Using the patient perspective to personalize psycho-oncological care for chronic cancer-related fatigue

Ongeveer een kwart van alle mensen met kanker ervaart chronische kanker-gerelateerde vermoeidheid (CKV) nadat de behandeling voor kanker is afgerond. Patiënten met CKV worden beperkt in hun dagelijkse activiteiten. Eerder onderzoek naar CKV richtte zich vooral op vrouwen met borstkanker tijdens de behandeling voor kanker en niet-helpende factoren van CKV. Ook werd in grote groepen onderzoek gedaan naar effectiviteit van psychosociale behandelingen voor CKV. Er is echter nog onvoldoende bekend over welke behandeling het beste werkt voor wie.Om dit te onderzoeken, werd in dit proefschrift onderzoek uitgevoerd bij het Helen Dowling Instituut naar ervaringen van het individu met CKV. Als eerste werd een overkoepelend overzicht gemaakt van zestien studies naar ervaringen en omgaan met CKV. Hieruit kwam naar voren dat het lichaam centraal staat in hoe patiënten CKV ervaren en ermee omgaan. Ook werden interviews afgenomen bij een diverse groep van 25 mensen met ernstige CKV om meer inzicht te krijgen in hoe CKV in het lichaam ervaren wordt. Deze mensen hadden verschillende vormen van kanker en kregen hiervoor verschillende behandelingen. De onzichtbaarheid van CKV en het chronisch vermoeide lichaam stonden vaak op een negatieve manier op de voorgrond, waardoor dagelijkse en sociale activiteiten niet langer mogelijk waren om te kunnen doen. Verder werd tijdens de interviews ook gevraagd naar wat kan helpen bij het omgaan met CKV, waarbij het vormen van nieuwe helpende gewoontes en acceptatie van CKV belangrijk bleek. De netwerkbenadering kijkt naar relaties tussen verschillende relevante factoren. Hierdoor is het mogelijk om met intensieve longitudinale dataverzameling binnen het individu te onderzoeken hoe het netwerk van factoren en CKV eruitziet voor die persoon. Door met behulp van netwerkanalyses te kijken naar het individuele netwerk, wordt inzicht verkregen in wat voor die persoon helpende en minder helpende factoren zijn en kan de behandeling daarop afgestemd worden. In een proof-of-concept studie werd deze netwerkbenadering toegepast en alle ervaringskennis, therapeutische ervaring en eerder onderzoek naar groepen patiënten met CKV samengebracht. Er werden 24 vragen over symptomen, emoties, helpende en niet-helpende manieren van omgaan met CKV en context geprogrammeerd als ‘Ecological Momentary Assessment’ (EMA)-app Energie InZicht. Vijf patiënten met als hoofdprobleem CKV op de wachtlijst voor psycho-oncologische zorg bij het Helen Dowling Instituut kregen vijf keer per dag gedurende drie weken op hun mobiele telefoon deze vragen in de app Energie InZicht voorgelegd. In een casestudie werd door één deelnemer de studieduur verlengd naar 101 dagen. Bij start van de psycho-oncologische zorg ontvingen alle deelnemers gepersonaliseerde feedback in de vorm van netwerken op basis van de verzamelde EMA-data die ze bespraken met hun therapeut om er samen betekenis aan te geven. Na uitgebreide evaluatie met patiënten en therapeuten, lijkt het gebruik van de EMA-dataverzameling met de app Energie InZicht tijdens de wachtlijst gevolgd door gepersonaliseerde netwerkfeedback bruikbaar en haalbaar om psycho-oncologische zorg op maat aan te bieden. Dit zou de gedeelde besluitvorming over de behandelrichting en het hoofddoel van de behandeling bij start van de psycho-oncologische zorg kunnen vergemakkelijken. Het is belangrijk om het ontwikkelen van gepersonaliseerde feedback te automatiseren. Daarnaast therapeuten te trainen in het bespreken van de netwerken en patiënt en therapeut eerst kennis te laten maken, zodat de terugkoppeling van de feedback optimaal is. Toekomstig onderzoek kan onderzoeken of het gebruik van de EMA-app Energie InZicht effectief is en ook zorgt voor een kortere behandelduur. SUMMARY ENGLISH Principal findings In this thesis, I explored the patient perspective on CCRF. I used idiographic and phenomenological methodologies to investigate how patients experience and respond to CCRF. This experiential knowledge of CCRF combined with network theory applied to EMA data are used to find an answer to the central research question: in what way(s) can we personalize psycho-oncological care for patients with CCRF? In the following paragraphs, I summarize the findings of five studies. The summary is followed by a critical reflection on the main results of this thesis to put them in a broader context, a discussion of the methodological strengths and limitations of the presented idiographic research, and an outline of the recommendations for clinical psycho-oncological practice and future research. Chapter 2: Experiencing and responding to chronic cancer-related fatigue: A metaethnography of qualitative research Chapter 2 consists of a meta-ethnography of qualitative studies, which included patients who suffered from CCRF. The aim of this meta-ethnography was to create an overarching interpretative narrative that focused on how patients’ experience and respond to CCRF. I performed a comprehensive systematic literature search. Of the 1178 selected studies, I included sixteen qualitative studies after deduplication and abstract and full-text screening. These studies included 705 patients (majority women) with different ages, cancer types (mainly breast cancer), stages, and (phase of) treatment(s). The quality of the included studies was variable according to the appraisal with the CASP criteria for qualitative research.1 I followed the seven phases of meta-ethnography first described by Noblit and Hare to extract and translate the first-order constructs (patients’ interpretations) and second-order constructs (authors’ interpretations) from the studies and synthesize these into third-order constructs (new interpretations).2 This interpretative qualitative review that focused on how patients experience and respond to CCRF showed an embodied structure of CCRF. I developed a figure of embodied CCRF (see figure 2 in Chapter 2) that consists of six interrelated third-order constructs with social, spatial and temporal dimensions: 1. Embodied experience: the negative awareness of the body; 2. (Mis)Recognition: the lack of recognition by patients, relatives and health professionals (social dimension);3. Small horizon: a narrowed world perspective (spatial dimension); 4. Role change: adopting other life roles (social dimension); 5. Loss of self: the impact on identity (temporal dimension); 6. Regaining one’s footing: the process of responding to CCRF by struggling, adapting and accepting (temporal dimension). These findings can help health professionals to recognize CCRF and take a person-centered approach. My first impression from psycho-oncological care practice is that the figure can be used as a tool to facilitate the communication between patients and health professionals. This can lead to recognition and normalization of the central problems, which can help patients to regain a sense of control. Chapter 3: Navigating severe chronic cancer-related fatigue: An interpretative phenomenological analysis In Chapter 3, I conducted semi-structured face-to-face interviews with adult participants who suffered from severe CCRF for at least three months after completion of cancer treatment. The purposively selected sample included a homogeneous sample of 25 participants. The aim of this interview study was to better understand the lived experiences of patients with severe CCRF. In this interview study, I used a theoretical framework of philosophical phenomenology to explore how patients with CCRF experience disruptions in embodiment, time, and space and how these are related.3–5 For qualitative analysis of the interviews, I followed the six steps of the IPA method of Smith.6 After discussion with our multidisciplinary research team, I identified