Long-Term Prognosis of Patients with Carbon Monoxide Poisoning: A Nationwide Cohort Study

Background

Carbon monoxide poisoning (COP) often produces severe complications and can be fatal. Because this topic has not been well delineated, we investigated long-term prognoses of patients with COP (COP^[+]).

Methods

In this retrospective nationwide cohort study, 441 COP^[+] patients and 8820 COP^[−] controls (120) from 1999 to 2010 were selected from Taiwan’s National Health Insurance Research Database.

Results

Thirty-seven (8.39%) COP^[+] patients and 142 (1.61%) controls died (P<0.0001) during follow-up. Incidence rate ratios (IRR) of death were 5.24 times higher in COP^[+] patients than in controls (P<0.0001). The risk of death was particularly high in the first month after COP (IRR: 308.78; 95% confidence interval [CI]: 40.79–2337.56), 1 to 6 months after (IRR: 18.92; 95% CI: 7.69–46.56), and 6–12 months after (IRR: 4.73; 95% CI: 1.02–21.90). After adjusting for age, gender, and selected comorbidities, the hazard ratio of death for COP^[+] patients was still 4.097 times higher than for controls. Moreover, older age (≥30 years old), male gender, diabetes mellitus, hypertension, and low income were also independent mortality predictors.

Conclusions

COP significantly increases the risk for long-term mortality. Early follow-up and secondary prevention of death are needed for patients with COP.     

Acute Myocardial Infarction Is a Risk Factor for New Onset Diabetes in Patients with Coronary Artery Disease

Objective

To test the hypothesis that acute myocardial infarction (AMI) might accelerate development of new onset diabetes in patients with coronary artery disease independent of known risk factors.

Methods

We conducted a retrospective cohort study within COACT (CathOlic medical center percutAneous Coronary inTervention) registry. From a total of 9,127 subjects, 2,036 subjects were diabetes naïve and followed up for at least one year with both index and follow-up laboratory data about diabetes. Cox proportional hazard model was used to derive hazard ratios (HRs) and 95% confidence interval (CI) for new onset diabetes associated with AMI in univariate and multivariate analysis after adjusting several covariates.

Results

The overall hazard for diabetes was higher in AMI compared to non-AMI patients (p by log rank <0.01) with HR of 1.78 and 95% CI of 1.37–2.32 in univariate analysis. This association remained significant after adjusting covariates (HR, 1.54; 95% CI, 1.14–2.07; p<0.01). AMI was an independent predictor for higher quartile of WBC count in multivariate ordinal logistic regression analysis (OR, 6.75; 95% CI, 5.53–8.22, p<0.01). In subgroup analysis, the diabetogenic effect of AMI was more prominent in the subgroup without MetS compared to MetS patients (p for interaction<0.05). Compared to the reference group of non-AMI+nonMetS, the group of AMI+non-MetS (HR, 2.44; 95% CI, 1.58–3.76), non-AMI+MetS (HR, 3.42; 95% CI, 2.34–4.98) and AMI+MetS (HR, 4.12; 95% CI, 2.67–6.36) showed higher HR after adjusting covariates. However, the hazard was not different between the non-AMI+MetS and AMI+non-MetS groups.

Conclusions

AMI patients have a greater risk of new-onset diabetes when compared to non AMI patients, especially those with mild metabolic abnormalities.     

Trends of Tuberculosis Case Notification and Treatment Outcomes in the Sidama Zone,Southern Ethiopia: Ten-Year Retrospective Trend Analysis in Urban-Rural Settings

BackgroundEthiopia is one of the high tuberculosis (TB) burden countries. An analysis of trends and differentials in case notifications and treatment outcomes of TB may help improve our understanding of the performance of TB control services.MethodsA retrospective trend analysis of TB cases was conducted in the Sidama Zone in southern Ethiopia. We registered all TB cases diagnosed and treated during 2003–2012 from all health facilities in the Sidama Zone, and analysed trends of TB case notification rates and treatment outcomes.ResultsThe smear positive (PTB+) case notification rate (CNR) increased from 55 (95% CI 52.5–58.4) to 111 (95% CI 107.4–114.4) per 10⁵ people. The CNRs of PTB+ in people older than 45 years increased by fourfold, while the mortality of cases during treatment declined from 11% to 3% for smear negative (PTB-) (X²_trend, P<0.001) and from 5% to 2% for PTB+ (X²_trend, P<0.001). The treatment success was higher in rural areas (AOR 1.11; CI 95%: 1.03–1.2), less for PTB- (AOR 0.86; CI 95%: 0.80–0.92) and higher for extra-pulmonary TB (AOR 1.10; CI 95%: 1.02–1.19) compared to PTB+. A higher lost-to-follow up was observed in men (AOR 1.15; CI 95%: 1.06–1.24) and among PTB- cases (AOR 1.14; CI 95%: 1.03–1.25). More deaths occurred in PTB-cases (AOR 1.65; 95% CI: 1.44–1.90) and among cases older than 65 years (AOR 3.86; CI 95%: 2.94–5.10). Lastly, retreatment cases had a higher mortality than new cases (6% vs 3%).ConclusionOver the past decade TB CNRs and treatment outcomes improved, whereas the disparities of disease burden by gender and place of residence reduced and mortality declined. Strategies should be devised to address higher risk groups for poor treatment outcomes.     

