Adverse Drug Reactions Due to Opioid Use in Oldest-Old Patients Visiting the Emergency Unit of the Geneva Geriatric Hospital.

Opioid use has much increased in several countries during the last two decades, accompanied by a rise in associated morbidity and mortality, especially in the United States. Data on a possible opioid crisis are scarcer in Europe. We performed a study aiming to assess the frequency of adverse drug reactions (ADR) related to opioids in patients presenting to the emergency unit (EU) of a geriatric tertiary Swiss University Hospital. This particular setting is intended for patients aged 75 and older. Our retrospective, monocentric survey of opioid use and related ADR was conducted over two months in 2018. The main and secondary outcomes were the frequency of EU visits considered due to an opioid ADR and insufficient pain relief, respectively. Current opioid use was identified in 20.3% (n=99) of the 487 included EU visits (mean age 86). An ADR was the suspected cause of the EU visit in 22 opioid users, mainly fall-related injury and gastrointestinal disorders. All these patients had at least one comorbid condition. In 19/22 cases (86%) of ADR, a drug-drug interaction might have been involved. In 12 opioid users (12%), insufficient pain relief was suspected as the cause of the EU visit. In conclusion, one-third of opioid users visiting a geriatric EU consulted for a problem related to its use mainly adverse drug-related reaction (22%) followed by insufficient pain relief (12%).

Association between beta-blockers, other antihypertensive drugs and psoriasis: population-based case-control study.

BACKGROUND: Several case reports have associated use of beta-blockers with an increased risk of psoriasis or psoriasiform drug eruptions. OBJECTIVES: To study the association between use of beta-blockers and other antihypertensive drugs and the risk of developing a first-time diagnosis of psoriasis. METHODS: We conducted a case-control analysis on the U.K.-based General Practice Research Database. We identified cases with an incident psoriasis diagnosis between 1994 and 2005 and matched them to one control patient on age, sex, general practice, calendar time (same index date) and years of history in the database. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of developing a first-time psoriasis diagnosis in relation to previous exposure to antihypertensive drugs, stratified by exposure timing (current vs. past use) and exposure duration based on the number of prescriptions. RESULTS: The study encompassed 36 702 cases with a first-time psoriasis diagnosis and the same number of matched controls. Adjusted ORs for current use of 1-4, 5-19 or >or= 20 prescriptions for beta-blockers, as compared with nonuse, were 0.93 (95% CI 0.76-1.13), 1.10 (95% CI 0.97-1.24), and 1.10 (95% CI 1.01-1.20), respectively. The risk estimates for current use of other antihypertensives at any exposure duration were all close to 1.0. CONCLUSIONS: This large population-based case-control analysis does not support the current proposition that beta-blocker use is associated with an increased risk of psoriasis, nor did we find evidence for a substantially altered psoriasis risk for other antihypertensive drugs.

Prevalence of anal incontinence and other anorectal symptoms in women.

We studied the prevalence of anal incontinence and other anorectal symptoms in women and evaluated the proportion of those who had sought medical help. A structured questionnaire was distributed to 1228 women attending the obstetrics and gynecology outpatient clinics (general, antenatal, urogynecology) of our university hospital. We also screened an additional sample of 984 women, representative of the general population aged 35-74. The prevalence of anal incontinence was 5.6% in the general outpatient clinic, 6.7% in the antenatal clinic, 15.9% in the urogynecology clinic and 4.4% in the general population. Only 20% of women affected by anal incontinence from the general outpatient clinic had reported their symptoms to a medical practitioner. Anal incontinence affects many women, but only a minority seek help. Obstetriciangynecologists should systematically inquire about the presence of this symptom.

Validation of self-reported smoking status by simultaneous measurement of carbon monoxide and salivary thiocyanate.

