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 ß 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, ß 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 ß 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 ß 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.

Addition of a general practitioner to the accident and emergency department: a cost-effective innovation in emergency care.

BACKGROUND: Many patients visit the accident and emergency department (AED) on their own initiative, although their medical problem can be adequately treated by a general practitioner (GP). Objective To evaluate the cost-effectiveness of addition of a GP to the AED (new care method) in comparison with usual care (usual care method). METHODS: This study followed a before/after design. Patients attending the AED without a referral on weekdays from 10:00 to 17:00 were invited to participate. Main outcome measures were process time, patient satisfaction and number of correct diagnoses. Costs were measured from a societal perspective. Bootstrapping was used to estimate uncertainty around differences in costs and incremental cost-effectiveness ratios. Cost-effectiveness planes and acceptability curves were presented. RESULTS: Addition of a GP to the AED resulted in significantly lower process time, significantly higher patient satisfaction and no statistically significant difference in the number of correct diagnoses. Total costs per patient were €217 in the new care period and €288 in the usual care period (mean difference -€71, 95% CI -121 to -23). The cost-effectiveness analysis showed that the new care method was dominant (more effective, less expensive) in comparison with the usual care method for process time and patient satisfaction. The new care method was considered cost-effective in comparison with the usual care method for ceiling ratios between €0 and €1363 for the number of correct diagnoses. CONCLUSION: The new care method consisting of addition of a GP to the AED is cost-effective in comparison with usual care for all outcome parameters measured.

Effectiveness of GPs in accident and emergency departments.

BACKGROUND: Many self-attending patients make inappropriate use of accident and emergency departments. AIM: To determine whether a new care method consisting of the involvement of a GP during the day with the staff of the accident and emergency department of an academic city hospital and application of the Nederlands Triage System by a practice nurse is more effective than usual care. DESIGN: Before and after intervention design. SETTING: Accident and emergency department in the VU University Medical Center in Amsterdam. METHOD: Participants were patients (n = 1527) attending the accident and emergency department without a referral, on weekdays from 10.00-17.00 hours, from 1 November 2006 to 30 April 2007. The intervention consisted of a new care method that combined the involvement of a GP in the accident and emergency department and allocation of patients by triage to either the GP or the accident and emergency department physician. Main outcome measures were patient satisfaction, number and type of additional examinations, quality of diagnosis, process time, and treatment time. RESULTS: Patient satisfaction with the treatment increased significantly. Compared to the usual care method, this new care method resulted in a 13% decrease in additional examinations. The percentage of incorrect diagnoses (1 %), as a measure of quality of care, was similar with the two methods. The mean process time decreased from 93 to 69 minutes (P<0.001). The mean treatment time decreased from 60 to 35 minutes (P<0.001). CONCLUSION: The new care method resulted in greater patient satisfaction and maintained the quality of care, with fewer additional examinations. It reduced both the process time and the treatment time.

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. DESIGN: Cross-sectional study. PATIENTS: A total of 613 adults aged 18-65 years from a random sample from general practices in the Netherlands (52 degrees N, 2003-05), stratified according to gender and ethnic group. MEASUREMENTS: Serum 25-hydroxyvitamin D [25(OH)D], PTH, ethnic group, sunlight exposure, consumption of foods and supplements rich in vitamin D. RESULTS: The prevalence (95% confidence interval) of vitamin D deficiency [serum 25(OH)D < 25 nmol/l] was higher in Turkish (41.3%; 32.5-50.1), Moroccan (36.5%; 26.9-46.1), Surinam South Asian (51.4%; 41.9-60.9), Surinam Creole (45.3%; 34.0-56.6), sub-Saharan African (19.3%; 9.1-29.5) and other adults (29.1%; 17.1-41.1) compared to the indigenous Dutch (5.9%; 1.3-10.5). Modifiable, significant determinants (standardized regression coefficients) for serum 25(OH)D concentration were: consumption of fatty fish (0.160), use of vitamin D supplements (0.142), area of uncovered skin (highest category 0.136; middle category 0.028), use of tanning bed (0.103), consumption of margarine (0.093) and preference for sun (0.089). We found no significant modification of ethnic group on the effect of sunlight determinants. CONCLUSION: Of the modifiable determinants, fatty fish and supplements are the greatest contributors to the serum 25(OH)D concentration in a multiethnic population.

