities or machine operator or assembler (OR: 3.28; CI95%: 2.12- 5.07) and being a worker without qualifications (OR=1.96; CI95%: 1.18-3.24) (versus an office worker) were associated with fatality in the event of an injury. Additionally, companies classified as maximum risk (OR=1.90; CI 95%: 1.38-2.62), workplace conditions (OR=7.15; CI95%: 3.63-14.10) and factors related to the work environment (OR=9.18; CI95%:4.36-19.33) were identified as risk factors for fatality in the event of an occupational injury.

Conclusions

Fatality in the event of an occupational injury is associated with factors related to sociodemographics (age, sex and occupation), the work environment and workplace conditions. Worker protection policies should be created for groups with a higher risk of fatal occupational injuries in Mexico.     

Advanced age, altered level of consciousness and a new diagnosis of diabetes are independently associated with hypernatreamia in hyperglycaemic crisis

Background

There is limited literature on hypernatreamia in the setting of hyperglycaemic crisis. This is despite the fact that the presence of hypernatreamia may impact on the classification of hyperglycaemic crisis and its management particularly with regards to the nature of fluid therapy. We determined the prevalence of hypernatreamia and its associated factors at presentation for hyperglycaemic crisis.

Methods

This was a retrospective review of data for hyperglycaemic crisis admissions in Nelson Mandela Academic Hospital, Mthatha, South Africa. The prevalence of hypernatreamia (uncorrected Serum Sodium at presentation >145 mmol/L) was determined. Hyperosmolality was defined by calculated effective osmolality >320 mosmols/Kg. Multivariate logistic regression was undertaken using variables that were statistically significant in univariate analysis to ascertain those that were independently associated (Odds Ratio (OR) with 95% Confidence Interval (CI)) with hypernatreamia.

Results

The prevalence of hypernatreamia in our admissions for hyperglycaemic crisis was 11.7% (n = 32/273 including 171 females and 102 males). All admissions with hypernatreamia met the criteria for hyperosmolality. Age ≥ 60 years (OR = 3.9 95% CI 1.3-12.3; P = 0.018), Altered level of consciousness (OR = 8.8 95% CI 2.3-32.8; P < 0.001) and a new diagnosis of diabetes (OR = 3.7 95%CI 1.2-11.5; P = 0.025) were independently associated with hypernatreamia.

Conclusion

The prevalence rate of hypernatreamia in hyperglycaemic admissions was high with all hypernatreamic admissions meeting the criteria for hyperosmolality. Advanced age, altered conscious level and a new diagnosis of diabetes were independently associated with hypernatreamia.