OBJECTIVE: The objective of this study was to determine the validity of tobacco questionnaires when using as gold standard either a single biomarker or a combination of two biomarkers. METHODS: The methods were self-reported smoking compared with salivary thiocyanate and expired carbon monoxide in a 1996, population-based, Swiss survey of 552 men and 565 women. RESULTS: Sensitivity of self-reported smoking relative to salivary thiocynate or carbon monoxide alone was low (38.2% for salivary thiocyanate > or = 100 mg/L, 56.4% for salivary thiocyanate > or = 150 mg/L and 62.6% for carbon monoxide > or = 9 ppm). When defining true positive smokers as people with high concentration of both salivary thiocyanate and carbon monoxide, overall, sensitivity was 88.6% and specificity was 87.2%. In women, sensitivity increased from 85 to 89% when removing subjects exposed to passive smoking. When excluding heavy smokers, sensitivity decreased to 63% in men and to 71% in women. Older women had tendency to misreport smoking. CONCLUSIONS: This comparison of questionnaire data with the simultaneous measurement of salivary thiocyanate and expired carbon monoxide indicates that valid responses can be obtained for self-reported, current smoking in population-based surveys. However, the validity of questionnaires can be underestimated if the gold standard (of exposure to tobacco smoke) is either high levels of carbon monoxide or high levels of salivary thiocyanate.

Relation of environmental tobacco smoke to diet and health habits: variations according to the site of exposure.

It has been postulated that the relationship of environmental tobacco smoke (ETS) exposure to cancer or cardiovascular diseases may be confounded by social class or diet because women exposed to ETS by their smoker spouse belong to lower social classes and have an unhealthy diet. In a population survey in Geneva, Switzerland, 914 female never-smokers were interviewed about sociodemographic factors, health habits including a semiquantitative food frequency questionnaire, and exposure to ETS according to the site (home, work, leisure). Compared to women unexposed to ETS, those exposed to ETS at work ate less fibers, cereals, vegetables, lean meat, had a lower intake of iron and beta-carotene, and had a lower total energy intake; women exposed during leisure time ate less cereals, drank less skim milk, and had a lower intake of complex carbohydrates. But the diet of women exposed at home did not differ from the diet of those unexposed to ETS. Thus, "living with a smoker" in Geneva does not necessarily imply adopting his health and dietary habits. We conclude that confounding factors of the association of ETS and disease vary according to site and populations and therefore should not be invoked as a systematic source of bias in all studies.

Effects of smoking and smoking cessation on dietary habits of a Swiss urban population.

OBJECTIVES: To assess whether current smokers eat differently than never smokers and the relation of smoking cessation to dietary change. DESIGN: Population-based survey from 1993-1997. SETTING: The Bus Sante 2000, epidemiologic observatory of Geneva, Switzerland. SUBJECTS: A representative sample of 2301 men and 2306 women resident of Geneva, Switzerland. RESULTS: In both genders, compared to never smokers, current heavy smokers (> or = 20 cigarettes/d) consumed daily less total vegetables proteins (P <0.03), carbohydrates (P<0.0001), saccharose (P<0.01), fibers (P < 0.0001), beta-carotene (P < 0.001), fruit (P < 0.0001) and vegetables (P < 0.04), but they drank more alcohol (P < 0.0001) and more coffee (P < 0.005). In addition, female current smokers ate less energy (P < 0.4), complex carbohydrates (P < 0.002), cereals (P < 0.003), vegetables (P < 0.0001) and less iron (P < 0.02). The diet of ex-smokers tended to become more similar to that of never smokers. When longer duration of smoking cessation increased, the consumption of total carbohydrates and complex carbohydrates increased (P < 0.01 and P < 0.06), and alcohol decreased (P < 0.07) in both genders. CONCLUSIONS: As in other Western countries, the diet of Swiss smokers appears less healthy than that of never smokers in both men and women, while smoking cessation has beneficial aspect on the quality of the diet. Current smoking appears to have an even stronger effect on the diet of women than on the diet of men.

Relation of BMI to a dual-energy X-ray absorptiometry measure of fatness.