Comorbid depression, but not comorbid anxiety disorders, predicts poor outcome in anxiety disorders.

Influence of type of comorbidity was studied over the course of 1 year in a sample of 141 outpatients with panic disorder with or without agoraphobia and generalized anxiety disorder, who were receiving different forms of cognitive behavior therapy. Influence of type of comorbidity was determined on the basis of change scores (linear regression analysis) and remission data (Kaplan-Meier survival analysis). Three categories, as assessed at baseline, were compared: no comorbidity, comorbidity among anxiety disorders, and comorbidity with mood disorders. Primary outcome variable: State-Trait Anxiety Inventory State subscale measured at four assessments (0, 12, 24, and 52 weeks). Analyses of change and remission indicated that comorbidity with mood disorders led to (i) less improvement and (ii) a lower remission rate than comorbidity among anxiety disorders and no comorbidity. Because comorbidity has a critical influence on prognosis, it seems to be important to make a reliable diagnosis of the disorders present.

Good generalizability of a prediction rule for prediction of persistent shoulder pain in the short term.

OBJECTIVE: To evaluate the generalizability of recently developed clinical prediction rules for the prognosis of shoulder pain in general practice. STUDY DESIGN AND SETTING: A large research program, consisting of a prognostic cohort study and three randomized controlled trials with 6 months follow-up, was carried out in The Netherlands. The clinical prediction rules were derived from the results of the prognostic cohort study (n=587). The main outcome measure was persistent symptoms at 6 weeks or 6 months. The control groups of the trials who received usual care were merged (n=212), and used to validate the prediction rules by studying calibration and discrimination. RESULTS: The prediction rule for short-term outcome showed reasonable calibration and discriminative ability in this validation cohort. The area under the receiver operating characteristic curve (AUC) was 0.72 compared to 0.74 in the derivation cohort. The prediction rule for long-term outcome performed less well. Discriminative ability (AUC) decreased to 0.56 in the validation cohort compared to 0.67 in the derivation cohort. CONCLUSION: The prediction rule for the short-term (6 weeks) prognosis showed good generalizability. The prediction rule for the long-term prognosis showed poor generalizability.

Vitamin D status predicts physical performance and its decline in older persons.

CONTEXT: Vitamin D deficiency is common among older people and can cause mineralization defects, bone loss, and muscle weakness. OBJECTIVE: The aim of this study was to investigate the association of serum 25-hydroxyvitamin D (25-OHD) concentration with current physical performance and its decline over 3 yr among elderly. DESIGN: The study consisted of a cross-sectional and longitudinal design (3-yr follow-up) within the Longitudinal Aging Study Amsterdam. SETTING: An age- and sex-stratified random sample of the Dutch older population was used. OTHER PARTICIPANTS: Subjects included 1234 men and women (aged 65 yr and older) for cross-sectional analysis and 979 (79%) persons for longitudinal analysis. MAIN OUTCOME MEASURE(S): Physical performance (sum score of the walking test, chair stands, and tandem stand) and decline in physical performance were measured. RESULTS: Serum 25-OHD was associated with physical performance after adjustment for age, gender, chronic diseases, degree of urbanization, body mass index, and alcohol consumption. Compared with individuals with serum 25-OHD levels above 30 ng/ml, physical performance was poorer in participants with serum 25-OHD less than 10 ng/ml [regression coefficient (B) = -1.69; 95% confidence interval (CI) = -2.28; -1.10], and with serum 25-OHD of 10-20 ng/ml (B = -0.46; 95% CI = -0.90; -0.03). After adjustment for confounding variables, participants with 25-OHD less than 10 ng/ml and 25-OHD between 10 and 20 ng/ml had significantly higher odds ratios (OR) for 3-yr decline in physical performance (OR = 2.21; 95% CI = 1.00-4.87; and OR = 2.01; 95% CI = 1.06-3.81), compared with participants with 25-OHD of at least 30 ng/ml. The results were consistent for each individual performance test. CONCLUSIONS: Serum 25-OHD concentrations below 20 ng/ml are associated with poorer physical performance and a greater decline in physical performance in older men and women. Because almost 50% of the population had serum 25-OHD below 20 ng/ml, public health strategies should be aimed at this group.