Renal Function in Chinese HIV-Positive Individuals following Initiation of Antiretroviral Therapy

Aim

To identify the prevalence and predictors of abnormal renal function among HIV-positive Chinese patients prior to antiretroviral therapy (ART) initiation and to evaluate subsequent changes in renal function after ART exposure.

Methods

We conducted a nationwide cohort study of subjects who enrolled in the national Chinese ART program from January 1, 2012 to December 31, 2012. We estimated the glomerular filtration rate (eGFR) of subjects prior to and after initiating ART. Risk factors for abnormal renal function, as defined by eGFR <60 ml/min/1.73m², at baseline and follow-up were assessed by logistic regression and Cox proportional hazards regression models, respectively.

Results

Among 41,862 subjects, at ART baseline, 3.3% had a baseline eGFR <60 ml/min/1.73m² and 24.2% had eGFR = 60–90 ml/min/1.73m². Adjusted baseline risk factors for baseline eGFR <60 ml/min/1.73m² were older age (Adjusted odds ratio [AOR] = 5.19, 95% confidence interval [CI]: 4.52–5.67), female (AOR = 1.68, 95% CI: 1.47–1.93), hemoglobin <120g/L (AOR = 1.68, 95% CI: 1.47–1.93), blood glucose >6.1 mmol/L (AOR = 1.46, 95% CI: 1.25–1.72), and hepatitis C co-infection (AOR = 1.36, 95% CI: 1.06–1.73). Among subjects with baseline eGFR >90 ml/min/1.73m², the incidence of the eGFR falling to <60 ml/min/1.73m² was 0.92/100 person-years after a median of 15.0 months of ART. Being on a tenofovir with lopinavir/ritonavir regimen (Adjusted hazard ratio [AHR] = 3.02, 95% CI: 1.96–4.66) and having an unsuppressed viral load (AHR = 2.70, 95% CI: 1.80–4.03) were independent predictors for eGFR <60 ml/min/1.73m² after ART initiation as well as older age, female, and hemoglobin <120 g/L.

Conclusion

A high proportion of HIV-positive subjects in China presented with abnormal renal function prior to ART initiation. But the incidence of the eGFR decrease after ART was low. Patient renal function should be regularly monitored by eGFR before initiating and during ART.     

Assessing Interactions between Common Genetic Variant on 2q35 and Hormone Receptor Status with Breast Cancer Risk: Evidence Based on 26 Studies

Genome-wide association studies have identified 2q35-rs13387042 as a new breast cancer (BC) susceptibility locus in populations of European descent. Since then, the relationship between 2q35-rs13387042 and breast cancer has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 26 studies involving a total of 101,529 cases and 167,363 controls for 2q35-rs13387042 polymorphism to evaluate its effect on genetic susceptibility for breast cancer. An overall random effects odds ratio of 1.14 (95% CI: 1.11–1.16, P<10⁻⁵) was found for rs13387042-A variant. Significant results were also observed using dominant (OR = 1.14, 95% CI: 1.12–1.17, P<10⁻⁵), recessive (OR = 1.17, 95% CI: 1.13–1.21, P<10⁻⁵) and co-dominant genetic model (heterozygous: OR = 1.15, 95% CI: 1.12–1.19, P<10⁻⁵; homozygous: OR = 1.20, 95% CI: 1.15–1.24, P<10⁻⁵). There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. Significant associations were found in East Asians, and White populations when stratified by ethnicity; while no significant associations were observed in Africans and other ethnic populations. An association was observed for both ER-positive (OR = 1.17, 95% 1.15–1.19; P<10⁻⁵) and ER-negative disease (OR = 1.08, 95% CI: 1.04–1.13; P<10⁻⁴) and both progesterone receptor (PR)-positive (OR = 1.18, 95% CI: 1.15–1.21; P<10⁻⁵) and PR-negative disease (OR = 1.10, 95% CI: 1.05–1.15; P<10⁻⁴). In conclusion, this meta-analysis demonstrated that the A allele of 2q35-rs13387042 is a risk factor associated with increased breast cancer susceptibility.     

