Could Reduced Fluid Intake Cause the Placebo Effect Seen in Overactive Bladder Clinical Trials? Analysis of a Large Solifenacin Integrated Database

Objective To assess the hypothesis that patients receiving placebo in overactive bladder (OAB) trials who experience less benefit from “treatment” continue with behavioral modifications such as fluid restriction, whereas those on active treatment adopt more normal drinking patterns. This may manifest itself as a reduction in micturition frequency (MF). Materials and Methods We interrogated a large integrated database containing pooled patient data from 4 randomized, placebo-controlled phase III OAB solifenacin studies. A statistical correction was applied to MF to remove the influence of fluid intake. Results Pooled analysis using patient-level data from 3011 patients and accounting for the studies within the models showed that all patients voided progressively less total urine per 24 hours during treatment than at baseline. However, reduction in total urine volume voided per 24 hours was larger in patients receiving placebo vs those on solifenacin; with a substantial decrease in 24-hour urine output in the placebo group from baseline to week 4, which was not the case in active groups. After correcting MF for volume voided for each patient using the statistical correction and averaging the corrected MF per treatment arm, the placebo effect almost disappeared. Patients on solifenacin voided less often, with a statistically significant increase in volume voided each time they voided, vs placebo. Conclusion Assuming volume voided is a good surrogate measure for fluid intake, this analysis shows that fluid restriction almost completely explains the reduction in MF in the placebo group. In contrast, patients receiving active treatment adopt more normal drinking patterns once they start to perceive improvement in their OAB symptoms

Ethnic differences in current smoking and former smoking in the Netherlands and the contribution of socioeconomic factors: a cross-sectional analysis of the HELIUS study.

OBJECTIVES: Data exploring how much of the ethnic differences in smoking prevalence and former smoking are explained by socioeconomic status (SES) are lacking. We therefore assessed ethnic differences in smoking prevalence and former smoking and the contribution of both educational level and occupational-related SES to the observed ethnic differences in smoking behaviour. METHODS: Data of 22 929 participants (aged 18-70 years) from the multiethnic cross-sectional Healthy Life in an Urban Setting study in the Netherlands were analysed. Poisson regression models with a robust variance were used to estimate prevalence ratios. RESULTS: Compared with the Dutch, after adjustment for age and marital status, smoking prevalence was higher in men of Turkish (prevalence ratio 1.69, 95% CI 1.54 to 1.86), African Surinamese (1.55, 95% CI 1.41 to 1.69) and South-Asian Surinamese origin (1.53, 95% CI 1.40 to 1.68), whereas among women, smoking prevalence was higher in Turkish, similar in African Surinamese but lower in all other ethnic origin groups. All ethnic minority groups, except Ghanaians, had a significantly lower smoking cessation prevalence than the Dutch. Socioeconomic gradients in smoking (higher prevalence among those lower educated and with lower level employment) were observed in all groups except Ghanaian women (a higher prevalence was observed in the higher educated). Ethnic differences in smoking prevalence and former smoking are largely, but not completely, explained by socioeconomic factors. CONCLUSIONS: Our findings imply that antismoking policies designed to target smoking within the lower socioeconomic groups of ethnic minority populations may substantially reduce ethnic inequalities in smoking particularly among men and that certain groups may benefit from targeted smoking cessation interventions

Body composition and body fat distribution are related to cardiac autonomic control in non-alcoholic fatty liver disease patients

