ABSTRACT
PURPOSE: To assess use of health care following a diagnosis of endometrial, cervical, and ovarian cancer in the Netherlands, Norway, and Denmark. Furthermore, to analyze the association between cancer worry and use of supportive care. METHODS: An international multicenter cross-sectional questionnaire study was undertaken among female cancer survivors with endometrial, cervical, or ovarian cancer 1-7 years post diagnosis. We investigated different aspects of cancer survivorship and follow-up care. Health care use included information on the use of supportive health care, general practitioner (GP), and follow-up visits to the department of gynecology. Cancer worry was assessed with the Impact of Cancer (IoCv2) questionnaire. RESULTS: A total of 1433 women completed the questionnaire. Health care use decreased from time of diagnosis and was higher among cervical and ovarian cancer survivors than endometrial cancer survivors. Twenty-five percent of the women with ovarian cancer reported severe cancer worry, in contrast to 10 and 15% of women diagnosed with endometrial and cervical cancer, respectively. Women with severe worry had significantly higher use of supportive care activities. In a multivariable regression analysis, cancer worry remained a significant correlate for use of supportive health care services irrespective of disease severity or prognosis. The strongest association was found for use of a psychologist (OR 2.1 [1.71-2.58]). CONCLUSION: Cancer worry is associated with increased use of supportive care. IMPLICATIONS FOR CANCER SURVIVORS: Targeted, timely, and accessible psychological support aimed at severe cancer worry may improve survivorship care and ensure optimal referral of patients in need of additional care.
Subject(s)
Cancer Survivors , Endometrial Neoplasms , Ovarian Neoplasms , Humans , Female , Cross-Sectional Studies , Delivery of Health Care , Endometrial Neoplasms/therapy , Surveys and Questionnaires , Ovarian Neoplasms/therapyABSTRACT
OBJECTIVE: Social support may reduce the amount of psychological distress and increase quality of life. This study assessed whether socio-demographic, personality, and clinical characteristics predict the level of perceived social support in patients with endometrial or ovarian cancer. METHODS: Patients with endometrial or ovarian cancer who participated in the ROGY Care study and completed the Multidimensional Scale of Perceived Social Support(MSPSS) 12 months after inclusion were eligible for this study (n=238). Logistic regression analysis was conducted to determine the predictive value of socio-demographic characteristics, personality and clinical characteristics after initial treatment on the perceived level of social support after 12 months. RESULTS: Of the 238 patients (mean age 64.8 ± 9.4 years), 139 patients had endometrial cancer (58%) and 99 patients had ovarian cancer (42%). One year after inclusion, the level of perceived social support was high in 79% of all patients (n=189). Patients experiencing low level of perceived social support (n=49) less often had a partner (69% versus 83% in patients with high level of perceived social support; p=0.029), had a higher education level (24% versus 15% respectively; p=0.013) and a distressed (type D) personality was more common (40% versus 16% respectively; p<0.001). In multivariable analysis, a type D personality, characterized by negative affect and social inhibition, was the only independent predictor of a low level of perceived social support (OR 2.96; 95% CI 1.37-6.37; p=0.006). CONCLUSIONS: In patients with endometrial or ovarian cancer, the level of perceived social support is mainly associated with a distressed (type D) personality. Those patients can be at risk of experiencing less social support. Future research is needed to assess whether they might benefit from additional support during cancer diagnosis and treatment.
Subject(s)
Endometrial Neoplasms/psychology , Ovarian Neoplasms/psychology , Quality of Life/psychology , Female , Humans , Male , Middle Aged , Psychological Distress , Social SupportABSTRACT
OBJECTIVE: Despite the positive effects of decision aids (DAs), implementation remains a significant challenge. The aim of the current study was to determine what barriers clinicians experience using a DA for pelvic organ prolapse (POP). METHODS: This study was conducted with a qualitative descriptive design including in-depth semi-structured interviews according to COREQ-criteria. Participants included clinicians and patients. Grounded theory analysis was used to describe the main themes. RESULTS: A total of 9 clinicians and 4 patients participated. Four major themes (1) opinions about shared decision making (SDM), (2) current practice, (3) experience with the DA, (4) suggestions for improvement and one minor theme (5) experience with the study, emerged. Clinicians were predominantly positive about the DA. CONCLUSION: Despite the positive attitudes of the clinicians in this study, the implementation of a DA is still challenging. The DA is forgotten regularly as improvement of logistics is needed, clinicians assume they already provide good care which might result in a reluctance to change and more engagement of physicians is needed. PRACTICE IMPLICATIONS: Regular contact with clinicians to remind, help and increase engagement and a decrease of the logistic burden is needed to ensure all patients can fully benefit of the DA.
