ObjectiveTo assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease.BackgroundMigraine has been linked to IBD and celiac... Show moreObjectiveTo assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease.BackgroundMigraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition.MethodsLinkage disequilibrium score regression and two-sample bidirectional Mendelian randomization analyses were performed using summary statistics from cohort-based genome-wide association studies of migraine (59,674 cases; 316,078 controls), IBD (25,042 cases; 34,915 controls) and celiac disease (11,812 or 4533 cases; 11,837 or 10,750 controls). Migraine with and without aura were analyzed separately, as were the two IBD subtypes Crohn's disease and ulcerative colitis. Positive control analyses and conventional Mendelian randomization sensitivity analyses were performed.ResultsMigraine was not genetically correlated with IBD or celiac disease. No evidence was observed for IBD (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.99–1.02, p = 0.703) or celiac disease (OR 1.00, 95% CI 0.99–1.02, p = 0.912) causing migraine or migraine causing either IBD (OR 1.08, 95% CI 0.96–1.22, p = 0.181) or celiac disease (OR 1.08, 95% CI 0.79–1.48, p = 0.614) when all participants with migraine were analyzed jointly. There was some indication of a causal association between celiac disease and migraine with aura (OR 1.04, 95% CI 1.00–1.08, p = 0.045), between celiac disease and migraine without aura (OR 0.95, 95% CI 0.92–0.99, p = 0.006), as well as between migraine without aura and ulcerative colitis (OR 1.15, 95% CI 1.02–1.29, p = 0.025). However, the results were not significant after multiple testing correction.ConclusionsWe found no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease, although we obtained some indications of causal associations with migraine subtypes. Show less
Over the past decade, the abundance of high-throughput omics approaches coupled with the use of machine learning techniques, has made it possible to investigate the full molecular complexity of... Show moreOver the past decade, the abundance of high-throughput omics approaches coupled with the use of machine learning techniques, has made it possible to investigate the full molecular complexity of health and aging. The primary forcus of this thesis was to study and improve biological aging prediction. To achieve this we developed, evaluated, and deployed state-of-the-art models predicting different aspects of human health risks by employing multiple omics measurement, with a particular attention given to 1H-NMR metabolomics. Availability, affordability, interpretability, and robustness of the 1H-NMR metabolomics platform by Nightingale Health makes it a powerful tool with implications in the risk prediction of common diseases. We explored this research line in epidemiological settings within the BBMRI-nl consortium, which incorporates 28 cohorts with various specific characteristics. Hence, we took advantage of the wide range of health statuses when examining the extensive BBMRI datasets, investigated specific subgroups such as elderly or night-working individuals respectively recruited for the Leiden Longevity Study (LLS) and LIFELINES, and even explored the potential complementarity and interaction of different omics (e.g., 1H-NMR metabolomics, DNA methylome) available within the subset known as BIOS Consortium. Show less
Posttraumatic stress disorder (PTSD) is a psychological disorder that develops following exposure to perceived life-threatening trauma. Characteristic features include behavioral changes caused by... Show morePosttraumatic stress disorder (PTSD) is a psychological disorder that develops following exposure to perceived life-threatening trauma. Characteristic features include behavioral changes caused by heightened arousal, including fear and anxiety. Glucocorticoid receptor (GR) hypersensitivity, as defined by strong negative feedback, has been one of the most robust findings of altered HPA axis function in PTSD. In this thesis, we evaluated GR-related changes that were exposed to the three consecutive stressors of the single prolonged stress (SPS) animal model for PTSD. We tested the potential of the GR antagonist RU486 treatment in reversing these stress-induced effects. We found that GR antagonism can normalize some stress-induced parameters. We demonstrated that varying the timing of RU486 administration and evaluation gave different behavioral results and dynamics of gene expression, that revealed complex interactions between stress and RU486 over time. We also tested the GR sensitivity after administered the exogenous corticosterone. Our data suggest the enhanced stress responsiveness after SPS to moderate but not mild stressors and a sensitization of brain GR signaling that extends beyond direct negative feedback regulation. Lastly, we provide evidence for a role of β-arrestin-2 as a modulator of regulating amygdala activity in response to fear/anxious memory of PTSD. Show less
In this thesis, we identified several novel modulators of TGF-β/SMAD signaling. We studied the role of these modulators in TGF-β-induced EMT and migration in breast and lung cancer cells, and... Show moreIn this thesis, we identified several novel modulators of TGF-β/SMAD signaling. We studied the role of these modulators in TGF-β-induced EMT and migration in breast and lung cancer cells, and elucidated the mechanisms by which they fine-tune TGF-β/SMAD signaling transduction. These studies contribute to a better understanding of the regulatory networks of TGF-β signaling and may offer new therapeutic potentials to target TGF-β signaling in patients with breast or lung cancer. Show less