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 (>or=CIN2), but data are required that enable long-term evaluation of screening. We investigated the >or=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 >or=CIN2 diagnosed within 36 months. hrHPV testing was more sensitive than cytology for >or=CIN2 (relative sensitivity 1.4, 95%CI: 1.3-1.5; absolute sensitivity 94.1 and 68.0%, respectively). The 18-month >or=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 >or=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 >or=CIN2 risk. Notably, women who had a double negative repeat test at 6 months had a >or=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 >or=CIN2 risk of 0% (95%CI: 0.0-0.8). Using hrHPV and/or cytology testing, risk of >or=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.

High prevalence of vitamin D deficiency in pregnant non-Western women in The Hague, Netherlands.

BACKGROUND: Vitamin D deficiency is common in dark-skinned persons living in northern countries. Vitamin D deficiency during pregnancy may have serious consequences for both mother and child. OBJECTIVE: The objective was to ascertain the prevalence of vitamin D deficiency in pregnant women of several ethnic backgrounds who were living in The Hague, a large city in the Netherlands. DESIGN: Midwives whose practice was visited by a large number of non-Western immigrants added the assessment of serum 25-hydroxyvitamin D [25(OH)D] to the standard blood test given to women who visited the practice during week 12 of pregnancy. Subsequently, the Municipal Health Service collected additional data from the midwives' files (June 2002 through March 2004): background variables, use of tobacco or alcohol or drugs, and infectious diseases. The women were grouped ethnically as Western, Turkish, Moroccan, and other non-Western. RESULTS: The vitamin D concentrations of 358 women were found in the midwives' files. Of these women, 29% were Western, 22% were Turkish, and 19% were Moroccan. Mean serum 25(OH)D concentrations in Turkish (15.2 +/- 12.1 nmol/L), Moroccan (20.1 +/- 13.5 nmol/L), and other non-Western women (26.3 +/- 25.9 nmol/L) were significantly (P

Prediction of Chlamydia trachomatis infection: application of a scoring rule to other populations.

BACKGROUND: Active case finding is crucial to reduce transmission and consequences of Chlamydia trachomatis (CT) infections. We previously proposed the use of a prediction rule for CT infection for selective screening of high-risk individuals in a population. To support such an application, the prediction rule needs to be validated in other populations. METHODS: We studied participants aged 15 to 29 years in a population-based study in Amsterdam (n = 1,788) and an outreach screening project among high-risk youth in Rotterdam (n = 172). Validity was indicated by discriminative ability (area under the receiver operating characteristic curve [AUC]) and by calibration, which was visualized in plots and tested with the Hosmer-Lemeshow (H-L) goodness-of-fit test. Cutoffs of predicted risk were examined for their effect on sensitivity and the fraction of participants that would need to be screened. RESULTS: Discriminative ability was reasonable both for the Amsterdam study (AUC 0.66; 95% confidence interval [CI], 0.58-0.74) and for the Rotterdam study (AUC 0.68; 95% CI, 0.58-0.79). The observed CT prevalence was lower than predicted in Amsterdam (H-L P = 0.02) and nonsignificantly higher in Rotterdam (H-L P = 0.20). By screening 77% of the Amsterdam population, 93% of the cases would have been detected, whereas in the Rotterdam study, no cases would be missed by screening 75%. CONCLUSION: The chlamydia prediction rule showed a reasonable external validity in two studies. These findings support the use of the rule as a tool for selective chlamydia screening, although only a limited fraction of participants can be excluded when a high sensitivity is required.

Overestimation of complication rates in evaluations of Chlamydia trachomatis screening programmes--implications for cost-effectiveness analyses.