Association between Blood Dioxin Level and Chronic Kidney Disease in an Endemic Area of Exposure

Background

Dioxin is an industrial pollutant related to various diseases, but epidemiological data on its effects on the kidney are limited. Therefore, we conducted a study to evaluate the association between dioxin exposure and chronic kidney disease (CKD) and identify the related factors.

Methods

We conducted a community-based cross-sectional study and recruited participants from an area where the residents were exposed to dioxin released from a factory. We defined a “high dioxin level” as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) ≥ 20 pg WHO₉₈-TEQ_DF/g lipid in the serum and defined CKD as having an estimated glomerular filtration rate (e-GFR) ≤ 60 mL/min/1.73m² or a diagnosis of CKD by a physician. The renal function was assessed between 2005 and 2010, and we excluded those who had had kidney diseases before the study started. Comparisons between patients of CKD and those who did not have CKD were made to identify the risk factors for CKD.

Results

Of the 2898 participants, 1427 had high dioxin levels, and 156 had CKD. In the univariate analyses, CKD was associated with high dioxin levels, age, gender, metabolic syndrome, diabetes mellitus, hypertension, and high insulin and uric acid levels. After adjusting for other factors, we found high dioxin levels (adjusted odds ratio [AOR] = 1.76, 95% confidence interval [CI]: 1.04–2.99), female gender (AOR = 1.74, 95%CI: 1.20–2.53), hypertension (AOR = 1.68, 95%CI: 1.17–2.42), high insulin levels (AOR = 2.14, 95% CI: 1.26–3.61), high uric acid levels (AOR = 4.25, 95% CI: 2.92–6.20), and older age (AOR = 4.66, 95% CI: 1.87–11.62 for 40–64 year and AOR = 26.66, 95% CI: 10.51–67.62 for age ≥ 65 year) were independent predictors of CKD.

Conclusion

A high dioxin level was associated with an increased prevalence of CKD. Therefore, the kidney function of populations with exposure to dioxin should be monitored.     

Prevalence and Associated Factors of Hypertension among Adults in Durame Town,Southern Ethiopia

Background

To date, non-communicable diseases, such as cardiovascular diseases, are becoming severe public health challenges particularly in developing countries. Hypertension is a modifiable risk factor that contributes the leading role for mortality. The problem is significant in low- and middle-income countries like sub-Saharan Africa. However, there are limited studies in developing countries, particularly in Ethiopia. Hence, determining the magnitude of hypertension and identifying risk groups are important.

Methods

A community based cross sectional study was conducted in April 2013 among adults (age>31 years) old. A systematic sampling technique was used to select a total of 518 study participants. Data were collected after full verbal informed consent was obtained from each participant. Multivariable logistic regressions were fitted to control the effect of confounding. Adjusted Odds ratios (OR) with their 95% confidence intervals (95% CI) were calculated to measure associations. Variables having P-value <0.05 were considered as significant.

Results

The overall prevalence of hypertension in Durame town was 22.4% (95% CI: 18.8–26.0). Nearly 40% of hypertensive patients were newly screened. Male sex [AOR  = 2.03, 95% CI; 1.05–3.93], age [AOR  = 29.49, 95% CI; 10.60–81.27], salt use [AOR  = 6.55, 95% CI; 2.31–18.53], eating vegetable three or fewer days per week [AOR  = 2.3,95% CI; 1.17–4.51], not continuously walking at least for 10 minutes per day [AOR  = 7.82, 95% CI; 2.37–25.82], having family history of hypertension [AOR  = 2.46, 95%CI; 1.31–4.61] and being overweight/obese [AOR  = 15.7, 95% CI 7.89–31.21)] were found to be risk factors for hypertension.

Conclusions

The prevalence of hypertension is found to be high. Older age, male sex, having family history of hypertension, physical inactivity, poor vegetable diet, additional salt consumption and obesity were important risk factors associated with hypertension among adults. Community level intervention measures with a particular emphasis on prevention by introducing lifestyle modifications are recommended.     