Subject(s)
Decision Making, Shared , Pelvic Organ Prolapse , Decision Making , Decision Support Techniques , Humans , Patient Participation , Pelvic Organ Prolapse/therapy , Qualitative ResearchABSTRACT
PURPOSE: In breast cancer patients, treatment-related health symptoms can occur that may affect their health-related quality of life (HRQoL). This study aimed to determine the impact of health symptoms on HRQoL in breast cancer patients up to 5 years after diagnosis. METHODS: Females surgically treated for early-stage breast cancer diagnosed between 2012 and 2016 (n = 876) were selected from the Netherlands Cancer Registry and invited for a survey about current health symptoms ('Symptoms and Perceptions questionnaire', SaP) and HRQoL ('EORTC-QLQ-C30'). From the latter, functioning and global health were included. Mean scores were compared to norm population scores (T test). Multivariable linear regression analyses were performed to determine the association between health symptoms and global health and functioning. RESULTS: 404 patients (46%) responded. The median age was 62.2 ± 10.9 years. Respondents had significantly lower mean scores for role, cognitive, emotional, and social functioning than the general population. The most frequently reported health symptoms were musculoskeletal (including pain/complaints in lower/upper extremities/back/neck; 71%) and central nervous system symptoms (including concentration impairment, dizziness, neuralgia; 66%), and fatigue (63%). While most symptoms affected functioning, irrespective of time since diagnosis, especially fatigue, musculoskeletal, central nervous system, and gastrointestinal symptoms were significantly associated (p < 0.05) with lower functioning. CONCLUSIONS: The majority of health symptoms that occur after breast cancer treatment were associated with lower functioning of patients in daily life. This paper urges healthcare providers to support breast cancer patients in alleviating or coping with health symptoms, even years after end of treatment, to improve their functioning.
Subject(s)
Breast Neoplasms/psychology , Cancer Survivors , Health Status , Quality of Life , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Breast Neoplasms/physiopathology , Breast Neoplasms/therapy , Cancer Survivors/psychology , Cancer Survivors/statistics & numerical data , Cross-Sectional Studies , Female , Health Surveys , Humans , Middle Aged , Netherlands/epidemiology , Registries , SurvivorshipABSTRACT
Background: Data showing the value of neoadjuvant chemotherapy (nact) followed by interval debulking surgery (ids) in the management of advanced-stage serous endometrial carcinoma (eca) are limited; the aim of the present study was to expand the knowledge about that treatment strategy in patients with advanced eca, including endometrioid eca. Methods: Data were collected retrospectively from all patients with advanced-stage eca treated with nact between 2005 and 2014 at 3 oncology referral centres. Primary outcomes were the radiologic response to nact and achievement of optimal or complete ids. Secondary outcomes were recurrence rate and progression-free and overall survival. Results: Of 102 eca cases included, a complete radiologic response was achieved in only 4 cases, with a partial response being achieved in 72% (64% of endometrioid cases, 80% of serous cases). Complete ids was achieved in 62% of the endometrioid cases and in 56% of the serous eca cases, with optimal ids achieved in 31% and 28% of those cases respectively. Survival rates were calculated for all patients with complete and optimal ids; recurrence was observed in 56% and 67% of the cases respectively, and progression-free survival was 18 months and 13 months respectively. Median survival duration was 24 months for endometrioid eca and 28 months for serous eca. Conclusions: For patients with advanced eca who are not suitable for primary debulking, nact followed by ids can be considered regardless of histologic subtype. The treatment options for this group of patients are limited and have to be explored.