four interrelated themes that expressed different dimensions of the embodied experience of CCRF: 1. Worn out: how CCRF is an overwhelming dynamic experience with different sensations (i.e., physical, emotional, sensory, and cognitive) in one’s body (e.g., limbs and/or mind), and could result in a loss of self (affective dimension); 2. Diminishment of one’s “I can”: how time and space to move ‘freely’ is restricted by the bodily experience of CCRF and impairs one’s activities and social life (functional dimension); 3. Invisibility: how the body with CCRF becomes an object within a social context because others cannot see CCRF (social and material dimension); 4. Regaining one’s “I can”: how one can adapt active time and movement in space to the embodied experience of CCRF, one’s limitations in functioning, and objectification of one’s body in a social context (functional and productive dimension).This phenomenological interview study showed that experiencing CCRF is a personal, complex, and dynamic process that consists of interconnected affective, social, material, functional, and productive dimensions. Chapter 4: Forming new habits in the face of chronic cancer-related fatigue: An interpretative phenomenological study In Chapter 4, I used the same interview sample of 25 participants with severe CCRF from Chapter 3 and focused on the question of what is helpful in responding to CCRF to facilitate adaptation. I followed the six steps of the IPA method of Smith:6 I identified five interrelated themes of the dynamic and mutually reinforcing habitual process of responding to CCRF: 1. Discovering physical and emotional boundaries: a learning process of selfmonitoring focused on how one’s body feels to protect boundaries and prevent exhaustion; 2. Communicating support needs: ways of searching for information and asking for (professional) help; 3. Reorganizing and planning activities and rest: finding a new way to balance activities and rest in one’s life; 4. Letting go of one’s habitual identity: stopping with old habits and changing one’s role into a less active person; 5. Recognizing and accepting CCRF: how the formation of new habitual ways to respond to CCRF creates room for new beliefs such as acceptance of one’s CCRF. This phenomenological interview study provided insight into what is helpful while responding to CCRF. In this process of habit formation, breaking with unhelpful habits and negative beliefs is essential. Chapter 5: Using smartphone-based ecological momentary assessment and personalized feedback for patients with chronic cancer-related fatigue: A proof-of-concept study A quantitative form of idiographic research is ecological momentary assessment (EMA), also called the experience sampling method. EMA is a structured diary technique, in which a participant receives questions (e.g., symptoms, affect, behavior) multiple times a day for multiple days on end in their daily living environment.7 Based on the findings from chapters 2-4 described above and from the perspective of the network theory as introduced in the first chapter, together with my colleagues, I developed the Energy InSight app, an EMA app specifically targeted at assessing CCRF idiographic as interrelated phenomenon. In Chapter 5, I conducted a proof-of-concept study implemented in routine psychooncological care with five participants on the waitlist for psychological treatment for severe CCRF and their therapists. Participants completed EMA questions (i.e., fatigue, mood, activity, coping with CCRF, and context) of the Energy InSight app on their mobile phone five times a day for a three-week period. In the following week they received personalized descriptive feedback from the researcher and during the first session with their therapist they discussed the network feedback together. The aims were to explore 1) to what extent and how a patient gained insight into CCRF by filling in the smartphone-based EMA and receiving personalized (network) feedback, and 2) how this insight can help patients and therapists improve the case conceptualization process in psycho-oncological care for CCRF. I used think-aloud interviews, semi-structured interviews, and observations to explore the user experiences of patients and their therapists. I performed inductive thematic analysis of the transcripts8. Based on patients’ and therapists’ experiences in this proof-of-concept study, using EMA data collection and discussing descriptive and network feedback seems feasible and usable to personalize and improve psycho-oncological care for CCRF. Patients’ experiences (N=5): The qualitative findings showed that using the EMA app (Energy InSight) for some patients resulted in negative reactions from others and increased the awareness of the body, (dis) abilities, and feelings. Using the EMA app (Energy InSight) and receiving the descriptive feedback report enabled for everyone visibility and acknowledgment of their main problem. The discussion of the descriptive and network feedback was emotionally confronting in a positive way for most patients. The descriptive and network feedback helped all patients to identify and recognize interrelated problems of CCRF. Using the EMA app (Energy InSight), followed by the descriptive feedback initiated for some patients a change in their behavior to respond to CCRF in helpful ways. The discussion of the network feedback report helped all patients to set treatment goals or change treatment direction. Therapists’ experiences (N=4): The qualitative findings demonstrated that some therapists reported limited use of the descriptive reports. Most therapists evaluated the network feedback as insightful, useful, and an accelerator in treatment to identify the main problems. However, exploring network associations and translating the findings to practical use in psycho-oncological care was challenging for all therapists. Chapter 6: Personalizing psychological care for chronic cancer-related fatigue: A case study on symptom dynamics In Chapter 6, I presented a case study to illustrate how feedback on person-specific networks can provide new insight into CCRF and how these insights can aid personalization of psychological treatment of CCRF. This case was part of the proof-of-concept study (Chapter 5). A 34-year-old woman with CCRF as her main problem was referred to a mental health institute for psycho-oncology. During the time on the waitlist, she completed the EMA questionnaire (Energy InSight) with 24 questions about fatigue, mood, activity, coping with fatigue, and context five times a day. She was willing to fill out the EMA app for 101 days. This allowed us to explore both moment-level and day-level partial (directed) correlation networks and to gain more insights into how symptom dynamics can change over time. The interplay between symptoms, cognitions and behavior was visualized in the personspecific moment-level and day-level networks, which were discussed with the patient. For example, accepting fatigue was an important node in the moment-level and day-level contemporaneous network. In the moment-level network, acceptance of fatigue in the last three hours had a connection with less hopelessness in the past three hours and less fatigue in the following moment. In the day-level contemporaneous network, acceptance was associated with less fatigue, less hopelessness, better mood, and more motivation to do things on the same day. The patient recognized this pattern. She explained that the unpredictability of CCRF can make her feel hopeless. These findings opened a dialogue with the patient about the importance of acceptance in responding to fatigue. She discussed these findings with her therapist. This case study demonstrated how symptom networks can provide insights into how to better respond to fatigue and might help to find a direction for treatment

