[The Personal Antipsychotic Choice Index]. / De Persoonlijke Antipsychotica Keuzewijzer.

BACKGROUND: More than half of the patients suffering from a first psychotic episode withdraw from antipsychotic medication within the first year of treatment. Shared decision making could enhance the therapeutic relationship and thus adherence. AIM: To describe an online decision aid for the selection of antipsychotic medication: the Personal Antipsychotic Choice Index (www.pakwijzer.nl). METHOD: Per effect and side effect, the 15 most commonly prescribed antipsychotics in the Netherlands have been ranked on the basis of data on the magnitude of a desired effect and the chance of a side effect, based on a systematic literature study. We assigned scores to antipsychotics for each desired and undesired effect and processed these scores in an algorithm. A personal ranking of antipsychotics is calculated based on the value that patients attach to these effects. RESULTS: These desired and undesired criteria used are rated in the PACindex: effectiveness concerning psychotic, depressive and cognitive symptoms, weight gain, sexual dysfunction, drowsiness, hypersomnia, extrapyramidal symptoms, anticholinergic adverse effects, hypersalivation, nausea, dizziness, energy loss, blunted affect/less need for companionship. High level evidence was available for ranking weight gain, sexual dysfunction, menstrual disorders, extrapyramidal symptoms and effectiveness on psychotic symptoms. We used lower level evidence ranking the remaining criteria. CONCLUSION: A ready applicable online choixe index for the use of an antipsychotic agent has been developed and put into use. The PACindex could be updated when new evidence of new antipsychotics became available..

Electron microscopy in the diagnosis of Ehlers-Danlos syndromes: correlation with clinical and genetic investigations.

BACKGROUND: The Ehlers-Danlos syndromes (EDS) consist of 13 subtypes with overlapping features including joint hypermobility, skin and vascular fragility and generalized connective tissue friability. As DNA analysis has become the gold standard for investigation of EDS, transmission electron microscopy (TEM) in clinical practice is decreasing. However, owing to the use of next-generation sequencing, the frequency of variants of uncertain significance (VUS) identified using DNA analysis is increasing. We hypothesized that TEM can provide evidence for or against pathogenicity of VUS. OBJECTIVES: The aim of this study was to evaluate the role of TEM in the diagnosis of EDS subtypes. METHODS: Data were collected from patients who underwent a skin biopsy between October 2012 and March 2017 at the London EDS National Diagnostic Service. TEM biopsies were categorized as 'normal' or 'abnormal' according to the description and conclusion in the TEM reports. Definitive diagnoses were reached via a combination of clinical features, structural and functional studies and DNA investigations. RESULTS: The analysis included 177 patients, comprising 30 abnormal and 147 normal TEM reports. A definitive diagnosis of monogenic EDS subtypes was made in 24 patients. Overall, 17 of these 24 patients (71%) had an abnormal biopsy report and seven (29%) had a normal biopsy report. No TEM findings were specifically associated with any EDS subtype, although collagen flowers were present in most patients with a genetically confirmed diagnosis of classical EDS. CONCLUSIONS: TEM analysis of collagen structure may have the potential to provide evidence for or against the pathogenicity of a VUS, but more work is needed to establish a clear role for TEM in this process. What's already known about this topic? Collagen fibril abnormalities can be seen in several Ehlers-Danlos syndrome (EDS) subtypes. What does this study add? This study provides clinical data, transmission electron microscopy (TEM) data and molecular data of one of the largest groups of patients suspected to have a monogenetic EDS subtype. No TEM findings were specifically associated with an EDS subtype. There was a higher percentage (71%) of abnormal biopsy findings in patients with a definitive diagnosis of a monogenetic EDS subtype and where a class 4/5 genetic variant was present.

[Monitoring with four recovery phases. First experiences in FACT]. / Monitoren met vier herstelfasen; eerste ervaringen binnen FACT.

BACKGROUND: Following an audit, the flexible assertive community treatment-teams (FACT-teams), in Winterswijk, the Netherlands, set out to discover a more recovery-oriented approach to treatment and monitoring. Their findings support researching four recovery phases described previously.
AIM: A pilot-study to investigate the possibilities to create a more recovery-oriented working method by applying the four recovery phases - ranging from being overwhelmed by the condition to living past the condition - in FACT-teams.
METHOD: The FACT-teams started to monitor patients during the recovery phases and developed a semi-structured interview that can be used to determine the current recovery phase. After the phase has been determined, a plan is written on how to progress to the next phase.
RESULTS: Monitoring during the recovery phases proved to be useful in showing both succesfull and stagnating treatments. The recovery phases also became part of the standard treatment plans in the electronic patient dossier. An important result of this project was the recovery-oriented interview we developed.
CONCLUSION: Monitoring and interviewing based on the four recovery phases subjectively leads to more in-depth and more recovery-oriented evaluations of treatment. More empirical research into this method is necessary.

