A Prospective Study of Lipids in Adult Women With Turner Syndrome.

Context: Turner syndrome (TS) is a rare genetic syndrome with an increased mortality, mainly attributed to cardiovascular disease. Objective: This work aimed to investigate and correlate the lipid profile in adult women with TS to clinical characteristics. Methods: A 12-year prospective cohort study, including 4 study visits, was conducted at a specialist hospital. A total of 102 women with TS qualified for inclusion. Excluding missing variables and participants lost to follow-up, 86 women (mean age 38.1 years; range, 18.4-62.1 years) were included in this study. Fifty-three women completed the study. Repeated-measurement analysis was performed, using total cholesterol (Total-C), low-density lipoprotein (LDL), triglycerides (TGs), and high-density lipoprotein (HDL) as outcome variables and age, karyotype, body mass index (BMI), treatment with statins, antidiabetics, and hormone replacement therapy as explanatory variables. Principal component analysis (PCA) and partial least squares (PLS) analysis were performed at the first study visit. Results: Hyperlipidemia was present in 30% of the TS cohort. Total-C increased with age (0.12 mmol/L/y; P = .016). LDL (P = .08), TGs (P = .14), and HDL (P = .24) were not associated with age. BMI significantly increased total-C (0.19 mmol/L/kg/m2; P = .006), LDL (0.63 mmol/L/kg/m2; P < .001), and TGs (0.80 mmol/L/kg/m2; P < .001) and decreased HDL (-0.59 mmol/L/kg/m2; P < .001). PCA and PLS analysis found correlations between weight and BMI and total-C, LDL, and TGs. Conclusion: Hyperlipidemia is more prevalent in adult women with TS across adulthood compared to the background population. Total-C, LDL, TGs, and HDL were significantly associated with BMI characterizing the atherogenic profile in adult women with TS.

Upscaling of Denitrification Rates from Point to Catchment Scales for Modeling of Nitrate Transport and Retention.

The spatial and temporal variability of denitrification makes it challenging to integrate conceptual, process-based understandings of nitrate transport and retention into numerical modeling at the catchment scale, although it is critical for the realism and predictive power of the model. In this study, we propose a novel approach where the conceptual understandings of the spatial structure of denitrification zones and the corresponding representative denitrification rates are transformed into a form that can be integrated into a multi-point statistical simulation framework. This is done by constructing a denitrification training image (TI) coupled to a geophysically based TI of the hydrogeological structure. The field observations and laboratory analyses of denitrification rates and the chemistry of water and sediment revealed that the study catchment's subsurface can be characterized by three zones: (1) the oxic zone with no nitrate reduction; (2) the slow-denitrification zone (mean of ln-transformed rate = -1.19 ± 0.52 mg N L-1 yr-1); and (3) the high-denitrification zone (mean of ln-transformed rate = 3.86 ± 1.96 mg N L-1 yr-1). The underlying controls on the spatial distribution of these zones and the representativeness of denitrification rates were investigated. Then, a TI illustrating the subsurface structure of the denitrification zone was constructed by synthesizing the results of these geochemical interpretations and the hydrogeology TI.

Natural History of Hypertension in Turner Syndrome During a 12-Year Pragmatic Interventional Study.

Turner syndrome is caused by complete or partial X monosomy in some or all cells. Cardiovascular complications are dominant, including increased blood pressure (BP), leading to early-onset hypertension. The aim is to describe the debut, development, and treatment of hypertension in Turner syndrome during a 12-year pragmatic interventional study to help identify risk factors associated with hypertension. One hundred and two women (aged 38±11 years, range: 18-62 years) with Turner syndrome verified by karyotyping (45, X: n=58 [57%]) were included consecutively. Ambulatory BPs were recorded over 24 hours with oscillometric measurements every 20 minutes. Antihypertensive treatment was recommended if the BP was above 135/85 mm Hg during the daytime. Overall, systolic BP, diastolic BP, and pulse pressure increased during the study, while heart rate decreased. The number of patients treated with antihypertensive medicine increased from 29 (28.71%) at baseline to 34 (53.13%) at the end of study. Twenty-four-hour systolic BP and 24-hour pulse pressure increased significantly with age, while 24-hour heart rate decreased with age, and diastolic BP was insignificantly affected by age. Antihypertensive treatment lowered systolic BP (24-hour: -5 mm Hg), diastolic BP (24-hour: -5 mm Hg), and diminished the pulse pressure (24-hour: -6 mm Hg) but did not affect nighttime systolic BP. Antihypertensive treatment did not affect heart rate. Our study showed that both systolic and diastolic BP increases significantly in women with Turner syndrome resulting in an increased risk of cardiovascular comorbidities. This increment should be considered of multifactorial origin with many contributing factors which is supported by our results.