BACKGROUND/OBJECTIVES: Heart rate recovery (HRR), a cardiac autonomic control marker, was shown to be related to body composition (BC), yet this was not tested in non-alcoholic fatty liver disease (NAFLD) patients. The aim of this study was to determine if, and to what extent, markers of BC and body fat (BF) distribution are related to cardiac autonomic control in NAFLD patients. SUBJECTS/METHODS: BC was assessed with dual-energy X-ray absorptiometry in 28 NAFLD patients (19 men, 51±13 years, and 9 women, 47±13 years). BF depots ratios were calculated to assess BF distribution. Subjects’ HRR was recorded 1 (HRR1) and 2 min (HRR2) immediately after a maximum graded exercise test. RESULTS: BC and BF distribution were related to HRR; particularly weight, trunk BF and trunk BF-to-appendicular BF ratio showed a negative relation with HRR1 (r 1⁄4 0.613, r 1⁄4 0.597 and r 1⁄4 0.547, respectively, Po0.01) and HRR2 (r 1⁄4 0.484, r 1⁄4 0.446, Po0.05, and r 1⁄4 0.590, Po0.01, respectively). Age seems to be related to both HRR1 and HRR2 except when controlled for BF distribution. The preferred model in multiple regression should include trunk BF-to-appendicular BF ratio and BF to predict HRR1 (r2 1⁄4 0.549; Po0.05), and trunk BF-to-appendicular BF ratio alone to predict HRR2 (r2 1⁄4 0.430; Po0.001). CONCLUSIONS: BC and BF distribution were related to HRR in NAFLD patients. Trunk BF-to-appendicular BF ratio was the best independent predictor of HRR and therefore may be best related to cardiovascular increased risk, and possibly act as a mediator in age-related cardiac autonomic control variation.info:eu-repo/semantics/publishedVersio

Intrauterine exposure to mild analgesics during pregnancy and the occurrence of cryptorchidism and hypospadia in the offspring: The Generation R Study

This article is available open access through the publisher’s website. Copyright @ 2012 The Authors.BACKGROUND - Recently, over-the-counter mild analgesic use during pregnancy has been suggested to influence the risk of reproductive disorders in the offspring. We examined the influence of maternal exposure to mild analgesics during pregnancy on the occurrence of cryptorchidism and hypospadia in their offspring. METHODS - Associations between maternal exposure to mild analgesics during pregnancy and cryptorchidism or hypospadia in the offspring were studied in 3184 women participating in a large population-based prospective birth cohort study from early pregnancy onwards in the Netherlands (2002–2006), the Generation R Study. Cryptorchidism and hypospadia were identified during routine screening assessments performed in child health care centres by trained physicians. The use of mild analgesics was assessed in three prenatal questionnaires in pregnancy, resulting in four periods of use, namely, periconception period, first 14 weeks of gestation, 14–22 weeks of gestation and 20–32 weeks of gestation. Logistic regression analyses were used to study the associations between maternal exposure to mild analgesics and cryptorchidism and hypospadia. RESULTS - The cumulative prevalence over 30 months of follow up was 2.1% for cryptorchidism and 0.7% for hypospadia. Use of mild analgesics in the second period of pregnancy (14–22 weeks) increased the risk of congenital cryptorchidism [adjusted odds ratio (OR) 2.12; 95% confidence interval (CI) 1.17–3.83], primarily due to the use of acetaminophen (paracetamol) (adjusted OR 1.89; 95% CI 1.01–3.51). Among mothers of cryptorchid sons, 33.8% reported (23 of 68) the use of mild analgesics during pregnancy, compared with 31.8% (7 of 22) of mothers with a boy with hypospadia and 29.9% (926 of 3094) of mothers with healthy boys. CONCLUSIONS - Our results suggest that intrauterine exposure to mild analgesics, primarily paracetamol, during the period in pregnancy when male sexual differentiation takes place, increases the risk of cryptorchidism.Erasmus University Rotterdam, School of Law and Faculty of Social Sciences, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR), Rotterdam

Body Size Measurements as Predictors of Type 2 Diabetes in Aboriginal People

OBJECTIVE: To investigate waist circumference, waist-to-hip ratio, body mass index (BMI), weight and hip circumference as risk factors for type 2 diabetes in Aboriginal Australians. DESIGN: Community-based cross-sectional study. SUBJECTS: In total, 915 Australian Aboriginal adults (age: 18-74 y) from a remote Aboriginal community in the Northern Territory of Australia. MEASUREMENTS: Body size measurements included waist circumference, waist-to-hip ratio, BMI, weight and hip circumference. Diabetes status was determined according to medical history and fasting and 2-h postload plasma glucose values. Logistic regression was used to calculate odds ratio for diabetes associated with 1 standard deviation (s.d.) increase in a body size measurement. The areas under the ROC curves of five body size measurements were calculated and compared. RESULTS: Risk of diabetes increased with increasing levels of body size. ORs (95% CI) for diabetes with adjustment for age and sex were 2.16 (1.75, 2.66), 1.80 (1.49, 2.17), 1.41 (1.17, 1.71), 1.81 (1.51, 2.19) and 1.84 (1.50, 2.24) associated with 1 s.d. increase in waist circumference, BMI, weight, waist-to-hip ratio, and hip circumference, respectively. The area under the ROC curve for waist circumference was significantly higher than those for other measurements. CONCLUSION: Waist circumference is the best body size measurement in predicting diabetes in Aboriginal people

