But what do we mean by "health"? A critical perspective on the concept of health in the adolescent transition program of a Norwegian university hospital.

BACKGROUND: To understand better what influences the practice of our transition program, we wanted to explore the underlying theory of health. METHODS: We performed a qualitative content analysis of the written material that guides the program, comprising a quality system guideline, two checklists, a guide to health professionals and managers, and three patient brochures. RESULTS: The analysis resulted in the formulation of three themes; "Being on top of medical management", "Ability to promote own health" and "Awareness of own goals and expectations". CONCLUSION: Our analysis indicates that the program content revolves mainly around medical management and that other dimensions of health are not emphasised. We question what the goals of the program are and if these goals are explicit and shared among the program stakeholders. An explicit program theory is vital and needs to be evident in material supporting transition programs.

Sleep-wake rhythm disturbances and perceived sleep in adolescent chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is characterized by long-lasting, disabling and unexplained fatigue that is often accompanied by unrefreshing sleep. The aim of this cross-sectional study was to investigate sleep-wake rhythm and perceived sleep in adolescent CFS patients compared to healthy individuals. We analysed baseline data on 120 adolescent CFS patients and 39 healthy individuals included in the NorCAPITAL project. Activity measures from a uniaxial accelerometer (activPAL) were used to estimate mid-sleep time (mid-point of a period with sleep) and time in bed. Scores from the Karolinska Sleep Questionnaire (KSQ) were also assessed. The activity measures showed that the CFS patients stayed significantly longer in bed, had a significantly delayed mid-sleep time and a more varied sleep-wake rhythm during weekdays compared with healthy individuals. On the KSQ, the CFS patients reported significantly more insomnia symptoms, sleepiness, awakening problems and a longer sleep onset latency than healthy individuals. These results might indicate that disrupted sleep-wake phase could contribute to adolescent CFS; however, further investigations are warranted.

Chronic fatigue in long-term survivors of childhood lymphomas and leukemia: persistence and associated clinical factors.

BACKGROUND: Chronic fatigue (CF) is an important late effect after childhood malignancies. Our aim was to assess CF persistence over time, concurrent comorbidities, and associations with clinical symptoms. PROCEDURE: A total of 102 long-term survivors of childhood lymphomas and acute lymphoblastic leukemia, 53 and 49 reporting CF and no CF, respectively, at time point (TP)1, were evaluated for CF at a second TP after a median interval of 2.7 years. At TP2 a survey, including self-reported and objectively measured variables, assessed depressive symptoms, pain, and physical activity. RESULTS: A total of 32 of the 53 reported CF cases at both TPs and 40/49 survivors had no CF at both TPs, whereas 30 had changed their fatigue status between first and second assessment (converters). Major somatic comorbidities were equally distributed among the groups. After exclusion of converters and survivors with major comorbidity/pregnancy, 27 persistent CF (PCF) cases and 35 controls were compared. PCF cases reported significantly more depression, sleeping problems, anxiety, pain, and reduced physical function. Further, they were less physically active than controls (steps/d; P=0.009). In a multiple regression analysis, depressive symptoms remained the only significant predictor of PCF. CONCLUSIONS: Long-term survivors of childhood cancer with PCF are characterized by more depressive symptoms, anxiety, pain, insomnia, and less physical activity.

'Sometimes it feels as if the world goes on without me': adolescents' experiences of living with chronic fatigue syndrome.

AIMS AND OBJECTIVES: To explore the experience of being an adolescent with chronic fatigue syndrome. BACKGROUND: Despite ample research, chronic fatigue syndrome is still poorly understood, and there are still controversies related to the illness. Adolescents with chronic fatigue syndrome are often unable to attend school and lose social relations with friends. The challenges they face will affect their quality of life. DESIGN: A qualitative, phenomenological hermeneutical design. METHOD: Six boys and twelve girls, aged 12-18, were interviewed, emphasising their own experiences living with chronic fatigue syndrome. Analyses were performed using a phenomenological hermeneutical method. RESULTS: The core theme, 'Sometimes it feels as if the world goes on without me', encompasses the feelings an adolescent living with chronic fatigue syndrome might have about life. The core theme was supported by four subthemes: 'On the side of life--locked in and shut out'; 'the body, the illness and me'; 'if the illness is not visible to others, does it exist?'; and 'handling life while hoping for a better future'. The subthemes reflect the experience of social isolation, their own and others' understanding of the illness and hope for the future. CONCLUSIONS: Not being able to be with friends, or attend school, made the adolescents feel different and forgotten. They felt alienated in their own bodies and were struggling to be visible to themselves and to their surroundings. Spending less time with friends and more time with their parents constituted a threat to independence and development. Yet they managed to envision a better future despite all the difficulties. RELEVANCE FOR CLINICAL PRACTICE: To provide effective support and constructive relations to adolescents with chronic fatigue syndrome, all health professions involved need insight from the persons who are themselves ill. Health centres could function as resource centres for patients and healthcare professionals.