A Quantitative General Population Job Exposure Matrix for Occupational Noise Exposure.

Occupational noise exposure is a known risk factor for hearing loss and also adverse cardiovascular effects have been suggested. A job exposure matrix (JEM) would enable studies of noise and health on a large scale. The objective of this study was to create a quantitative JEM for occupational noise exposure assessment of the general working population. Between 2001-2003 and 2009-2010, we recruited workers from companies within the 10 industries with the highest reporting of noise-induced hearing loss according to the Danish Working Environment Authority and in addition workers of financial services and children day care to optimize the range in exposure levels. We obtained 1343 personal occupational noise dosimeter measurements among 1140 workers representing 100 different jobs according to the Danish version of the International Standard Classification of Occupations 1988 (DISCO 88). Four experts used 35 of these jobs as benchmarks and rated noise levels for the remaining 337 jobs within DISCO 88. To estimate noise levels for all 372 jobs, we included expert ratings together with sex, age, occupational class, and calendar year as fixed effects, while job and worker were included as random effects in a linear mixed regression model. The fixed effects explained 40% of the total variance: 72% of the between-jobs variance, -6% of the between-workers variance and 4% of the within-worker variance. Modelled noise levels showed a monotonic increase with increasing expert score and a 20 dB difference between the highest and lowest exposed jobs. Based on the JEM estimates, metal wheel-grinders were among the highest and finance and sales professionals among the lowest exposed. This JEM of occupational noise exposure can be used to prioritize preventive efforts of occupational noise exposure and to provide quantitative estimates of contemporary exposure levels in epidemiological studies of health effects potentially associated with noise exposure.

A placebo-controlled randomized study with testosterone in Klinefelter syndrome: beneficial effects on body composition.

CONTEXT AND OBJECTIVE: Males with Klinefelter syndrome (KS) are typically hypogonadal with a high incidence of metabolic disease, increased body fat and mortality. Testosterone treatment of hypogonadal patients decrease fat mass, increase lean body mass and improve insulin sensitivity, but whether this extends to patients with KS is presently unknown. RESEARCH DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled, BMI-matched cross-over study, 13 males with KS (age: 34.8 years; BMI: 26.7 kg/m2) received testosterone (Andriol®) 160 mg per day (testosterone) or placebo treatment for 6 months. Thirteen age- and BMI-matched healthy controls were recruited. DEXA scan, abdominal computed tomography (CT) scan and a hyperinsulinemic-euglycemic clamp, muscle strength and maximal oxygen uptake measurement were performed. RESULTS: Total lean body mass and body fat mass were comparable between testosterone-naïve KS and controls using DEXA, whereas visceral fat mass, total abdominal and intra-abdominal fat by CT was increased (P < 0.05). Testosterone decreased total body fat (P = 0.01) and abdominal fat by CT (P = 0.04). Glucose disposal was similar between testosterone-naïve KS and controls (P = 0.3) and unchanged during testosterone (P = 0.8). Free fatty acid suppression during the clamp was impaired in KS and maximal oxygen uptake was markedly lower in KS, but both were unaffected by treatment. Testosterone increased hemoglobin and IGF-I. CONCLUSION: Testosterone treatment in adult males with KS for 6 months leads to favorable changes in body composition with reductions in fat mass, including abdominal fat mass, but does not change measures of glucose homeostasis.