The association between ethnicity and vaginal microbiota composition in Amsterdam, the Netherlands

To evaluate whether ethnicity is independently associated with vaginal microbiota (VMB) composition in women living in Amsterdam, the Netherlands, as has been shown for American women. Women (18-34 years, non-pregnant, N = 610) representing the six largest ethnic groups (Dutch, African Surinamese, South-Asian Surinamese, Turkish, Moroccan, and Ghanaian) were sampled from the population-based HELIUS study. Sampling was performed irrespective of health status or healthcare seeking behavior. DNA was extracted from self-sampled vaginal swabs and sequenced by Illumina MiSeq (16S rRNA gene V3-V4 region). The overall prevalence of VMBs not dominated by lactobacilli was 38.5%: 32.2% had a VMB resembling bacterial vaginosis and another 6.2% had a VMB dominated by Bifidobacteriaceae (not including Gardnerella vaginalis), Corynebacterium, or pathobionts (streptococci, staphylococci, Proteus or Enterobacteriaceae). The most prevalent VMB in ethnically Dutch women was a Lactobacillus crispatus-dominated VMB, in African Surinamese and Ghanaian women a polybacterial G. vaginalis-containing VMB, and in the other ethnic groups a L. iners-dominated VMB. After adjustment for sociodemographic, behavioral and clinical factors, African Surinamese ethnicity (adjusted odds ratio (aOR) 5.1, 95% confidence interval (CI) 2.1-12.0) and Ghanaian ethnicity (aOR 4.8, 95% CI 1.8-12.6) were associated with having a polybacterial G. vaginalis-containing VMB, and African Surinamese ethnicity with a L. iners-dominated VMB (aOR 2.8, 95% CI 1.2-6.2). Shorter steady relationship duration, inconsistent condom use with casual partners, and not using hormonal contraception were also associated with having a polybacterial G. vaginalis-containing VMB, but human papillomavirus infection was not. Other sexually transmitted infections were uncommon. The overall prevalence of having a VMB not dominated by lactobacilli in this population-based cohort of women aged 18-34 years in Amsterdam was high (38.5%), and women of sub-Saharan African descent were significantly more likely to have a polybacterial G. vaginalis-containing VMB than Dutch women independent of modifiable behavior

Central obesity as a precursor to the metabolic syndrome in the AusDiab study and Mauritius

Evidence from epidemiologic studies that central obesity precedes future metabolic change and does not occur concurrently with the appearance of the blood pressure, glucose, and lipid abnormalities that characterize the metabolic syndrome (MetS) has been lacking. Longitudinal surveys were conducted in Mauritius in 1987, 1992, and 1998, and in Australia in 2000 and 2005 (AusDiab). This analysis included men and women (aged 25 years) in three cohorts: AusDiab 2000&ndash;2005 (n = 5,039), Mauritius 1987&ndash;1992 (n = 2,849), and Mauritius 1987&ndash;1998 (n = 1,999). MetS components included waist circumference, systolic blood pressure, fasting and 2-h postload plasma glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, and homeostasis model assessment of insulin sensitivity (HOMA-S) (representing insulin sensitivity). Linear regression was used to determine which baseline components predicted deterioration in other MetS components over 5 years in AusDiab and 5 and 11 years in Mauritius, adjusted for age, sex, and ethnic group. Baseline waist circumference predicted deterioration (P &lt; 0.01) in four of the other six MetS variables tested in AusDiab, five of six in Mauritius 1987&ndash;1992, and four of six in Mauritius 1987&ndash;1998. In contrast, an increase in waist circumference between baseline and follow-up was only predicted by insulin sensitivity (HOMA-S) at baseline, and only in one of the three cohorts. These results suggest that central obesity plays a central role in the development of the MetS and appears to precede the appearance of the other MetS components.<br /