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1.
J Eur Acad Dermatol Venereol ; 38(3): 530-542, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38031478

ABSTRACT

BACKGROUND: Evidence on the (long-term) safety of systemic immunomodulating therapies in atopic dermatitis (AD) generated by real-world data is sparse. OBJECTIVES: To describe real-world reported adverse drug reactions (AEs) related to systemic immunomodulating therapy in patients with AD and to compare the incidence rates of AEs with the Summaries of Product Characteristics (SmPCs). METHODS: We conducted an observational prospective multi-centre cohort study, using the TREAT NL registry. All severe AEs, AEs of special interest and serious AEs in adult and paediatric patients on systemic immunomodulating treatment (ciclosporin, methotrexate, azathioprine, mycophenolic acid, dupilumab, tralokinumab, baricitinib and upadacitinib) were assessed. Incidences rates of all (potentially) drug-related AEs were standardized in patient years and compared to the cumulative incidences in the associated SmPCs. RESULTS: We collected 422 patient years of safety data from 266 patients, of whom 129 (48.5%) reported a total of 224 (potentially) drug-related AEs. Compared to dupilumab's SmPC, higher incidence rates were found for four AEs (reported ≥5 times): eosinophilia, blepharitis, dry eyes and head and neck erythema (i.e. dupilumab facial redness). A higher incidence rate of fatigue was found in patients on oral methotrexate in our cohort compared to the SmPC. Two new drug-related AEs (reported ≥5 times) were found in patients on dupilumab, including non-infectious conjunctivitis and meibomian gland dysfunction. CONCLUSIONS: Real-world reported AEs captured in AD patient registries can add information on the estimated incidence of AEs and benefit clinical decision aids. Future studies using data derived from the TREAT NL registry combined with data from other registries within the TREAT Registry Taskforce will provide more information on (rare) AEs associated with immunomodulating therapy in AD patients.


Subject(s)
Dermatitis, Atopic , Adult , Humans , Child , Netherlands/epidemiology , Cohort Studies , Dermatitis, Atopic/drug therapy , Methotrexate/adverse effects , Prospective Studies
2.
BMC Med Educ ; 23(1): 224, 2023 Apr 07.
Article in English | MEDLINE | ID: mdl-37029404

ABSTRACT

BACKGROUND: Person-centered care is needed to effectively support workers with chronic health conditions. Person-centered care aims to provide care tailored to an individual person's preferences, needs and values. To achieve this, a more active, supportive, and coaching role of occupational and insurance physicians is required. In previous research, two training programs and an e-learning training with accompanying tools that can be used in the context of person-centered occupational health care were developed to contribute to this changing role. The aim was to investigate the feasibility of the developed training programs and e-learning training to enhance the active, supportive, and coaching role of occupational and insurance physicians needed for person-centered occupational health care. Information about this is important to facilitate implementation of the tools and training into educational structures and occupational health practice. METHODS: A qualitative study was conducted, with N = 29 semi-structured interviews with occupational physicians, insurance physicians, and representatives from occupational educational institutes. The aim was to elicit feasibility factors concerning the implementation, practicality and integration with regard to embedding the training programs and e-learning training in educational structures and the use of the tools and acquired knowledge and skills in occupational health care practice after following the trainings and e-learning training. Deductive analysis was conducted based on pre-selected focus areas for a feasibility study. RESULTS: From an educational perspective, adapting the face-to-face training programs to online versions, good coordination with educational managers and train-the-trainer approaches were mentioned as facilitating factors for successful implementation. Participants underlined the importance of aligning the occupational physicians' and insurance physicians' competences with the educational content and attention for the costs concerning the facilitation of the trainings and e-learning training. From the professional perspective, factors concerning the content of the training and e-learning training, the use of actual cases from practice, as well as follow-up training sessions were reported. Professionals expressed good fit of the acquired skills into their consultation hour in practice. CONCLUSION: The developed training programs, e-learning training and accompanying tools were perceived feasible in terms of implementation, practicality, and integration by occupational physicians, insurance physicians and educational institutes.