Aortic growth rates are not increased in Turner syndrome-a prospective CMR study.

BACKGROUND: Aortic disease is a key determinant of outcomes in Turner syndrome (TS). The present study characterized aortic growth rates and outcomes over nearly a decade in adult women with TS. METHODS AND RESULTS: Prospective observational study assessing aortic diameters twice with cardiovascular magnetic resonance imaging in women with TS [N = 91; mean follow-up 8.8 ± 3.3 (range 1.6-12.6) years] and healthy age-matched female controls [N = 37; mean follow-up 6.7 ± 0.5 (range 5.9-8.1) years]. Follow-up also included aortic outcomes and mortality, antihypertensive treatment and ambulatory blood pressure. Aortic growth rates were similar or smaller in TS, but the variation was larger. The proximal aorta in TS grew by 0.20 ± 0.26 (mid-ascending) to 0.32 ± 0.36 (sinuses) mm/year. This compared to 0.26 ± 0.14 (mid-ascending) and 0.32 ± 0.17 (sinuses) mm/year in the controls. During 799 years at risk, 7 suffered an aortic outcome (1 aortic death, 2 aortic dissections, 2 aortic interventions, 2 surgical aortic listings) with further 2 aortic valve replacements. At baseline, two women were excluded. One died during subacute aortic surgery (severe dilatation) and one had a previously undetected type A dissection. The combined aortic outcome rate was 1126 per 100 000 observation years. The aortic and all-cause mortality rates were 1 per 799 years (125 deaths per 100 000 observation years) and 9 per 799 years (1126 deaths per 100 000 observation years). Aortic growth patterns were particularly perturbed in bicuspid aortic valves (BAV) and aortic coarctation (CoA). CONCLUSION: Aortic growth rates in TS are not increased. BAVs and CoA are major factors that impact aortic growth. Aortic outcomes remain a concern.

Crowding in the emergency department in the absence of boarding - a transition regression model to predict departures and waiting time.

BACKGROUND: Crowding in the emergency department (ED) is associated with increased mortality, increased treatment cost, and reduced quality of care. Crowding arises when demand exceed resources in the ED and a first sign may be increasing waiting time. We aimed to quantify predictors for departure from the ED, and relate this to waiting time in the ED before departure. METHODS: We utilised administrative data from the ED and calculated number of arrivals, departures, and the resulting queue in 30 min time steps for all of 2013 (N = 17,520). We build a transition model for each time step using the number of past departures and pre-specified risk factors (arrivals, weekday/weekend and shift) to predict the expected number of departures and from this the expected waiting time in the ED. The model was validated with data from the same ED collected March through August 2014. RESULTS: We found that the number of arrivals had the greatest independent impact on departures with an odds ratio of 0.942 (95%CI: 0.937;0.948) corresponding to additional 7 min waiting time per new arrival in a 30 min time interval with an a priori time spend in the ED of two hours. The serial correlation of departures was present up to one and a half hour previous but had very little effect on the estimates of the risk factors. Boarding played a negligible role in the studied ED. CONCLUSIONS: We present a transition regression model with high predictive power to predict departures from the ED utilising only system level data. We use this to present estimates of expected waiting time and ultimately crowding in the ED. The model shows good internal validity though further studies are needed to determine generalisability to the performance in other settings.

Five-Year Randomized Study Demonstrates Blood Pressure Increases in Young Women With Turner Syndrome Regardless of Estradiol Dose.