Rapid testing requires clinical evaluation for accurate diagnosis of dengue disease: A passive surveillance study in Southern Malaysia

BackgroundDengue fever is the most common mosquito-borne infection worldwide where an expanding surveillance and characterization of this infection are needed to better inform the healthcare system. In this surveillance-based study, we explored the prevalence and distinguishing features of dengue fever amongst febrile patients in a large community-based health facility in southern peninsular Malaysia.MethodsOver six months in 2018, we recruited 368 adults who met the WHO 2009 criteria for probable dengue infection. They underwent the following blood tests: full blood count, dengue virus (DENV) rapid diagnostic test (RDT), ELISA (dengue IgM and IgG), nested RT-PCR for dengue, multiplex qRT-PCR for Zika, Chikungunya and dengue as well as PCR tests for Leptopspira spp., Japanese encephalitis and West Nile virus.ResultsLaboratory-confirmed dengue infections (defined by positive tests in NS1, IgM, high-titre IgG or nested RT-PCR) were found in 167 (45.4%) patients. Of these 167 dengue patients, only 104 (62.3%) were positive on rapid diagnostic testing. Dengue infection was significantly associated with the following features: family or neighbours with dengue in the past week (AOR: 3.59, 95% CI:2.14–6.00, p<0.001), cutaneous rash (AOR: 3.58, 95% CI:1.77–7.23, p<0.001), increased temperature (AOR: 1.33, 95% CI:1.04–1.70, p = 0.021), leucopenia (white cell count < 4,000/μL) (AOR: 3.44, 95% CI:1.72–6.89, p<0.001) and thrombocytopenia (platelet count <150,000/μL)(AOR: 4.63, 95% CI:2.33–9.21, p<0.001). Dengue infection was negatively associated with runny nose (AOR: 0.47, 95% CI:0.29–0.78, p = 0.003) and arthralgia (AOR: 0.42, 95% CI:0.24–0.75, p = 0.004). Serotyping by nested RT-PCR revealed mostly mono-infections with DENV-2 (n = 64), DENV-1 (n = 32) and DENV-3 (n = 17); 14 co-infections occurred with DENV-1/DENV-2 (n = 13) and DENV-1/DENV-4 (n = 1). Besides dengue, none of the pathogens above were found in patients’ serum.ConclusionsAcute undifferentiated febrile infections are a diagnostic challenge for community-based clinicians. Rapid diagnostic tests are increasingly used to diagnose dengue infection but negative tests should be interpreted with caution as they fail to detect a considerable proportion of dengue infection. Certain clinical features and haematological parameters are important in the clinical diagnosis of dengue infection.     

High prevalence of intestinal parasite infestations among stunted and control children aged 2 to 5 years old in two neighborhoods of Antananarivo,Madagascar

BackgroundThis study aimed to compare the prevalence of intestinal parasite infestations (IPIs) in stunted children, compared to control children, in Ankasina and Andranomanalina Isotry (two disadvantaged neighborhoods of Antananarivo, Madagascar), to characterize associated risk factors and to compare IPI detection by real-time PCR and standard microscopy techniques.Methodology/Principal findingsFecal samples were collected from a total of 410 children (171 stunted and 239 control) aged 2–5 years. A single stool sample per subject was examined by simple merthiolate-iodine-formaldehyde (MIF), Kato-Katz smear and real-time PCR techniques. A total of 96.3% of the children were infested with at least one intestinal parasite. The most prevalent parasites were Giardia intestinalis (79.5%), Ascaris lumbricoides (68.3%) and Trichuris trichiura (68.0%). For all parasites studied, real-time PCR showed higher detection rates compared to microscopy (G. intestinalis [77.6% (n = 318) versus 20.9% (n = 86)], Entamoeba histolytica [15.8% (n = 65) versus 1.9% (n = 8)] and A. lumbricoides [64.1% (n = 263) versus 50.7% (n = 208)]). Among the different variables assessed in the study, age of 4 to 5 years (AOR = 4.61; 95% CI, (1.35–15.77)) and primary and secondary educational level of the mother (AOR = 12.59; 95% CI, (2.76–57.47); AOR = 9.17; 95% CI, (2.12–39.71), respectively) were significantly associated with IPIs. Children drinking untreated water was associated with infestation with G. intestinalis (AOR = 1.85; 95% CI, (1.1–3.09)) and E. histolytica (AOR = 1.9; 95% CI, (1.07–3.38)). E. histolytica was also associated with moderately stunted children (AOR = 0.37; 95% CI, 0.2–0.71). Similarly, children aged between 4 and 5 years (AOR = 3.2; 95% CI (2.04–5.01)) and living on noncemented soil types (AOR = 1.85; 95% CI, (1.18–2.09)) were associated with T. trichiura infestation.Conclusions/SignificanceThe prevalence of IPIs is substantial in the studied areas in both stunted and control children, despite the large-scale drug administration of antiparasitic drugs in the country. This high prevalence of IPIs warrants further investigation. Improved health education, environmental sanitation and quality of water sources should be provided.     