Subject(s)
Occupational Health , Humans , Feasibility Studies , Learning , Health Personnel/education , Patient-Centered Care
4.
J Eur Acad Dermatol Venereol ; 36(6): 807-819, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35170821

ABSTRACT

Atopic dermatitis is a heterogeneous disease, accompanied by a wide variation in disease presentation and the potential to identify many phenotypes that may be relevant for prognosis and treatment. We aimed to systematically review previously reported phenotypes of atopic dermatitis and any characteristics associated with them. Ovid EMBASE, Ovid MEDLINE and Web of Science were searched from inception till 12 February 2021 for studies attempting to classify atopic dermatitis. Primary outcomes are atopic dermatitis phenotypes and characteristics associated with them in subsequent analyses. A secondary outcome is the methodological approach used to derive them. In total, 8511 records were found. By focussing only on certain clinical phenotypes, 186 studies were eligible for inclusion. The majority of studies were hospital-based (59%, 109/186) and cross-sectional (76%, 141/186). The number of included patients ranged from seven to 526 808. Data-driven approaches to identify phenotypes were only used in a minority of studies (7%, 13/186). Ninety-one studies (49%) investigated a phenotype based on disease severity. A phenotype based on disease trajectory, morphology and eczema herpeticum was investigated in 56 (30%), 22 (12%) and 11 (6%) studies respectively. Thirty-six studies (19%) investigated morphological characteristics in other phenotypes. Investigated associated characteristics differed between studies. In conclusion, we present an overview of phenotype definitions used in literature for severity, trajectory, morphology and eczema herpeticum, including associated characteristics. There is a lack of uniform and consistent use of atopic dermatitis phenotypes across studies.


Subject(s)
Dermatitis, Atopic , Eczema , Kaposi Varicelliform Eruption , Cross-Sectional Studies , Dermatitis, Atopic/therapy , Humans , Phenotype , Severity of Illness Index
5.
J Occup Rehabil ; 32(3): 438-451, 2022 09.
Article in English | MEDLINE | ID: mdl-34731392

ABSTRACT

Purpose Health problems among employees with a lower socioeconomic position (SEP) often result from an interplay of problems on multiple life domains. Contextual factors greatly affect implementation of interventions that aim to solve these type of problems. The aim of this study was to gain insight into the organizational and socio-political context for implementation of preventive interventions that consider multiple life domains among employees with a lower SEP. Methods In total 16 semi-structured interviews were conducted with stakeholders at organizational level, occupational health service (OHS) level, and at socio-political macro level. Thematic analysis was performed to identify themes that describe the perceptions of stakeholders about the impact of contextual factors on implementation. Results The following themes were identified: (1) the importance of addressing problems on multiple life domains among employees with a lower SEP, (2) unclarity of responsibilities for solving problems on multiple life domains, (3) necessity of better collaboration between occupational and curative healthcare, (4) insufficient investments in prevention by employers, (5) difficulties in early identification of employees at risk for health problems, and (6) risk of conflicting role for supervisors in addressing problems on multiple life domains. Conclusions Implementation of preventive interventions considering multiple life domains among lower SEP employees is challenging, due to various contextual factors. To improve the feasibility, many different stakeholders both in- and outside occupational health practice need to be involved, collaborate, and need to be convinced of the added value to prevent problems on multiple life domains among employees with a lower SEP.