We evaluated the development in blood pressure (BP) and heart rate in young women with Turner syndrome (TS) and investigated potential influencing cofactors. Twenty TS women (mean±SD, 22.9±2.3 years of age) were investigated in a 5-year prospective setting. Data were derived from a randomized controlled clinical trial investigating 2 different doses of estradiol treatment (2 mg 17ß-estradiol per day and placebo or 2+2 mg 17ß-estradiol per day). A control group of 12 healthy age-matched young women (mean±SD, 23.11±2.2 years of age) was examined at the end of the study. BP and lipids were monitored yearly. At the end of the study, TS (n=15) and controls were examined by 24-hour ambulatory BP monitoring. Systolic and diastolic BPs increased regardless of estradiol dose ( P=0.005 and P=0.009) in TS patients, whereas heart rate decreased ( P=0.05). Neither body mass index, height, weight, nor lipids contributed significant to the changes. There was no difference in BP, heart rate, or lipids because of treatment. At the end of the study, diastolic BP and heart rate were significantly higher in TS during day, night, and over 24 hours. Systolic BP increased insignificantly. Lipids did not change during the study period, but body mass index determined individual levels. In conclusion, systolic and diastolic BPs increase significantly in late adolescence and early adulthood in TS. It remains an enigma why BP increases early in life in TS. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00134745.

Integrated model of insulin and glucose kinetics describing both hepatic glucose and pancreatic insulin regulation.

BACKGROUND AND OBJECTIVES: Modeling of glucose kinetics has to a large extent been based on models with plasma insulin as a known forcing function. Furthermore, population-based statistical methods for parameter estimation in these models have mainly addressed random inter-individual variations and not intra-individual variations in the parameters. Here we present an integrated whole-body model of glucose and insulin kinetics which extends the well-known two-compartment glucose minimal model. The population-based estimation technique allow for quantification of both random inter- and intra-individual variation in selected parameters using simultaneous data series on glucose and insulin. METHODS: We extend the two-compartment glucose model into a whole-body model for both glucose and insulin using a simple model for the pancreas compartment which includes feedback of glucose on both insulin secretion and formation of insulin in pancreas. The model has 15 unknown parameters of which 8 have been selected for both intra- and inter-individual variations. The statistical technique for parameter estimation is based on first order conditional estimation. RESULTS: The model has been evaluated on two datasets: Study group 1 includes 13 healthy subjects with 3-5 repeated IVGTT series of simultaneous plasma glucose and insulin measurements and Study group 2 includes 26 obese patients (3 subgroups: 10 type 2 diabetes (T2D), 7 impaired glucose tolerance (IGT) and 9 normal glucose tolerance (NGT)) with a single IVGTT series. In general the estimated population parameters compares well with reported values in similar studies. Overall the model fits the data series well and the random variation in the 8 selected parameters can account for both intra- and inter-individual variations in the data series. Simulation studies perform reasonable in response to either a slow glucose infusion or a staircase experiment with increasing glucose infusion. Furthermore, the parameters related to the pancreas compartment add useful interpretations in relation to discrimination between populations with varying degree of glucose intolerance. CONCLUSIONS: We report a new and improved whole-body model of glucose and insulin kinetics which performs robustly under differing conditions and adds useful interpretations in relation to glucose intolerance.

Determinants for adherence to continuous positive airway pressure therapy in obstructive sleep apnea.

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is an efficacious treatment for patients diagnosed with obstructive sleep apnea (OSA). However, there are only few data on long-term adherence. The aim of this study is to quantify the extent of non-adherence and describe the clinical characteristics. METHODS: A retrospective study including 695 patients with newly diagnosed OSA and prescribed CPAP therapy within an inclusion period of 14 months. All patients were offered free of charge individually adjusted CPAP therapy. Data on comorbidity, medication, BMI and Epworth Sleepiness Score (ESS) were obtained by questionnaires and consultation with an otorhinolaryngeal specialist. RESULTS: The median follow-up time after initiating CPAP therapy was 3.0 (range 2.4-3.6) years. An adherence rate of 89% was found for severe OSA, 71% for moderate OSA and 55% for mild OSA. 18% initiated humidification. Patients adherent to CPAP had a significantly higher Body Mass Index (BMI), Apnea Hypopnea Index (AHI), Oxygen Desaturation Index (ODI) and ESS compared to non-adherent patients. Furthermore, adherence was associated with a higher frequency of observed interrupted breathing, a less frequent use of hypnotic drugs, fewer smokers, and they were more often offered humidification. Age, gender and comorbidity were not significantly associated with adherence. In a Cox model only AHI (Hazard Ratio (HR) 0.963, p < 0.001), ESS (HR 0.939, p = 0.001) and smoking (HR 1.576, p = 0.022) were independently associated with CPAP non-adherence. CONCLUSIONS: The severity of OSA, subjective daytime sleepiness and smoking status are independently related to adherence to CPAP therapy.