A Cross-Sectional Survey of HIV Testing and Prevalence in Twelve Brazilian Correctional Facilities

BackgroundPrior studies have reported higher HIV prevalence among prisoners than the general population in Brazil, but data have been derived from single prisons. The aim of this study was to evaluate HIV testing practices, prevalence and linkage to care among inmates in a network of 12 prisons.MethodsWe administered a questionnaire to a population-based sample of inmates from 12 prisons in Central-West Brazil and collected sera for HIV and syphilis testing from January to December 2013. We evaluated factors associated with HIV testing and infection using multivariable logistic regression models. Six months after HIV testing, we assessed whether each HIV-infected prisoner was engaged in clinical care and whether they had started antiretroviral therapy.ResultsWe recruited 3,362 inmates, of whom 2,843 (85%) were men from 8 prisons, and 519 (15%) were women from 4 prisons. Forty-five percent of participants reported never having been tested for HIV previously. In multivariable analysis, the variables associated with previous HIV testing were lack of a stable partner (adjusted odds ratio [AOR]: 1.38; 95% CI: 1.18–1.60), completed more than four years of schooling (AOR 1.40; 95% CI: 1.20–1.64), history of previous incarceration (AOR: 1.68; 95% CI: 1.43–1.98), history of mental illness (AOR 1.52; 95% CI: 1.31–1.78) and previous surgery (AOR 1.31; 95% CI: 1.12–1.52). Fifty-four (1.6%) of all participants tested positive for HIV; this included 44 (1.54%) men and 10 (1.92%) women. Among male inmates, HIV infection was associated with homosexuality (AOR 6.20, 95% CI: 1.73–22.22), self-report of mental illness (AOR 2.18, 95% CI: 1.13–4.18), history of sexually transmitted infections (AOR 3.28, 95% CI: 1.64–6.56), and syphilis sero-positivity (AOR 2.54, 95% CI: 1.20–5.39). Among HIV-infected individuals, 34 (63%) were unaware of their HIV status; only 23 of these 34 (68%) newly diagnosed participants could be reached at six month follow-up, and 21 of 23 (91%) were engaged in HIV care.ConclusionsHIV testing rates among prison inmates are low, and the majority of HIV-infected inmates were unaware of their HIV diagnosis. Incarceration can be an opportunity for diagnosis and treatment of HIV among vulnerable populations who have poor access to health services, but further work is needed on transitional HIV care for released inmates.     

Khat Chewing and Restrictive Dietary Behaviors Are Associated with Anemia among Pregnant Women in High Prevalence Rural Communities in Eastern Ethiopia

Background

Anemia affects a high proportion of pregnant women in the developing countries. Factors associated with it vary in context. This study aimed to determine the prevalence and predictors of anemia among pregnant women in the rural eastern Ethiopia.

Methods

A community-based cross-sectional study was done on 1678 pregnant women who were selected by a cluster random sampling technique. A pregnant woman was identified as anemic if her hemoglobin concentration was <11 g/dl. Data were collected in a community-based setting. Multilevel mixed effect logistic regression was used to determine the adjusted odds ratios (AOR) with 95% confidence intervals (CI) for the predictors of anemia.

Results

Anemia was observed among 737(43.9%) of the 1678 pregnant women studied (95% CI 41.5%–46.3%). After controlling for the confounders, the risk of anemia was 29% higher in the women who chewed khat daily than those who sometimes or never did so (AOR, 1.29; 95% CI, 1.02–1.62). The study subjects with restrictive dietary behavior (reduced either meal size or frequency) had a 39% higher risk of anemia compared to those without restrictive dietary behavior (AOR, 1.39; 95% CI, 1.02–1.88). The risk of anemia was increased by 68% (AOR, 1.68; 95% CI, 1.15–2.47), and 60% (AOR, 1.60; 95% CI, 1.08–2.37) in parity levels of 2 births and 3 births, respectively. Compared to the first trimester, the risk of anemia was higher by two-fold (AOR, 2.09; 95% CI, 1.46–3.00) in the second trimester and by four-fold (AOR, 4.23; 95% CI, 2.97–6.02) in the third trimester.