Subject(s)
Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/surgery , Adult , Aged , Chemotherapy, Adjuvant , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Female , Humans , Middle Aged , Neoadjuvant Therapy , Neoplasm Recurrence, Local , Neoplasm Staging , Survival AnalysisABSTRACT
OBJECTIVE: To assess long-term differences in health-related quality of life (HRQoL) of older ovarian cancer survivors compared to both an age-matched normative population and to younger survivors. In addition, the differential effect of chemotherapy on HRQoL between older and younger survivors was compared. METHODS: Ovarian cancer survivors (nâ¯=â¯348) diagnosed between 2000 and 2010, as registered by the Dutch population-based Eindhoven Cancer Registry, were invited to complete the EORTC QLQ-C30 HRQoL questionnaire in 2012. HRQoL outcomes of survivors were compared with an age-matched normative population and older survivors (≥70â¯years) were compared with younger survivors. RESULTS: The questionnaire was returned by 191 ovarian cancer survivors (55%), 31% were aged ≥70â¯years (nâ¯=â¯59). Compared to the normative population, survivors ≥70â¯years scored lower on global health status and all functioning subscales except emotional functioning, and they reported more symptoms. Survivors aged <70â¯years only reported worse physical and cognitive functioning in comparison with the normative population. Most differences were of medium to small clinical relevance. Age appeared to moderate the effect of chemotherapy on HRQoL. Older survivors who had received chemotherapy experienced better physical functioning and less pain and insomnia while the opposite was found in younger survivors. CONCLUSION: In comparison with an age-matched normative population, older ovarian cancer survivors report lower HRQoL scores than younger survivors. As this represents a selection of long-term survivors, future research should focus on the trajectory of HRQoL from diagnosis throughout treatment and follow-up to identify which factors are related to worse HRQoL in the entire older ovarian cancer population and whether timely interventions are able to improve HRQoL.
Subject(s)
Cancer Survivors/psychology , Ovarian Neoplasms/psychology , Age Factors , Aged , Case-Control Studies , Female , Humans , Middle Aged , Patient Reported Outcome Measures , Quality of Life , Registries , Self Report , Surveys and QuestionnairesABSTRACT
OBJECTIVES: Compliance of physicians with guidelines has emerged as an important indicator for quality of care. We evaluated compliance of physicians with adjuvant therapy guidelines for endometrial cancer patients in the Netherlands in a population-based cohort over a period of 10years. METHODS: Data from all patients diagnosed with endometrial cancer between 2005 and 2014, without residual tumor after surgical treatment, were extracted from the Netherlands Cancer Registry (N=14,564). FIGO stage, grade, tumor type and age were used to stratify patients into risk groups. Possible changes in compliance over time and impact of compliance on survival were assessed. RESULTS: Patients were stratified into low/low-intermediate (52%), high-intermediate (21%) and high (20%) risk groups. Overall compliance with adjuvant therapy guidelines was 85%. Compliance was highest in patients with low/low-intermediate risk (98%, no adjuvant therapy indicated). The lowest compliance was determined in patients with high risk (61%, external beam radiotherapy with/without chemotherapy indicated). Within this group compliance decreased from 64% in 2005-2009 to 57% in 2010-2014. In high risk patients with FIGO stage III serous disease compliance was 55% (chemotherapy with/without radiotherapy indicated) and increased from 41% in 2005-2009 to 66% in 2010-2014. CONCLUSION: While compliance of physicians with adjuvant therapy guidelines is excellent in patients with low and low-intermediate risk, there is room for improvement in high risk endometrial cancer patients. Eagerly awaited results of ongoing randomized clinical trials may provide more definitive guidance regarding adjuvant therapy for high risk endometrial cancer patients.
Subject(s)
Adenocarcinoma, Clear Cell/therapy , Carcinoma, Endometrioid/therapy , Chemotherapy, Adjuvant/statistics & numerical data , Endometrial Neoplasms/therapy , Guideline Adherence/statistics & numerical data , Hysterectomy , Neoplasms, Cystic, Mucinous, and Serous/therapy , Practice Guidelines as Topic , Radiotherapy, Adjuvant/statistics & numerical data , Registries , Adenocarcinoma, Clear Cell/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Endometrioid/pathology , Endometrial Neoplasms/pathology , Female , Humans , Middle Aged , Neoplasm Grading , Neoplasm Staging , Neoplasms, Cystic, Mucinous, and Serous/pathology , Netherlands , Quality Improvement , RiskABSTRACT
BACKGROUND: Pre-operative risk stratification based on endometrial sampling determines the extent of surgery for endometrial cancer (EC). We investigated the concordance of pre- and post-operative risk stratifications and the impact of discordance on survival. METHODS: Patients diagnosed with EC within the first 6 months of the years 2005-2014 were selected from the Netherlands Cancer Registry (N = 7875). Pre- and post-operative risk stratifications were determined based on grade and/or histological subtype for 3784 eligible patients. RESULTS: A discordant risk stratification was found in 10% of patients: 4% (N = 155) had high pre- and low post-operative risk and 6% (N = 215) had low pre- and high post-operative risk. Overall survival of patients with high pre- and low post-operative risk was less favourable compared to those with a concordant low risk (80% versus 89%, p = 0.002). This difference remained significant when correcting for age, stage, surgical staging and adjuvant therapy (hazard ratio 1.80, 95% confidence interval 1.28-2.53, p = 0.001). Survival of patients with low pre- and high post-operative risk did not differ from those with a concordant high risk (64% versus 62%, p = 0.295). CONCLUSION: Patients with high pre- and low post-operative risk have a less favourable prognosis compared to patients with a concordant low risk. Pre-operative risk stratifications contain independent prognostic information and should be incorporated into clinical decision-making.