Evaluation of interarm blood pressure differences using the Microlife WatchBP Office in a clinical setting.

OBJECTIVE: The aim of this study was to evaluate the usefulness of Microlife WatchBP Office and the effect of increasing the number of measurements in the clinical evaluation of systolic interarm difference (IAD). PATIENTS AND METHODS: Office blood pressure was measured simultaneously on both arms in 339 patients (85% diabetic) using the Microlife WatchBP Office, a fully automatic, oscillometric device. The patients included were all scheduled for ambulatory blood pressure measurement at the outpatient clinic of endocrinology at Silkeborg Regional Hospital, Denmark. Two successive sets of three individual measurements were made. A statistical analysis of variance was carried out on the measurements. RESULTS: In the first set of measurements, the mean IAD was -0.3 mmHg and the prevalence of IAD greater than or equal to 10 mmHg was 9.1%. Only 7.6% of the patients with an IAD less than 10 mmHg in the first set of measurements had an IAD greater than or equal to 10 mmHg in the second set of measurements. The 95% limits of agreement for the mean IAD for a single set of three measurements were ±13.16 mmHg. The probability of detecting an IAD more than 10 mmHg only increased slightly with an increasing number of measurements. CONCLUSION: A single set of triplicate measurements using Microlife WatchBP is an acceptable method for evaluating IAD as more measurements do little to improve the probability of detecting an IAD more than 10 mmHg because of high intraindividual variation.

The role of retinopathy distribution and other lesion types for the definition of examination intervals during screening for diabetic retinopathy.

PURPOSE: It has previously been shown that the intervals between screening examinations for diabetic retinopathy can be optimized by including individual risk factors for the development of the disease in the risk assessment. However, in some cases, the risk model calculating the screening interval may recommend a different interval than an experienced clinician. The purpose of this study was to evaluate the influence of factors unrelated to diabetic retinopathy and the distribution of lesions for discrepancies between decisions made by the clinician and the risk model. METHODS: Therefore, fundus photographs from 90 screening examinations where the recommendations of the clinician and a risk model had been discrepant were evaluated. Forty features were defined to describe the type and location of the lesions, and classification and ranking techniques were used to assess whether the features could predict the discrepancy between the grader and the risk model. RESULTS: Suspicion of tumours, retinal degeneration and vascular diseases other than diabetic retinopathy could explain why the clinician recommended shorter examination intervals than the model. Additionally, the regional distribution of microaneurysms/dot haemorrhages was important for defining a photograph as belonging to the group where both the clinician and the risk model had recommended a short screening interval as opposed to the other decision alternatives. CONCLUSIONS: Features unrelated to diabetic retinopathy and the regional distribution of retinal lesions may affect the recommendation of the examination interval during screening for diabetic retinopathy. The development of automated computerized algorithms for extracting information about the type and location of retinal lesions could be expected to further optimize examination intervals during screening for diabetic retinopathy.

A generic method for evaluating crowding in the emergency department.

BACKGROUND: Crowding in the emergency department (ED) has been studied intensively using complicated non-generic methods that may prove difficult to implement in a clinical setting. This study sought to develop a generic method to describe and analyse crowding from measurements readily available in the ED and to test the developed method empirically in a clinical setting. METHODS: We conceptualised a model with ED patient flow divided into separate queues identified by timestamps for predetermined events. With temporal resolution of 30 min, queue lengths were computed as Q(t + 1) = Q(t) + A(t) - D(t), with A(t) = number of arrivals, D(t) = number of departures and t = time interval. Maximum queue lengths for each shift of each day were found and risks of crowding computed. All tests were performed using non-parametric methods. The method was applied in the ED of Aarhus University Hospital, Denmark utilising an open cohort design with prospectively collected data from a one-year observation period. RESULTS: By employing the timestamps already assigned to the patients while in the ED, a generic queuing model can be computed from which crowding can be described and analysed in detail. Depending on availability of data, the model can be extended to include several queues increasing the level of information. When applying the method empirically, 41,693 patients were included. The studied ED had a high risk of bed occupancy rising above 100 % during day and evening shift, especially on weekdays. Further, a 'carry over' effect was shown between shifts and days. CONCLUSIONS: The presented method offers an easy and generic way to get detailed insight into the dynamics of crowding in an ED.

