Shorter durations and lower doses of peginterferon alfa-2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C.

UNLABELLED: As there is currently a lack of consensus on the most appropriate dose and duration of peginterferon alfa-2a (PEG-IFNα-2a) therapy in hepatitis B e antigen (HBeAg)-positive patients, the efficacy and safety of either 24 or 48 weeks' duration and 90 µg/week or 180 µg/week doses were compared. HBeAg-positive patients (n = 544; 34% genotype B, 51% genotype C) were randomized to receive PEG-IFNα-2a (2 × 2 factorial design) for 24 or 48 weeks and at 90 µg/week or 180 µg/week and included in the per-protocol population. The primary efficacy endpoint of the noninferiority study was HBeAg seroconversion 6 months posttreatment. The prespecified odds ratio (OR) noninferiority margin was 1.88 with a one-sided significance level of 0.025. The highest rates of HBeAg seroconversion 6 months posttreatment were in the 180/48 arm (36.2% versus 14.1%-25.8% in the other arms). When the dose and duration arms were pooled, the OR for noninferiority of 24 weeks versus 48 weeks was 2.17 (95% confidence interval [CI] 1.43, 3.31; P = 0.749) and for 90 µg versus 180 µg was 1.79 (95% CI 1.18, 2.72; P = 0.410). As the upper limit of the 95% CI of the ORs were >1.88, 24 weeks were inferior to 48 weeks and 90 µg/week was inferior to 180 µg/week. The highest rates of response in the 180/48 arm were achieved by patients with HBsAg <1,500 IU/mL at Week 12 (58%) or Week 24 (57%), whereas patients with HBsAg >20,000 IU/mL did not respond. Adverse events were typical of those associated with PEG-IFNα-2a. CONCLUSION: Compared with lower doses and shorter durations, the licensed PEG-IFNα-2a treatment regimen (180 µg/48 weeks) was the most efficacious and beneficial for HBeAg-positive patients predominantly infected with hepatitis B virus genotypes B or C.

Can strenuous leisure time physical activity prevent psychological complaints in a working population?

AIMS: To investigate the longitudinal relation between strenuous leisure time physical activity and psychological complaints (depression and emotional exhaustion) in a Dutch working population in order to find evidence for the preventive role of physical activity in the development of psychological complaints. METHODS: All data came from the Study on Musculoskeletal disorders, Absenteeism, Stress, and Health (SMASH), a three year follow up study that started between 1994 and 1995. The study population consisted of 1747 workers from 34 companies. Generalised estimating equation (GEE) analyses were performed to investigate the longitudinal relation between strenuous leisure time physical activity and psychological complaints using models with and without a time lag. Logistic regression analyses were performed to study the relation between physical activity and sickness absence due to psychological complaints during the three year follow up study. RESULTS: Only in workers with a sedentary job was strenuous leisure time physical activity (1-2 times per week) significantly associated with a reduced risk of future depression and emotional exhaustion. This was not the case for physical activity at higher frequencies (> or =3 times per week). There was a dose-response relation between strenuous leisure time physical activity and poor general health which was strongest in workers with a sedentary job. Strenuous leisure time physical activity (1-2 times per week) was associated with a lower risk of long term absenteeism (>21 days), whereas physical activity at a higher frequency was not. CONCLUSIONS: Results suggest that strenuous leisure time physical activity might play a role in the prevention of future psychological complaints, poor general health, and long term absenteeism in a working population. Workers with a sedentary job seem to benefit more from strenuous leisure time physical activity than workers without a sedentary job.

Smoking behaviour and biological maturation in males and females: a 20-year longitudinal study. Analysis of data from the Amsterdam Growth and Health Longitudinal Study.

PRIMARY OBJECTIVE: (1) Describe the longitudinal smoking behaviour of boys and girls during adolescence in relation to calendar age, skeletal age, years from peak height velocity (PHV) and years from menarche (in girls). (2) and (3) Investigate the timing of biological maturation (early or late maturation) in relation to smoking behaviour in adolescence and in adulthood (i.e. calendar age 32/33). HPOTHESIS: We hypothesized skeletal age, years from PHV and years from menarche to be better predictors of smoking than calendar age. RESEARCH DESIGN: This study is part of the Amsterdam Growth and Health Longitudinal Study (AGAHLS) that was started in 1977 with 619 pupils from two secondary schools (mean age 13.0 SD 0.6). METHODS AND PROCEDURES: Smoking behaviour was assessed four times between 1977 and 1980 and once in 1996/1997. Calendar age and skeletal age were measured annually whereas height and menarche were measured every 4 months. Maturation rate (skeletal age minus calendar age), age at PHV and age at menarche were used to estimate timing of biological maturation. Generalized Estimating Equation (GEE) analysis was used to study maturation rate in relation to smoking during adolescence, whereas logistic regression analyses were used to study mean maturation rate, years from PHV and years from menarche in relation to smoking in adulthood. OUTCOME AND RESULTS: Skeletal age, years from PHV and years from menarche are no better predictors of smoking during adolescence than calendar age. The prevalence of smoking rises gradually with the increase in all four estimates of biological maturation. Timing of biological maturation was positively related to smoking but only at calendar age 13 (OR 3.34, CI 1.58, 7.07). None of the three measures to estimate timing of biological maturation was significantly related to smoking status in adulthood.