Dual-energy X-ray absorptiometry (DXA) is a valid technique for measuring the fat, bone and lean (muscle, organs and water) masses of the body. We evaluated relationships of BMI (kg/m2) with independent measurements of fat and lean masses using DXA in 226 adult volunteers. The evaluation was an application of a general approach to compositional data which has not previously been used for describing body composition. Using traditional regression analyses, when lean mass was held constant, BMI varied with fat mass (men r 0.75, P < 0.05; women r 0.85, P < 0.05); when fat mass was held constant, BMI varied with lean mass (men r 0.63, P < 0.05; women r 0.47, P < 0.05). In contrast, a regression model for compositional data revealed that BMI was: (a) strongly associated with log fat mass in both sexes (b1 4.86, P < 0.001 for all women and b1 5.96, P < 0.001 for all men); (b) not associated with bone mass, except in older men; (c) related to lean mass in women but not in men (b3 -4.04, P < 0.001 for all women and b1 -2.59, P < 0.15 for all men). Women with higher BMI tended to have more fat mass and more lean mass than women with lower BMI. Men with higher BMI had more fat mass but similar lean mass to men with lower BMI. Investigators need to be alert to the inaccuracy of BMI to assign a fatness risk factor to individuals, especially among women.

Lifetime exposure to environmental tobacco smoke among urban women: differences by socioeconomic class.

This study sought to determine cumulative lifetime exposure to environmental tobacco smoke (ETS) among urban women in relation to sociodemographic factors. In a population survey carried out in Geneva, Switzerland, during 1993-1995, a representative sample of 1,883 women aged 35-74 years answered interview questions on lifetime ETS exposure. Exposed women were defined as those who had spent at least 1 hour daily in a smoky environment during 1 or more years. The prevalence of current ETS exposure was 31.0% among 1,458 never or former smokers. Lifetime prevalence was 58.3% among 1,061 never smokers. The home (42.1%) and the workplace (39.6% of employed women) were the most frequent sources of ETS exposure, leisure time activity being a secondary source. Throughout a lifetime, work accounted for the greatest average intensity of exposure (on average, 19 hours of exposure per week), while the longest duration of exposure (on average, 18 years) was in the home. Cumulative lifetime exposure (intensity (in hours/week) x duration) from all sources combined was 308 hours/week-years, which can correspond to 30.8 hours/week over a period of 10 years or 20.5 hours/week over a period of 15 years. Women from low socioeconomic classes had more intense and longer exposures than women from higher socioeconomic classes, mainly because of work exposure. Both the intensity and the duration of lifetime ETS exposure were greater than previously suspected. Reduction of ETS exposure in the workplace should be a public health priority.

Multiple correlations and Bonferroni's correction.

Correlation coefficients between biological measurements and clinical scales are often calculated in psychiatric research. Calculating numerous correlations increases the risk of a type I error, i.e., to erroneously conclude the presence of a significant correlation. To avoid this, the level of statistical significance of correlation coefficients should be adjusted. Threshold levels of significance for correlation coefficients were adjusted for multiple comparisons in a set of k correlation coefficients (k = 1, 5, 10, 20, 50, 100) by Bonferroni's correction. Significant correlation coefficients were then calculated according to sample size. The change in the threshold values of significance is larger when the number of correlations goes from 1 to 5 than when it goes from 50 to 100. A correlation coefficient, statistically significant at 5% when calculated alone, can be under the threshold level of significance when calculated even among a few other coefficients. Focusing on the most relevant variables or the use of multivariate statistics is advocated.

Clinical experience with diffusion-weighted MR in patients with acute stroke.

PURPOSE: Our purpose was to evaluate the clinical efficacy, sensitivity, and specificity of echo-planar diffusion-weighted MR imaging in patients with acute infarction. METHODS: We retrospectively analyzed 194 cases of acute ischemic stroke diagnosed clinically within 24 hours of onset and studied with echo-planar diffusion-weighted MR imaging. Examinations were considered to be positive for infarction when an increase in signal was noted on images acquired at a high b value but absent on images with a low b value. A final clinical diagnosis of acute stroke was used as the standard of reference. A subset of 48 patients scanned within 6 hours was also analyzed. RESULTS: Diffusion-weighted MR imaging studies were positive in 133 of 151 cases of infarction (88% sensitivity) and negative in 41 of 43 cases with no infarction (95% specificity). Two cases identified as positive on diffusion-weighted images had nonischemic diagnoses (1.5% false-positive rate). Diffusion-weighted imaging had a positive predictive value of 98.5% and a negative predictive value of 69.5%. Use of T2-weighted sequences as well as diffusion-weighted imaging produced no false-positive findings. Of the negative scans, 69.5% corresponded to transient ischemic attacks or infarcts (mostly small brain stem infarcts). When only cases scanned within 6 hours of onset were considered, the sensitivity rose to 94% and the specificity to 100%. CONCLUSION: Despite bias due to dependence between diffusion-weighted imaging and the final diagnosis, this analysis suggests high sensitivity and specificity for echo-planar diffusion-weighted imaging in the diagnosis of acute cerebral infarction, although negative scans did not rule out an ischemic pathogenesis.

