Search

Background The aim of this nationwide cohort study was to examine the course of symptoms and trajectories of health-related quality of life (HR-QoL) and psychological distress during follow-up and to identify vulnerable patients. Methods Patients with pathological stage I–III colorectal cancer (CRC) between 2013 and 2018 were included. Baseline characteristics were collected from the Netherlands Cancer Registry, and patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30/CR29, Hospital Anxiety and Depression Scale and low anterior resection syndrome (LARS) questionnaires at the baseline and subsequently at 3, 6, 12, 18 and 24 months. Latent class growth and multinomial logistic regression analyses were performed to outline 24-month trajectories in HR-QoL and distress and to identify predictive factors. Results : A total of 1535 patients with colon cancer or rectal cancer were included. Trajectory analysis of HR-QoL identified three patient classes: high HR-QoL (62.7%), improving HR-QoL (29.0%) and low HR-QoL (8.3%). The following patient groups were identified with having low distress (64.0%), moderate distress (26.9%) and high distress (9.1%). Around 13% of the total cohort had either persistent low HR-QoL or high psychological distress throughout follow-up. Patients belonging to this vulnerable group were significantly more likely to be female, to be younger aged, to have lower education, to have disease stage II–III or to have major LARS. Conclusions Although most patients treated for stage I–III CRC fared well, a small but significant proportion of around 13% did not recover during follow-up and reported low HR-QoL and/or high psychological distress levels throughout. This study's findings should be taken into account when organising and selecting patients for tailored follow-up.

Background: Evidence concerning third-line life-prolonging drugs (LPDs) in the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients is incomplete. Objective: To evaluate third-line LPD outcomes in a real-world cohort of mCRPC patients, identify variables associated with overall survival (OS), and establish a prognostic model. Design, setting, and participants: Patients with mCRPC who were progressive on second-line LPD before July 1, 2017 were retrospectively identified from the Dutch Castration-resistant Prostate Cancer Registry (CAPRI) and followed until December 31, 2017. Outcome measurements and statistical analysis: Association of potential risk factors with OS was tested by Cox proportional hazard models after multiple imputation of missing baseline characteristics. A predictive score was computed from the regression coefficient and used to classify patients into risk groups. Results and limitations: Of 1011 mCRPC patients progressive on second-line LPD, 602 (60%) received third-line LPD. Patients receiving third-line LPD had a more favorable prognostic profile at baseline and longer median OS than patients with best supportive care (10.4 vs 2.4 mo, p < 0.001). Eastern Cooperative Oncology Group performance status 1 and ≥2 (hazard ratio [HR] 1.51, p < 0.007 and HR 3.08, p < 0.001, respectively), opioid use (HR 1.55, p = 0.019), visceral metastases (HR 2.09, p < 0.001), hemoglobin

Real-world data (RWD) sources are important to advance clinical oncology research and evaluate treatments in daily practice. Since 2013, the Prospective Dutch Colorectal Cancer (PLCRC) cohort, linked to the Netherlands Cancer Registry, serves as an infrastructure for scientific research collecting additional patient-reported outcomes (PRO) and biospecimens. Here we report on cohort developments and investigate to what extent PLCRC reflects the “real-world”. Clinical and demographic characteristics of PLCRC participants were compared with the general Dutch CRC population (n = 74,692, Dutch-ref). To study representativeness, standardized differences between PLCRC and Dutch-ref were calculated, and logistic regression models were evaluated on their ability to distinguish cohort participants from the Dutch-ref (AU-ROC 0.5 = preferred, implying participation independent of patient characteristics). Stratified analyses by stage and time-period (2013–2016 and 2017–Aug 2019) were performed to study the evolution towards RWD. In August 2019, 5744 patients were enrolled. Enrollment increased steeply, from 129 participants (1 hospital) in 2013 to 2136 (50 of 75 Dutch hospitals) in 2018. Low AU-ROC (0.65, 95% CI: 0.64–0.65) indicates limited ability to distinguish cohort participants from the Dutch-ref. Characteristics that remained imbalanced in the period 2017–Aug’19 compared with the Dutch-ref were age (65.0 years in PLCRC, 69.3 in the Dutch-ref) and tumor stage (40% stage-III in PLCRC, 30% in the Dutch-ref). PLCRC approaches to represent the Dutch CRC population and will ultimately meet the current demand for high-quality RWD. Efforts are ongoing to improve multidisciplinary recruitment which will further enhance PLCRC’s representativeness and its contribution to a learning healthcare system.