Conclusion

In this study, two out of five women were anemic. Chewing khat and restrictive dietary habits that are associated with anemia in the setting should be addressed through public education programs. Interventions should also focus on the women at higher parity levels and those who are in advanced stages of pregnancy.     

Association between Secreted Phosphoprotein-1 (SPP1) Polymorphisms and Low Bone Mineral Density in Women

Background

A recent meta-analysis found that secreted phosphoprotein-1 (SPP1) can predict the risk of both osteoporosis and fracture. No study has explored the association of SPP1 haplotype-tagging single nucleotide polymorphisms (htSNPs) and haplotypes with bone mineral density (BMD).

Methods

This is a cross-sectional study. A total of 1,313 healthy Taiwanese women aged 40 to 55 years were recruited from MJ Health Management Institute from 2009 to 2010. BMD was dichotomized into high and low BMD groups. Three common (allele frequency ≥5%) htSNPs were selected to examine the association between sequence variants of SPP1 and BMD.

Results

Homozygosity for the T allele of rs4754 were protective from low BMD [TT vs. CC: adjusted OR (AOR)  = 0.58, 95% confidence interval (CI)  = 0.83–0.89]. A protective effect was also found for women carrying 2 copies of Hap3 TCT (AOR  = 0.57, 95% CI  = 0.34–0.95). Menopausal status marginally interacted with SPP1 rs6839524 on BMD (p = 0.049). Postmenopausal women carrying variant rs6839524 (GG+GC vs. CC: AOR  = 2.35, 95% CI  = 1.06–5.20) or Hap1 TGC (AOR  = 2.36, 95% CI  = 1.06–5.24) were associated with 2.4-fold risk of low BMD. For women with low BMI (<18.5 kg/m²), variant rs6839524 (AOR  = 7.64) and Hap1 (AOR  = 6.42) were associated with increased risk of low BMD. These findings did not reach statistical significance after correction for multiple tests.

Conclusions

SPP1 htSNP protected against low BMD in middle-aged women. SPP1 genetic markers may be important for the prediction of osteoporosis at an early age.     

Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto''s thyroiditis), as well as autoimmune hyperthyroidism (Graves'' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10⁻⁸) were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores) of these variants on (subclinical) hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68–2.81, P = 8.1×10⁻⁸), a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26–1.82, P = 2.9×10⁻⁶), as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66–0.89, P = 6.5×10⁻⁴). The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves'' disease (OR: 1.37, 95% CI 1.22–1.54, P = 1.2×10⁻⁷ and OR: 1.25, 95% CI 1.12–1.39, P = 6.2×10⁻⁵). The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18–2.10, P = 1.9×10⁻³). This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which TPOAb-positives are particularly at risk of developing clinical thyroid dysfunction.     

Trends in the Use of Guideline-Recommended Medications and In-Hospital Mortality of Patients with Acute Myocardial Infarction in a Chinese Population

ObjectiveCurrent practice guidelines recommend the routine use of several cardiac medications early in the course of acute myocardial infarction (AMI). Our objective was to analyze temporal trends in medication use and in-hospital mortality of AMI patients in a Chinese population.MethodsThis is a retrospective observational study using electronic medical records from the hospital information system (HIS) of 14 Chinese hospitals. We identified 5599 patients with AMI between 2005 and 2011. Factors associated with medication use and in-hospital mortality were explored by using hierarchical logistic regression.ResultsThe use of several guideline-recommended medications all increased during the study period: statins (57.7%–90.1%), clopidogrel (61.8%–92.3%), β-Blockers (45.4%–65.1%), ACEI/ARB (46.7%–58.7%), aspirin (81.9%–92.9%), and the combinations thereof increased from 24.9% to 42.8% (P<0.001 for all). Multivariate analyses showed statistically significant increases in all these medications. The in-hospital mortality decreased from 15.9% to 5.7% from 2005 to 2011 (P<0.001). After multivariate adjustment, admission year was still a significant factor (OR = 0.87, 95% CI 0.79–0.96, P = 0.007), the use of aspirin (OR = 0.64, 95% CI 0.46–0.87), clopidogrel (OR = 0.44, 95% CI 0.31–0.61), ACEI/ARB (OR = 0.73, 95% CI 0.56–0.94) and statins (OR = 0.54, 95% CI 0.40–0.73) were associated with a decrease in in-hospital mortality. Patients with older age, cancer and renal insufficiency had higher in-hospital mortality, while they were generally less likely to receive all these medications.ConclusionUse of guideline-recommended medications early in the course of AMI increased between 2005 and 2011 in a Chinese population. During this same time, there was a decrease in in-hospital mortality.     