This dissertation is a call to place the health of adults with autistic traits and autism-caregivers higher on the agenda of clinicians, researchers, policymakers, and autistic adults and autism... Show moreThis dissertation is a call to place the health of adults with autistic traits and autism-caregivers higher on the agenda of clinicians, researchers, policymakers, and autistic adults and autism-caregivers themselves. Primarily, clinicians should be educated about the increased health risks in autistic adults and autism-caregivers, in order to be able to prevent or recognize these comorbidities timely. This is relevant because of the higher prevalence of both metabolic syndrome and gastrointestinal symptoms in adults from the general population with higher levels of autistic traits, as shown in this dissertation. The associations we found between biopsychosocial factors and respectively metabolic syndrome and gastrointestinal symptoms ask for more psychiatric and somatic integrated care for autistic adults. Future research could use the associations we found between the biopsychosocial model and autistic traits to develop preventive interventions specifically targeted for adults with autism (or higher levels of autistic traits). To make sure future preventive measures and the treatment of physical health problems are effective for this target population to improve their health, barriers in the healthcare for autistic people should be reduced. Therefore, this dissertation also offers recommendations for improvement of primary care, the gatekeeper of adequate healthcare for autistic adults. Show less
A crucial step of the radiotherapy workflow is the segmentation of the tumors. Currently, this is done manually, which is very time-consuming and therefore puts a lot of burden in the clinical... Show moreA crucial step of the radiotherapy workflow is the segmentation of the tumors. Currently, this is done manually, which is very time-consuming and therefore puts a lot of burden in the clinical workflow. Deep learning techniques, currently state of the art for computer vision tasks, are a potential solution to speed up the process. Even though they have been applied to segment other structures of interest for the RT workflow, they still underperform for the case of tumors. Furthermore, there is limited research in automatic segmentation of tumors for the particular case of MRI, even though this imaging modality presents better soft tissue contrast and it is therefore ideal to visualize tumors. The goal of this thesis was to develop automatic segmentation techniques for tumors on MRI images that deliver clinically acceptable segmentations. The different automatic segmentation methods were applied in two different tasks: the automatic segmentation of the oropharyngeal primary tumor in multiparametric diagnostic MRI images and the automatic segmentation of the cervical cancer gross tumor volume in the MRI images of the brachytherapy treatment images. Show less
This research focuses on creating composite biomarkers that can classify diagnoses, estimate symptom severity, and detect treatment effects using data from wearable sensors and smartphone... Show moreThis research focuses on creating composite biomarkers that can classify diagnoses, estimate symptom severity, and detect treatment effects using data from wearable sensors and smartphone applications. The thesis consists of an introduction to machine learning techniques and their use in developing biomarkers for the central nervous system; a narrative review of the relevant literature; and detailed studies on the application of these techniques in various health conditions. Specifically, the research includes observational and cross-sectional studies on facioscapulohumeral muscular dystrophy (FSHD) and major depressive disorder (MDD), demonstrating how smartphone and wearable sensor data can be used to monitor disease severity and progression. Additionally, the research identified the use of a tablet-based finger tapping task to monitor the real-time effects of antiparkinson's drugs on Parkinson's symptom severity. Key findings highlight the potential of mHealth biomarkers to provide continuous, real-time monitoring of patients, which can enhance the accuracy of clinical assessments and potentially reduce the burden on patients and healthcare systems. The thesis also addresses the challenges of variability in mHealth device data and emphasizes the need for robust validation and standardization to ensure the reliability of these biomarkers in clinical settings. Show less
