Increased Risk of Coronary Heart Disease in Patients with Primary Fibromyalgia and Those with Concomitant Comorbidity—A Taiwanese Population-Based Cohort Study

Objectives

Fibromyalgia has seldom been associated with coronary heart disease (CHD). The aim of this study was to evaluate the risk of CHD in patients with fibromyalgia.

Methods

We used a dataset of one million participants, systemically scrambled from the Taiwanese national insurance beneficiaries, to identify 61,612 patients with incident fibromyalgia (ICD-9-CM 729.0–729.1) and 184,834 reference subjects matched by sex, age and index date of diagnosis in a 1:3 ratio from 2000 to 2005, with a mean 8.86 ± 2.68 years of follow-up until 2011. Risk of CHD was analyzed by Cox proportional hazard modeling.

Results

Patients with fibromyalgia had a mean age of 44.1 ± 16.5 years. CHD events developed in fibromyalgia patients (n = 8,280; 15.2 per 10³ person-years) and reference subjects (n = 15,162; 9.26 per 10³ person-years) with a significant incidence rate ratio of 1.64 (95% confidence interval: 1.61–1.68). The adjusted hazard ratio for CHD in fibromyalgia patients relative to reference subjects was 1.47 (1.43–1.51), after adjusting for age, gender, occupation, monthly income, traditional cardiovascular comorbidities, depression and anxiety. We noted that fibromyalgia and cardiovascular comorbidities had a significant interaction effect on CHD risk (p for interaction <0.01), which was markedly enhanced in fibromyalgia patients with concomitant comorbidities relative to patients with primary fibromyalgia and reference subjects (no fibromyalgia, no comorbidity).

Conclusions

Our report shows that fibromyalgia patients have an independent risk for CHD development. Fibromyalgia patients with concomitant comorbidities have markedly increased CHD risk relative to those with primary fibromyalgia.     

Severe Obesity and Cardiometabolic Risk in Children: Comparison from Two International Classification Systems

Objectives

There is no agreed-upon definition for severe obesity (Sev-OB) in children. We compared estimates of Sev-OB as defined by different cut-points of body mass index (BMI) from the Centers for Disease Control and Prevention (CDC) or the World Health Organization (WHO) curves and the ability of each set of cut-points to screen for the presence of cardiometabolic risk factors.

Research Design and Methods

Cross-sectional, multicenter study involving 3,340 overweight/obese young subjects. Sev-OB was defined as BMI ≥99^th percentile or ≥1.2 times the 95^th percentile of the CDC or the WHO curves. High blood pressure, hypertriglyceridemia, low High Density Lipoprotein -cholesterol and impaired fasting glucose were considered as cardiometabolic risk factors.

Results

The estimated prevalence of Sev-OB varied widely between the two reference systems. Either using the cut-point ≥99^th percentile or ≥1.2 times the 95^th percentile, less children were defined as Sev-OB by CDC than WHO (46.8 vs. 89.5%, and 63.3 vs. 80.4%, respectively p<0.001). The CDC 99^th percentile had lower sensitivity (58.5 vs 94.2), higher specificity (57.6 vs 12.3) and higher positive predictive value (34.4 vs 28.9) than WHO in identifying obese children with ≥2 cardiometabolic risk factors. These differences were mitigated using the 1.2 times the 95^th percentile (sensitivity 73.9 vs. 88.1; specificity 40.7 vs. 22.5; positive predictive value 32.1 vs. 30.1). Substantial agreement between growth curves was found using the 1.2 times the 95^th percentile, in particular in children ≤10 years.

Conclusions

Estimates of Sev-OB and cardiometabolic risk as defined by different cut-points of BMI are influenced from the reference systems used. The 1.2 times the 95^th percentile of BMI of either CDC or WHO standard has a discriminatory advantage over the 99^th percentile for identifying severely obese children at increased cardiometabolic risk, particularly under 10 years of age.     

