Objectives: Efficient procedures for obtaining informed (proxy) consent may contribute to high influenza vaccination rates in nursing homes. Yet are such procedures justified? This study’s objective was to gain insight in informed consent policies in Dutch nursing homes; to assess how these may affect influenza vaccination rates and to answer the question whether deviating from standard informed consent procedures could be morally justified. Design: A survey among nursing home physicians. Setting & Participants: We sent a questionnaire to all (356) nursing (...) homes in the Netherlands, to be completed by one of the physicians. Results: We received 245 completed questionnaires. As 21 institutions appeared to be closed or merged into other institutions, the response was 73.1% (245/335). Of all respondents 81.9% reported a vaccination rate above 80%. Almost 50% reported a vaccination rate above 90%. Most respondents considered herd immunity to be an important consideration for institutional policy. Freedom of choice for residents was considered important by almost all. Nevertheless, 106 out of 245 respondents follow a tacit consent procedure, according to which vaccination will be administered unless the resident or her proxy refuses. These institutions show significantly higher vaccination rates (p < 0.03). Conclusions: In our discussion we focus on the question whether tacit consent procedures can be morally justifiable. Such procedures assume that vaccination is good for residents either as individuals or as a group. Even though this assumption may be true for most residents, there are good reasons for preferring express consent procedures. (shrink)

Postnatally, heart muscle cells almost completely lose their ability to divide, which makes their loss after trauma irreversible. Potential repair by cell grafting or mobilizing endogenous cells is of particular interest for possible treatments for heart disease, where the poor capacity for cardiomyocyte proliferation probably contributes to the irreversibility of heart failure. Knowledge of the molecular mechanisms that underly formation of heart muscle cells might provide opportunities to repair the diseased heart by induction of (trans) differentiation of endogenous or exogenous (...) cells into heart muscle cells. We briefly review the molecular mechanisms involved in early development of the linear heart tube by differentiation of mesodermal cells into heart muscle cells. Because the initial heart tube does not comprise all the cardiac compartments present in the adult heart, heart muscle cells are added to the distal borders of the tube and within the tube. At both distal borders, mesodermal cell are recruited into the cardiac lineage and, within the heart tube, muscular septa are formed. In this review, the relative late additions of heart muscle cells to the linear heart tube are described and the potential underlying molecular mechanisms are discussed. BioEssays 26:248–261, 2004. Wiley Periodicals, Inc. (shrink)

© 2015 Elsevier Inc.Postnatal organogenesis occurs in an immune competent environment and is tightly controlled by interplay between positive and negative regulators. Innate immune cells have beneficial roles in postnatal tissue remodeling, but roles for the adaptive immune system are currently unexplored. Here we show that adaptive immune responses participate in the normal postnatal development of a non-lymphoid epithelial tissue. Since the mammary gland is the only organ developing predominantly after birth, we utilized it as a powerful system to study (...) adaptive immune regulation of organogenesis. We found that antigen-mediated interactions between mammary antigen-presenting cells and interferon-γ -producing CD4+ T helper 1 cells participate in MG postnatal organogenesis as negative regulators, locally orchestrating epithelial rearrangement. IFNγ then affects luminal lineage differentiation. This function of adaptive immune responses, regulating normal development, changes the paradigm for studying players of postnatal organogenesis and provides insights into immune surveillance and cancer transformation. Plaks et al. (shrink)

Background Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy. Methods We compared preferences of (...) parents/patients at enrolment, documented by a questionnaire, with preferences developed during follow-up by an interview-study to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study. This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug, currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment. Results Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received. Conclusions Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians’ research question is in line with preferences of the patient-group. By exploring so-called ‘informed patient-group’-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms. (shrink)

BackgroundWith advances in sequencing technologies, increasing numbers of people are being informed about a genetic disease identified in their family. In current practice, probands are asked to inform at-risk relatives about the diagnosis. However, previous research has shown that relatives are sometimes not informed due to barriers such as family conflicts. Research on family communication in genetic diseases aims to explore the difficulties encountered in informing relatives and to identify ways to support probands in this.Main bodyResearch on family communication may (...) also reveal that participants did not inform their relatives about the risk of a serious genetic condition, even when preventive and treatment options are available. Researchers may then face a dilemma: Do they need to warn at-risk relatives about the finding? Or do they keep silent due to prior confidentiality agreements with study participants?ConclusionsWe believe that the absolute confidence promised to research participants outweighs the interests of their relatives, even though it can be claimed that relatives at risk of a genetic disease do, in principle, have a right to know information collected about their health. Not respecting confidentiality agreements could cause distrust between researchers and research participants and possibly harm the relationship between probands and relatives. Relatives' health interests can still be taken into account without jeopardizing participant trust, by considering alternative scenarios, including sharing general study findings on the barriers participants experience with their healthcare professionals and by offering participants psychosocial support for family communication. (shrink)

