One application of personalized medicine is the tailoring of medication to the individual, so that the medication will have the highest chance of success. In order to individualize medication, one... Show moreOne application of personalized medicine is the tailoring of medication to the individual, so that the medication will have the highest chance of success. In order to individualize medication, one must have a complete inventory of all current pharmaceutical compounds (a detailed formulary) combined with pharmacogenetic datasets, the genetic makeup of the patient, their (medical) family history and other health-related data. For healthcare professionals to make the best use of this information, it must be visualized in a way that makes the most medically relevant data accessible for their decision-making. Similarly, to enable bioinformatics analysis of these data, it must be prepared and provided through an interface for controlled computational analysis. Due to the high degree of personal information gathered for such initiatives, privacy-sensitive implementation choices and ethical standards are paramount. The Personal Genetic Locker project provides an approach to enable the use of personal genomic data in primary care. In this paper, we provide a description of the Personal Genetic Locker project and show its utility through a use case based on open standards, which is illustrated by the 4MedBox system. Show less
Introduction: Clinical and laboratory studies demonstrate that placebo and nocebo effects influence various symptoms and conditions after the administration of both inert and active treatments.... Show moreIntroduction: Clinical and laboratory studies demonstrate that placebo and nocebo effects influence various symptoms and conditions after the administration of both inert and active treatments. Objective: There is an increasing need for up-to-date recommendations on how to inform patients about placebo and nocebo effects in clinical practice and train clinicians how to disclose this information. Methods: Based on previous clinical recommendations concerning placebo and nocebo effects, a 3-step, invitation-only Delphi study was conducted among an interdisciplinary group of internationally recognized experts. The study consisted of open- and closed-ended survey questions followed by a final expert meeting. The surveys were subdivided into 3 parts: (1) informing patients about placebo effects, (2) informing patients about nocebo effects, and (3) training clinicians how to communicate this information to the patients. Results: There was consensus that communicating general information about placebo and nocebo effects to patients (e.g., explaining their role in treatment) could be beneficial, but that such information needs to be adjusted to match the specific clinical context (e.g., condition and treatment). Experts also agreed that training clinicians to communicate about placebo and nocebo effects should be a regular and integrated part of medical education that makes use of multiple formats, including face-to-face and online modalities. Conclusions: The current 3-step Delphi study provides consensus-based recommendations and practical considerations for disclosures about placebo and nocebo effects in clinical practice. Future research is needed on how to optimally tailor information to specific clinical conditions and patients' needs, and on developing standardized disclosure training modules for clinicians. Show less
BackgroundElectronic health records (EHRs) are increasingly used for research; however, multicomponent outcome measures such as daily functioning cannot yet be readily extracted.AimTo evaluate... Show moreBackgroundElectronic health records (EHRs) are increasingly used for research; however, multicomponent outcome measures such as daily functioning cannot yet be readily extracted.AimTo evaluate whether an electronic frailty index based on routine primary care data can be used as a measure tor daily functioning in research with community-dwelling older persons [aged >=( )years].Design and settingCohort study among participants of the Integrated Systemic Care lot Older People (ISCOPE) trial (11 476 eligible; 7285 in observational cohort; 3141 in trial; over-representation of trail people).MethodAt baseline (T0) and after 12 months (112), daily functioning was measured with the Groningen Activities Restriction Scale (GARS, range 18-72). Electronic frailty index scores (range 0-1) at T0 and T12 were computed from the EHRs. The electronic frailty index (electronic Frailty Index - Utrecht) was tested for responsiveness and compared with the GARS as a gold standard for daily functioning.ResultsIn total, 1390 participants with complete EHR and follow-up data were selected (31.4% male; median age - 81 years. interguartile range = 78-851. The electronic frailty index increased with age, was higher for females, and lower for participants living with a partner. It Was responsive after an acute major - medical event; however, the correlation between the electronic frailty index arid GARS at T0 arid over time was limited.ConclusionBecause the electronic frailly index does riot reflect daily functioning, further research on new methods to measure daily functioning with routine care data (for example, other proxies) is needed before EHRs can be a useful data source for research with older persons. Show less
Ravensbergen, W.M.; Blom, J.W.; Evers, A.W.M.; Numans, M.E.; De Waal, M.W.M.; Gussekloo, J. 2020
Background Placebo or sham controls are the standard against which the benefits and harms of many active interventions are measured. Whilst the components and the method of their delivery have been... Show moreBackground Placebo or sham controls are the standard against which the benefits and harms of many active interventions are measured. Whilst the components and the method of their delivery have been shown to affect study outcomes, placebo and sham controls are rarely reported and often not matched to those of the active comparator. This can influence how beneficial or harmful the active intervention appears to be. Without adequate descriptions of placebo or sham controls, it is difficult to interpret results about the benefits and harms of active interventions within placebo-controlled trials. To overcome this problem, we developed a checklist and guide for reporting placebo or sham interventions. Methods and findings We developed an initial list of items for the checklist by surveying experts in placebo research (n = 14). Because of the diverse contexts in which placebo or sham treatments are used in clinical research, we consulted experts in trials of drugs, surgery, physiotherapy, acupuncture, and psychological interventions. We then used a multistage online Delphi process with 53 participants to determine which items were deemed to be essential. We next convened a group of experts and stakeholders (n = 16). Our main output was a modification of the existing Template for Intervention Description and Replication (TIDieR) checklist; this allows the key features of both active interventions and placebo or sham controls to be concisely summarised by researchers. The main differences between TIDieR-Placebo and the original TIDieR are the explicit requirement to describe the setting (i.e., features of the physical environment that go beyond geographic location), the need to report whether blinding was successful (when this was measured), and the need to present the description of placebo components alongside those of the active comparator. Conclusions We encourage TIDieR-Placebo to be used alongside TIDieR to assist the reporting of placebo or sham components and the trials in which they are used. Show less