Subject(s)
Occupational Health Services , Occupational Health , Delivery of Health Care , Humans , Occupational Health Services/methods , Risk Assessment , Socioeconomic Factors
7.
Clin Exp Dermatol ; 46(6): 1089-1092, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33969522

ABSTRACT

Dupilumab is a relatively new treatment option for patients with moderate to severe atopic dermatitis. There is a lack of knowledge about the effects of treatment with dupilumab during conception for both men and women, as well as during pregnancy and lactation in women. We report four patients (two men, two women) who expressed a wish to conceive during treatment with dupilumab in daily practice. Both men conceived during dupilumab treatment, while the two women discontinued dupilumab because of anticipated pregnancy. Apart from disease flares in both of the patients who discontinued treatment, no complications were reported concerning the ability to conceive, the course of the pregnancy or the fetal outcome. We present an overview of the current available literature on dupilumab during conception, pregnancy and lactation, which can guide considerations for patients on dupilumab wishing to conceive a child. Until more data are available, preference should be given to treatment with topical corticosteroids, phototherapy, systemic corticosteroids and ciclosporin.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Dermatitis, Atopic/drug therapy , Dermatologic Agents/therapeutic use , Fertilization , Adult , Female , Humans , Lactation , Male , Pregnancy , Pregnancy Outcome , Withholding Treatment
8.
BMC Public Health ; 21(1): 592, 2021 03 25.
Article in English | MEDLINE | ID: mdl-33765993

ABSTRACT

BACKGROUND: Supporting employees with chronic conditions can prevent work-related problems and facilitate sustainable employment. Various stakeholders are involved in providing support to these employees. Understanding their current practices and experienced barriers is useful for the development of an organizational-level intervention to improve this support. The aim of this study was to explore the current practices of occupational physicians and organizational representatives, identifying both barriers to providing support and opportunities for improvement. METHODS: Two focus groups with sixteen occupational physicians and seven semi-structured interviews with organizational representatives were held between January and June 2018. Data was analyzed using thematic content analysis. RESULTS: Several barriers to offer support were identified, including barriers at the organizational level (negative organizational attitudes towards employees with chronic conditions), the employee level (employees' reluctance to collaborate with employers in dealing with work-related problems), and in the collaboration between occupational physicians and organizational representatives. In addition, barriers in occupational health care were described, e.g. occupational physicians' lack of visibility and a lack of utilization of occupational physicians' support. Opportunities to optimize support included a shared responsibility of all stakeholders involved, actively anchoring prevention of work-related problems in policy and practice and a more pronounced role of the health care sector in preventing work-related problems. CONCLUSIONS: Preventing work-related problems for employees with chronic conditions can be achieved by addressing the identified barriers to provide support. In addition, both occupational physicians and organizational representatives should initiate and secure preventive support at the organizational level and in occupational health care. These insights are helpful in developing an intervention aimed at supporting employees with chronic conditions to stay at work.


Subject(s)
Occupational Health , Chronic Disease , Employment , Humans , Qualitative Research , Workplace
9.
BMC Public Health ; 20(1): 961, 2020 Jun 19.
Article in English | MEDLINE | ID: mdl-32560709

ABSTRACT

BACKGROUND: Workers with a low socioeconomic position (SEP) have a higher risk for health problems and premature dropout from the workforce. Unfavorable working conditions and unhealthy behaviors are more prevalent among this group of workers. The Participatory Approach (PA), is an evidence-based method to identify and solve problems at the workplace related to health issues of the worker. Health problems among workers with a low SEP are usually caused by an interplay of problems in and outside the workplace. To solve health problems on multiple life domains for workers with a low SEP we aim to adapt this approach to a broader perspective. METHODS: An Intervention Mapping (IM) protocol was used to adapt the PA. First, a needs assessment was conducted combining literature with data from interviews and focus groups with workers with a low SEP, employers and occupational health professionals (OHPs). Based on the needs assessment a program goal and performance and change objectives were defined, which resulted in methods and practical strategies to solve problems on multiple life domains. Based on the results of these steps, the PA was adapted and an implementation and evaluation plan were developed. RESULTS: The needs assessment confirmed that an interplay of problems on multiple life domains affect work functioning and health of workers with a low SEP. Moreover, they perceived difficulties with solving problems or used passive or avoidant coping styles towards these problems. The program goal is to identify and solve problems on multiple life domains that affect healthy functioning at work. To achieve this workers need support from OHPs to solve problems. The PA protocol and materials were adapted using theoretical concepts of the Self-Determination Theory (SDT), which resulted in the Grip on Health intervention. For OHPs a training was developed on how to implement this intervention in practice. The intervention will be evaluated in a pilot implementation study among workers with a low SEP and other relevant stakeholders. CONCLUSIONS: IM was a valuable tool for the adaptation of the PA to better support workers with a low SEP to improve their work functioning and health from a broader perspective.