Subject(s)
Endometrial Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Chemoradiotherapy, Adjuvant/methods , Clinical Decision-Making/methods , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Staging , Postoperative Care , Preoperative Care/methods , Preoperative Care/mortality , Prognosis , Registries , Retrospective Studies , Risk Assessment/methodsABSTRACT
After completing treatment, most patients follow a pre-determined schedule of regular hospital outpatient appointments, which includes clinical examinations, consultations and routine tests. After several years of surveillance, patients are transferred back to primary care. However, there is limited evidence to support the effectiveness and efficiency of this approach. This paper examines the current rationale and evidence base for hospital-based follow-up after treatment for gynaecological cancer. We investigate what alternative models of care have been formally evaluated and what research is currently in progress in Europe, in order to make tentative recommendations for a model of follow-up. The evidence base for traditional hospital based follow-up is limited. Alternative models have been reported for other cancer types but there are few evaluations of alternative approaches for gynaecological cancers. We identified five ongoing European studies; four were focused on endometrial cancer patients and one feasibility study included all gynaecological cancers. Only one study had reached the reporting stage. Alternative models included nurse-led telephone follow-up and comparisons of more intensive versus less intensive regimes. Outcomes included survival, quality of life, psychological morbidity, patient satisfaction and cost effectiveness of service. More work is needed on alternative strategies for all gynaecological cancer types. New models will be likely to include risk stratification with early discharge from secondary care for early stage disease with fast track access to specialist services for suspected cancer recurrence or other problems.
Subject(s)
Aftercare/standards , Genital Neoplasms, Female , Medical Oncology/standards , Aftercare/economics , Female , Humans , Randomized Controlled Trials as TopicABSTRACT
Information on treatment patterns for ovarian cancer (OC) is limited. The aim of this study was to describe current patterns of chemotherapy and other systemic treatments for OC in the Netherlands and evaluate survival outcomes following subsequent lines of treatment. Data from the Eindhoven Cancer Registry, including on newly diagnosed cancer patients, were linked to the PHARMO Database Network, including information on in- and out-patient drug use. Patients diagnosed with OC between January 2000 and December 2010 were selected. An algorithm was used to identify separate lines of treatment. Data were studied descriptively. Detailed data on systemic drug use were available for 261 patients (17%) with OC. In first-line treatment, 87% of the patients (227/261) received platinum-based chemotherapy. Of the 161 patients receiving second-line treatment, 101 patients (63%) received platinum-based chemotherapy. In third line, this was 51% (53/103). The median number of treatment lines received by patients was two (interquartile range 1-3), and eight or more lines of chemotherapy were identified for 12 patients. Median survival from diagnosis onwards was 47 months from the end of first-line treatment, median survival was 32 months, and from the end of second-line treatment, it was 14 months. Predominantly beyond second-line treatment, there is much variety in treatment patterns with chemotherapy for OC. Although uncertainty remains regarding the desirability of this observed treatment variation, there seems a need for detailed clinical guidance, assuring that physicians can properly choose the most suitable treatment for each patient.
