A. Joan P. Boeke

POBASCAM, a population‐based randomized controlled trial for implementation of high‐risk HPV testing in cervical screening: Design, methods and baseline data of 44,102 women

Cytological cervical screening is rather inefficient because of relatively high proportions of false negative and false positive smears. To evaluate the efficiency of high‐risk human papillomavirus (hrHPV) testing, by GP5+/6+ PCR‐enzyme immunoassay (EIA), in conjunction with cytology (Intervention Group) to that of the classical cytology (Control Group), we initiated the Population Based Screening Study Amsterdam (POBASCAM). POBASCAM is a population‐based randomized controlled trial for implementation of hrHPV testing in cervical screening. The outcome measure is the proportion of histologically confirmed ≥CIN3 lesions in each study arm up to and including the next screening round after 5 years. We present the design, methods and baseline data of POBASCAM. When, in the next 5 years, the follow‐up will be completed, the data obtained will be used in model studies, including a cost‐effectiveness study, to advise the Dutch Ministry of Public Health in deciding whether cervical screening should be based on combined hrHPV and cytology testing instead of cytology alone. Between January 1999 and September 2002, 44,102 women (mean age = 42.8 years; range = 29–61) that participated in the regular Dutch screening program were included in our study. In the Intervention Group the distribution of cytology and hrHPV by cytology class was as follows: normal cytology 96.6% (3.6% hrHPV positive); borderline and mild dyskaryosis (BMD) 2.5% (34.6% hrHPV positive); and moderate dyskaryosis or worse (>BMD) 0.8% (88.3% hrHPV positive), i.e., 0.4% moderate dyskaryosis (82.9% hrHPV positive), 0.3% severe dyskaryosis (92.5% hrHPV positive), 0.1% carcinoma in situ (95.2% hrHPV positive), <0.1% suspected for invasive cancer (hrHPV positive 100.0%). In the Control Group 96.5% of the women had normal cytology, 2.4% BMD and 0.8% >BMD, i.e., 0.4% moderate dyskaryosis, 0.3% severe dyskaryosis, 0.1% carcinoma in situ, <0.1% suspected for invasive cancer. The presence of hrHPV was age‐dependent, decreasing from 12.0% at 29–33 years to 2.4% at 59–61 years. Among women with a positive hrHPV test, the prevalence of BMD was age‐dependent ranging from 20.2% at 29–33 years to 7.8% at 54–58 years. In contrast, the risk of >BMD of 13.7% among women with a positive hrHPV test was not age‐dependent. Our study indicates that large‐scale hrHPV testing by GP5+/6+ PCR‐EIA in the setting of population‐based cervical screening is practically feasible, is accepted by both participating women and general practitioners and yields highly reproducible results.

The natural course of asymptomatic Chlamydia trachomatis infections: 45% clearance and no development of clinical PID after one-year follow-up

The natural course of asymptomatic Chlamydia trachomatis infections in women was studied during one year in a cohort based nested case-control study. Healthy women (n = 744, from four company health services in Amsterdam) with a medical check-up prior to job engagement were included. C. trachomatis-positive women (n = 30, cases) and a randomly selected control group of C. trachomatis-negative women (n = 186, controls) were followed for one year. Urine specimens (at one, six and 12 months) were analysed for the presence of C. trachomatis-DNA and the C. trachomatis-serovars, and questionnaires were filled in. The C trachomatis prevalence and natural course in relation to demographic and sexual characteristics after one, six and 12 months were studied. The main outcome measures were 1) the prevalence of C. trachomatis using urine specimens; 2) self-reported complaints; 3) clinical symptoms reported to the coordinating physicians. The prevalence of asymptomatic C. trachomatis infections was 4% and there was no correlation with demographic and sexual characteristics. The person/year clearance rate was 44.7% per year. None of the C. trachomatis-positive women developed clinical symptoms or used C. trachomatis specific antibiotic treatment. Women with or without an asymptomatic infection had the same number of self-reported urogenital complaints during follow-up. In persisting infections twice as many C. trachomatis-serovar E infections were detected as compared to clearing infections. Our findings showed that almost half of the asymptomatic C. trachomatis infections in women cleared during one year of follow-up and none developed clinical pelvic inflammatory disease (PID), which is a much lower figure than previously suggested. Therefore these data are important for cost effectiveness calculations in screening programmes for asymptomatic C. trachomatis infections.