Using smartphone-based ecological momentary assessment and personalized feedback for patients with chronic cancer-related fatigue:A proof-of-concept study

Introduction Chronic cancer-related fatigue (CCRF) is a complex multidimensional problem warranting person-centered care. Providing patients and therapists personalized feedback based on network analysis applied to ecological momentary assessment (EMA) data could facilitate case conceptualization in psycho-oncological care. The aim was to explore patients' and therapists' experiences of using an EMA app and personalized feedback based on network theory to aid case conceptualization in psycho-oncological care. Methods A n = 5 proof-of-concept study was implemented in routine psycho-oncological care. We purposively selected adult cancer patients suffering from severe CCRF who were on the waitlist for psycho-oncological care. During a 3-week period participants filled out the EMA app Energy InSight (fatigue, mood, activity, responding, and context) five times a day. Participants received a descriptive and network feedback report, which they reflected upon during the first therapy sessions. Thematic analysis was used to analyze user experiences. Results Patients experienced that filling out the Energy InSight app, as well as receiving descriptive and network-based personalized feedback provided them with insight into their CCRF. Although therapists experienced the discussion of network feedback as challenging, it facilitated the case conceptualization. Discussion Using EMA during waitlist for psychological care seemed feasible. Patients experienced beneficial effects from filling out the EMA app and talking over the personalized feedback reports, which in turn aided case conceptualization and personalized care. Based on this evaluation, an improved version of the Energy InSight app and a therapist training for providing network feedback is developed for implementation in psycho-oncological care

