Identification of extreme motor phenotypes in Huntington's disease.

The manifestation of motor signs in Huntington's disease (HD) has a well-known inverse relationship with HTT CAG repeat length, but the prediction is far from perfect. The probability of finding disease modifiers is enhanced in individuals with extreme HD phenotypes. We aimed to identify extreme HD motor phenotypes conditional on CAG and age, such as patients with very early or very late onset of motor manifestation. Retrospective data were available from 1,218 healthy controls and 9,743 HD participants with CAG repeats ≥40, and a total of about 30,000 visits. Boundaries (2.5% and 97.5% quantiles) for extreme motor phenotypes (UHDRS total motor score (TMS) and motor age-at-onset) were estimated using quantile regression for longitudinal data. More than 15% of HD participants had an extreme TMS phenotype for at least one visit. In contrast, only about 4% of participants were consistent TMS extremes at two or more visits. Data from healthy controls revealed an upper cut-off of 13 for the TMS representing the extreme of motor ratings for a normal aging population. In HD, boundaries of motor age-at-onset based on diagnostic confidence or derived from the TMS data cut-off in controls were similar. In summary, a UHDRS TMS of more than 13 in an individual carrying the HD mutation indicates a high likelihood of motor manifestations of HD irrespective of CAG repeat length or age. The identification of motor phenotype extremes can be useful in the search for disease modifiers, for example, genetic or environmental such as medication. © 2016 Wiley Periodicals, Inc.

Pre-pregnancy obesity compromises obstetric and neonatal outcomes.

OBJECTIVE: Obesity is an important issue among fertile women as it may affect obstetric and neonatal outcomes. METHODS: Obstetric and neonatal outcomes of primiparous women were retrospectively analyzed in non-obese (n=11387) and obese (n=943) women. A subgroup analysis was performed in obese women divided into three groups: Grade I obesity (Group A, n=654), Grade II obesity (Group B, n=192), and Grade III obesity (Group C, n=97). Odds ratios (OR) were expressed with the corresponding 95% confidence intervals (CI). RESULTS: The incidence of gestational diabetes (non-obese, 1.9%; obese, 7.6%; Group C, 19.6%) and preeclampsia (non-obese, 3.3%; obese, 13.5%; Group C, 17.5%) increased with rising weight. The risk of non-elective cesarean section was significantly higher in obese women than in non-obese women (21.7% vs. 13.2%). The risk of extreme preterm birth (before 28 weeks of gestation) doubled in the Grade I obesity group (OR, 2.1; 95% CI, 1.4-3.2) and nearly tripled in women with body mass index ≥35 kg/m2 (OR, 2.9; 95% CI, 1.7-4.9). CONCLUSION: Pre-pregnancy obesity is associated with higher incidences of gestational diabetes and preeclampsia. Our study shows that obese women have a higher risk of non-elective cesarean section and preterm birth.

Which variables are associated with blood glucose levels outside the target range in surgical critically ill patients? A retrospective observational study.

BACKGROUND: The aim of the present study is to determine the variables affecting blood glucose concentrations outside the target range of 80 and 150 mg/dl in critically ill surgical patients. METHODS: All critically ill surgical patients admitted to a university ICU, from 01/2007 to 12/2008, were surveyed daily using computer assistance with respect to minimal and maximal daily blood glucose concentrations, application of insulin and demographic/clinical variables. Multiple logistic regression for clustered data with backward elimination was performed to identify variables strongly associated with blood glucose concentrations < 80 mg/dl or ≥ 150 mg/dl in 804 patients with an ICU stay > 72 hours. RESULTS: Application of insulin (odds ratio (OR) 2.1, with corresponding 95% confidence interval (CI) 1.7; 2.6), noradrenaline (OR 1.4, 95% CI 1.2 - 1.8) or steroids (1.3, 1.003 - 1.7), and age (per year) (1.02, 1.01 - 1.03) were associated with an increased risk of blood glucose concentrations < 80 mg/dl. In analogy, application of insulin (OR 2.4, 95% CI 2.0 - 2.7), noradrenaline (1.4, 1.2 - 1.6) or steroids (1.4, 1.2 - 1.7), severe sepsis (1.2, 1.1 - 1.4), neurosurgery (OR 1.0) compared to abdominal, vascular and trauma surgery, and age (per year) (1.01, 1.01 - 1.02), were associated with an increased risk of blood glucose concentrations ≥ 150 mg/dl. CONCLUSIONS: Critically ill surgical patients are at an increased risk for fluctuating blood glucose concentrations ranging < 80 mg/dl or ≥ 150 mg/dl in particular if they are of advanced age and require administration of insulin, noradrenaline, and/or steroids. Patients who underwent neurosurgery and/or presented with severe sepsis/shock are those in particular at risk for blood glucose concentrations ≥ 150 mg/dl.