Workers' health surveillance: implementation of the Directive 89/391/EEC in Europe.

BACKGROUND: European Union (EU) Directive 89/391 addressed occupational health surveillance, which recommends to provide workers with 'access to health surveillance at regular intervals', aiming to prevent work-related and occupational diseases. AIMS: To investigate how EU countries adopted this Directive. METHODS: We invited one selected representative per member state to complete a questionnaire. RESULTS: All 28 EU countries implemented the Directive in some form. Workers' health surveillance (WHS) is available to all workers in 15 countries, while in 12, only specific subgroups have access. In 21 countries, workers' participation is mandatory, and in 22, the employer covers the cost. In 13 countries, access to WHS is not available to all workers but depends on exposure to specific risk factors, size of the enterprise or belonging to vulnerable groups. In 26 countries, the employer appoints and revokes the physician in charge of WHS. Twelve countries have no recent figures, reports or cost-benefit analyses of their WHS programmes. In 15 countries where reports exist, they are often in the native language. CONCLUSIONS: Coverage and quality of occupational health surveillance should be evaluated to facilitate learning from good practice and from scientific studies. We propose a serious debate in the EU with the aim of protecting workers more effectively, including the use of evidence-based WHS programmes.

Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment.

Recently, the genetic heterogeneity in osteogenesis imperfecta (OI), proposed in 1979 by Sillence et al., has been confirmed with molecular genetic studies. At present, 17 genetic causes of OI and closely related disorders have been identified and it is expected that more will follow. Unlike most reviews that have been published in the last decade on the genetic causes and biochemical processes leading to OI, this review focuses on the clinical classification of OI and elaborates on the newly proposed OI classification from 2010, which returned to a descriptive and numerical grouping of five OI syndromic groups. The new OI nomenclature and the pre-and postnatal severity assessment introduced in this review, emphasize the importance of phenotyping in order to diagnose, classify, and assess severity of OI. This will provide patients and their families with insight into the probable course of the disorder and it will allow physicians to evaluate the effect of therapy. A careful clinical description in combination with knowledge of the specific molecular genetic cause is the starting point for development and assessment of therapy in patients with heritable disorders including OI. © 2014 The Authors. American Journal of Medical Genetics Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Undergraduate teaching of occupational medicine in European schools of medicine.

PURPOSE: General practitioners play or should play a role in occupational medicine (OM), either in diagnosing occupational diseases or in counseling on return to work. Nevertheless, their training has been reported to be insufficient in most single country studies. AIMS: The objectives of this study were to analyze the content and extent of undergraduate teaching of OM in European medical schools. METHODS: An e-mail questionnaire survey of the teaching of OM to undergraduates was undertaken from December 2010 to April 2011 in all medical schools and medical faculties listed in 27 European countries (n = 305). RESULTS: Among the 305 universities identified, 135 answered to the questionnaire, giving a response rate of 44%. The mean number of hours given to formal instruction in occupational medicine to medical undergraduates was 25.5 h. Nevertheless, this number of hours varied widely between countries, but also within countries. Overall, 27% of medical schools gave their students 10 h of teaching or less, 52% 20 h or less and 69% 30 h or less. Whereas occupational diseases and principles of prevention were covered in most schools, disability and return to work were very poorly represented among the topics that were taught to students. CONCLUSION: Dedicated undergraduate teaching on occupational health or OM in European medical schools is present in most medical schools, usually at a low level, but is very variable between and within countries. Medical schools across Europe are very unequal to provide qualifying doctors education on the topics they will frequently come across in their working lives.

Ethical issues of genetic susceptibility testing for occupational diseases: opinions of trainees in a high-risk job.

PURPOSE: Genetic research has opened up possibilities for identification of persons with an increased susceptibility for occupational disease. However, regulations considering the ethical issues that are inevitably associated with the use of genetic tests for susceptibility for occupational diseases are scarce. We investigated whether opinions of an intended stakeholder group, that is, student nurses, are sufficiently addressed by existing recommendations. METHODS: Attitudes and opinions of Dutch student nurses toward a genetic test for susceptibility to occupational contact eczema were studied in a qualitative setup using focus groups, interviews and electronic questionnaires. The results were compared with guidelines and recommendations extracted from the literature. RESULTS: Sixty-nine percent of the student nurses said they would partake in a genetic test for susceptibility to occupational contact eczema when available. Concerns were expressed regarding the difficulty of interpreting test results, the utility of the test result in practice and the necessity of genetic tests for non-severe diseases. For the issue of privacy and confidentiality, the students expressed few worries and much confidence. The existing guidelines largely covered the students' opinions. Still, the data emphasized the need for good individual risk communication both before and after testing, taking into account that the test concerns susceptibility. CONCLUSIONS: Comparing the students' statements with the issues addressed by the guidelines, we conclude that the guidelines should pay more attention to risk communication and practical advice accompanying the test results.