Visual vs Fully Automatic Histogram-Based Assessment of Idiopathic Pulmonary Fibrosis (IPF) Progression Using Sequential Multidetector Computed Tomography (MDCT)

Objectives

To describe changes over time in extent of idiopathic pulmonary fibrosis (IPF) at multidetector computed tomography (MDCT) assessed by semi-quantitative visual scores (VSs) and fully automatic histogram-based quantitative evaluation and to test the relationship between these two methods of quantification.

Methods

Forty IPF patients (median age: 70 y, interquartile: 62-75 years; M:F, 33:7) that underwent 2 MDCT at different time points with a median interval of 13 months (interquartile: 10-17 months) were retrospectively evaluated. In-house software YACTA quantified automatically lung density histogram (10^th-90^th percentile in 5^th percentile steps). Longitudinal changes in VSs and in the percentiles of attenuation histogram were obtained in 20 untreated patients and 20 patients treated with pirfenidone. Pearson correlation analysis was used to test the relationship between VSs and selected percentiles.

Results

In follow-up MDCT, visual overall extent of parenchymal abnormalities (OE) increased in median by 5 %/year (interquartile: 0 %/y; +11 %/y). Substantial difference was found between treated and untreated patients in HU changes of the 40th and of the 80th percentiles of density histogram. Correlation analysis between VSs and selected percentiles showed higher correlation between the changes (Δ) in OE and Δ 40^th percentile (r=0.69; p<0.001) as compared to Δ 80^th percentile (r=0.58; p<0.001); closer correlation was found between Δ ground-glass extent and Δ 40^th percentile (r=0.66, p<0.001) as compared to Δ 80^th percentile (r=0.47, p=0.002), while the Δ reticulations correlated better with the Δ 80^th percentile (r=0.56, p<0.001) in comparison to Δ 40^th percentile (r=0.43, p=0.003).

Conclusions

There is a relevant and fully automatically measurable difference at MDCT in VSs and in histogram analysis at one year follow-up of IPF patients, whether treated or untreated: Δ 40^th percentile might reflect the change in overall extent of lung abnormalities, notably of ground-glass pattern; furthermore Δ 80^th percentile might reveal the course of reticular opacities.     

Systematic Examination of Infant Size and Growth Metrics as Risk Factors for Overweight in Young Adulthood

Objective

To systematically examine infant size and growth, according to the 2006 WHO infant growth standards, as risk factors for overweight status in young adulthood in a historical cohort. Specifically, to assess: Whether accounting for length (weight-for-length) provides a different picture of risk than weight-for-age, intervals of rapid growth in both weight-for-age and weight-for-length metrics, and what particular target ages for infant size and intervals of rapid growth associate most strongly with overweight as a young adult.

Patients/Methods

Data analysis of 422 appropriate for gestational age white singleton infants enrolled in the Fels Longitudinal Study. Odds ratios (OR) for overweight and obesity in young adulthood (age 20–29) were calculated using logistic regression models for the metrics at each target age (0, 1, 3, 6, 9, 12, 18, 24 months) comparing ≥85^th v. <85^th percentile, as well as rapid growth (Δ≥0.67 Z-score) through target age intervals. Models accounted for both maternal and paternal BMI.

Results

Infants ≥85^th percentile of weight-for-age at each target age (except 3 months) had a greater odds of being overweight as a young adult. After accounting for length (weight-for-length) this association was limited to 12, and 18 months. Rapid weight-for-age growth was infrequently associated with overweight as a young adult. Rapid weight-for-length growth from 0 to 24 months, 1 to 6, 9, 12, 18, and 24 months and from 3 to 9, 12, 18, and 24 months was strongly associated with overweight status as a young adult.

Conclusions

The WHO weight-for-length metric associates differently with risk of being overweight as a young adult compared to weight-for-age. Intervals of rapid weight-for-length growth ranging from months (0–24), (1–12, 18, and 24) and (3–9, and 12) displayed the largest OR for being overweight as a young adult.     

Risk Factors for Mercury Exposure of Children in a Rural Mining Town in Northern Chile

Objective

Traditional gold mining is associated with mercury exposure. Especially vulnerable to its neurotoxic effects is the developing nervous system of a child. We aimed to investigate risk factors of mercury exposure among children in a rural mining town in Chile.