Background: Recently, internet-based cognitive behavioral therapy (ICBT) and serious gaming interventions have been suggested to enhance accessibility to interventions and engagement in... Show moreBackground: Recently, internet-based cognitive behavioral therapy (ICBT) and serious gaming interventions have been suggested to enhance accessibility to interventions and engagement in psychological interventions that aim to promote health outcomes. Few studies, however, have investigated their effectiveness in the context of simulated real-life challenges.Objective: We aimed to examine the effectivity of a guided ICBT combined with a serious gaming intervention in improving self-reported psychophysiological and immunological health endpoints in response to psychophysiological and immune-related challenges.Methods: Sixty-nine healthy men were randomly assigned to the intervention condition, receiving ICBT combined with serious gaming for 6 weeks, or the control condition, receiving no intervention. Self-reported vitality was the primary endpoint. Other self-reported psychophysiological and immunological endpoints were assessed following various challenges, including a bacillus Calmette-Guerin vaccination evoking pro-inflammatory responses, 1 and 4 weeks after the intervention period.Results: Although the intervention did not affect vitality-associated parameters, self-reported sleep problems (P=.027) and bodily sensations (P=.042) were lower directly after the intervention compared with controls. Furthermore, wellbeing (P=.024) was higher in the intervention group after the psychophysiological challenges. Although no significant group differences were found for the psychophysiological and immunological endpoints, the data provided preliminary support for increased immunoglobulin antibody responses at the follow-up time points (P<.05). Differential chemokine endpoints between conditions were observed at the end of the test day.Conclusions: The present study provides some support for improving health endpoints with an innovative ICBT intervention. Future research should replicate and further extend the present findings by consistently including challenges and a wide range of immune parameters into the study design. Show less
Nocebo hyperalgesia is a clinically relevant phenomenon and may be formed as a result of associative learning, implemented by classical conditioning. This study explored for the first time distinct... Show moreNocebo hyperalgesia is a clinically relevant phenomenon and may be formed as a result of associative learning, implemented by classical conditioning. This study explored for the first time distinct nocebo conditioning methods and their consequences for nocebo attenuation methods. Healthy participants (N = 140) were recruited and randomized to the following nocebo hyperalgesia induction groups: conditioning with continuous reinforcement (CRF), conditioning with partial reinforcement (PRF), and a sham-conditioning control group. In the attenuation phase, counterconditioning was compared with extinction. During induction, participants experienced increased thermal pain in 100% of nocebo trials in the CRF groups, while in only 70% of nocebo trials in the PRF groups. During evocation, pain stimulation was equivalent across all trials. During attenuation, pain stimulation was decreased on nocebo trials relative to control trials for the counterconditioning groups, while pain remained equivalent across all trials for the extinction groups. Results showed that both PRF and CRF significantly induced nocebo hyperalgesia, but CRF was a more potent nocebo induction method, as compared to PRF. Counterconditioning was more effective than extinction in attenuating nocebo hyperalgesia. Neither CRF nor PRF resulted in resistance to extinction. However, compared with CRF, conditioning with PRF resulted in more resistance to counterconditioning. These findings demonstrate that the more ambiguous learning method of PRF can induce nocebo hyperalgesia and may potentially explain the treatment resistance and chronification seen in clinical practice. Further research is required to establish whether attenuation with counterconditioning is generalizable to clinical settings. Show less
It has been demonstrated that secretion of several hormones can be classically conditioned, however, the underlying brain responses of such conditioning have never been investigated before. In this... Show moreIt has been demonstrated that secretion of several hormones can be classically conditioned, however, the underlying brain responses of such conditioning have never been investigated before. In this study we aimed to investigate how oxytocin administration and classically conditioned oxytocin influence brain responses. In total, 88 females were allocated to one of three groups: oxytocin administration, conditioned oxytocin, or placebo, and underwent an experiment consisting of three acquisition and three evocation days. Participants in the conditioned group received 24 IU of oxytocin together with a conditioned stimulus (CS) during three acquisition days and placebo with the CS on three evocation days. The oxytocin administration group received 24 IU of oxytocin and the placebo group received placebo during all days. On the last evocation day, fMRI scanning was performed for all participants during three tasks previously shown to be affected by oxytocin: presentation of emotional faces, crying baby sounds and heat pain. Region of interest analysis revealed that there was significantly lower activation in the right amygdala and in two clusters in the left superior temporal gyrus in the oxytocin administration group compared to the placebo group in response to observing fearful faces. The activation in the conditioned oxytocin group was in between the other two groups for these clusters but did not significantly differ from either group. No group differences were found in the other tasks. Preliminary evidence was found for brain activation of a conditioned oxytocin response; however, despite this trend in the expected direction, the conditioned group did not significantly differ from other groups. Future research should, therefore, investigate the optimal timing of conditioned endocrine responses and study whether the findings generalize to other hormones as well. Show less