BACKGROUND: Cost-effectiveness analyses of screening programmes for asymptomatic Chlamydia trachomatis infection suggest that screening at low prevalences in the population is cost-effective. However, the decision models in these studies are based on assumptions about the risk of complications, which are derived from the literature. Incorrect assumptions may lead to under- or overestimation of the effectiveness of screening. The first objective of this paper is to evaluate the assumptions about the probability of complications after an asymptomatic C. trachomatis infection. The second objective is to calculate alternative rates by using available data on the incidence of complications. METHODS: We identified cost-effectiveness studies via Medline, and evaluated these for the evidence for the quoted probabilities. In addition, the probability of complications was calculated for Amsterdam from available registration data. RESULTS: In the three studies that were identified, the assumptions for the rates of pelvic inflammatory disease (PID) (clinical and subclinical) after C. trachomatis infection varied from 15% to 80%, and for ectopic pregnancy, tubal factor infertility, and chronic pelvic pain after PID from 5-25%, 10-20%, and 18-30%, respectively. The assumptions were based on data from high-risk populations, case-control data, and data not accounting for misdiagnoses. Using data obtained from local registrations, we estimated the probability of a clinical PID (0.43%), ectopic pregnancy (0.07%), and tubal factor infertility (0.02%) for women with a current infection. These estimates were consistently lower than the estimates based on the literature. CONCLUSIONS: We argue that an overestimation of the current complication rates is likely. The effect of overestimation is potentially the greatest in populations with a low prevalence, since the currently assumed cost savings associated with screening may disappear when using more realistic estimates for complications.

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 > or =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.

Follow-up, treatment, and reinfection rates among asymptomatic chlamydia trachomatis cases in general practice.

BACKGROUND: Adequate treatment and follow-up of patients is essential to the success of a screening programme for Chlamydia trachomatis. There has been a lack of data on follow-up, confirmation of infections, and reinfection rates among asymptomatic patients in general practice. AIM: 7b study the rates of diagnostic confirmation of C trachomatis infection, successful treatment, and reinfection one year after cases were detected in a screening programme for asymptomatic infections. DESIGN OF STUDY: Prospective cohort study SETTING: Fifteen general practices in Amsterdam, The Netherlands. METHOD: One hundred and twenty-four patients with asymptomatic C trachomatis infections were requested to provide a cervical or urethral swab and a urine specimen, for the purpose of diagnostic confirmation before being treated. One year after the first screening, all of the patients were invited for a second screening. All samples were tested using the ligase chain reaction (Abbott Laboratories, Chicago, USA). RESULTS: Out of 124 patients, 110 (89%) attended the scheduled appointment for diagnostic confirmation and treatment; 92 (84%) of them were confirmed to be positive and received treatment. At the second screening a year later, none of the 56 patients who had received treatment and who had been screened a second time were reinfected. CONCLUSION: No asymptomatic patients werefound to have reinfections with C trachomatis one year after diagnostic confirmation and treatment. This underlines the effectiveness of the screening and treatment strategy

Partner notification among asymptomatic Chlamydia trachomatis cases, by means of mailed specimens.

The objective of the study was to evaluate the prevalence of Chlamydia trachomatis infection and the participation, among partners of asymptomatic cases in general practice. Index cases were requested to invite partners for testing by mailed urine samples. One or more partners of 62% of the index cases participated, and the prevalence of infection among partners was 48%. A steady relationship was a determinant of both participation and prevalence. In conclusion, the mailing strategy is an effective strategy for partner notification. A high prevalence wasfound among partners.

Do questions on sexual behaviour and the method of sample collection affect participation in a screening programme for asymptomatic Chlamydia trachomatis infections in primary care?

We examined the effect of a questionnaire addressing sexual behaviour on participation in a systematic screening programme for asymptomatic Chlamydia trachomatis infections. Furthermore, we compared participation among persons requested to mail a home-obtained urine sample directly to the laboratory and persons requested to bring a sample to the physician's office. Seven hundred and fifty men and women were randomly assigned to receive a questionnaire with or without intimate questions and to deliver or mail the samples. The inclusion of questions about sexual behaviour did not affect participation among both men and women. Among women there was no difference in participation between delivering or mailing the sample. Among men delivering the sample, participation was 18% (95% confidence interval [CI]: 5-32) lower. This study shows that questions on sexual behaviour can be included in a screening questionnaire without adversely affecting participation. Furthermore, mailing the specimens is the most efficient strategy for men, when screening for C. trachomatis by means of home-obtained urine specimens.

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.