Evaluation of Endothelial Pump Function in Fuchs Endothelial Dystrophy Before and After Endothelial Keratoplasty.

PURPOSE: To evaluate the endothelial pump function in vivo after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: In a prospective controlled trial, a group of 17 patients with Fuchs endothelial corneal dystrophy (FECD) eligible for DSAEK surgery and a group of 15 patients with cataract but with normal corneas eligible for cataract surgery (controls) were formed. A low oxygen-permeable contact lens was used to induce corneal edema. Changes in central corneal thickness were monitored as an indirect measure of endothelial cell pump function. Experiments were performed before surgery and repeated 12 months after surgery. RESULTS: Comparing the FECD and control groups before surgery, there was 24.8% (13.5-36.1) more edema in the FECD group after 2 hours (P < 0.001) and 19.9% (8.6-31.3) more edema in the FECD group after 3 hours (P < 0.001). In the FECD group, there was 15% (3.1-26.9) less edema after DSAEK than before surgery (P = 0.015) after 3 hours. Comparing the DSAEK-treated eyes with the control eyes 12 months after surgery; there was 12.8% (3.5-22.1) more edema in the DSAEK group after 2 hours (P = 0.007), but after 3 hours, the percentages of edema were similar (P = 0.11). CONCLUSIONS: Twelve months after DSAEK surgery, the grafted endothelium cleared the induced edema as fast as the control group, indicating a viable and near-normal endothelial pump function. However, significant differences in the deswelling patterns were detected, which may be caused by the added corneal stroma after DSAEK.

Interleukin 20 regulates dendritic cell migration and expression of co-stimulatory molecules.

BACKGROUND: Psoriasis is an inflammatory disease characterized by leukocyte skin infiltration. Interestingly, recent works suggest that the migration of dendritic cells (DCs) is abnormal in psoriatic skin. DCs have significant role in regulating the function of T lymphocytes, at least in part influenced by the local environment of cytokines. In psoriatic skin lesions the expression of IL-20 is highly up-regulated. It is unclear if this cytokine has any influence on DCs. METHODS: Here, we investigated the influence of IL-20 in monocyte-derived dendritic cell (MDDCs) in vitro. This work addressed IL-20 effects on DC maturation, receptor expression and signaling. By use of extra cellular matrix components mimicking the skin environment, we also studied the functional effects of IL-20 on the chemotactic migration of DCs. Based on the recent finding that CD18 integrin are shed during migration of myeloid leukocytes, the concentration of these adhesion molecules was measured in MDDCs culture supernatants post migration. RESULTS: Following stimulation with IL-20, immature human MDDCs enhanced the expression of the co-stimulatory molecule CD86, further enabling activation of the p38 MAPK, but not the STAT3, pathway. IL-20 increased the migration of MDDCs in a biphasic response narrowly controlled by the interleukin concentration. A concomitant change in the shedding of CD18 integrins suggested that these adhesion molecules play a role in the migration of the MDDCs through the extracellular matrix layer. CONCLUSION: Taken together, our findings points to a possible, yet subtle, role of IL-20 in DCs migration. The biphasic response suggests that the aberrant IL-20 expression in psoriasis impedes DC migration, which could be a part of the processes that precipitates the dysregulated inflammatory response associated with this disease.

Comparison of sensitivity and specificity of 4 methods for detection of Giardia duodenalis in feces: immunofluorescence and PCR are superior to microscopy of concentrated iodine-stained samples.