Protection against laryngeal and pharyngeal carcinoma: Heterozygous vs. homozygous deletions of GSTM1 and GSTT1

Deletions in GSTM1 and GSTT1 genes are considered to be a risk factor for cancer development but the exact location of these deletions in the genome was unknown. Three main objectives of the current study were to: (a) identify the boundaries of these deletions in the human genome, (b) screen homozygous (−/−) and heterozygous (+/−) deleted, as well as homozygous present (+/+) individuals using PCR assays, (c) detect associations of pharyngeal (PC) and laryngeal cancer (LC) with the respective genotypes. In total, 102 PC and 92 LC patients were screened and compared with 150 controls. PCR mapping and sequencing revealed a 6 kbp deletion for GSTM1 and a 9 kbp deletion for the GSTT1 gene. The mean age of PC cases was 48.1 (±16.7) years; for LC cases it was 48.5 (±17.4) years and for controls 46 (±17.7) years. The OR (odds ratio) for the GSTM1 null genotype in PC and LC cases was 10.2 and 1.0 (95% CI 5.04–20.7 and 1.1–1.7) respectively. Similarly, for GSTT1 the OR was 4.02 with a 95% CI of 2.3–7.1 in PC cases. For LC cases the OR was 0.8 with 95% CI of 0.4–1.7. A non-significant number of LC and PC patients had heterozygous deletions of GSTM1 compared to controls (OD 0.5, 95% CI 0.2– 1.6 and OR 0.5, 95% CI 0.2– 1.5 respectively). The GSTT1 gene also showed a non-significant association in PC (OD 0.9, 95% CI 0.4–1.9), as well as in LC patients (OD 0.7, 95% CI 0.3–1.7). The homozygous genotype was significantly associated with PC and LC, whereas the heterozygous was not so. The GSTM1 (−/−) and GSTT1 (−/−) genotypes are a risk factor for LC and PC, whereas the (+/−) genotypes are not.     

Factors Associated with Ever Being HIV-Tested in Zimbabwe: An Extended Analysis of the Zimbabwe Demographic and Health Survey (2010–2011)

Introduction

Zimbabwe has a high human immunodeficiency virus (HIV) burden. It is therefore important to scale up HIV-testing and counseling (HTC) as a gateway to HIV prevention, treatment and care.

Objective

To determine factors associated with being HIV-tested among adult men and women in Zimbabwe.

Methods

Secondary analysis was done using data from 7,313 women and 6,584 men who completed interviewer-administered questionnaires and provided blood specimens for HIV testing during the Zimbabwe Demographic and Health Survey (ZDHS) 2010–11. Factors associated with ever being HIV-tested were determined using multivariate logistic regression.

Results

HIV-testing was higher among women compared to men (61% versus 39%). HIV-infected respondents were more likely to be tested compared to those who were HIV-negative for both men [adjusted odds ratio (AOR) = 1.53; 95% confidence interval (CI) (1.27–1.84)] and women [AOR = 1.42; 95% CI (1.20–1.69)]. However, only 55% and 74% of these HIV-infected men and women respectively had ever been tested. Among women, visiting antenatal care (ANC) [AOR = 5.48, 95% CI (4.08–7.36)] was the most significant predictor of being tested whilst a novel finding for men was higher odds of testing among those reporting a sexually transmitted infection (STI) in the past 12 months [AOR = 1.86, 95%CI (1.26–2.74)]. Among men, the odds of ever being tested increased with age ≥20 years, particularly those 45–49 years [AOR = 4.21; 95% CI (2.74–6.48)] whilst for women testing was highest among those aged 25–29 years [AOR = 2.01; 95% CI (1.63–2.48)]. Other significant factors for both sexes were increasing education level, higher wealth status and currently/formerly being in union.

Conclusions

There remains a high proportion of undiagnosed HIV-infected persons and hence there is a need for innovative strategies aimed at increasing HIV-testing, particularly for men and in lower-income and lower-educated populations. Promotion of STI services can be an important gateway for testing more men whilst ANC still remains an important option for HIV-testing among pregnant women.     