Is calculating pack-years retrospectively a valid method to estimate life-time tobacco smoking? A comparison between prospectively calculated pack-years and retrospectively calculated pack-years.

AIMS: To investigate the relative validity of retrospectively calculated pack-years (py-retro) by comparing py-retro with prospectively calculated pack-years (py-pro). DESIGN: A 23-year ongoing cohort study (1977-2000). PARTICIPANTS: One hundred and fifty-four males and females, 13 years old in 1977 and 36 years old in 2000. SETTING: Amsterdam, the Netherlands. MEASUREMENTS: To calculate py-pro, current smoking and quitting efforts were investigated nine times in a period of 23 years with the help of an interview or a questionnaire. At the age of 36, subjects filled out a comprehensive questionnaire about their smoking history, to calculate py-retro. Individual differences between py-pro and py-retro were calculated. In addition, Cohen's kappa was calculated after categorising py-pro and py-retro into three groups. FINDINGS: (1) Py-retro does not under- or overestimate life-time tobacco smoking. (2) The relative validity of py-retro was moderate due to large individual differences between py-pro and py-retro. (3) The individual differences between py-pro and py-retro became larger, the higher the number of pack-years. (4) Mean difference (and 95% limits of agreement) between py-pro and py-retro was -0.039 (-5.23, 5.32) when average pack-years was < 5.2 and -1.17 (-10.00, 14.65) when pack-years > or = 5.2. 5. Cohen's kappa between categorized py-pro and py-retro was 0.79. CONCLUSIONS: Future researchers in the field of smoking should be aware of the moderate relative validity of py-retro. Categorizing py-retro into smoking groups results in a misclassification error that is smaller than the quantitative error in continuous py-retro, but goes together with a loss of information.

Time course of effects of testosterone administration on sexual arousal in women.

BACKGROUND: The assumption that testosterone is involved in human female sexual functioning is mainly based on results of studies of women with hypogonadotropic hypogonadism. This study sought to determine the effect of testosterone administration on physiological and subjective sexual arousal in sexually functional women. METHODS: In a double-masked, randomly assigned, placebo-controlled crossover design, we examined whether administration of a single dose of testosterone to sexually functional women increases vaginal and subjective sexual arousal when they are exposed to erotic visual stimuli. To search for a time lag in the effect of testosterone therapy, we exposed 8 healthy women to 6 erotic film excerpts depicting intercourse. The first and second excerpts were shown immediately before and 15 minutes after, respectively, intake of placebo or testosterone; the last 4 excerpts were then shown at 1(1/2)-hour intervals. RESULTS: Sublingual intake of testosterone caused a sharp increase in plasma testosterone levels within 15 minutes; these levels declined to baseline values within 90 minutes. Three to 4(1/2) hours after reaching peak testosterone level, we found a statistically significantly increase in genital responsiveness (P = .04). Furthermore, on the day of testosterone treatment, there also was a strong and statistically significant association between the increase in genital arousal and subjective reports of "genital sensations" (P = .02) and "sexual lust" (P = .01) after 4(1/2) hours. CONCLUSIONS: There is a time lag in the effect of sublingually administered testosterone on genital arousal in women. In addition, a consecutive increase in vaginal arousal might cause higher genital sensations and sexual lust.

Influence of Imputation and EM Methods on Factor Analysis when Item Nonresponse in Questionnaire Data is Nonignorable.

This study deals with the influence of each of twelve imputation methods and two methods using the EM algorithm on the results of maximum likelihood factor analysis as compared with results obtained from the complete data factor analysis (no missing scores). Complete questionnaire rating scale data were simulated and, next, missing item scores were created under both ignorable and nonignorable nonresponse mechanisms. Next, imputation methods were used to fill the gaps and factor analysis was applied to both the original complete data and to the data sets including imputed scores. Each imputation method was implemented once with residual error and once without residual error. Also, one EM method estimated the factor loadings directly and the other estimated the complete data covariance matrix, which subsequently was factor analyzed. A design was analyzed with design factors Latent Trait Structure (technically called Mixing Configuration), Correlation Between Latent Traits, Nonresponse Mechanism, Percentage of Missingness, Sample Size, and Imputation Method. We found that, in general, methods that impute a score based on a respondent's mean score obtained from his/her observed item scores best recovered the factor loadings structure from the complete data. Moreover, for unidimensional data person mean methods with a residual error gave better results than the other imputation methods, either with or without a residual error component. For the EM methods a smaller design was analyzed. The conclusion was that both EM methods better recovered the complete data factor loadings than the imputation methods.