Methods

Using a validated questionnaire distributed to the parents of the children, a priori mercury risk factors, potential exposure pathways and demographics of the children were obtained. Mercury levels were measured through analyzing fingernail samples. Logistic regression modeling the effect of risk factors on mercury levels above the 75^th percentile were made, adjusted for potential confounders.

Results

The 288 children had a mean age of 9.6 years (SD = 1.9). The mean mercury level in the study population was 0.13 µg/g (SD 0.11, median 0.10, range 0.001–0.86 µg/g). The strongest risk factor for children’s odds of high mercury levels (>75^th percentile, 0.165 µg/g) was to play inside a house where a family member worked with mercury (OR adjusted 3.49 95% CI 1.23–9.89). Additionally, children whose parents worked in industrial gold mining had higher odds of high mercury levels than children whose parents worked in industrial copper mining or outside mining activities.

Conclusion

Mercury exposure through small-scale gold mining might affect children in their home environments. These results may further help to convince the local population of banning mercury burning inside the households.     

Optimal Skin-to-Stone Distance Is a Positive Predictor for Successful Outcomes in Upper Ureter Calculi following Extracorporeal Shock Wave Lithotripsy: A Bayesian Model Averaging Approach

Objectives

To investigate whether skin-to-stone distance (SSD), which remains controversial in patients with ureter stones, can be a predicting factor for one session success following extracorporeal shock wave lithotripsy (ESWL) in patients with upper ureter stones.

Patients and Methods

We retrospectively reviewed the medical records of 1,519 patients who underwent their first ESWL between January 2005 and December 2013. Among these patients, 492 had upper ureter stones that measured 4–20 mm and were eligible for our analyses. Maximal stone length, mean stone density (HU), and SSD were determined on pretreatment non-contrast computed tomography (NCCT). For subgroup analyses, patients were divided into four groups. Group 1 consisted of patients with SSD<25^th percentile, group 2 consisted of patients with SSD in the 25^th to 50^th percentile, group 3 patients had SSD in the 50^th to 75^th percentile, and group 4 patients had SSD≥75^th percentile.

Results

In analyses of group 2 patients versus others, there were no statistical differences in mean age, stone length and density. However, the one session success rate in group 2 was higher than other groups (77.9% vs. 67.0%; P = 0.032). The multivariate logistic regression model revealed that shorter stone length, lower stone density, and the group 2 SSD were positive predictors for successful outcomes in ESWL. Using the Bayesian model-averaging approach, longer stone length, lower stone density, and group 2 SSD can be also positive predictors for successful outcomes following ESWL.

Conclusions

Our data indicate that a group 2 SSD of approximately 10 cm is a positive predictor for success following ESWL.     

Sex Specific Incidence Rates of Type 2 Diabetes and Its Risk Factors over 9 Years of Follow-Up: Tehran Lipid and Glucose Study

Objective

To investigate the population-based incidence of type 2 diabetes and its potential risk factors in a sex-split cohort of Iranian population.

Materials and Methods

A total of 8400 non-diabetic participants, aged ≥20 years (3620 men and 4780 women) entered the study. Crude and age standardized incidence rates per 1000 person-years were calculated for whole population and each sex separately. Cox proportional hazard models were used to evaluate hazard ratios (HR) and 95% confidence intervals for all potential risk factors in both uni-variable and multivariable models.

Results

During a median follow-up of 9.5 years, 736 new cases of diabetes were identified, including 433 women and 303 men. The annual crude and age-standardized incidence rates (95% CI) of diabetes in the total population were 10.6 (9.92–11.4) and 9.94 (7.39–13.6) per 1000 person-years of follow-up and the corresponding sex specific rates were 10.2 (9.13–11.4) and 9.36 (5.84–14.92) in men and 11.0 (9.99–12.0) and 10.1 (7.24–13.9) in women, respectively. In the multivariable model, the risk for incident diabetes was significantly associated with fasting and 2 hour post challenge plasma glucose as well as family history of diabetes in both men and women. However, among women, only the contribution of wrist circumference to incident diabetes achieved statistical significance [HR: 1.16 (1.03–1.31)] with waist/height ratio being marginally significant [HR: 1.02 (0.99–1.04)]; while among men, only body mass index was a significant predictor [HR: 1.12 (1.02–1.22)]. Additionally, low education level conferred a higher risk for incident diabetes only among men [HR: 1.80 (1.23–2.36); P for interaction with sex = 0.003].