Factors Associated to Prevalence and Incidence of Carbapenem-Resistant Enterobacteriaceae Fecal Carriage: A Cohort Study in a Mexican Tertiary Care Hospital

Background

Carbapenem-resistant Enterobacteriaceae (CRE) infections have emerged as a serious threat to health worldwide. They are associated with increased morbidity and mortality and are capable of silently colonizing the gastrointestinal tract. Because of this, there is great interest to characterize the epidemiology of CRE carriage and acquisition in healthcare facilities. The aim of this study was to determine the prevalence and factors associated with CRE fecal carriage (CRE-fc), and risk factors for incident cases.

Methods/Results

A cohort study was conducted at a tertiary care hospital from January 1^st to April 30^th, 2014 during a CRE outbreak. Weekly rectal swabs were performed in patients considered at risk until discharge. CRE-fc prevalence was 10.9% (CI 95% 7.7–14.7) among 330 patients. Treatment with carbapenems (OR 2.54, CI 95% 1.15–5.62); transfer from an institution (OR 2.16, CI 95% 1.02–4.59); multi-drug resistant infection within the previous six months (OR 2.81, CI 95% 1.47–5.36); intensive care unit admission (OR 0.42, CI 95% 0.20–0.88); hematologic malignancy (OR 4.02, CI 95% 1.88–8.06); invasive procedures (OR 2.18, CI 95% 1.10–4.32); and sharing a room with a known CRE carrier (OR 3.0, CI 95% 1.43–6.31) were independently associated factors for CRE-fc. Risk factors associated with CRE-fc incidence were determined for 87 patients initially negative and with subsequent screening; the incidence rate was 2.5 cases, per 1000 person-years (CI 95% 1.5–3.9). Independently associated risk factors were carbapenem treatment (HR 2.68, CI 95% 1.03–6.98), hematologic malignancy (HR 5.74, 95% CI 2.46–13.4) and a mean daily colonization pressure ≥10% (HR 5.03, IC 95% 1.77–14.28). OXA-48-like (OXA-232) and CTX-M-15 were the predominantly identified mechanisms of resistance.

Conclusions

We found an elevated incidence and prevalence of CRE-fc in our hospital. Hematologic patients need to be considered a population at risk, and antibiotic stewardship along with infection control programs need to be improved to avoid nosocomial spread.     

One Dose versus Three Weekly Doses of Benzathine Penicillin G for Patients Co-Infected with HIV and Early Syphilis: A Multicenter,Prospective Observational Study

Background

One dose of benzathine penicillin G (BPG) has been recommended for HIV-infected patients with early syphilis (primary, secondary, and early latent syphilis) in the sexually transmitted diseases treatment guidelines, but clinical data to support such a recommendation are limited.

Methods

We prospectively observed the serological response to 1 or 3 weekly doses of BPG in HIV-infected adults who sought treatment of early syphilis at 8 hospitals around Taiwan. Rapid plasma reagin (RPR) titers were followed every 3–6 months after treatment. The serological response was defined as a 4-fold or greater decline in RPR titers at 12 months of treatment. The missing values were treated by following the last-observed-carried-forward principle. We hypothesized that 1 dose was non-inferior to 3 weekly doses of BPG with the non-inferiority margin for the difference of serological response set to 10%.

Results

Between 2007 and 2012, 573 patients completed at least 12 months of follow-up: 295 (51.5%) receiving 1 dose of BPG (1-dose group) and 278 (48.5%) 3 doses (3-dose group). Overall, 198 patients (67.1%; 95% confidence interval [CI], 61.4–72.5%) in the 1-dose group achieved serological response at 12 months, as did 208 patients (74.8%; 95% CI, 69.3–79.8%) in the 3-dose group (one-sided 95% CI of the difference, 15.1%). In the multivariate analysis, secondary syphilis (adjusted odds ratio [AOR], 1.90; 95% CI 1.17–3.09), RPR titer ≥32 (AOR, 1.93; 95% CI, 1.38–2.69), and 3 doses of BPG (AOR, 1.68; 95% CI, 1.20–2.36) were independently associated with a serological response. The time to the first episode of treatment failure was 1184 (standard deviation [SD], 70.5) and 1436 (SD, 80.0) days for 1- and 3-dose group, respectively.

Conclusions

Single-dose BPG resulted in a higher serological failure rate and shorter time to treatment failure than 3 weekly doses of BPG in the treatment of early syphilis in HIV-infected patients.