How many general and inflammatory variables need to be fulfilled when defining sepsis due to the 2003 SCCM/ESICM/ACCP/ATS/SIS definitions in critically ill surgical patients: a retrospective observational study.

BACKGROUND: It has never been specified how many of the extended general and inflammatory variables of the 2003 SCCM/ESICM/ACCP/ATS/SIS consensus sepsis definitions are mandatory to define sepsis. OBJECTIVES: To find out how many of these variables are needed to identify almost all patients with septic shock. METHODS: Retrospective observational single-centre study in postoperative/posttraumatic patients admitted to an University adult ICU. The survey looked at 1355 admissions, from 01/2007 to 12/2008, that were monitored daily computer-assisted for the eight general and inflammatory variables temperature, heart rate, respiratory rate, significant edema, positive fluid balance, hyperglycemia, white blood cell count and C-reactive protein. A total of 507 patients with infections were classified based on the first day with the highest diagnostic category of sepsis during their stay using a cut-off of 1/8 variables compared with the corresponding classification based on a cut-off of 2, 3, 4, 5, 6, 7 or 8/8 variables. RESULTS: Applying cut-offs of 1/8 up to 8/8 variables resulted in a decreased detection rate of cases with septic shock, i.e., from 106, 105, 103, 93, 65, 21, 3 to 0. The mortality rate increased up to a cut-off of 6/8 variables, i.e., 31% (33/106), 31% (33/105), 31% (32/103), 32% (30/93), 38% (25/65), 43% (9/21), 33% (1/3) and 0% (0/0). CONCLUSIONS: Frequencies and mortality rates of diagnostic categories of sepsis differ depending on the cut-off for general and inflammatory variables. A cut-off of 3/8 variables is needed to identify almost all patients with septic shock who may benefit from optimal treatment.

Effects of low-dose alcohol consumption on postural control with a particular focus on the role of the visual system.

There is clear evidence that vision contributes to stabilizing posture and that large quantities of alcohol affect balance. It has, however, not yet been investigated whether and how the consumption of low doses of ethanol affects postural control and the visual system. The purpose of this study was therefore to assess the influence of low-dose alcohol intake on balance. After having performed stability tests in a sober condition, 26 healthy males were instructed to consume 0.32 g of ethanol/kg body weight. At predefined time points, blood samples were collected and stability index scores were calculated using computerized dynamic posturography. Thirty minutes after ethanol intake, blood alcohol levels reached a mean peak of 0.037%. Whereas the ability to maintain balance significantly deteriorated during eyes-open testing, it surprisingly did not decrease during eyes-closed testing. Apparently, the visual system is particularly affected by ethanol and plays a major role in maintaining postural stability.

Vitamin C supplement use may protect against gallstones: an observational study on a randomly selected population.