Exploring the interconnectedness of fatigue, depression, anxiety and potential risk and protective factors in cancer patients:a network approach

Researchers have extensively studied fatigue, depression and anxiety in cancer patients. Several risk and protective factors have been identified for these symptoms. As most studies address these constructs, independently from other symptoms and potential risk and protective factors, more insight into the complex relationships among these constructs is needed. This study used the multivariate network approach to gain a better understanding of how patients’ symptoms and risk and protective factors (i.e. physical symptoms, social withdrawal, illness cognitions, goal adjustment and partner support) are interconnected. We used cross-sectional data from a sample of cancer patients seeking psychological care (n = 342). Using network modelling, the relationships among symptoms of fatigue, depression and anxiety, and potential risk and protective factors were explored. Additionally, centrality (i.e. the number and strength of connections of a construct) and stability of the network were explored. Among risk factors, the relationship of helplessness and physical symptoms with fatigue stood out as they were stronger than most other connections in the network. Among protective factors, illness acceptance was most centrally embedded within the network, indicating it had more and stronger connections than most other variables in the network. The network identified key connections with risk factors (helplessness, physical symptoms) and a key protective factor (acceptance) at the group level. Longitudinal studies should explore these risk and protective factors in individual dynamic networks to further investigate their causal role and the extent to which such networks can inform us on what treatment would be most suitable for the individual cancer patient

Carriage of Blastocystis spp. in travellers - A prospective longitudinal study

Introduction: A lack of prospective and longitudinal data on pre- and post-travel carriage of Blastocystis spp. complicates interpretation of a positive test post-travel. Therefore we studied dynamics of Blastocystis carriage in a cohort of Dutch travellers. Methods: From the prospective, multicentre COMBAT study among 2001 Dutch travellers, a subset of 491 travellers was selected based on travel destination to 7 subregions (70 or 71 travellers each). Faecal samples taken directly before and after travel were screened for Blastocystis with qPCR, followed, when positive, by sequence analysis to determine subtypes. Results: After exclusion of 12 samples with missing samples or inhibited qPCR-reactions, stool samples of 479 travellers were analysed. Before travel, 174 of them (36.3%) carried Blastocystis and in most of these, the same subtype was persistently carried. However, in 48/174 of those travellers (27.6%; CI95 20.8–36.6%) no Blastocystis or a different subtype was detected in the post-travel sample, indicating loss of Blastocystis during travel. Only 26 (5.4%; CI95 3.7%–8.0%) of all travellers acquired Blastocystis, including two individuals that were already positive for Blastocystis before travel but acquired a different subtype during travel. Discussion: This study shows that Blastocystis carriage in travellers is highly dynamic. The observed acquisition and loss of Blastocystis could either be travel-related or reflect the natural course of Blastocystis carriage. We demonstrate that the majority of Blastocystis detected in post-travel samples were already carried before travel

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Forming new habits in the face of chronic cancer-related fatigue: An interpretative phenomenological study

Purpose The growing group of patients who suffer from chronic cancer-related fatigue (CCRF) after cancer have helpful and less helpful ways of responding to this long-lasting and disruptive problem. This qualitative study aimed to gain insight in essential elements of how patients respond to CCRF, with a focus on helpful responses to facilitate adaptation. Methods We conducted semi-structured interviews with a purposive sample of 25 participants who experienced severe CCRF for at least 3 months. Participants were recruited via media, patient associations, meetings, and health professionals until data saturation was attained. We used a topic guide with open-ended questions about lived experiences. Interpretative phenomenological analysis (IPA) was used for analysis of the transcripts. Results We identified five interrelated themes of how patients respond to CCRF: (1) discovering physical and emotional boundaries; (2) communicating support needs; (3) reorganizing and planning activities and rest; (4) letting go of one’s habitual identity; and (5) recognizing and accepting CCRF. Conclusion This study highlights the development of new habits and positive beliefs in the face of CCRF and the importance of (social) support in this process. This experiential knowledge on helpful responses can be used to inform patients and their significant others and improve self-efficacy. Health professionals could use these insights to improve recognition of CCRF and personalize treatment