For decades, microscopy of feces after formol-ethylacetate (FEA) concentration and iodine staining has been the routine test for intestinal protozoa. Lately, polymerase chain reaction or fluorescence-labeled parasite-specific antibodies have been introduced, but their place in everyday routine diagnostics has not yet been established. We compared FEA and salt-sugar flotation (SSF) concentration followed by microscopy of iodine-stained concentrate and immunofluorescence assay (IFA) and real-time polymerase chain reaction (qPCR) for detection of Giardia duodenalis in human feces. The median number of Giardia cysts found by FEA in 19 Giardia-positive samples was 50 cysts per gram (CPG), by SSF 350 CPG, by IFA 76,700 CPG, and by qPCR 316,000 CPG. We next tested 455 consecutive samples for presence of Giardia cysts. Using IFA as reference, qPCR had a sensitivity of 91%, specificity of 95.1%, a false-positive rate of 50%, a false-negative rate of 0.48%, a positive predictive value of 50%, and a negative predictive value of 99.5%. In conclusion, qPCR and IFA were significantly more sensitive than microscopy of iodine-stained concentrates using either FEA or SSF. We suggest, when using qPCR, that positive samples are verified by IFA to prevent false-positive results.

The magnitude of placebo analgesia effects depends on how they are conceptualized.

OBJECTIVE: Placebo effects are usually calculated as the difference between placebo treatments and no treatments. Recently, placebo-like effects have been investigated using open and hidden administrations of active treatments. The aim of the study was to directly compare the two types of placebo effects and examine how they are influenced by personality traits. METHODS: In a within-subject, randomized, blinded, balanced placebo trial design study with 48 healthy volunteers, we compared placebo and placebo-like effects and tested if expectancy, absorption and suggestibility correlated with these effects. Subjects completed the Tellegen Absorption Scale and the Sensory Suggestibility Scale, and pain was induced by injections of hypertonic saline into the masseter muscle. Participants received four injections of hypertonic saline with lidocaine or matching placebo in randomized order: open treatment, hidden treatment, placebo and control. The placebo effect was defined as the difference in pain between the placebo and the control condition and the placebo-like effect as the difference in pain between the open and hidden condition. RESULTS: Placebo effects were significant both in the traditional paradigm: mean placebo effect AUC 1626 mm(2) (95% CI 958-2293) and the open-hidden paradigm: mean placebo-like effect AUC 801 mm(2) (95% CI 134-1469), but there was a significant difference between the magnitude of the two effects (p=0.049). Absorption and suggestibility did not predict the placebo or the placebo-like effect. Estimated expected pain relief correlated with placebo effects but not placebo-like effects. CONCLUSION: The magnitude of placebo effects differs depending on how they are conceptualized and calculated.

Clinical findings in a multi-ethnic adult hepatitis B virus patient population in Denmark with emphasis on genotypic characteristics.

OBJECTIVE: Most knowledge about chronic hepatitis B virus (HBV) infection is based upon studies in high-endemic areas with one or two predominant genotype(s). The aim of the study was to describe clinical characteristics of a heterogeneous genotypic HBV patient population in a low-endemic European country. METHODS: Data from HBV patients currently followed in a Danish university hospital and affiliated regional clinics were reviewed in accordance to genotype status. RESULTS: Of 540 HBV patients, 462 (86%) were of non-Danish ethnicity originating from 43 different countries. HBV genotype was known in 37% of the patients: A (11%), B (25%), C (25%), D (37%) and E (2%). Logistic regression analysis of pre-treatment data among genotype A-D patients receiving nucleos(t)ide analogue (NA) therapy revealed a decreased HBeAg rate by age (OR = 0.93; CI: 0.89-0.97; p < 0.01) and an increased rate in genotype C patients (OR = 20.5; CI: 3.3-129; p < 0.01). Among untreated patients HBeAg rate was also significantly decreased by age (OR = 0.90 (0.85:0.95; p < 0.0001), whereas the rate was increased in both genotype B and C patients (OR = 7.5; CI: 1.8-30.5; p < 0.01 and OR = 12.2; CI: 3.2-46.6; p < 0.001, respectively). No significant variation was found in HBV DNA level in any of the two groups when adjusting for age, gender, genotype and HBeAg. Increased liver pathology prevalence was, irrespectively of treatment status, associated to age and male gender, but not to any genotype. CONCLUSION: In this study population, genotype B and C was found associated with higher HBeAg rate but not with increased liver pathology.