BACKGROUND: Animal experiments have shown a protective effect of vitamin C on the formation of gallstones. Few data in humans suggest an association between reduced vitamin C intake and increased prevalence of gallstone disease. The aim of this study was to assess the possible association of regular vitamin C supplementation with gallstone prevalence. METHODS: An observational, population-based study of 2129 subjects aged 18-65 years randomly selected from the general population in southern Germany was conducted. Abdominal ultrasound examination, completion of a standardized questionnaire, compilation of anthropometric data and blood tests were used. Data were collected in November and December 2002. Data analysis was conducted between December 2005 and January 2006. RESULTS: Prevalence of gallstones in the study population was 7.8% (167/2129). Subjects reporting vitamin C supplementation showed a prevalence of 4.7% (11/232), whereas in subjects not reporting regular vitamin C supplementation, the prevalence was 8.2% (156/1897). Female gender, hereditary predisposition, increasing age and body-mass index (BMI) were associated with increased prevalence of gallstones. Logistic regression with backward elimination adjusted for these factors showed reduced gallstone prevalence for vitamin C supplementation (odds ratio, OR 0.34; 95% confidence interval, CI 0.14 to 0.81; P = 0.01), increased physical activity (OR 0.62; 95% CI, 0.42 to 0.94; P = 0.02), and higher total cholesterol (OR 0.65; 95% CI, 0.52 to 0.79; P < 0.001). CONCLUSION: Regular vitamin C supplementation and, to a lesser extent, increased physical activity and total cholesterol levels are associated with a reduced prevalence of gallstones. Regular vitamin C supplementation might exert a protective effect on the development of gallstones.

Different patient case mix by applying the 2003 SCCM/ESICM/ACCP/ATS/SIS sepsis definitions instead of the 1992 ACCP/SCCM sepsis definitions in surgical patients: a retrospective observational study.

BACKGROUND: Revised consensus sepsis definitions have been published in 2003. The present study was performed to compare the prevalence of different stages of sepsis and ICU mortality rates and find out the case mix within the same collective of postoperative/posttraumatic patients applying either the original 1992 ACCP/SCCM or the revised 2003 SCCM/ESICM/ACCP/ATS/SIS sepsis definitions. METHODS: Retrospective observational single-centre study in surgical critically ill patients admitted to an University adult ICU. From 01/2007 to 12/2007, 742 patients were surveyed daily computer-assisted with respect to different stages of sepsis. RESULTS: Within the same patient collective, applying the 2003 definitions instead of the 1992 definitions, prevalence of severe sepsis (61 vs. 56) and septic shock (205 vs. 162) was higher (p < 0.001). In patients with septic shock according to the 2003 definitions, mortality rate of 22% was lower than that of 27%, when the 1992 definitions were used. Risk of death was increased for those patients classified to be in septic shock with any of the definitions (OR 6.5, p = 0.001). Sensitivity to predict deaths was slightly higher with the 2003 definitions (92%) than with the 1992 definitions (88%), and specificity was lower (31% vs. 49%). CONCLUSION: The prevalence and mortality rates of various sepsis severity stages differ if defined by the 1992 or the 2003 definitions. Thus, transferring conclusions drawn from data sets regarding severity of sepsis generated with the 1992 definitions to the same population applying the 2003 definitions may be misleading. The 1992 definitions may under-classify patients with severe sepsis.

Arg64 variant of the beta3-adrenergic receptor is associated with gallstone formation.

OBJECTIVES: The beta3-adrenergic receptor (ADRB3) is a transmembrane receptor highly expressed in adipose tissue and thought to be involved in the regulation of lipolysis. ADRB3 is also highly expressed in gallbladder tissue where it may be involved in gallbladder contraction. Because polymorphisms of ADRB3 are present in populations with a high prevalence of gallstones (e.g., Pima-Indians, obese subjects), we hypothesized that known polymorphisms for ADRB3 (Trp64Arg) may represent an independent risk factor for gallstone disease. METHODS: The EMIL cross-sectional study investigated the health behavior and prevalence of chronic diseases in a small Southwestern German town of 12,475 inhabitants. From 3,893 randomly selected citizens 2,147 subjects were enrolled and screened for gallstones employing ultrasonography. Blood samples were drawn for biochemical analysis and isolation of genomic DNA. ADBR3 genotypes were determined by TaqMan SNP Assay. RESULTS: We identified 171 (8%) gallstone carriers of whom 143 participated (46 male, 97 female), with a mean age of 51.4, and mean BMI of 29.3 kg/m2. For these subjects an age, gender and BMI matched partner without gallstones was recruited from the study population. Genotyping for ADRB3 revealed an Arg64 allele frequency of 5.9 versus 0.7% (HR = 11.9, P < 0.05) compared with controls. CONCLUSIONS: Our results indicate that the ADRB3 Trp64Arg polymorphism is associated with gallstone disease thereby representing a genetic marker that identifies subjects at higher risk for gallstone formation.