Direct and buffer effects of social support and personal coping resources in individuals with arthritis

The direct and buffer effects of various aspects of social support and personal coping resources on depressive symptoms were examined. The study concerned a community-based sample of 1690 older persons aged 55-85 yrs, of whom 719 had no chronic disease, 612 had mild arthritis and 359 had severe arthritis. Persons with arthritis reported more depressive symptoms than persons with no chronic diseases. Irrespective of arthritis, the presence of a partner, having many close social relationships, feelings of mastery and a high self-esteem were found to have direct, favourable effects on psychological functioning. Mastery, having many diffuse social relationships, and receiving emotional support seem to mitigate the influence of arthritis on depressive symptoms, which is in conformity with the buffer hypothesis. Favourable effects of these variables on depressive symptomatology were only, or more strongly, found in persons suffering from severe arthritis.

Social Network, Social Support, and Loneliness in Older Persons with Different Chronic Diseases

Objectives:This study examines whether patterns of social network size, functional social support, and loneliness are different for older persons with different types of chronic diseases. Methods:In a community-based sample of 2,788 men and women age 55 to 85 years participating in the Longitudinal Aging Study Amsterdam, chronic diseases status, social network size, support exchanges, and loneliness were assessed. Results:Social network size and emotional support exchanges were not associated with disease status. The only differences between healthy and chronically ill people were found for receipt of instrumental support and loneliness. Disease characteristics played a differential role: greater feelings of loneliness were mainly found for persons with lung disease or arthritis, and receiving more instrumental support was mainly found for persons with arthritis or stroke. Discussion:The specifics of a disease appear to play a (small) role in the receipt of instrumental support and feelings of loneliness of chronically ill older persons.

Psychological status among elderly people with chronic diseases: Does type of disease play a part?

Psychological status, including depressive symptoms, anxiety, and mastery, was measured in a community-based sample of 3,076 persons aged 55 to 85 with various chronic diseases. Strong, linear associations were found between the number of chronic diseases and depressive symptoms and anxiety, indicating that psychological distress among elderly people is more apparent in the presence of (more) diseases. Furthermore, in contrast to general assumptions that mastery is a relatively stable state, our results indicate that mastery is affected by having chronic diseases. The 8 groups of chronically ill patients (with cardiac disease, peripheral atherosclerosis, stroke, diabetes, lung disease, osteoarthritis, rheumatoid arthritis, or cancer) did differ in their associations with psychological distress. Psychological distress is most frequently experienced by patients with osteoarthritis, rheumatoid arthritis, and stroke, whereas diabetic and cardiac patients appear to be the least psychologically distressed. Differences in disease characteristics, such as functional incapacitation and illness controllability, may partly explain these observed psychological differences across diseases.

Clinical prediction rules for the prognosis of shoulder pain in general practice

Abstract Shoulder pain is common in primary care and has an unfavourable outcome in many patients. Information about predictors of outcome is scarce and inconsistent. The objective of this study was to develop clinical prediction rules for calculating the absolute risk of persistent shoulder symptoms for individual patients, 6 weeks and 6 month after the first consultation in general practice. A prospective cohort study with 6 months follow‐up was carried out in three geographic areas in The Netherlands. In this study, 587 patients with a new episode of shoulder pain were included. The main outcome measure was persistent symptoms at 6 weeks and 6 months, perceived by the patient. Potential predictors included the results of a physical examination, sociodemographic variables, disease characteristics (duration of symptoms, pain intensity, disability and comorbidity), physical activity, physical workload and psychosocial factors. Response rates to the follow‐up questionnaires were 83% at 6 weeks and 92% at 6 months. A longer duration of symptoms, gradual onset of pain and high pain severity at presentation were consistently associated with persistent symptoms at 6 weeks and 6 months. The discriminative validity of our prediction rules was satisfactory with area under the curves of 0.74 (95% CI 0.70, 0.79) at 6 weeks and 0.67 (95% CI 0.63, 0.71) at 6 months. The performance of our rules needs to be tested in other populations of patients with shoulder pain to enable valid and reliable use of the rules in everyday clinical practice.

Fatty fish and supplements are the greatest modifiable contributors to the serum 25-hydroxyvitamin D concentration in a multiethnic population

Objective  Because vitamin D synthesis is lower in a heavily pigmented skin than in a lighter skin, the relative contribution of determinants to the vitamin D concentration might differ between ethnic groups. The aim of this study was to assess the prevalence of vitamin D deficiency and the relative contribution of vitamin D consumption and exposure to sunlight to the vitamin D concentration in a multiethnic population.

