Acceptability of hepatitis C virus testing methods among injecting drug users

Introduction and Aims . The acceptability of testing methods and procedures has implications for uptake of blood‐borne virus screening in sentinel samples of injecting drug users (IDUs) likely to participate in surveillance. The aim of the current study was to determine the acceptability of three methods of hepatitis C virus (HCV) testing among injecting drug users (IDUs): oral fluid, capillary blood and venous blood sampling. Design and Methods . A cross‐sectional survey of IDUs was conducted in inner‐city Sydney in 2005 for a laboratory validation study of HCV antibody testing. Participants were tested using the three different specimen collection methods and asked about the acceptability of each method and a particular preference documented. Results . Two‐hundred and twenty‐nine IDUs participated in the study. Before and after specimen collection, the acceptability of all three collection methods for HCV testing was high (>85%). Oral fluid remained the preferred method after sample collection, with females (65%) significantly more likely than males (49%) to report a preference (unadjusted odds ratio 2.0; 95% confidence interval 1.1–3.5, p = 0.03) for that method. Discussion and Conclusions . Findings suggest that oral fluid testing is an acceptable and preferred alternative for HCV testing among IDUs. However, concerns reported by participants in the study indicate that information and education regarding the nature and diagnostic value of oral fluid testing is necessary prior to its implementation for surveillance purposes among this population.     

Biotransformation of Chlorzoxazone by Heptatic Microsomes from Humans and Ten Other Mammalian Species

The 6-hydroxylation of chlorzoxazone (CLZ) is currently being used in both in vivo and in vitro studies to quantify cytochrome P450 2E1 (CYP2E1) activity in humans. Comparatively little is known with regard to the biotransformation of this drug in other species. The NADPH-dependent biotransformation of CLZ was therefore studied using hepatic microsomes derived from humans and ten other mammalian species. In all species, 6-hydroxychlorzoxazone (6OH-CLZ) was the only metabolic product that could be identified by HPLC with ultraviolet detection. Enzyme kinetic analysis was used to characterize this CLZ 6-hydroxylase activity. Although the majority of kinetic data conformed to a single-enzyme Michaelis–Menten model, a two-enzyme (high and low affinity) model was required for four species (ferret, monkey, pig, and rat). Apparent K_m values for the high-affinity component ranged from 12 μM (pig) to 95 μM (rabbit). The rank order of V_max/K_m, an index of intrinsic clearance, was: mouse>horse>monkey>rabbit>cow>ferret>pig>human1>rat>human2>cat>dog. Diethyldithiocarbamate (DDC), a CYP2E1 inhibitor in humans, was a potent mechanism-based inhibitor of 6OH-CLZ formation in microsomes from all species examined. Preincubation of microsomes for 15 min in the presence of DDC and NADPH significantly enhanced the maximum degree of inhibition but had no effect on inhibitor potency. Inhibitor concentrations at 50% of maximum inhibition (IC_50max) for DDC with preincubation ranged from 9 μM (human) to 45 μM (cow). In conclusion, DDC-sensitive CLZ 6-hydroxylation was identified as the principal NADPH-dependent pathway for chlorzoxazone metabolism in liver microsomes from humans and ten other mammalian species. These data indicate a species-conserved mechanism for the oxidative biotransformation of chlorzoxazone. © 1997 John Wiley & Sons, Ltd.     

PHARMACOKINETICS AND SAFETY OF SINGLE INTRAVENOUS AND ORAL DOSES OF DOLASETRON MESYLATE IN HEALTHY WOMEN

Twenty-four healthy women received 2·4 mg kg⁻¹ dolasetron mesylate (1·8 mg kg⁻¹ dolasetron base) by a 10 min intravenous administration and by oral administration. Pharmacokinetics of dolasetron and of its active reduced metabolite MDL 74 156 were monitored for 48 h in plasma. Urine was collected from 0 to 48 h, blood pressure and heart rate were measured at 0, 0·08, 1, 2, 12, 24, and 36 h, and ECGs were measured at 0, 0·08 (intravenous only), 1, 2, and 36 h after dosing. Dolasetron was widely distributed and rapidly reduced (mean t_1/2=0·23 h) to MDL 74 156 (mean t_1/2=8·05 and 9·12 h after intravenous and oral administration respectively). MDL 74 156 was extensively distributed; between 27 (oral route) and 33% (intravenous route) was eliminated unchanged in urine. Safety assessment showed mild to moderate headache, dizziness, and hot flushes after the intravenous administration and headache, abdominal cramps or pain, and constipation after oral administration. Small and clinically non-significant changes in PR, QRS, and QT_c intervals were observed. We conclude that there is no obvious difference in dolasetron pharmacokinetics between healthy women and men and that dolasetron can be used as safely in women as in men. ©1997 by John Wiley & Sons, Ltd.     