Conclusion

Overall, sex did not significantly modify the impact of risk factors associated with diabetes among Iranian adults; however, among modifiable risk factors, the independent role of lower education and general adiposity in men and central adiposity in women might require different preventive strategies.     

Isolated Short Fetal Femur Length in the Second Trimester and the Association with Adverse Perinatal Outcome: Experiences from a Tertiary Referral Center

Objective

To determine the association between isolated mid-trimester short fetal femur length and adverse perinatal outcome.

Methods

This is a retrospective cohort study of patients with singleton gestations routinely assessed by second trimester ultrasound examination during 2006-2013. A fetal isolated short femur was defined as a femur length (FL) below the 5^th percentile in a fetus with an abdominal circumference greater than the 10^th percentile. Cases of aneuploidy, skeletal dysplasia and major anomalies were excluded. Primary outcomes of interest included the risk of small for gestational age neonates, low birth weight and preterm birth (PTB). Secondary outcome parameters were a 5-min Apgar score less than 7 and a neonatal intensive care unit admission. A control group of 200 fetuses with FL ≥ 5th percentile was used to compare primary and secondary outcome parameters within both groups. Chi-square and Student’s t-tests were used where appropriate.

Results

Out of 608 eligible patients with a short FL, 117 met the inclusion criteria. Isolated short FL was associated with an increased risk for small for gestational age (19.7% versus 8.0%, p = 0.002) neonates, low birth weight (23.9% versus 8.5%, p<0.001), PTB (19.7% versus 6.0%, p<0.001) and neonatal intensive care unit admissions (13.7% versus 3.5%, p = 0.001). The incidence of a 5-min Apgar score less than 7 was similar in both groups.

Conclusion

Isolated short FL is associated with a subsequent delivery of small for gestational age and Low birth weight neonates as well as an increased risk for PTB. This information should be considered when counseling patients after mid-trimester isolated short FL is diagnosed.     

Earlier Menarche Is Associated with Lower Insulin Sensitivity and Increased Adiposity in Young Adult Women

Objective

We aimed to assess whether age at menarche was associated with insulin sensitivity in young adult women.

Methods

We studied 54 healthy young women aged 20–30 years. Participants were grouped according to age at menarche: Early (≤11.0 years; n=13), Average (>12.0 and ≤13.0 years; n=28), and Late (≥14.0 years, n=13). Primary outcome was insulin sensitivity measured using intravenous glucose tolerance tests and Bergman’s minimal model. Body composition was assessed using whole-body dual-energy X-ray absorptiometry.

Results

Earlier menarche was associated with lower insulin sensitivity (p=0.015). There was also a continuous increase in adiposity with younger age at menarche, which was associated with increased weight (p=0.001), BMI (p=0.002), total body fat (p=0.049), and truncal fat (p=0.020). Stratified analyses showed that insulin sensitivity in Early women (5.5 x10^-4·min^-1(mU/l)) was lower than in Average (8.0 x10^-4·min^-1(mU/l), p=0.021) and Late (8.6 x10^-4·min^-1(mU/l), p=0.033) groups. Early women (weight=66.1 kg; BMI=24.1 kg/m²) were considerably heavier and fatter than Average (59.0 kg, p=0.004; 21.4 kg/m², p=0.002) and Late (57.0 kg, p=0.001; 20.8 kg/m², p=0.0009) women.

Conclusions

Early menarche is associated with lower insulin sensitivity and increased adiposity in young adulthood, potentially increasing the risk of type 2 diabetes and the metabolic syndrome later in life.     