Proteinuria is an independent risk factor for the progression of kidney injury, cardiovascular morbidity, and overall mortality. In this thesis, the pathways leading to proteinuria are explored by... Show moreProteinuria is an independent risk factor for the progression of kidney injury, cardiovascular morbidity, and overall mortality. In this thesis, the pathways leading to proteinuria are explored by revisiting elements previously considered essential, investigating known pathways, and identifying new players in the field of proteinuria. First, a zebrafish embryo model for developing new therapeutic options for the rare but devastating disease of nephropathic cystinosis is presented. The studies presented in thesis also investigate loss of heparan sulphate glycosaminoglycans in a zebrafish embryo model and in multiple osteochondroma patients. These studies show that loss of heparan sulphate glycosaminoglycans does not always lead to proteinuria. Next, dynamin is described as a promising potential therapeutic target for treating proteinuria. The final study introduces transmembrane protein 14A as an essential factor in maintaining glomerular filtration barrier function. Overall, these studies contribute to elucidating the pathways to proteinuria in the hope to keep advancing the field towards targeted treatment of proteinuria for the benefit of our patients. Show less
In this thesis we examined patient readiness for shared decision making (SDM) about treatment. We first assessed associations between patient-related characteristics and the occurrence of SDM.... Show moreIn this thesis we examined patient readiness for shared decision making (SDM) about treatment. We first assessed associations between patient-related characteristics and the occurrence of SDM. Overall, we did not find consistent associations between characteristics such as age or education level, and the extent to which SDM occurred (measured from the perspective of patients, clinicians, or observers). Second, we assessed what patients need to be ready, i.e., enabled and well-equipped, to participate in SDM about treatment. We identified a wide range of skills, cognitions, and emotions. For instance, patients need to be able to understand the relevant information, be able to and dare to express themselves in consultations with clinicians, and experience an adequate amount of time to talk to clinicians and to consider the options. Finally, we developed a questionnaire, the ReadySDM. The aim of the ReadySDM is to retrospectively measure the extent to which patients felt ready for SDM during a treatment decision-making process. The questionnaire has the potential to identify novel insights into patients’ support needs and ways to enhance SDM in daily practice. Show less
Drug candidates with a covalent binding mode have gained interest since the approval of multiple covalent anticancer drugs, but were long avoided due to concerns regarding promiscuous reactivity... Show moreDrug candidates with a covalent binding mode have gained interest since the approval of multiple covalent anticancer drugs, but were long avoided due to concerns regarding promiscuous reactivity with off-target proteins. In this dissertation, the scope and versatility of the newly discovered in situ thiol–alkyne reaction is evaluated: the nonactivated alkynes exhibit an unprecedented target reactivity with excellent thiol selectivity, thus potentially outperforming currently used cysteine-reactive warheads. Chapter 1 starts with the history of (ir)reversible covalent inhibition, the reactivity of (non)activated alkynes, and the serendipitous discovery of the thiol–alkyne reaction. Established technologies for direct detection of covalent protein–drug adducts are reviewed in Chapter 2, and in Chapter 3 a detailed guide for the evaluation of (ir)reversible covalent inhibitors to obtain relevant kinetic parameters is provided, accompanied by kinetic simulations and step-wise protocols for enzymatic activity assays. In Chapter 4, the nitrile warhead in reversible CatK inhibitor odanacatib (ODN) is replaced with alkyne warheads to investigate whether it an irreversible covalent adduct is formed with cysteine protease cathepsin K (CatK) despite having a small recognition element. In Chapter 5, we evaluate if nonactivated alkynes can target noncatalytic cysteine residues by replacing the irreversible covalent acrylamide warhead in EGFR/HER2 inhibitor neratinib by an alkyne warhead. In Chapter 6, the impact of substituents on the alkyne warhead is explored using a panel of ubiquitin-based ABPs bearing substituents on the propargylamide warhead. Finally, the most important findings are summarized in Chapter 7, and placed in the context of covalent drug discovery. Show less
Mental health problems among children and youths are common and have numerous negative consequences for young people and their social network. Therewith, these problems pose a social issue. GPs... Show moreMental health problems among children and youths are common and have numerous negative consequences for young people and their social network. Therewith, these problems pose a social issue. GPs play an important role in early detection and management of these problems. Insight into their clinical decision- making and, as a result, way of working would be helpful to develop methods for providing children and youths with the help they need. Previous literature suggest many doctors(-to-be), of whom some are or will become GPs, have (lived) experience related to mental health problems themselves. Previous studies also suggest having (lived) experience influences GPs’ clinical decision-making, and consequently their way of working. It would have clinical benefits for GPs and patients to explore this process. This thesis is constructed of four different articles, each contributing to answering the main question: ‘How do GPs decide on child and youth mental health problems and what is the influence of their(lived) experience regarding these problems on this decision?’ Article 1: How do GPs make decisions regarding mental health problems in children and youths? For answering this subquestion, a mixed methods design was used: interviews among 14 and an online survey among 15 GPs. GPs were asked about their clinical decision-making process on children and youths with mental health problems using three vignettes describing children and youths with mental health problems representative of clinical practice. The findings suggest GPs differ with regards to their decision- making regarding child and youth mental health problems, and that their decision-making is influenced by factors related to 1) the GP, for example if the GP approaches the problem somatically or psychosocially, if the GP considers themself competent enough to solve the problem with regards to their interest in and knowledge about youth mental health care, 2) the child and its social context, for example if the child or youth has psychiatric (co)morbidity, if the problem is likely to solve itself and if the problem could be assessed as being complex and 3) the GPs’ collaboration with other youth care providers, for example if GPs have existing collaboration agreements with these youth care providers and how they view their collaboration. Article 2: Can GPs’ decisions on child and youth mental health problems be supported by means of a decision-support method?For answering this subquestion, a literature search was conducted to retrieve studies that involved clinical decision support methods for GPs’ clinical decision-making related to mental health problems among children and youths. This systematic review yielded 25 studies on 18 clinical decision-support methods, divided into computer-based methods (such as MyGRaCE), telecommunication methods (such as CAP PC) and methods with a combination of components related to computer-based methods and telecommunication methods (such as Collaborative care for depression intervention). The article provides insight into (possible) beneficial clinical implications of clinical decision-support methods. These methods could give more insight into possible mental health problems, they could provide structured information which can be used by the GP and/or parents during their next consultation with the child or youth, and they could also decrease time and costs spent by the primary care practice and the GP. There are also less beneficial clinical implications, such as an inability for some computer-based methods to be used in emergency situations, when time is short, problems for children and youths when using computer-based methods because of their mental status, and impediment to discuss certain topics freely because the decision-support method gives too much direction to the consultation. The article describes certain considerations for GPs when choosing a decision-support method, which may indirectly have a positive impact on the implementation of such methods into general practice. For example, the GP can take into account their way of working, user flexibility of the method for the GP, the child/youth and their parent(s) with regards to understandability and ease of use, if the GP already uses a clinical decision-support method, if the GP already has collaboration agreements with youth care providers, as well as their own attitude and knowledge regarding mental health problems among children and youths.Article 3: Do doctors-to-be, among whom future GPs, have (lived) experience regarding mental health problems? Study focused on preclinical medical students.For answering this subquestion, self-report questionnaires were sent to 1311 preclinical medical students of Leiden University Medical Center to measure burnout-, depression- and anxiety-related symptoms. The article concludes that symptoms related to mental health problems are common among preclinical medical students. Burnout-related symptoms were found in 46%, depression-related symptoms in 27% and anxiety- related symptoms in 29% of preclinical medical students. Burnout-related symptoms among preclinical medical students were correlated with a sleep duration of less than 6 hours per night, low happiness and a high need for recovery after a day of study. Depression- and anxiety-related symptoms were mainly correlated with low optimism, low happiness, and a high need for recovery after a day of study. These findings suggest preclinical medical students are at risk to develop mental health problems, which can inspire universities to come up with preventive interventions.Article 4: Do doctors-to-be, among whom future GPs, have (lived) experience regarding mental health problems? Study focused on medical interns.For answering this subquestion, self-report questionnaires were sent to 709 medical interns of the same institution mentioned in article 3 to measure burnout-related symptoms. Burnout-related symptoms were found in 30% of medical interns. Burnout-related symptoms among medical interns were related to low dedication with regards to work, a high work pace and quantity, a high need for recovery after a day of work and low optimism. These correlates could be used to prevent mental health problems among medical interns by making adjustments to the medical curriculum. The articles of this thesis suggest GPs’ decision-making on mental health problems in