Subject(s)
Needs Assessment , Occupational Health Services/methods , Occupational Health , Poverty/statistics & numerical data , Risk Assessment/methods , Adult , Female , Health Promotion/methods , Humans , Male , Workplace
11.
J Occup Rehabil ; 30(4): 624-634, 2020 12.
Article in English | MEDLINE | ID: mdl-32200483

ABSTRACT

Purpose This study describes the development of an evidence-based intervention to create a supportive work environment for employees with chronic conditions. Occupational physicians (OPs) play an important role in guiding organizations in this process of organizational change. Supportive work environments can aid in preventing work-related problems and facilitate sustainable employment. Current workplace interventions for employees with chronic conditions are mainly focused on return to work or a reduction in sick leave at the individual worker's level. This study contributes to the literature an organizational-level intervention which utilizes a preventive approach. Methods Intervention mapping (IM) is a six-step, structured protocol that was used to develop this intervention. In step 1, a needs assessment was conducted to define the problem and explore the perspectives of all stakeholders involved. The program outcomes and the performance objectives of employees with chronic conditions and occupational physicians were specified in step 2. In step 3, appropriate methods and practical applications were chosen. Step 4 describes the actual development of the intervention, consisting of (1) a training for occupational physicians to teach them how to guide organizations in creating a supportive work environment; (2) a practical assignment; and (3) a follow-up meeting. The intervention will be implemented in a pilot study in which occupational physicians will put their acquired knowledge and skills into practice within one of their organizations, which is delineated in step 5. Conclusions IM proved to be a valuable and practical tool for the development of this intervention, aiming to facilitate sustainable employment for employees with chronic conditions.


Subject(s)
Sick Leave , Workplace , Chronic Disease , Employment , Humans , Pilot Projects
12.
BMC Public Health ; 20(1): 201, 2020 Feb 07.
Article in English | MEDLINE | ID: mdl-32033556

ABSTRACT

BACKGROUND: Working with a chronic condition can be challenging. Providing support to workers with a chronic condition can help them to stay at work and prevent work-related problems. Workers with a chronic condition who successfully stay at work can provide valuable input for the development of effective supportive interventions to prevent exit from work and facilitate sustainable employment. The aim of this study is to explore the lived experiences of workers with a chronic condition and identify existing barriers, facilitators and possible support needs for staying at work. METHODS: Four focus groups were conducted between August and December 2017 with workers with one or more chronic conditions (n = 30). Participants included employees and (partially) self-employed workers. All focus group data were transcribed verbatim and thematically analyzed. RESULTS: Disclosure and expressing one's needs were considered important personal facilitators for staying at work. Environmental facilitators included receiving practical information on working with a chronic condition and social and employer support. Environmental barriers were identified in the work environment, the health care system and service provision, e.g., manager and co-worker's lack of knowledge about working with a chronic condition, a lack of focus on work in the course of treatment for a chronic condition, dissatisfaction with occupational physician support, and the absence of support for self-employed workers. Provided support should be available to all workers, and be proactive and tailored to the workers' specific support needs. CONCLUSIONS: A variety of facilitators, barriers and support needs were identified in various domains. By addressing environmental barriers (e.g., by integrating work in the course of treatment and creating supportive work environments), sustainable employment by workers with a chronic condition can be promoted.