Application of Probabilistic Multiple-Bias Analyses to a Cohort- and a Case-Control Study on the Association between Pandemrix?and Narcolepsy

Background

An increase in narcolepsy cases was observed in Finland and Sweden towards the end of the 2009 H1N1 influenza pandemic. Preliminary observational studies suggested a temporal link with the pandemic influenza vaccine Pandemrix™, leading to a number of additional studies across Europe. Given the public health urgency, these studies used readily available retrospective data from various sources. The potential for bias in such settings was generally acknowledged. Although generally advocated by key opinion leaders and international health authorities, no systematic quantitative assessment of the potential joint impact of biases was undertaken in any of these studies.

Methods

We applied bias-level multiple-bias analyses to two of the published narcolepsy studies: a pediatric cohort study from Finland and a case-control study from France. In particular, we developed Monte Carlo simulation models to evaluate a potential cascade of biases, including confounding by age, by indication and by natural H1N1 infection, selection bias, disease- and exposure misclassification. All bias parameters were evidence-based to the extent possible.

Results

Given the assumptions used for confounding, selection bias and misclassification, the Finnish rate ratio of 13.78 (95% CI: 5.72–28.11) reduced to a median value of 6.06 (2.5^th- 97.5^th percentile: 2.49–15.1) and the French odds ratio of 5.43 (95% CI: 2.6–10.08) to 1.85 (2.5^th—97.5^th percentile: 0.85–4.08).

Conclusion

We illustrate multiple-bias analyses using two studies on the Pandemrix^™-narcolepsy association and advocate their use to better understand the robustness of study findings. Based on our multiple-bias models, the observed Pandemrix^™-narcolepsy association consistently persists in the Finnish study. For the French study, the results of our multiple-bias models were inconclusive.     

High Blood Pressure and Its Association with Body Weight among Children and Adolescents in the United Arab Emirates

Objectives

To estimate the prevalence of high blood pressure (BP) and its relationship with obesity among children and adolescents.

Methodology/Principal Findings

In this cross-sectional population (Emirati) representative study, we invited a random sample of 1600 students (grades 1–12) attending 23 out of all 246 schools in the Emirate of Abu Dhabi, United Arab Emirates. But analysis was restricted to Emirati nationals aged 6–17 years. We measured BP, height, weight, waist circumferences (WC), and calculated body mass index (BMI) by standard methods. BP levels ≥90^th percentile but <95^th percentile and ≥ 95^th for age, sex, and height (CDC percentiles) were classified as pre-hypertension (pre-HTN) and hypertension (HTN), respectively. Associations between BP, age, BMI, WC, and sex, were investigated by (multiple) linear regression methods. A total of 999 (47% girls) students provided complete results. The prevalence of pre-HTN was 10.5% and 11.4% and the prevalence of HTN was 15.4% and 17.8% among boys and girls, respectively. The prevalence of systolic/diastolic HTN was 14.4%/2.5% and 14.8/7.4% among boys and girls, respectively. BMI CDC percentile was positively correlated with WC percentile (r = 0.734, p<0.01), and both systolic (r = 0.34, p<0.001) and diastolic (r = 0.21, p<0.001) standardized BP. WC percentile was less strongly correlated with standardized SBP (r = 0.255, p<0.01) and DBP (r = 0.175, p<0.01) than BMI.

Conclusions/Significance

The prevalence of elevated BP, notably systolic was significantly high among the Emirati children and adolescents in Abu Dhabi. High BP was strongly related to body weight, and appears more strongly associated with BMI than WC. Further studies are required to investigate the impact of childhood obesity on HTN.     

Prevalence of Dental Caries and Fissure Sealants in a Portuguese Sample of Adolescents

Introduction

The aims of this study were to assess the prevalence of dental caries and the DMFT index, as well as the distribution pattern of pit and fissure sealants on permanent teeth in a Portuguese sample of adolescents, and to assess whether the existing usage of sealants and socio-demographic factors are correlated to caries prevalence on the examined sample.

Materials and Methods

A cross-sectional study was designed with a sample of 447 adolescents aged 12 to 18 years old, attending a public school in Sátão, Portugal. A self-administered questionnaire with questions about oral health behaviours and socio-economic status was answered by adolescents in the classroom. Clinical examination of oral health status and assessment of fissure sealants were accomplished by only one trained member of the research team.