Risk of high-grade cervical intra-epithelial neoplasia based on cytology and high-risk HPV testing at baseline and at 6-months†

Adding a test for high‐risk human papillomavirus (hrHPV) to cytological screening enhances the detection of high‐grade cervical intraepithelial neoplasia (≥CIN2), but data are required that enable long‐term evaluation of screening. We investigated the ≥CIN2 risk for women participating in population‐based screening as a function of hrHPV and cytology testing results at baseline and at 6 months. We included 2,193 women aged 30–60 years participating in a population‐based screening trial who received colposcopy or a repeat testing advice at baseline. The main endpoint was histologically confirmed ≥CIN2 diagnosed within 36 months. hrHPV testing was more sensitive than cytology for ≥CIN2 (relative sensitivity 1.4, 95%CI: 1.3–1.5; absolute sensitivity 94.1 and 68.0%, respectively). The 18‐month ≥CIN2 risks in women with a hrHPV‐positive smear and in women with abnormal cytology were similar (relative risk 0.9, 95%CI: 0.8–1.1). Women with HPV16 and/or HPV18 had a higher ≥CIN2 risk than other hrHPV‐positive women irrespective of the cytological grade. Repeat testing showed that both cytological regression and viral clearance were strongly associated with a decrease in ≥CIN2 risk. Notably, women who had a double negative repeat test at 6 months had a ≥CIN2 risk of only 0.2% (95%CI: 0.0–1.1) and hrHPV‐negative women with baseline borderline or mild dyskaryosis and normal cytology at 6 months had a ≥CIN2 risk of 0% (95%CI: 0.0–0.8). Using hrHPV and/or cytology testing, risk of ≥CIN2 can be assessed more accurately by repeat testing than single visit testing. Hence, when hrHPV testing is implemented, patient management with repeat testing is a promising strategy to control the number of referrals for colposcopy.

Reproducibility, Construct Validity, and Responsiveness of the “How Are You?” (HAY), a Self-Report Quality of Life Questionnaire for Children with Asthma

This study assesses the reproducibility, construct validity, and responsiveness of a new self-report quality of life questionnaire, the “How Are You?” (HAY), for 8-12-year-old children with asthma, which contains both a generic and a disease-specific part. Two hundred twenty-eight children with asthma completed the HAY and the Child Attitude Toward Illness Scale (CATIS), while their parents monitored the actual asthma status; 80 children were measured three times in order to assess reproducibility and responsiveness; 296 healthy children completed the generic section of the HAY. Significant differences were found between children with asthma and healthy children, and among asthmatic children differing in actual asthma status. Reproducibility was adequate and supportive evidence was found for construct validity. Responsiveness was demonstrated by significant score changes for most dimensions in clinically changed children. The HAY seems useful for both discriminative and evaluative research in children with asthma.

Effect of moderate-dose vitamin D supplementation on insulin sensitivity in vitamin D–deficient non-Western immigrants in the Netherlands: a randomized placebo-controlled trial

BACKGROUND Low serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with insulin resistance, the metabolic syndrome, and type 2 diabetes. Because many non-Western immigrants in the Netherlands are vitamin D deficient, obese, and at high risk of diabetes, vitamin D supplementation may contribute to prevent diabetes and insulin resistance. OBJECTIVE We examined the effect of vitamin D supplementation on insulin sensitivity and β cell function in overweight, vitamin D-deficient, non-Western immigrants at high risk of diabetes. DESIGN The study was a 16-wk, randomized, placebo-controlled trial. A total of 130 non-Western immigrants with prediabetes (fasting glucose concentration >5.5 mmol/L or random glucose concentration from 7.8 to 11.1 mmol/L) and vitamin D deficiency (serum 25[OH]D concentration <50 nmol/L) were randomly assigned after stratification by sex to receive either cholecalciferol (1200 IU/d) or a placebo for 16 wk. All participants received 500 mg Ca/d as calcium carbonate. The primary outcome was the difference in the area under the curve of insulin and glucose after a 75-g oral-glucose-tolerance test after 4 mo of treatment. Secondary outcomes were insulin-sensitivity variables, β cell-function variables, and metabolic syndrome. RESULTS Mean serum 25(OH)D concentrations increased significantly in the vitamin D compared with placebo groups. After 4 mo of therapy, the mean between-group difference was 38 nmol/L (95% CI: 32.1, 43.9 nmol/L; P < 0.001). There was no significant effect on insulin sensitivity and β cell function. In a post hoc analysis, when patients with diabetes at baseline were excluded, a significant increase in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L (P = 0.040). CONCLUSIONS Vitamin D supplementation in non-Western vitamin D-deficient immigrants with prediabetes did not improve insulin sensitivity or β cell function or change the incidence of metabolic syndrome. However, after the exclusion of diabetic subjects, an improvement in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L. This trial was registered at trialregister.nl as NTR1827.