children and youths is multifactorial and consists of objective and subjective components. Furthermore, decision-making seems to differ between GPs, which may be an explanation why there are a variety of clinical decision support methods. Some clinical decision support methods have been implemented in the context of research into general practice, like MyGRaCE, CHICA, Mobiletype, Youth StepCare, consultation-liason method(between GPs and psychiatrists), telepsychiatry consultation practice and the MC3 Program. A clinical implication is GPs can choose a decision-support method which match their personal style of clinical decision-making. However, the validity, trustworthiness and usability of available methods need to be further explored. A clinical implication with regards to medical students’ mental health comprises universities provide accessible proactive mental support to preclinical medical interns and medical interns, because many do not seek help themselves. Furthermore, universities could stimulate a stigma-reducing educational environment, for example in collaboration with the department of (Child- and Adolescent) Psychiatry. Therefore, medical students could be equipped with effective strategies to cope with mental health problems. Also, they might be made aware of their vulnerability, so that they may know their subjectivity and use their personal experiences in practice. The results of this thesis invite more (longitudinal) research on the diagnostic precision, predictive value and cost-efficiency of clinical decision-support methods. Furthermore, more research is needed on the prevalence of mental health problems among graduated doctors, like GPs, and possible effects of these problems on their way of working, their decision-making and their contacts with patients. Strengths of this thesis include exploration of a relatively unknown research area, namely GPs’ clinical decision-making regarding mental health problems among children and youths. Therefore, this thesis used multiple research methodologies and it used a practical scope. This thesis also contains several limitations, such as inclusion of a small GP population, as well as self-selection bias in the studies on preclinical medical students, medical interns and GPs. Finally, interpretation of the results of this thesis was impeded because the research has been conducted in one university, because cause and effect of results could not always be disentangled and because of low statistical power. Because having mental health problems may influence GPs’ clinical decision-making, one could explore how (future) doctors work, study and relax. Therefore, it is recommended to strive for educating balanced doctors: persons who, in collaboration with their colleagues, are – through reflection – aware of their needs and wants between professional boundaries. Show less
Adverse drug reactions on sexual functioning (sADRs) may seriously decrease a person's quality of life. This topic is barely discussed in healthcare practice, partly because of little knowledge... Show moreAdverse drug reactions on sexual functioning (sADRs) may seriously decrease a person's quality of life. This topic is barely discussed in healthcare practice, partly because of little knowledge about the association between drugs and sexual function. Research in this thesis supplements this knowledge with quantitative methods, identifying drugs associated with sADRs and taking the first steps in characterizing the population with these drugs in use. In the second part of the thesis, qualitative methods were used to describe the current practice and the potential role of healthcare providers regarding sADRs in primary care, especially in the community pharmacy. With the acquired knowledge, materials have been developed for primary healthcare providers to discuss and agree on local policy about sADRs in their own region. Initial experiences with these materials showed greater awareness of the subject among the healthcare providers concerned. Show less
The aim of this thesis is to develop noise robust electrical properties tomography (EPT) reconstruction methods that are free from tissue transition artifacts to support clinical applications for... Show moreThe aim of this thesis is to develop noise robust electrical properties tomography (EPT) reconstruction methods that are free from tissue transition artifacts to support clinical applications for complex tissue structures such as the brain. In particular the contrast-source inversion approach is pursued. This focus of this thesis is on the reconstruction of the electrical properties from the transmit field of radiofrequency coils most frequently available in magnetic resonance imaging. Show less
This research concerns the role of metabolic sensor AMPK, which is activated during low energy levels, and known to suppress the activation of some immune cells. I studied how AMPK regulates the... Show moreThis research concerns the role of metabolic sensor AMPK, which is activated during low energy levels, and known to suppress the activation of some immune cells. I studied how AMPK regulates the function of dendritic cells (DCs), immune cells that are key regulators of the adaptive immune response. Key findings include that drug-induced AMPK activation in DCs results in metabolic rewiring that leads to immunosuppressive DCs. Furthermore, we show that the AMPK signaling axis in DCs is important for protection against obesity-induced inflammation, while AMPK in DCs inhibits the anti-tumor immune response and thereby promoting tumor growth. Therefore, AMPK activation in DCs may be a promising strategy for the generation of therapeutic tolerogenic DCs, while AMPK inhibition may be beneficial for DC-based cancer therapies. Together, these findings contribute to a better understanding of AMPK as regulator of immunity and tolerance in dendritic cells. Show less