Prevalence of the metabolic syndrome in southwest Germany.

The metabolic syndrome is a highly prevalent multifaceted clinical entity. Obesity, which is part of the metabolic syndrome, is the fastest growing health-related problem worldwide. Since currently prevalence data of the metabolic syndrome are lacking from Germany, we have applied ATP III-criteria in two urban and rural cohorts. Our population-based studies provide evidence that the prevalence of the metabolic syndrome increases with age. It was found to be more prevalent in a rural population and in this group it clustered in males. As a consequence of our population-based studies evidence that especially the rural population is at high risk for future macrovascular complications is substantiated. The urgent need for preventive measures aimed at reducing the significantly increased health risk is underscored.

Pregnancy is not a risk factor for gallstone disease: results of a randomly selected population sample.

AIM: To investigate the prevalence, risk factors, and selection of the study population for cholecystolithiasis in an urban population in Germany, in relation to our own findings and to the results in the international literature. METHODS: A total of 2 147 persons (1,111 females, age 42.8+/-12.7 years; 1,036 males, age 42.3+/-13.1 years) participating in an investigation on the prevalence of Echinococcus multilocularis were studied for risk factors and prevalence of gallbladder stone disease. Risk factors were assessed by means of a standardized interview and calculation of body mass index (BMI). A diagnostic ultrasound examination of the gallbladder was performed. Data were analyzed by multiple logistic regression, using the SAS statistical software package. RESULTS: Gallbladder stones were detected in 171 study participants (8.0%, n=2,147). Risk factors for the development of gallbladder stone disease included age, sex, BMI, and positive family history. In a separate analysis of female study participants, pregnancy (yes/no) and number of pregnancies did not exert any influence. CONCLUSION: Findings of the present study confirm that age, female sex, BMI, and positive family history are risk factors for the development of gallbladder stone disease. Pregnancy and the number of pregnancies, however, could not be shown to be risk factors. There seem to be no differences in the respective prevalence for gallbladder stone disease in urban and rural populations.

Prevalence of symptoms and risk of sleep apnea in primary care.

BACKGROUND: To obtain prevalence estimates for key symptoms and features that can indicate the presence of obstructive sleep apnea (OSA) in a broad range of primary care settings. DESIGN: Cross-sectional survey. SETTING: Forty offices and clinics in the United States, Germany, and Spain. PARTICIPANTS: Consecutive patients who were > 15 years of age, regardless of the reason for the visit. MEASUREMENTS: We collected demographic information, prevalence of self-reported chronic snoring, sleepiness, obesity (body mass index [BMI] > 30), hypertension, and calculation of OSA risk, and we also compared results between the United States and Europe. RESULTS: There was a 78% return rate for 8,000 surveys (mean age, 51 years; age range, 15 to 98 years; 52% women). One third of participants (32%) had a high pretest probability for OSA, with a higher rate in the United States (35.8% of 3,915 participants) than in Europe (26.3% of 2,308 participants; p < 0.001; age-matched and sex-adjusted odds ratio [OR], 1.37; 95% confidence interval [CI], 1.16 to 1.61). Sleepiness (32.4% vs 11.8%, respectively; p < 0.001) followed by obesity and/or hypertension (44.8% vs 37.1%, respectively; p < 0.01) contributed to the OSA risk difference between participants in the United States and Europe, as frequent snoring and breathing pauses were similarly reported (44%). A high pretest probability for OSA was more often present in men than in women (37.9% vs 27.8%, respectively; p < 0.005; OR, 1.96; CI, 1.59 to 2.88) and in those that were obese (ie, BMI, > or = 30 kg/m(2)), a condition that is generally more common in the US population than in the European population (27.9% vs 17.2%, respectively; p < 0.01). CONCLUSIONS: Primary care physicians in the United States and Europe will encounter a high demand for services to confirm or manage sleep apnea, sleepiness, and obesity.