Subject(s)
Chronic Disease , Employment/statistics & numerical data , Needs Assessment , Social Support , Workplace/organization & administration , Adult , Aged , Female , Focus Groups , Humans , Male , Middle Aged , Young Adult
13.
Br J Dermatol ; 182(2): 418-426, 2020 02.
Article in English | MEDLINE | ID: mdl-31145810

ABSTRACT

BACKGROUND: Dupilumab is the first biologic registered for the treatment of moderate-to-severe atopic dermatitis (AD), and efficacy was shown in phase III clinical trials (primary outcome at week 16 was reached in 38% of patients). Currently, there are limited daily practice data available for dupilumab, especially when it is combined with systemic immunosuppressants. OBJECTIVES: To evaluate dupilumab treatment in daily practice in patients with AD. METHODS: In this observational cohort study, we prospectively included all adult patients with AD who had been treated with dupilumab in two university hospitals in the Netherlands. Concomitant systemic immunosuppressive treatment was monitored. Physician-reported outcome measures and patient-reported outcome measures (PROMs) after ≥ 12 weeks of follow-up were analysed. We used a linear mixed-effects model to determine changes in scores during follow-up. RESULTS: Ninety-five patients were included. Of these, 62 patients were using systemic immunosuppressants at baseline; the use of systemic immunosuppressants was continued during dupilumab treatment in 43 patients. From baseline to 16 weeks of treatment, the estimated mean Eczema Area and Severity Index score (0-72) decreased from 18·6 [95% confidence interval (CI) 16·0-21·4)] to 7·3 (95% CI 5·4-10·0), and the estimated mean PROMs showed a decrease of 41-66%. Investigator's Global Assessment 0 or 1 (clear/almost clear) was reached in 38% of the patients. Five patients discontinued dupilumab treatment due to side-effects or ineffectiveness. Eye symptoms and orofacial (nonocular) herpes simplex virus (HSV) reactivation were reported in 62% and 8% of the patients, respectively. CONCLUSIONS: Dupilumab treatment in daily practice shows a clinically relevant improvement of physician-reported outcome measures and PROMs, which is in line with efficacy data from clinical trials. Besides frequently reported eye symptoms and orofacial (nonocular) HSV reactivation, there were no apparent safety concerns. What's already known about this topic? Dupilumab has been shown to be an efficacious treatment for atopic dermatitis in several clinical trials. However, it is known that there may be considerable differences in patient characteristics and treatment responses between clinical trials and daily practice. What does this study add? This study presents the first experience with dupilumab treatment in 95 patients with atopic dermatitis in daily practice in two Dutch university hospitals. Less stringent inclusion and exclusion criteria and follow-up schedules, in contrast to those used in clinical trials, might better represent daily practice. Dupilumab treatment shows a clinically relevant improvement of physician- and patient-reported outcome measures; besides patient-reported eye symptoms (in 59 of 95 patients; 62%) and an apparent increase in orofacial (nonocular) herpes simplex virus reactivation (eight of 95 patients; 8%), there were no other safety concerns during follow-up up to 16 weeks of dupilumab treatment.


Subject(s)
Dermatitis, Atopic , Eczema , Adult , Antibodies, Monoclonal, Humanized , Dermatitis, Atopic/drug therapy , Humans , Netherlands , Treatment Outcome
14.
Br J Dermatol ; 182(6): 1423-1429, 2020 06.
Article in English | MEDLINE | ID: mdl-31444799

ABSTRACT

BACKGROUND: A long-term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. OBJECTIVES: To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate-to-severe atopic eczema, to assess the long-term safety risk of these therapies in a routine clinical care setting. METHODS: We describe a registry-embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. CONCLUSIONS: This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long-term data on the safety of systemic immunomodulating therapies in patients with atopic eczema. Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long-term safety profile against established therapies. Large numbers of patients with a long duration of follow-up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries. We present a protocol for an investigator-initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate-to-severe atopic eczema. This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations.