Cancer immunotherapy has experienced remarkable advances in the last decades. Striking clinical responses have been achieved for several solid cancers, particularly cancer types with a high... Show moreCancer immunotherapy has experienced remarkable advances in the last decades. Striking clinical responses have been achieved for several solid cancers, particularly cancer types with a high mutation burden, which placed tumour-mutated antigens (neoantigens) centre stage as targets of tumour immunity and cancer immunotherapy. Neoantigens can be presented in complex with HLA molecules on the tumour cell surface, where T cells with the correct specificity can recognize the neoantigen as ‘non-self’ which will trigger killing of the tumour cell by the T cell. In theory, cancers with a low/moderate mutation burden that present neoantigens in complex with HLA class molecules could still be eligible for T cell-mediated immunotherapy. This thesis, describes the finding that neoantigen-specific T cells are present in mismatch-repair proficient (MMR-p) colorectal cancer patients, a low mutation burden cancer type. Moreover, CD39 and CD103 were found as cell surface markers that pinpoint the T cell population that contains the neoantigen-specific T cells. In addition, subsequent metastasis of a melanoma patient cohort were studied and revealed that also at advanced, late-stage disease, neoantigen-directed T cell therapy is, in theory, still applicable. Taken together, the studies reveal potential for the development of neoantigen-directed cancer immunotherapy for a broader patient population. Show less
Targeted therapy using EGFR inhibitors cetuximab and panitumumab has anti-tumor efficacy in colorectal cancer, though only in patients without a KRAS mutation in their tumor. This thesis aims to... Show moreTargeted therapy using EGFR inhibitors cetuximab and panitumumab has anti-tumor efficacy in colorectal cancer, though only in patients without a KRAS mutation in their tumor. This thesis aims to give insight on several aspects of EGFR inhibitors en RAS mutations in colorectal cancer. It reviews aspects of mutational analysis, aims to find ways to restore sensitivity to EGFR inhibitors in patients with KRAS mutated colorectal cancer and discusses the distinctive skin toxicity of cetuximab en pantiumumab. Show less
Oxygen supplementation is a cornerstone of supportive medical treatment for critically ill patients. We studied self-reported attitudes towards oxygen therapy and actual clinical practice of ICU... Show moreOxygen supplementation is a cornerstone of supportive medical treatment for critically ill patients. We studied self-reported attitudes towards oxygen therapy and actual clinical practice of ICU clinicians. We found that clinicians are concerned with oxygen induced lung injury and will change mechanical ventilation settings accordingly. However, we performed a large, randomized trial assessing whether a conservative oxygenation strategy resulted in reduced mortality compared to a liberal oxygenation strategy and found there was no significant difference in mortality between the two groups. This thesis has brought to light an important problem of studying ICU patients regarding the consent procedure. We had to exclude patients because no consent had been obtained, losing valuable data and risking selection bias. Afterwards we asked patients how they experienced participating in the trial and most were not aware of their participation but did agree with their participation. This challenges the feasibility of informed consent in critically ill patients. Moreover, we researched disturbances in the homeostasis of sodium and found that an increase in serum sodium was associated with mortality, even in patients with normonatremia and moderate hyponatremia. This challenges the assumption that correcting hyponatremia would lead to lower mortality. Show less
This thesis explores the 4 pillars of Primary Healthcare (PC), the innovations that have been implemented to improve them, and the role digital technologies may have had as part of these... Show moreThis thesis explores the 4 pillars of Primary Healthcare (PC), the innovations that have been implemented to improve them, and the role digital technologies may have had as part of these innovations, with a focus on their impact in the management of chronic conditions. This thesis seeks to identify the optimal way to incorporate digital technologies in PC and how they could improve the PC consultation, in particular, and the PC field in general. It is composed of three parts: the first revises the concept of PC and explores interventions to improve it; the second part, delves into the role digital technologies have had in improving PC and looks at how apps may impact the treatment of chronic conditions. And the third, explores the digital competencies required for PC professionals to use these technologies. Show less