Exposure-affecting factors of dairy farmers' exposure to inhalable dust and endotoxin.

INTRODUCTION: Studies on determinants of dairy farmers' exposure to dust and endotoxin have been sparse and so far none has addressed the combined effect of tasks and farm characteristics. OBJECTIVE: To study whether and how work tasks and specific stable characteristics influence the level of dairy farmers' personal exposure to inhalable dust and endotoxin. METHODS: We applied an observational design involving full-shift repeated personal measurements of inhalable dust and endotoxin exposure among 77 subjects (owners and farm workers) from 26 dairy farms. Performed tasks were self-registered in activity diaries, and information on stable characteristics was collected through personal interviews and walk-through surveys. Associations between exposure, tasks, and stable characteristics were examined in linear mixed-effect models with individual and farm treated as random effects. Separate as well as combined models for tasks and stable characteristics were elaborated. RESULTS: The 124 personal samples collected had a geometric mean level (geometric standard deviation) of 360 EU m(-3) (3.8) for endotoxin exposure and of 1.0mg m(-3) (2.7) for dust exposure. Identified factors that increased endotoxin exposure included a lower outdoor temperature and use of slope-based or back-flushed slurry systems along with milking, distribution of bedding, and handling of feed and seeds in barns. For dust, exposure was higher when fully automatic (robotic) milking was used and during re-penning of animals, handling of feed and seeds, handling of silos and when distributing bedding. Dust exposure increased also as a result of use of rail feed dispensers in a model without fully automatic milking. CONCLUSIONS: The current exposure to dust and in particular endotoxin among Danish dairy farmers demand effective strategies to reduce their exposure. The present findings suggest that future interventions should focus on feeding and manure handling systems. Use of respirators during handling of feed and distribution of bedding should be advised until adequate risk management measures have been established. The expected increased use of fully automatic milking in the future might increase dust exposure of dairy farmers.

Prediction of aortic dilation in Turner syndrome--the use of serial cardiovascular magnetic resonance.

BACKGROUND: Identification of the subset females with Turner syndrome who face especially high risk of aortic dissection is difficult, and more optimal risk assessment is pivotal in order to improve outcomes. This study aimed to provide comprehensive, dynamic mathematical models of aortic disease in Turner syndrome by use of cardiovascular magnetic resonance (CMR). METHODS: A prospective framework of long-term aortic follow-up was used, which comprised diameters of the thoracic aorta prospectively assessed at nine positions by CMR at the three points in time (baseline [n = 102, age 38 ± 11 years], follow-up [after 2.4 ± 0.4 years, n = 80] and end-of-study [after 4.8 ± 0.5 years, n = 78]). Mathematical models were created that cohesively integrated all measurements at all positions, from all visits and for all participants, and using these models cohesive risk factor analyses were conducted based on which predictive modeling was performed on which predictive modelling was performed. RESULTS: The cohesive models showed that the variables with effect on aortic diameter were aortic coarctation (P < 0.0001), bicuspid aortic valves (P < 0.0001), age (P < 0.0001), diastolic blood pressure (P = 0.0008), body surface area (P = 0.015) and antihypertensive treatment (P = 0.005). Oestrogen replacement therapy had an effect of borderline significance (P = 0.08). From these data, mathematical models were created that enabled preemption of aortic dilation from CMR derived aortic diameters in scenarios both with and without known risk factors. The fit of the models to the actual data was good. CONCLUSION: The presented cohesive model for prediction of aortic diameter in Turner syndrome could help identifying females with rapid growth of aortic diameter, and may enhance clinical decision-making based on serial CMR.