Subject(s)
Antineoplastic Agents/administration & dosage , Ovarian Neoplasms/drug therapy , Practice Patterns, Physicians'/statistics & numerical data , Algorithms , Cohort Studies , Data Interpretation, Statistical , Databases, Pharmaceutical , Female , Humans , Middle Aged , Netherlands/epidemiology , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/mortality , Registries , Treatment OutcomeABSTRACT
BACKGROUND: There is wide variation in the application of adjuvant chemotherapy in early-stage epithelial ovarian cancer. Our aim was to assess differences in health-related quality of life (hrqol) between patients with early-stage ovarian cancer who did or did not receive chemotherapy as adjuvant treatment. METHODS: All patients diagnosed with early-stage ovarian cancer between 2000 and 2010 within the population-based Eindhoven Cancer Registry (n = 191) were enrolled in this study. Patients were requested to complete questionnaires, including the cancer-specific (qlq-C30) and ovarian cancer-specific (qlq-OV28) quality of life measures from the European Organisation for Research and Treatment of Cancer. Primary outcome measures were the generic-and cancer-specific domain scores for hrqol in ovarian cancer survivors. RESULTS: Of the 107 patients (56%) who returned the questionnaires, 57 (53.3%) had received adjuvant chemotherapy and 50 (46.7%) had been treated with surgery alone. Significant differences in hrqol between those groups were found in the symptom scales for peripheral neuropathy, attitude toward sickness, and financial situation, with worse scores in the chemotherapy group. CONCLUSIONS: Results of our study show that patients who receive adjuvant chemotherapy have a significantly worse score for 3 aspects of hrqol. Efforts should be made to reduce use of adjuvant chemotherapy in early-stage ovarian cancer. Moreover, preventive strategies to improve long-term quality of life for those who need adjuvant chemotherapy should be explored.
Subject(s)
Adenocarcinoma, Clear Cell/mortality , Carcinoma, Endometrioid/mortality , Endometrial Neoplasms/mortality , Hospitals/statistics & numerical data , Hysterectomy/statistics & numerical data , Neoplasms, Cystic, Mucinous, and Serous/mortality , Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Clear Cell/surgery , Aged , Cancer Care Facilities/statistics & numerical data , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/surgery , Cohort Studies , Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Female , Hospitals, General/statistics & numerical data , Hospitals, High-Volume/statistics & numerical data , Hospitals, Low-Volume/statistics & numerical data , Hospitals, Teaching/statistics & numerical data , Humans , Middle Aged , Neoplasm Staging , Neoplasms, Cystic, Mucinous, and Serous/pathology , Neoplasms, Cystic, Mucinous, and Serous/surgery , Netherlands , Retrospective Studies , Survival RateABSTRACT
BACKGROUND: Approximately 25% of endometrial cancer patients present with high-grade tumors. Unlike the clearly defined work-up for non-endometrioid endometrial cancer, no consensus exists for surgical staging and adjuvant therapy in high-grade endometrioid endometrial cancer. We compared the recurrence rate and disease-related mortality (DRM) after treatment between endometrioid and non-endometrioid endometrial cancer. METHODS: A total of 123 patients diagnosed with early-stage high-grade endometrial cancer at the Dutch Comprehensive Cancer Centre South (CCCS) between January 2005 and December 2011 were included. All patients underwent abdominal hysterectomy and bilateral salpingo-oophorectomy. Patient and tumor characteristics, primary and adjuvant treatment, and outcome were analyzed. RESULTS: After a median follow-up of 27.9 months, 27.6% (n = 34) of patients had recurrent disease. Distant recurrence rate was equal among endometrioid (14.5%), papillary serous (14.8%), and clear cell (15.4%) types. The total DRM was 15.4% (n = 19). The 5 year recurrence-free survival was not significantly different between early-stage high-grade endometrioid versus non-endometrioid endometrial cancer (P = 0.72). CONCLUSION: Distant recurrence and DRM was high in patients with endometrial cancer regardless of histological type, suggesting the need for different therapies in early-stage high-grade non-endometrioid and endometrioid tumors.
Subject(s)
Carcinoma, Endometrioid/mortality , Carcinoma, Endometrioid/pathology , Cystadenocarcinoma, Papillary/mortality , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Carcinoma, Endometrioid/therapy , Cystadenocarcinoma, Papillary/pathology , Cystadenocarcinoma, Papillary/therapy , Endometrial Neoplasms/therapy , Female , Follow-Up Studies , Humans , Hysterectomy , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local , Ovariectomy , Radiotherapy, Adjuvant , Retrospective Studies , SalpingectomyABSTRACT
BACKGROUND: The objectives of the study were to examine the prevalence of health literacy (HL) among colorectal cancer (CRC) survivors and the relation between HL and health behaviors and to explore whether or not HL and health behaviors are independently associated with health-related quality of life (HRQoL) and mental distress. METHODS: This analysis is part of a longitudinal, population-based survey among CRC survivors diagnosed between 2000 and 2009 and registered by the Eindhoven Cancer Registry. Data collected during the second data wave was used (n = 1643; response rate 83%). Patients filled out a screening question on subjective functional HL, questions on health behaviors, HRQoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30), and mental distress (Hospital Anxiety and Depression Scale). RESULTS: Subjective HL was low among 14%, medium among 45%, and high among 42% of the participants. CRC survivors with low HL were more often smokers and did not meet the prescribed physical activity guidelines compared with survivors with medium or high HL. CRC survivors with low HL reported statistically significantly lower levels of mental and physical HRQoL and higher distress levels compared with survivors with medium and high HL. HL, in addition to sociodemographic and clinical characteristics and health behaviors, significantly explained 1.5-6.2% of the variance in HRQoL and mental distress levels. Partial mediation is indicated for HRQoL and feelings of depression, but not for anxiety. CONCLUSION: Low subjective functional HL among CRC survivors is associated with lower levels of physical activity, higher frequency of smoking, poorer HRQoL, and more mental distress. HL and health behaviors have both a unique as well as an overlapping contribution to the explained variances of HRQoL and mental distress.