Purpose Tamoxifen, a widely used agent for the prevention and treatment of breast cancer, is mainly metabolized by CYP2D6 and CYP3A to form its most abundant active metabolite, endoxifen. Interpatient variability in toxicity and efficacy of tamoxifen is substantial. Contradictory results on the value of CYP2D6 genotyping to reduce the variable efficacy have been reported. In this pharmacokinetic study, we investigated the value of dextromethorphan, a known probe drug for both CYP2D6 and CYP3A enzymatic activity, as a potential phenotyping probe for tamoxifen pharmacokinetics. Methods In this prospective study, 40 women using tamoxifen for invasive breast cancer received a single dose of dextromethorphan 2 hours after tamoxifen intake. Dextromethorphan, tamoxifen, and their respective metabolites were quantified. Exposure parameters of all compounds were estimated, log transformed, and subsequently correlated. Results A strong and highly significant correlation (r = −0.72; P < .001) was found between the exposures of dextromethorphan (0 to 6 hours) and endoxifen (0 to 24 hours). Also, the area under the plasma concentration–time curve of dextromethorphan (0 to 6 hours) and daily trough endoxifen concentration was strongly correlated (r = −0.70; P < .001). In a single patient using the potent CYP2D6 inhibitor paroxetine, the low endoxifen concentration was accurately predicted by dextromethorphan exposure. Conclusion Dextromethorphan exposure after a single administration adequately predicted endoxifen exposure in individual patients with breast cancer taking tamoxifen. This test could contribute to the personalization and optimization of tamoxifen treatment, but it needs additional validation and simplification before being applicable in future dosing strategies.

Background: Trials in castration-resistant prostate cancer (CRPC) treatment have shown improved outcomes, including survival. However, as trial populations are selected, results may not be representative for the real-world population. The aim of this study was to assess the differences between patients treated in a clinical trial versus standard care during the course of CRPC in a real-world CRPC population. Design, setting, and participants: Castration-resistant Prostate Cancer Registry is a population-based, observational, retrospective registry. CRPC patients from 20 hospitals in the Netherlands have been included from 2010 to 2013. Outcome measurements and statistical analysis: Baseline characteristics, systemic treatment, and overall survival were the main outcomes. Descriptive statistics, multivariate Cox regression, and multiple imputations with the Monte Carlo Markov Chain method were used. Results and limitations: In total, 1524 patients were enrolled of which 203 patients had participated in trials at any time. The median follow-up period was 23 mo. Patients in the trial group were significantly younger and had less comorbidities. Docetaxel treatment was more frequently used in trial patients (85% vs 40%). Despite an observed unadjusted median overall survival difference of 35 mo versus 24 mo between the trial and standard care group, this difference was not retained after adjustment for baseline characteristics and treatment effect. Conclusions: At CRPC diagnosis, the baseline characteristics of the patients who had been enrolled in trials notably differed from patients who received standard treatment options only. The survival difference between the trial and standard care group could be explained by baseline differences and treatment effects. These results indicate that trial results cannot easily be translated to real-world practice. Patient summary: We observed that patients treated in clinical trials differed from patients who were not. We concluded that this may lead to differential treatment and survival. Caution is warranted when real-world outcomes are compared with trial results. We observed that castration-resistant prostate cancer patients treated in clinical trials differ from patients who are not. We conclude that this may lead to differential treatment and survival. This warrants caution when comparing real-world outcomes to trial results.