A MODEL FOR THE EFFECT OF CIGARETTE SMOKING ON LUNG CANCER INCIDENCE IN CONNECTICUT

Population based data on smoking history derived from NCHS surveys were used to develop a model for lung cancer incidence in Connecticut. Trends in smoking prevalence suggest that, while the prevalence in men increased earlier than women, more male smokers have quit than their female counterparts. These trends in smoking prevalence suggest striking gender differences in a period effect for the smoking prevalence. Estimates of the proportion of current smokers, ex-smokers, and the mean duration of smoking were used in a model for the lung cancer incidence rates. The form for the relationship between smoking history and the incidence rate for these subgroups was based on information from cohort studies. The models represented a mixture of the smoking subgroups where the effect of smoking was considered to be either a multiplicative effect on the underlying age distribution, or a separate effect in which the level of exposure was the sole contribution to risk among smokers. The multiplicative model explained more than 80 per cent of the deviance for the period and cohort effects, while the non-multiplicative model could only account for trends in females. Hence, these results suggest that a sizeable portion of the period and cohort contributions to the lung cancer incidence trends in Connecticut can be attributed to the multiplicative model that utilizes this smoking information, although the lack of more detailed information is a limiting factor in developing the model.     

ROBUSTNESS AND POWER OF ANALYSIS OF COVARIANCE APPLIED TO DATA DISTORTED FROM NORMALITY BY FLOOR EFFECTS: HOMOGENEOUS REGRESSION SLOPES

We investigate through computer simulations the robustness and power of two group analysis of covariance tests applied to small samples distorted from normality by floor effects when the regression slopes are homogeneous. We consider four parametric analysis of covariance tests that vary according to the treatment of the homogeneity of regression slopes and two t-tests on unadjusted means and on difference scores. Under the null hypothesis of no difference in means, we estimated actual significance levels by comparing observed test statistics to appropriate values from the F and t distributions for nominal significance levels of 0⋅10, 0⋅05, 0⋅02 and 0⋅01. We estimated power by similar comparisons under various alternative hypotheses. The hierarchical approach (that adjusts for non-homogeneous slopes if found significant), the test that assumes homogeneous regression slopes, and the test that estimates separate regression slopes in each treatment were robust. In general, each test produced power at least equal to that expected from normal theory. The textbook approach, which does not test for mean differences when there is significant non-homogeneity, was conservative but also had good power. The t-tests were robust but had poorer power properties than the above procedures.     

Passive smoking and behavioural problems in children: Results from the LISAplus prospective birth cohort study

Objective

To analyse the association between pre- and postnatal exposure to tobacco smoke and child behavioural problems and to further investigate the influence of trimester-specific exposure to maternal smoking and the impact of paternal smoking at home on the same outcome.

Methods

Data of 3097 German children recruited at birth for a population-based, prospective study were used. Detailed information on children's tobacco smoke exposure was collected by self-administered questionnaires at each follow-up. Behavioural outcomes were measured by the Strengths and Difficulties Questionnaire applied at 10-year follow-up.

Results

Children exposed to environmental tobacco smoke at home showed increased risks of hyperactivity/inattention problems. Only smoking during the entire pregnancy increased the risk for conduct and hyperactivity/inattention problems (proportional odds ratio (pOR)=1.58, 95% confidence interval (CI)=1.06–2.37 and pOR=1.67, CI=1.03–2.72). Pre- and postnatal exposure to paternal smoking was associated with hyperactivity/inattention problems in children of non-smoking mothers (pOR=1.97, CI=1.06–3.65). Effect estimates were adjusted for study centre, sex, parental educational level, mother's age at birth, having a single parent and time spent in front of a screen.

Conclusions

Not only maternal smoking during pregnancy but also paternal smoking at home should be considered as a risk for hyperactivity/inattention problems in children.     

CONTINUING BONDS IN BEREAVEMENT: AN ATTACHMENT THEORY BASED PERSPECTIVE

ABSTRACT

An attachment theory based perspective on the continuing bond to the deceased (CB) is proposed. The value of attachment theory in specifying the normative course of CB expression and in identifying adaptive versus maladaptive variants of CB expression based on their deviation from this normative course is outlined. The role of individual differences in attachment security on effective versus ineffective use of CB in coping with bereavement also is addressed. Finally, the moderating influence of type of loss (e.g., death of a spouse vs. child), culture, and religion on type of CB expression within an overarching attachment framework is discussed.     

Food Prices and Obesity: Evidence and Policy Implications for Taxes and Subsidies

Context: Pricing policies have been posited as potential policy instruments to address the increasing prevalence of obesity. This article examines whether altering the cost of unhealthy, energy-dense foods, compared with healthy, less-dense foods through the use of fiscal pricing (tax or subsidy) policy instruments would, in fact, change food consumption patterns and overall diet enough to significantly reduce individuals' weight outcomes.
Methods: This article examined empirical evidence regarding the food and restaurant price sensitivity of weight outcomes based on a literature search to identify peer-reviewed English-language articles published between 1990 and 2008. Studies were identified from the Medline, PubMed, Econlit, and PAIS databases. The fifteen search combinations used the terms obesity , body mass index , and BMI each in combination with the terms price , prices , tax , taxation , and subsidy .
Findings: The studies reviewed showed that when statistically significant associations were found between food and restaurant prices (taxes) and weight outcomes, the effects were generally small in magnitude, although in some cases they were larger for low–socioeconomic status (SES) populations and for those at risk for overweight or obesity.
Conclusions: The limited existing evidence suggests that small taxes or subsidies are not likely to produce significant changes in BMI or obesity prevalence but that nontrivial pricing interventions may have some measurable effects on Americans' weight outcomes, particularly for children and adolescents, low-SES populations, and those most at risk for overweight. Additional research is needed to be able to draw strong policy conclusions regarding the effectiveness of fiscal-pricing interventions aimed at reducing obesity.