Results

We obtained a DMFT index of 3.32 (2.92), which indicates a moderate level of prevalence of dental caries. When considering a DMFT = 0, we found significant statistical differences between the parents´ level of education (≤ 4^th grade = 26.3 vs 5^th–12^th grade = 18.8 vs <12^th grade = 43.3, p = 0.001), gender (male = 27.3 vs female = 19.6, p = 0.04), age (≤15 years = 27.1 vs <15 years = 18.5, p = 0.02), presence of fissure sealants (yes = 30.6 vs no = 13.5, p = 0.001) and experience of dental pain (no = 25.4 vs yes = 16.8, p = 0.02). When analyzing the prevalence of fissure sealants, we verified that 58.8% of adolescents had at least one fissure sealant applied. Significant statistical differences were found when analyzing the presence of fissure sealants related with parents´educational level (<9^th grade, OR = 1.56 CI95% = 1.05–2.54), gender (female, OR = 1.86 CI95% = 1.19–2.98), experience of dental pain (yes, OR = 0.62 CI95% = 0.39–0.97) and presence of dental caries (yes, OR = 0.35 CI95% = 0.19–0.65).

Conclusions

The moderate level of caries prevalence reveals the need of improvement of primary prevention interventions among Portuguese adolescents. The establishment of a more targeted preventive program with better and more effective oral health education is essential, having into account socio-demographic aspects.     

Effects of Weight Loss Speed on Kidney Function Differ Depending on Body Mass Index in Nondiabetic Healthy People: A Prospective Cohort

Background

Obesity is associated with diabetes mellitus and cardiovascular diseases. However, it has been reported that weight loss is associated with incident chronic kidney disease (CKD) in healthy males. The purpose of this prospective cohort study is to investigate the effects of weight loss on kidney function in healthy people in terms of body mass index (BMI) and gender.

Methods

A total of 8447 nondiabetic healthy people were enrolled in the Saitama Cardiometabolic Disease and Organ Impairment Study, Japan. Relationships between estimated glomerular filtration rate (eGFR) change, BMI, and BMI change were evaluated using 3D-scatter plots with spline and generalized additive models (GAMs) adjusted for baseline characteristics.

Results

The subjects were stratified into four groups according to BMI. The mean±standard deviations for males and females were, respectively, 40.11±9.49, and 40.3±9.71 years for age and 76.39±17.72 and 71.49±18.4 ml/min/1.73m² for eGFR. GAMs showed that a decreasing BMI change (<-1 kg/m²/year) was associated with a decreasing eGFR change in males with high normal BMIs (22 kg/m²≤BMI<25 kg/m²). A decreasing BMI change (<-2 kg/m²/year) was associated with an increasing eGFR change in overweight males (25 kg/m²≤BMI). Among underweight females (BMI<18.5 kg/m²), decreasing BMI was observed with decreasing eGFR.

Conclusions

These findings suggest that the benefit and risk of weight loss in relation to kidney function differs depending on BMI and weight loss speed, especially in males.     

Red Blood Cell Fatty Acids and Incident Diabetes Mellitus in the Women’s Health Initiative Memory Study

Context

The relations between dietary and/or circulating levels of fatty acids and the development of type 2 diabetes is unclear. Protective associations with the marine omega-3 fatty acids and linoleic acid, and with a marker of fatty acid desaturase activity delta-5 desaturase (D5D ratio) have been reported, as have adverse relations with saturated fatty acids and D6D ratio.

Objective

To determine the associations between red blood cell (RBC) fatty acid distributions and incident type 2 diabetes.

Design

Prospective observational cohort study nested in the Women’s Health Initiative Memory Study.

Setting

General population.

Subjects

Postmenopausal women.

Main Outcome Measures

Self-reported incident type 2 diabetes.