BACKGROUND: Acute respiratory tract infections (ARTIs) are responsible for considerable morbidity in the community, but little is known about the presence of respiratory pathogens in asymptomatic individuals. We hypothesized that asymptomatic persons could have a subclinical infection and thus act as a source of transmission. METHODS: During the period of 2000-2003, all patients with ARTI who visited their sentinel general practitioner had their data reported to estimate the incidence of ARTI in Dutch general practices. A random selection of these patients (case patients) and an equal number of asymptomatic persons visiting for other complaints (control subjects) were included in a case-control study. Nose and throat swabs of participants were tested for a broad range of pathogens. RESULTS: The overall incidence of ARTI was 545 cases per 10,000 person-years, suggesting that, in the Dutch population, an estimated 900,000 persons annually consult their general practitioner for respiratory complaints. Rhinovirus was most common in case patients (24%), followed by influenza virus type A (11%) and coronavirus (7%). Viruses were detected in 58% of the case patients, beta -hemolytic streptococci group A were detected in 11%, and mixed infections were detected in 3%. Pathogens were detected in approximately 30% of control subjects, particularly in the youngest age groups. CONCLUSION: This study confirms that most ARTIs are viral and supports the reserved policy of prescribing antibiotics. In both case and control subjects, rhinovirus was the most common pathogen. Of bacterial infections, only group A beta-hemolytic streptococci were more common in case patients than in control subjects. Furthermore, we demonstrated that asymptomatic persons might be a neglected source of transmission.(aut. ref.)

During a 30-month prospective study in The Netherlands, the distribution of Mycoplasma pneumoniae and respiratory viruses among 1172 patients with acute respiratory infection (ARI) who were treated in the outpatient general practitioner setting was studied. M. pneumoniae, as detected by polymerase chain reaction analysis, was present in 39 (3.3%) patients. The infection rate was similar in all age groups. Nose and throat samples collected from 79 household contacts of M. pneumoniae-positive index patients revealed M. pneumoniae in 12 (15%) cases. The frequency of M. pneumoniae among household contacts of index patients treated with appropriate antibiotics and untreated index patients was similar. Nine of the 12 M. pneumoniae-positive household contacts were16 years old (P=.02), and 4 (44%) of them did not develop ARI. Apparently, children are a relevant reservoir for M. pneumoniae.

Objective This Dutch epidemiological study used primary care-based data to examine changes in the incidence of eating disorders in the 1990s compared to the 1980s. Method A nationwide network of general practitioners, serving a representative sample of the total Dutch population, recorded newly diagnosed patients with anorexia nervosa (AN) and bulimia nervosa (BN) in their practices during 1985–1989 and 1995–1999. Results The overall incidence of AN was stable (from 7.4 to 7.7 per 100,000). However, the incidence among 15–19-year-old females increased significantly (from 56.4 to 109.2 per 100,000). The incidence rate of BN decreased nonsignificantly from 8.6 to 6.1 per 100,000. Conclusion The time trend of an increasing AN incidence among the high risk group continued to the end of the past century. The BN incidence did not rise as was expected. © 2006 by Wiley Periodicals, Inc. Int J Eat Disord 2006

General practitioners are regarded as well placed to help prevent the transmission of HIV infection.1 2 3 In 1988 a study was started in the Netherlands to get more information on concerns about AIDS among the non-infected population and on the general practitioner's role in providing advice and health education about AIDS. In this paper we present the results after five years (April 1988-April 1993). Since April 1988 general practitioners participating in the Dutch sentinel practice network recorded all face to face consultations with non-infected patients in which the subject of AIDS was brought up, either by the patient or by the general practitioner. When the subject of AIDS was a substantial part of the consultation, the general practitioners filled in a questionnaire giving information on the contents of this HIV related consultation and on the patient. If an arrangement for HIV testing was made the result of …

OBJECTIVE To assess possible changes in the incidence of diabetes in all age-groups in The Netherlands during a 10-year period (1980–1983/1990–1992). RESEARCH DESIGN AND METHODS Since 1970, a network of sentinel stations (the Dutch Sentinel Practice Network) consisting of ∼ 1% of the Dutch population has been in operation to gain insight into the morbidity patterns of the Dutch population as recorded by general practitioners. One of the items recorded from 1990 to 1992 was the incidence of diabetes. The first study with a similar design that registered the incidence of diabetes was conducted from 1980 to 1983. RESULTS The overall incidence of diabetes increased significantly by 12.1% in the period between the two studies. This overall increase can largely be attributed to a statistically significant increase in the age-group 45–64 years (30.5%). Although not statistically significant, the 36% increase of diabetes in the age-group 0–19 years is in accordance with the increase of type I diabetes based on the first and second nationwide retrospective studies covering the total Dutch population. CONCLUSIONS There is a marked increase in the incidence of diabetes in the age-group 45–64 years. This selective increase is probably not due to a real rise caused by changes in exposure to risk factors but to an earlier recognition of symptoms and signs of diabetes followed by blood glucose measurements and/or to more intensive case finding in general practice.