High levels of somatic symptom distress represent a core component of both mental and physical illness. The exact aetiology and pathogenesis of this transdiagnostic phenomenon remain largely unknown. The Affective Picture Paradigm (APP) represents an innovative experimental paradigm to study somatic symptom distress. Based on the HiTOP framework and a population-based sampling approach, associations between facets of somatic symptom distress and symptoms induced by the APP were explored in two studies (N1 = 201; N2 = 254) using structural equation bi-factor (...) models. Results showed that the APP effect was significantly positively correlated with general somatic symptom distress (PHQ-15, HiTOP), cardio-respiratory symptoms (PHQ-15), as well as difficulties identifying feelings. In conclusion, negative affective cues in the APP can elicit somatic symptoms, particularly in people with higher levels of somatic symptom distress. Difficulties identifying feelings might contribute to this phenomenon. Results are compatible with a predictive processing account of somatic symptom perception. (shrink)

Background Speech understanding may rely not only on auditory, but also on visual information. Non-invasive functional neuroimaging techniques can expose the neural processes underlying the integration of multisensory processes required for speech understanding in humans. Nevertheless, noise (from fMRI) limits the usefulness in auditory experiments, and electromagnetic artefacts caused by electronic implants worn by subjects can severely distort the scans (EEG, fMRI). Therefore, we assessed audio-visual activation of temporal cortex with a silent, optical neuroimaging technique: functional near-infrared spectroscopy (fNIRS). Methods (...) We studied temporal cortical activation as represented by concentration changes of oxy- and deoxy-hemoglobin in four, easy-to-apply fNIRS optical channels of 33 normal-hearing adult subjects and 5 post-lingually deaf cochlear implant (CI) users in response to supra-threshold unisensory auditory and visual, as well as to congruent auditory-visual speech stimuli. Results Activation effects were not visible from single fNIRS channels. However, by discounting physiological noise through reference channel subtraction, auditory, visual and audiovisual speech stimuli evoked concentration changes for all sensory modalities in both cohorts (p<0.001). Auditory stimulation evoked larger concentration changes than visual stimuli (p<0.001). A saturation effect was observed for the audiovisual condition. Conclusions Physiological, systemic noise can be removed from fNIRS signals by reference channel subtraction. The observed multisensory enhancement of an auditory cortical channel can be plausibly described by a simple addition of the auditory and visual signals with saturation. (shrink)

BackgroundObtaining informed consent for intravenous thrombolysis in acute ischemic stroke can be challenging, and little is known about if and how the informed consent procedure is performed by neurologists in clinical practice. This study examines the procedure of informed consent for intravenous thrombolysis in acute ischemic stroke in high-volume stroke centers in the Netherlands.MethodsIn four high volume stroke centers, neurology residents and attending neurologists received an online questionnaire concerning informed consent for thrombolysis with tissue-type plasminogen activator (tPA). The respondents were (...) asked to report their usual informed consent practice for tPA treatment and their considerations on whether informed consent should be obtained.ResultsFrom the 203 invited clinicians, 50% (n = 101) completed the questionnaire. One-third of the neurology residents (n = 21) and 21% of the neurologists (n = 8) reported that they always obtain informed consent for tPA treatment. If a patient is not capable of providing informed consent, 30% of the residents (n = 19) reported that they start tPA treatment without informed consent. In these circumstances, 53% of the neurologists (n = 20) reported that the resident under their supervision would start tPA treatment without informed consent. Most neurologists (n = 21; 55%) and neurology residents (n = 45; 72%) obtained informed consent within one minute. None of the respondents used more than five minutes for informed consent. Important themes regarding obtaining informed consent for treatment were patients’ capacity, and medical, ethical and legal considerations.ConclusionThe current practice of informed consent for thrombolysis in acute ischemic stroke varies among neurologists and neurology residents. If informed consent is obtained, most clinicians stated to obtain informed consent within one minute. In the future, a shortened information provision process may be applied, making a shift from informed consent to informed refusal, while still considering the patient’s capacity, stroke severity, and possible treatment delays. (shrink)