Results

There were 703 new cases of type 2 diabetes over 11 years of follow up among 6379 postmenopausal women. In the fully adjusted models, baseline RBC D5D ratio was inversely associated with incident type 2 diabetes [Hazard Ratio (HR) 0.88, 95% confidence interval (CI) 0.81–0.95) per 1 SD increase. Similarly, baseline RBC D6D ratio and palmitic acid were directly associated with incident type 2 diabetes (HR 1.14, 95% CI 1.04–1.25; and HR 1.24, 95% CI 1.14–1.35, respectively). None of these relations were materially altered by excluding incident cases in the first two years of follow-up. There were no significant relations with eicosapentaenoic, docosahexaenoic or linoleic acids.

Conclusions

Whether altered fatty acid desaturase activities or palmitic acid levels are causally related to the development of type 2 diabetes cannot be determined from this study, but our findings suggest that proportions of certain fatty acids in RBC membranes are associated with risk for type 2 diabetes.     

Midregional Proadrenomedullin Improves Risk Stratification beyond Surgical Risk Scores in Patients Undergoing Transcatheter Aortic Valve Replacement

Background

Conventional surgical risk scores lack accuracy in risk stratification of patients undergoing transcatheter aortic valve replacement (TAVR).Elevated levels of midregional proadrenomedullin (MR-proADM) levels are associated with adverse outcome not only in patients with manifest chronic disease states, but also in the general population.

Objectives

We investigated the predictive value of MR-proADM for mortality in an unselected contemporary TAVR population.

Methods

We prospectively included 153 patients suffering from severe aortic stenosis who underwent TAVR from September 2013 to August 2014. This population was compared to an external validation cohort of 205 patients with severe aortic stenosis undergoing TAVR. The primary endpoint was all cause mortality.

Results

During a median follow-up of 258 days, 17 out of 153 patients who underwent TAVR died (11%). Patients with MR-proADM levels above the 75^th percentile (≥ 1.3 nmol/l) had higher mortality (31% vs. 4%, HR 8.9, 95% CI 3.0–26.0, P < 0.01), whereas patients with EuroSCORE II scores above the 75^th percentile (> 6.8) only showed a trend towards higher mortality (18% vs. 9%, HR 2.1, 95% CI 0.8–5.6, P = 0.13). The Harrell’s C-statistic was 0.58 (95% CI 0.45–0.82) for the EuroSCORE II, and consideration of baseline MR-proADM levels significantly improved discrimination (AUC = 0.84, 95% CI 0.71–0.92, P = 0.01). In bivariate analysis adjusted for EuroSCORE II, MR-proADM levels ≥1.3 nmol/l persisted as an independent predictor of mortality (HR 9.9, 95% CI (3.1–31.3), P <0.01) and improved the model’s net reclassification index (0.89, 95% CI (0.28–1.59). These results were confirmed in the independent validation cohort.

Conclusions

Our study identified MR-proADM as a novel predictor of mortality in patients undergoing TAVR. In the future, MR-proADM should be added to the commonly used EuroSCORE II for better risk stratification of patients suffering from severe aortic stenosis.     

Low Incidence of Renal Dysfunction among HIV-Infected Patients on a Tenofovir-Based First Line Antiretroviral Treatment Regimen in Myanmar

Background

Since 2004, Médecins Sans Frontières-Switzerland has provided treatment and care for people living with HIV in Dawei, Myanmar. Renal function is routinely monitored in patients on tenofovir (TDF)-based antiretroviral treatment (ART), and this provides an opportunity to measure incidence and risk factors for renal dysfunction.

Methods

We used routinely collected program data on all patients aged ≥15 years starting first-line TDF-based ART between January 2012 and December 2013. Creatinine clearance (CrCl) was assessed at base line and six-monthly, with renal dysfunction defined as CrCl < 50ml/min/1.73m². We calculated incidence of renal dysfunction and used Cox regression analysis to identify associated risk factors.

Results

There were 1391 patients, of whom 1372 had normal renal function at baseline. Of these, 86 (6.3%) developed renal dysfunction during a median time of follow-up 1.14 years with an incidence rate of 5.4 per 100 person-years: 78 had CrCl between 30–50ml/min/1.73m² and were maintained on TDF–based ART, but 5 were changed to another regimen: 4 because of CrCl <30ml/min/1.73m². Risk factors for renal dysfunction included age ≥45 years, diagnosed diabetes, underlying renal disease, underweight and CD4 count <200cells/mm³. There were 19 patients with baseline renal dysfunction and all continued on TDF-based ART: CrCl stayed between 30–49 ml/min/1.73m² in five patients while the remainder regained normal renal function.