Effect evaluation of a self-management program for dutch workers with a chronic somatic disease: a randomized controlled trial.

PURPOSE: The objective of this study is to investigate the effect of a Self-Management Program for workers with a chronic disease. This program is based on the Chronic Disease Self-Management Program of Stanford University, modified for workers with a chronic somatic disease. METHODS: In a randomized controlled trial, the effectiveness of a Self-Management Program was evaluated. Participants were randomly assigned to the experimental group (n = 57) and the control group (n = 47). The experimental group received an intervention, the control group received care as usual. Primary outcome measures were self-efficacy at work and the attitude towards self-management at work. Secondary outcomes were the SF-12 health survey questionnaire, job satisfaction and intention to change job. The results were measured at baseline, after the intervention and 8 months after the intervention. RESULTS: The attitude towards self-management at work (enjoyment) improved after 8 months for the intervention group (p = 0.030). No other outcome variable differed significantly. As an interaction effect, it was found that low educated workers developed a better physical health quality (SF-12) in the intervention group compared with the control group. The attitude towards self-management at work (importance) improved in the intervention group for older and female workers and the attitude toward enjoying self-management at work improved for female workers only. CONCLUSION: The results show that low educated workers, older workers and women benefit significantly more from the training than higher educated workers, younger workers and men.

Severe spinal cord decompression illness after an uneventful North Sea dive.

The aim of this case report is to illustrate that, even under moderate conditions, a dive can result in spinal cord decompression illness (DCI). The diver in question completed five dives with the same profile. The first four included substantial physical strain, while the final dive was for observation only, without physical strain. The spinal cord was the target organ for DCI. We discuss the roles of various diver-related risk factors and of factors related to the dive itself. Older divers have a higher risk for decompression incidents. The nature of the dive profile is a major factor in the uptake and release of inert gas. Physical exertion during pressure-exposure boosts the inert gas load, increases bubbling in tissues and raises the risk of DCI in the decompression phase of the dive. We discuss the causal involvement of such risk factors in this case, given the characteristics of the diver and the circumstances of the dive. Finally, we want to express our concern for physical fitness and smoking habits, especially for divers over the age of 40.

Workers with a chronic disease and work disability. Problems and solutions.

The prevalence of chronic diseases in the age group 18-65 years is high. Cardiometabolic conditions and musculoskeletal diseases are the most frequent chronic diseases. Depending on disease and comorbidity, the employment rates are considerably lower than for healthy individuals. Chronically ill workers may have problems in meeting job demands, they may experience physical, cognitive or sensory limitations, have fatigue or pain complaints or other disease symptoms. Psychological distress, depressive feelings, feelings of shame or guilt, lack of coping or communicative skills, and non-supportive colleagues and supervisors may add to work-related problems. The ICF Model (International Classification of Functioning, Disability and Health) of the WHO offers a framework for understanding and considering health-related problems at work and finding solutions. Interventions to prevent problems in functioning, sickness absence and work disability may focus on the worker, the workplace, or health care. Multidisciplinary vocational rehabilitation, exercise therapy, cognitive behavioural interventions, workplace interventions and empowerment are interventions with at least some evidence of effectiveness. Future policy could focus more on promotion of workers' health and future research should include the interests and motivations of employers concerning disability management, skills of line managers, the feasibility of interventions to prevent work disability and the context sensitivity of study outcomes.

Non-oral manifestations in adults with a clinical and molecularly confirmed diagnosis of periodontal Ehlers-Danlos syndrome.

Introduction: Periodontal Ehlers-Danlos Syndrome (pEDS) is a rare autosomal dominant type of EDS characterised by severe early-onset periodontitis, lack of attached gingiva, pretibial plaques, joint hypermobility and skin hyperextensibility as per the 2017 International EDS Classification. In 2016, deleterious pathogenic heterozygous variants were identified in C1R and C1S, which encode components of the complement system. Materials and Methods: Individuals with a clinical suspicion of pEDS were clinically and molecularly assessed through the National EDS Service in London and Sheffield and in genetic services in Austria, Sweden and Australia. Transmission electron microscopy and fibroblast studies were performed in a small subset of patients. Results: A total of 21 adults from 12 families were clinically and molecularly diagnosed with pEDS, with C1R variants in all families. The age at molecular diagnosis ranged from 21-73 years (mean 45 years), male: female ratio 5:16. Features of easy bruising (90%), pretibial plaques (81%), skin fragility (71%), joint hypermobility (24%) and vocal changes (38%) were identified as well as leukodystrophy in 89% of those imaged. Discussion: This cohort highlights the clinical features of pEDS in adults and contributes several important additional clinical features as well as novel deleterious variants to current knowledge. Hypothetical pathogenic mechanisms which may help to progress understanding and management of pEDS are also discussed.