Psychosocial profile of Swiss sexual offenders.

Background data on psychosocial characteristics of sexual offenders are sparse in Europe. From 67 experts' reports done between 1982 and 1995 in Geneva, Switzerland, demographic, criminological and psychiatric characteristics were collected for three groups of sexual offenders: offenders against adults, offenders against non-relative minors (< 18 yr), and offenders against minors with incest. The results showed that the offenders against adults were younger (p = 0.02), more frequently single (p = 0.0007) and with a lower educational level (p = 0.05) than the offenders against minors. Incest offenders had no prior conviction compared with 50% of the other offenders. Violence was more often used by offenders against adults (86%) than by offenders against minors (45%) (p = 0.005). About two-thirds of the sexual offenders had no psychiatric history, but a personality disorder (mainly borderline) was diagnosed in half of the offenders. A history of sexual abuse during childhood was reported by a third of the offenders against minors and by 5% of the offenders against adults (p = 0.04). It is concluded that a low socio-economic status and social isolation characterized offenders against adults, whereas offenders against minors had a relatively normal psychosocial profile.

Smoking behavior in a Swiss urban population: the role of gender and education.

BACKGROUND: Smoking has become more prevalent among U.S. men and women and European men in lower socioeducational groups. The relation between socioeducational status and smoking among European women has been studied less. METHODS: A survey assessing the smoking behavior and educational level of 943 women and 961 men ages 35 to 74 years from Geneva, Switzerland, was conducted. RESULTS: The prevalence of never smokers has declined among younger women but has remained stable among men. More men than women have ever smoked, but the difference has decreased among younger generations. Ever smoking was more prevalent among women with secondary (47.6%, age-adjusted OR 2.03, 95% CI 1.29 to 3.18) or tertiary (46.6%, age-adjusted OR 1.83, 95% CI 1.13 to 2.97) education relative to women with primary education (30.7%). Among males, ever smoking was slightly more prevalent among lower levels of education. There were moderate differences in quit ratio (ex-smokers/ever smokers) across educational levels among women (trend P = 0.08). In contrast, men with tertiary education stopped smoking more often (63.6%) than those with secondary (54.2%) or primary (47.6%) education (trend P = 0.008). For most women, primary education was associated with a later age at start of smoking while the inverse was true for men. CONCLUSION: Smoking behavior is evolving across generations of women in Geneva. It is more prevalent among educated women of the older generations, but this is less so among the younger generations. Women from Geneva may be currently experiencing the transition of smoking from upper to lower social classes.

Reward dependence is positively related to urinary monoamines in normal men.

According to Cloninger, three major personality dimensions, novelty seeking, harm avoidance, and reward dependence, are dependent on central monoaminergic systems. This study examined the relationship between the urinary levels of different monoamines and the above personality dimensions. Fifty normal men answered the Tridimensional Personality Questionnaire (TPQ); their levels of dopamine, norepinephrine, epinephrine, normetanephrine, metanephrine, 3-methoxy-4-hydroxyphenylglycol, vanilmandelic acid, homovanilic acid, and serotonin metabolite 5-hydroxyindolacetic acid were measured in urine on two consecutive nights. Significant and positive correlations were found between reward dependence, 3-methoxy-4-hydroxyphenylglycol, and epinephrine (r = .50 and r = .51, respectively). Monoamine levels explained 44% of the variance of reward dependence. Cluster analysis identified three groups of subjects presenting specific patterns of monoamine excretion. The TPQ scores could discriminate among subjects belonging to these clusters. These results point out a narrow relationship between urinary monoamine excretion and the basic personality dimension of reward dependence.

Body mass index compared to dual-energy x-ray absorptiometry: evidence for a spectrum bias.