Subject(s)
Dermatitis, Atopic , Eczema , Adolescent , Adult , Antibodies, Monoclonal, Humanized , Child , Dermatitis, Atopic/drug therapy , Humans , Observational Studies as Topic , Prospective Studies , Registries , Treatment Outcome
15.
Br J Dermatol ; 181(3): 492-504, 2019 09.
Article in English | MEDLINE | ID: mdl-30719709

ABSTRACT

BACKGROUND: Comparative, real-life and long-term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate-to-severe atopic eczema (AE) is limited. Such data must come from well-designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling. OBJECTIVES: To reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE. METHODS: Proposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face-to-face consensus meetings, one teleconference and via e-mail. The frequency of follow-up visits was determined by an expert survey. RESULTS: A total of 16 experts from seven countries participated in the 'how to measure' consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow-up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined. CONCLUSIONS: This core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long-term effectiveness and safety of phototherapy and systemic therapy used in patients with AE. What's already known about this topic? Comparable, real-life and long-term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed. There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling. What does this study add? Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries. This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data. What are the clinical implications of this work? The data collected through this core dataset will help to gain better insights into the long-term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice. Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment-related adverse events that require large patient numbers).


Subject(s)
Advisory Committees/standards , Consensus , Dermatitis, Atopic/therapy , Registries/standards , Adult , Aftercare/standards , Child , Datasets as Topic , Dermatologic Agents/therapeutic use , Humans , Phototherapy/statistics & numerical data , Prospective Studies , Registries/statistics & numerical data , Severity of Illness Index , Treatment Outcome
16.
Crime Delinq ; 64(8): 1001-1032, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29880980

ABSTRACT

Studies indicated that detainees are not always allocated to treatment programs based on official guidelines. Street-level bureaucracy theory suggests that this is because government employees do not always perform policies as prescribed. This study aimed to assess whether this also applies to the allocation of offenders to treatment in Dutch penitentiary institutions, and aimed to determine which factors influenced this. The proposed questions were addressed by studying a group of 541 male prisoners who participated in the Dutch prison-based Prevention of Recidivism program. Results showed that official guidelines were, in most cases, not leading when referring detainees to programs. Instead, treatment referrals were influenced by a broad range of risk factors, as well as the length of an offender's sentence.

17.
Nat Commun ; 9(1): 684, 2018 02 15.
Article in English | MEDLINE | ID: mdl-29449556

ABSTRACT

Regulatory B cells (Breg) express high levels of CD1d that presents lipid antigens to invariant natural killer T (iNKT) cells. The function of CD1d in Breg biology and iNKT cell activity during inflammation remains unclear. Here we show, using chimeric mice, cell depletion and adoptive cell transfer, that CD1d-lipid presentation by Bregs induces iNKT cells to secrete interferon (IFN)-γ to contribute, partially, to the downregulation of T helper (Th)1 and Th17-adaptive immune responses and ameliorate experimental arthritis. Mice lacking CD1d-expressing B cells develop exacerbated disease compared to wild-type mice, and fail to respond to treatment with the prototypical iNKT cell agonist α-galactosylceramide. The absence of lipid presentation by B cells alters iNKT cell activation with disruption of metabolism regulation and cytokine responses. Thus, we identify a mechanism by which Bregs restrain excessive inflammation via lipid presentation.


Subject(s)
Antigens, CD1d/immunology , B-Lymphocytes, Regulatory/immunology , B-Lymphocytes/immunology , Natural Killer T-Cells/immunology , Adoptive Transfer/methods , Animals , Antigens, CD1d/genetics , Antigens, CD1d/metabolism , Arthritis, Experimental/genetics , Arthritis, Experimental/immunology , Arthritis, Experimental/metabolism , B-Lymphocytes/drug effects , B-Lymphocytes/metabolism , Cells, Cultured , Galactosylceramides/pharmacology , Interferon-gamma/immunology , Interferon-gamma/metabolism , Male , Mice, Inbred C57BL , Mice, Knockout , Natural Killer T-Cells/drug effects , Natural Killer T-Cells/metabolism , Th1 Cells/immunology , Th1 Cells/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism
18.
Ned Tijdschr Geneeskd ; 161: D1061, 2017.
Article in Dutch | MEDLINE | ID: mdl-28558848

ABSTRACT

Erythema nodosum is a skin disorder that is characterised by the presence of painful erythematous nodules and plaques, mainly located on the shins. This disorder is associated with comorbidities and can be considered as an aspecific reaction pattern to a broad range of causes. However, an idiopathic variant also exists, which occurs in 22-72% of cases. Erythema nodosum is pre-eminently a skin disease which, due to its multifactorial pathogenesis, occurs in a wider field than dermatology alone. Therefore, knowledge of this disorder is important for all practicing physicians. To illustrate this we describe three patients with erythema nodosum attributable to different causes.