170 GHz Uni-Traveling Carrier Photodiodes for InP-based photonic integrated circuits.

We demonstrate the capability of fabricating extremely high-bandwidth Uni-Traveling Carrier Photodiodes (UTC-PDs) using techniques that are suitable for active-passive monolithic integration with Multiple Quantum Well (MQW)-based photonic devices. The devices achieved a responsivity of 0.27 A/W, a 3-dB bandwidth of 170 GHz, and an output power of -9 dBm at 200 GHz. We anticipate that this work will deliver Photonic Integrated Circuits with extremely high bandwidth for optical communications and millimetre-wave applications.

146-GHz millimeter-wave radio-over-fiber photonic wireless transmission system.

We report the experimental implementation of a wireless transmission system with a 146-GHz carrier frequency which is generated by optical heterodyning the two modes from a monolithically integrated quantum dash dual-DFB source. The monolithic structure of the device and the inherent low noise characteristics of quantum dash gain material allow us to demonstrate the transmission of a 1 Gbps ON-OFF keyed data signal with the two wavelengths in a free-running state at 146-GHz carrier wave frequency. The tuning range of the device fully covers the W-band (75 - 110 GHz) and the F-band (90 - 140 GHz).

High-speed photodiodes for InP-based photonic integrated circuits.

We demonstrate the feasibility of monolithic integration of evanescently coupled Uni-Traveling Carrier Photodiodes (UTC-PDs) having a bandwidth exceeding 100 GHz with Multimode Interference (MMI) couplers. This platform is suitable for active-passive, butt-joint monolithic integration with various Multiple Quantum Well (MQW) devices for narrow linewidth millimeter-wave photomixing sources. The fabricated devices achieved a high 3-dB bandwidth of up to 110 GHz and a generated output power of more than 0 dBm (1 mW) at 120 GHz with a flat frequency response over the microwave F-band (90-140 GHz).

Case-based e-learning to improve the attitude of medical students towards occupational health, a randomised controlled trial.

OBJECTIVES: Undergraduate medical teaching in occupational health (OH) is a challenge in universities around the world. Case-based e-learning with an attractive clinical context could improve the attitude of medical students towards OH. The study question is whether case-based e-learning for medical students is more effective in improving knowledge, satisfaction and a positive attitude towards OH than non-case-based textbook learning. METHODS: Participants, 141 second year medical students, were randomised to either case-based e-learning or text-based learning. Outcome measures were knowledge, satisfaction and attitude towards OH, measured at baseline, directly after the intervention, after 1 week and at 3-month follow-up. RESULTS: Of the 141 participants, 130 (92%) completed the questionnaires at short-term follow-up and 41 (29%) at 3-month follow-up. At short-term follow-up, intervention and control groups did not show a significant difference in knowledge nor satisfaction but attitude towards OH was significantly more negative in the intervention group (F=4.041, p=0.047). At 3-month follow-up, there were no significant differences between intervention and control groups for knowledge, satisfaction and attitude. CONCLUSIONS: We found a significant decrease in favourable attitude during the internship in the experimental group compared with the control group. There were no significant differences in knowledge or satisfaction between case-based e-learning and text-based learning. The attitude towards OH should be further investigated as an outcome of educational programmes.

Impaired work functioning due to common mental disorders in nurses and allied health professionals: the Nurses Work Functioning Questionnaire.