Conclusions

In a resource-poor country like Myanmar, the low incidence of renal toxicity in our patient cohort suggests that routine assessment of CrCl may not be needed and could be targeted to high risk groups if resources permit.     

Development of an HbA1c-Based Conversion Equation for Estimating Glycated Albumin in a Korean Population with a Wide Range of Glucose Intolerance

Background

Compared to the golden standard glycation index of HbA1c, glycated albumin (GA) has potentials for assessing insulin secretory dysfunction and glycemic fluctuation as well as predicting diabetic vascular complications. However, the reference ranges of GA and a conversion equation need to be clearly defined. We designed this study to determine the reference ranges in patients with normal glucose tolerance (NGT) based on conventional measures of glycemic status and to devise a conversion equation for calculating HbA1c and GA in a Korean population.

Methodology/Principal Findings

In this multicenter, retrospective, cross-sectional study, we recruited antidiabetic drug-naïve patients with available glycemic variables including HbA1c, GA, and fasting plasma glucose regardless of glucose status. For the reference interval of serum GA, 5^th to 95^th percentile value of GA in subjects with NGT was adopted. The conversion equation between HbA1c and GA was devised using an estimating regression model with unknown break-points method. The reference range for GA was 9.0–14.0% in 2043 subjects. The 95^th percentile responding values for FPG, and HbA1c were approximately 5.49 mmol/l, and 5.6%, respectively. The significant glycemic turning points were 5.868% HbA1c and 12.2% GA. The proposed conversion equation for below and above the turning point were GA (%) = 6.960+0.8963 × HbA1c (%) and GA (%) = −9.609+3.720 × HbA1c (%), respectively.

Conclusions/Significance

These results should be helpful in future studies on the clinical implications of high GA relative to HbA1c and the clinical implementation of diabetes management.     

Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium

Background

Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting.

Methods

We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10⁻⁶ in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up.

Results

In Stage I 15 loci passed the threshold of 5×10⁻⁶; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10⁻³) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10⁻⁹). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10⁻³).

Conclusions

QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders.     

Factors Associated with the Perception of Speed among Recreational Skiers

Background

Skiers have to differ between slow to moderate and fast skiing speed to determine their skiing style according to the ISO 11088 standard for setting binding release values. Despite existing evidence that males ski significantly faster than females, no sex-specific factor was inserted into the ISO 11088 standard.

Objective

To evaluate factors potentially associated with the perception of individual skiing speed among recreational skiers.

Methods

Skiing speeds of 416 adult skiers (62% males,) were measured with a radar speed gun. Skiers were interviewed about their age, sex, skill level, risk taking behaviour and helmet use. Finally, skiers had to rate their perceived speed on one out of three speed categories (fast, moderate, slow).

Results

The measured mean speed of this cohort was 48.2±14.3 km/h (30.0±8.9 mph). A total of 32%, 52%, and 16% of skiers perceived their actual speed as fast, moderate and slow, respectively. Mean speed differed significantly between the 3 speed categories with a mean of about 53.5±13.7 km/h (33.2±8.5 mph) for fast, 47.6±14.0 km/h (29.6±8.7 mph) for moderate, and 39.4±12.2 km/h (24.5±7.6 mph) for slow skiing, respectively. Sex (η² = .074), skill level (η² = .035) and risk taking behavior (η² = .033) showed significant differences of skiing speeds with regard to the 3 categories of speed perception (all p < .001) while age groups and ski helmet use did not. Males, more skilled skiers and risky skiers perceived their actual speed as fast, moderate and slow, when skiing up to 10 km/h (6 mph) faster compared to females, less skilled and cautious skiers.

Conclusion

The perception of skiing speed as fast, moderate or slow depends on sex, skill level, and risk taking behaviour. These findings should be considered when discussing the introduction of a sex factor into the ISO 11088 standard for setting binding release values.