A theory of the joint measurement of quantum mechanical observables is generalized in order to make it applicable to the measurement of the local observables of field theory. Subsequently, the property of local commutativity, which is usually introduced as a postulate, is derived by means of the theory of measurement from a requirement of mutual nondisturbance, which, for local observables performed at a spacelike distance from each other, is interpreted as a requirement of macrocausality. Alternative attempts at establishing a deductive (...) relationship between relativistic causality and local commutativity are reviewed, but found wanting, either because of the assumption of an unwarranted objectivity of the object system (algebraic approach) or because of the use of a projection postulate (operational approach). Finally, the quantum mechanical nonobjectivity is related to certain features of nonlocality which are present in the formalism of quantum mechanics. (shrink)

Vaccination programmes against infectious diseases aim to protect individuals from serious illness but also offer collective protection once a sufficient number of people have been immunized. This so-called ‘herd immunity’ is important for individuals who, for health reasons, cannot be immunized or who respond less well to vaccines. For these individuals, it is pivotal that others establish group protection. However, herd immunity can be compromised when people deliberately decide not to be immunized and benefit from the herd’s protection. These agents (...) are often referred to as free riders: their omissions are deemed to be unfair to those who do contribute to the collective’s health. This article addresses the unfairness of such ‘free riding’. An argument by Garett Cullity is examined, which asserts that the unfairness of moral free riding lies neither in one’s intentions, nor in one’s reluctance to embrace a public good. This argument offers a strong basis for justifiably arguing that free riding is unfair. However, it is then argued that other considerations also need to be taken into account before simply holding free riding against non-compliers. (shrink)

OBJECTIVES: Cognitive and sensory difficulties frequently jeopardize informed consent of frail elderly patients This study is the first to test whether preliminary research experience could enhance geriatric patients' capacity to consent. DESIGN/SETTING: A step-wise consent procedure was introduced in a study on fluid balance in geriatric patients. Eligible patients providing verbal consent participated in a try-out of a week, during which bioelectrical impedance and weight measurements were performed daily. Afterwards, written informed consent was requested. Comprehension, risk and inconvenience scores (ranges: (...) 0-10) were obtained before and after the try-out by asking ten questions about the study's essentials and by asking for a risk and inconvenience assessment on a ten-points rating scale. SUBJECTS AND RESULTS: Seventy of the 78 eligible subjects started the try-out and 53 (68%) provided written consent. The comprehension score increased from 5.0 (+/- 2.3) to 7.0 (+/- 1.9) following the try-out (P < 0.001). The number of subjects capable of weighing risks and inconveniences increased from 32 to 48 (P < 0.001). CONCLUSIONS: Research experience improved the capacity to consent, still enabling an acceptable participation rate. Therefore, experienced consent seems a promising tool to optimize informed consent in frail elderly subjects. (shrink)

Background:Women's health has received renewed attention in the last few years including health rehabilitation options for women affected by breast cancer. Dancing has often been regarded as one attractive option for supporting women's well-being and health, but research with women recovering from breast cancer is still in its infancy. Dancing with Health is multi-site pilot study that aimed to evaluate a dance programme for women in recovery from breast cancer across five European countries.Methods:A standardized 32 h dance protocol introduced a (...) range of Latin American dances presented within a sports and exercise framework with influences from dance movement therapy. Fifty-four women (M age 53.51; SD 7.99) participated in the study who had a breast cancer diagnosis 6 weeks, no indication of metastasis, or scheduled surgery/chemotherapy/radiation treatment for the duration of the intervention. Primary outcome data was collected for anthropometric and fitness measures next to cancer-related quality of life.T-tests and Wilcoxon signed ranked tests were used to establish differences pre and post intervention. Cohen's d was also calculated to determine the effect size of the intervention.Results:Statistically significant changes were found for: (i) weight, right and left forearm circumference and hip; (ii) 6 min walking, right and left handgrip, sit-to-stand and sit-and-reach; (iii) the EORTC-QLQ C30 summary score as well as the subscales of emotional and social functioning and symptoms. In all cases the direction of change was positive, while Cohen's d calculated showed that the effect of the intervention for these parameters ranged from intermediate to large.Conclusion:Changes on the above anthropometric, fitness and quality of life measures suggest that the intervention was of value to the participating women recovering from breast cancer. Results also advocate collaborative efforts across countries to further research. (shrink)