PURPOSE: Common mental disorders (CMD) negatively affect work functioning. In the health service sector not only the prevalence of CMDs is high, but work functioning problems are associated with a risk of serious consequences for patients and healthcare providers. If work functioning problems due to CMDs are detected early, timely help can be provided. Therefore, the aim of this study is to develop a detection questionnaire for impaired work functioning due to CMDs in nurses and allied health professionals working in hospitals. METHODS: First, an item pool was developed by a systematic literature study and five focus group interviews with employees and experts. To evaluate the content validity, additional interviews were held. Second, a cross-sectional assessment of the item pool in 314 nurses and allied health professionals was used for item selection and for identification and corroboration of subscales by explorative and confirmatory factor analysis. RESULTS: The study results in the Nurses Work Functioning Questionnaire (NWFQ), a 50-item self-report questionnaire consisting of seven subscales: cognitive aspects of task execution, impaired decision making, causing incidents at work, avoidance behavior, conflicts and irritations with colleagues, impaired contact with patients and their family, and lack of energy and motivation. The questionnaire has a proven high content validity. All subscales have good or acceptable internal consistency. CONCLUSION: The Nurses Work Functioning Questionnaire gives insight into precise and concrete aspects of impaired work functioning of nurses and allied health professionals. The scores can be used as a starting point for purposeful interventions.

Exome sequencing in a family segregating for celiac disease.

Celiac disease is a multifactorial disorder caused by an unknown number of genetic factors interacting with an environmental factor. Hence, most patients are singletons and large families segregating with celiac disease are rare. We report on a three-generation family with six patients in which the inheritance pattern is consistent with an autosomal dominant model. To date, 27 loci explain up to 40% of the heritable disease risk. We hypothesized that part of the missing heritability is because of low frequency or rare variants. Such causal variants could be more prominent in multigeneration families where private mutations might co-segregate with the disease. They can be identified by linkage analysis combined with whole exome sequencing. We found three linkage regions on 4q32.3-4q33, 8q24.13-8q24.21 and 10q23.1-10q23.32 that segregate with celiac disease in this family. We performed exome sequencing on two affected individuals to investigate the positional candidate regions and the remaining exome for causal nonsense variants. We identified 12 nonsense mutations with a low frequency (minor allele frequency <10%) present in both individuals, but none mapped to the linkage regions. Two variants in the CSAG1 and KRT37 genes were present in all six affected individuals. Two nonsense variants in the MADD and GBGT1 genes were also present in 5 of 6 and 4 of 6 individuals, respectively; future studies should determine if any of these nonsense variants is causally related to celiac disease.

Fatigue and its correlates in cancer patients who had returned to work--a cohort study.

OBJECTIVES: Fatigue and other symptoms in cancer patients often interfere with social and occupational activities. Only a few studies, however, have examined relationship between fatigue and work-related outcomes. The aim of this study was to investigate which disease-related factors (treatment, diagnosis, cognitive dysfunction, depression, pain, and sleep disturbance) and work-related factors (work-load, work pressure, relationship to supervisor and colleagues, size of the company, and workplace accommodations) were related to fatigue in employed cancer survivors. METHODS: Data was collected by questionnaire at 6 months (baseline) and 18 months (end of the follow-up) after cancer diagnosis from 135 people with different types of cancer who had returned to work at follow-up. Fatigue was measured with a four-item sub-scale of MFI. Scores ranged from 4 to 20, with higher scores indicating more fatigue. RESULTS: The mean rate of general fatigue was 11.9 at baseline decreasing to 10.4 at the end of the follow-up (p<0.0001). At 6 months, higher work pressure (p = 0.02), physical workload (p<0.05) and less workplace accommodations (p = 0.03) were related to higher levels of fatigue. From disease-related factors, depression was associated with fatigue (p<0.0001) at baseline. Lack of workplace accommodations was the only factor affecting higher levels of fatigue at 18 months (p<0.001) and was also related to higher levels of depression at 6 months (p = 0.02) and at 18 months (p<0.001). CONCLUSIONS: Lack of workplace accommodations was significantly related to fatigue at the end of the follow-up, which suggests that accommodations for illness can help to reduce fatigue and depression.

Work-related upper extremity disorders: one-year follow-up in an occupational diseases registry.

PURPOSE: To study the course and consequences of work-related upper extremity disorders in the registry of the Netherlands Centre for Occupational Diseases (NCvB). METHODS: A follow-up study was performed in a sample of consecutive cases of work-related upper extremity disorders notified to the NCvB. Perceived severity was measured with VAS (0-100), quality of life with VAS (0-100) and SF-36, functional impairment with DASH and sickness absence with a questionnaire. Measurements took place directly after notification (T0) and after 3, 6 and 12 months (T1-T3). A linear mixed model was used to compare scores over time. RESULTS: Average age of the 48 consecutive patients (89% response) was 42 years; 48% were men. Perceived severity, functional impairment and sickness absence decreased statistically significant during the follow-up period, and quality of life scores improved. Patients older than 45 years scored worse on perceived severity of the disease, functional impairment and quality of life than did younger patients. CONCLUSIONS: The role of registries of occupational diseases for preventive policy can be extended by creating longitudinal data in sample projects. In the sample from our registry, work-related upper extremity disorders had a favourable course.