Subject(s)
Colorectal Neoplasms/psychology , Health Behavior , Health Literacy , Health Status , Quality of Life/psychology , Registries , Survivors/psychology , Aged , Anxiety/psychology , Depression/psychology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Motor Activity , Smoking , Stress, Psychological/psychology , Surveys and QuestionnairesABSTRACT
UNLABELLED: Process evaluations can help us to better interpret intervention effects and provide guidance in improving interventions. This study describes the use and appreciation of FATaintPHAT, a computer-tailored intervention to prevent excessive weight gain in adolescents and link these data to the intervention effects. Use and appreciation were assessed among students (12-13 years old) from the intervention group of the FATaintPHAT evaluation study, using computer log (n = 458) and questionnaire data (n = 233, 48% response). Differences in use and appreciation between socio-demographic groups (gender, education, ethnicity, weight category), and associations with behavioural outcomes were analysed using descriptive and regression analyses. The results showed that a majority of the students (81%) was exposed to all intervention modules and 73% reported to have put the advice into practise. Half and one-third of the students appreciated the tailored advice positively and neutrally, respectively. Students attending vocational training appreciated FATaintPHAT better than students attending university preparation education. No associations were found between behavioural outcomes with appreciation and use. In conclusion, the school-based FATainPHAT intervention was used and appreciated well among adolescents. The fact that the intervention was appreciated better among the lower compared with higher educated students indicates that the technique of computer-tailoring is also suitable for lower educated students. TRIAL REGISTRATION: Netherlands Trial Registry, ISRCTN 15743786.
Subject(s)
Adolescent Behavior , Computer-Assisted Instruction/methods , Health Behavior , Health Education/methods , Overweight/prevention & control , School Health Services , Adolescent , Behavior Therapy , Child , Diet , Educational Status , Exercise , Female , Health Promotion/methods , Humans , Logistic Models , Male , Netherlands , Risk Reduction Behavior , Sex Factors , Surveys and QuestionnairesABSTRACT
OBJECTIVE: To provide a comprehensive understanding of the humoral immune response that takes place at the site of inflammation in rheumatoid arthritis (RA), we studied the functional properties of synovial B cells. In particular, the response to various modes of mitogen stimulation was investigated. METHODS: Purified synovial fluid (SF) B cells were cultured in the presence of CD40 ligand (CD40L)-expressing fibroblasts and cytokines, activated T cells, or phorbol myristate acetate (PMA)/ionomycin. Proliferation was determined by 3H-thymidine incorporation. Release of intracellular calcium was studied by flow cytometry. RESULTS: The inflamed joints of RA patients contained a population of CD20+,CD38- B cells with dramatically impaired mitogen responsiveness. Although the Ig-producing capacity was intact, these cells failed to proliferate in response to (a) CD40 in the presence of interleukin-2 (IL-2) and IL-10, (b) activated T cells, or (c) stimulation via the B cell receptor. Moreover, SF CD20+,CD38- B cells revealed a defective B cell receptor-induced Ca2+ influx, reminiscent of anergic B cells. Release of intracellular Ca2+ by ionomycin in the presence of the protein kinase C activator PMA did not restore the proliferative capacity. These findings indicate blockades in the proximal and distal intermediates involved in mitogen signaling. CONCLUSION: SF CD20+,CD38- B cells have functionally impaired proliferative responsiveness. The capacity of these cells to respond to activation by the production of Ig supports the notion that these cells might serve as Ig-producing effector cells and, as such, play a role in the pathophysiology of RA.