The objective of this study was to evaluate the accuracy of body mass index (BMI) in the diagnosis of obesity. The relationship of this weight-for-height index to body composition was determined using dual-energy x-ray absorptiometry (DEXA) in 226 Caucasian subjects. BMI-obesity was defined as a BMI greater than 27.8 kg/m2 in males and greater than 27.3 kg/m2 in females. BMI-obesity was weakly sensitive (males: 12.5%, females 13.6%) compared with diagnosis by DEXA, defined as percent body fat mass (%BF) greater than 20% in males and greater than 25% in females. Conversely, the specificity of BMI-obesity was high (males and females: 100%). When analyzing subgroups of subjects according to weight, sensitivity was higher among heavier subjects than among lighter ones. In both sexes and in all subgroups, the specificity was 100%. The clinical implication of this spectrum bias is that, in men or women weighing less than 80 kg, measures of obesity other than BMI, such as bioelectrical impedance, should be preferred.

Lower sex hormones in men during anticipatory stress.

Free cortisol, luteinizing hormone (LH), total testosterone and monoamines were measured in two successive nocturnal urine collections in 50 healthy men to assess the influence of anticipatory stress. The first collection (N-2) was two nights before and the second (N-1) was just on the night before a one-day experimental stressor consisting of participation in a one-day clinical research protocol. The mean cortisol level increased from 23.4 (N-2) to 66.6 micrograms (N-1), while mean LH level decreased from 2.68 (N-2) to 1.71 IU (N-1) and the mean testosterone level fell from 1.31 (N-2) to 0.70 microgram (N-1). There were no changes in monoamines. Inhibition of sex hormones is a relatively neglected area of stress research.

Day-to-day intraindividual reliability and interindividual differences in monoamines excretion.

The urine of 44 normal men was collected during 2 nights to evaluate components of biological variation, i.e., intraindividual day-to-day variability and interindividual variability in monoamines excretion. Monoamines presented important interindividual variability [interindividual coefficients of variation (%): dopamine 18.3, norepinephrine 66.7, epinephrine 85.3, normetanephrine 22.4, metanephrine 76.8, 3-methoxy-4-hydroxyphenylglycol (MHPG) 77.0, vanilmandelic acid (VMA) 64.3, homovanilic acid (HVA) 71.3, 5-hydroxyindolacetic acid (5-HIAA) 20.4]. The reliability of these amounts was high, with intraclass correlation coefficients ranging from 0.43 (P < 0.001) for MHPG free form to 0.65 (P < 10(-6)) for dopamine and normetanephrine (intraindividual coefficients of variation (%): dopamine 8.5, norepinephrine 39.9, epinephrine 45.9, normetanephrine 10.3, metanephrine 46.3, MHPG 37.5, VMA 30.7, HVA 41.0, 5-HIAA 12.3).

4-Oxalocrotonate tautomerase, an enzyme composed of 62 amino acid residues per monomer.

The xylH gene encoding 4-oxalocrotonate tautomerase (4-OT) has been located on a subclone of the Pseudomonas putida mt-2 TOL plasmid pWW0 and inserted into an Escherichia coli expression vector. Several of the genes of the metafission pathway encoded by pWW0 have been cloned in E. coli, but the overexpression of their gene products has met with limited success. By utilizing the E. coli alkaline phosphatase promoter (phoA) coupled with the proper positioning of a ribosome-binding region, we are able to express functional 4-OT in yields of at least 10 mg of pure enzyme/liter of culture. 4-OT has been previously characterized and shown to be an extremely efficient catalyst (Whitman, C. P., Aird, B. A., Gillespie, W. R., and Stolowich, N. J. (1991) J. Am. Chem. Soc. 113, 3154-3162). Kinetic and physical characterization of the E. coli-expressed protein show that it is identical with that of the 4-OT isolated from P. putida. The functional unit is apparently a pentamer of identical subunits, each consisting of only 62 amino acid residues. This is the smallest enzyme subunit reported to date. The amino acid sequence, determined in part from automated Edman degradation and also deduced from the primary sequence of xylH, did not show homology with any of the sequences in the current data bases nor with any of the sequences of enzymes that catalyze similar reactions. We propose that the active site of 4-OT may be established by an overlap of subunits and comprised of amino acid residues belonging to several, if not all, of the subunits.