Subject(s)
Erythema Nodosum/diagnosis , Erythema Nodosum/etiology , Adult , Child , Diagnosis, Differential , Female , Humans , Male , Pain , Young Adult
19.
Diabet Med ; 32(10): 1385-92, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25763774

ABSTRACT

AIMS: Genetic testing for maturity-onset diabetes of the young (MODY) facilitates a correct diagnosis, enabling treatment optimization and allowing monitoring of asymptomatic family members. To date, the majority of people with MODY remain undiagnosed. To identify patients' needs and areas for improving care, this study explores the experiences of patients and family members who have been genetically tested for MODY. METHODS: Fourteen semi-structured interviews with patients and the parents of patients, and symptomatic and asymptomatic family members were conducted. Atlas.ti was used for thematic analysis. RESULTS: Most people with MODY were initially misdiagnosed with Type 1 or Type 2 diabetes; they had been seeking for the correct diagnosis for a long time. Reasons for having a genetic test included reassurance, removing the uncertainty of developing diabetes (in asymptomatic family members) and informing relatives. Reasons against testing were the fear of genetic discrimination and not having symptoms. Often a positive genetic test result did not come as a surprise. Both patients and family members were satisfied with the decision to get tested because it enabled them to adjust their lifestyle and treatment accordingly. All participants experienced a lack of knowledge of MODY among healthcare professionals, in their social environment and in patient organizations. Additionally, problems with the reimbursement of medical expenses were reported. CONCLUSIONS: Patients and family members are generally positive about genetic testing for MODY. More education of healthcare professionals and attention on the part of diabetes organizations is needed to increase awareness and optimize care and support for people with MODY.


Subject(s)
Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/psychology , Family/psychology , Genetic Testing , Adult , Aged , Attitude to Health , Diabetes Mellitus, Type 2/epidemiology , Female , Genetic Testing/statistics & numerical data , Health Behavior , Hepatocyte Nuclear Factor 1-alpha/genetics , Humans , Interviews as Topic , Male , Middle Aged , Netherlands/epidemiology , Young Adult
20.
Ann Oncol ; 23(10): 2642-2649, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22532585

ABSTRACT

BACKGROUND: Tumor location of extrahepatic cholangiocarcinoma (CCA) might influence survival after resection. METHODS: A consecutive series of 175 patients who had undergone a potentially curative resection of extrahepatic CCA was analyzed. We calculated concordance indices of different constructed prognostic models for survival including TNM (tumour-node-metastasis) staging and developed a nomogram of the most sensitive model. RESULTS: Overall cancer-specific survival rates were 83%, 58%, and 26% at 1, 2, and 5 years, respectively. Cancer-specific survival according to location was 42% for proximal, 23% for mid, and 19% for distal CCA after 5 years. Tumor location was not an independent significant predictor (P = 0.06). A prognostic model using all potential prognostic variables predicted survival better compared with TNM staging (concordance index 0.65 versus 0.63). A reduced model containing only lymph node status, microscopically residual tumor status, and tumor differentiation grade, also outperformed TNM staging (concordance index 0.66). CONCLUSIONS: Tumor location of extrahepatic CCA does not independently predict cancer-specific survival after resection. We developed a nomogram, based on a prognostic model with lymph node status, microscopically residual tumor status of resection margins, and tumor differentiation grade, that predicted survival better than TNM staging.


Subject(s)
Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/surgery , Cholangiocarcinoma/surgery , Survival Analysis , Aged , Female , Humans , Male , Middle Aged
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