Fatigue in myasthenia gravis: is it more than muscular weakness?

BACKGROUND: Few studies have focused on fatigue in myasthenia gravis (MG), and fatigue in relation to the autonomic system has never been systematically explored in these patients. The study aimed to document the prevalence of MG-related fatigue in ethnic Norwegians and to examine whether MG severity is associated with symptoms of autonomic disturbance, which in turn is associated with fatigue and functional disability. METHODS: Eighty two of the 97 who fulfilled the study inclusion criteria participated in the study. Controls were 410 age- and sex-matched subjects drawn from a normative sample (n = 2136) representative of the Norwegian population. Bivariate analyses and multivariate linear regression analyses were used to assess associations between questionnaire-reported MG severity, symptoms of autonomic disturbance, fatigue (mental and physical) and functional disability. RESULTS: Forty-four per cent (36/82) of patients fulfilled the criteria for fatigue compared with 22% (90/410) of controls (odds ratio 2.0; p = 0.003). Twenty-one per cent of patients (17/82) met the criteria for chronic fatigue versus 12% (48/410) of controls (odds ratio 1.96; p = 0.03). MG patients had higher total fatigue scores than controls (p < 0.001) and a high prevalence of autonomic symptoms, especially poor thermoregulation and sleep disturbance. According to multivariate analyses controlled for MG score, symptoms of autonomic disturbances were independently positively associated with fatigue (p < 0.001), and fatigue was independently negatively associated with functional level (p < 0.001). CONCLUSION: Norwegian ethnic patients with MG have higher levels of fatigue and a higher prevalence of chronic fatigue than controls, even in patients in full remission. MG severity is highly suggestive to be associated with symptoms of autonomic disturbance, which in turn is associated with fatigue and the level of functional disability.

"I can't pose a whole heap of questions that I know I don't have time to follow up"-Exploring perceptions of an adolescent transition program.

BACKGROUND: Adolescent transition programs are patient education programs. They are geared towards enabling adolescents with chronic or long-term illnesses to become active partners in their health care and manage their own health. Although there is agreement about their importance, there is not an agreement on content or how they should be delivered. The study reported here was part of the first steps of an action research project. AIM: Our aim was to explore how health professionals understand the program at our hospital, and their opinions of its implementation. This would advance our knowledge of the practice of the program to support its development. METHODS: We conducted semi-structured individual interviews with 18 physicians and nurses. Data were analysed using qualitative content analysis. In our discussion of the generated data, we use the theory of practice architectures as a lens. RESULTS AND DISCUSSION: We generated four themes through the analysis, namely "We are (back) at scratch", "Time is always an issue", "Getting them ready for what is to come-transition as a synonym to transfer" and "Raising topics that go beyond medical issues". Changes to a practice requires changes to the practice architectures. Practice architectures can both enable and constrain a practice. Our analysis suggests a need for a more unified perception of the program goals, the cultural-discursive arrangements. Health professionals see time as a significant barrier to implementation and changes to the material-economic arrangements are particularly called for, i.e., more time, space and staff to practice the program. These also tie into the social-political arrangements of the program. CONCLUSION: There are arrangements in the practice architecture that currently seem to constrain the practice of the program. The practice is currently fragmented both within and across subspecialties. Efforts should be made to establish a more shared understanding of the program among health professionals. Furthermore, we should investigate how the practice of the program can be better supported.

Factors Associated With Sinoatrial Reinnervation After Heart Transplantation.

Background: Factors associated with sympathetic and parasympathetic sinoatrial reinnervation after heart transplantation (HTx) are inadequately studied. Methods: Fifty transplant recipients were examined at 7 to 12 wk (index visit), 6, 12, 24, and 36 mo after HTx. Supine rest heart rate variability in the low-frequency (LF) domain (sympathetic and parasympathetic sinoatrial reinnervation) and the high-frequency (HF) domain (parasympathetic sinoatrial reinnervation) were measured repeatedly and related to selected recipient, donor, and perisurgical characteristics. We primarily aimed to identify index visit factors that affect the sinoatrial reinnervation process. Secondarily, we examined overall associations between indices of reinnervation and repeatedly measured recipient characteristics to generate new hypotheses regarding the consequences of reinnervation. Results: LF and HF variability increased time dependently. In multivariate modeling, a pretransplant diagnosis of nonischemic cardiomyopathy (P = 0.038) and higher index visit handgrip strength (P = 0.028) predicted improved LF variability. Recipient age, early episodes of rejection, and duration of extracorporeal circulation were not associated with indices of reinnervation. Study average handgrip strength was positively associated with LF and HF variability (respectively, P = 0.005 and P = 0.029), whereas study average C-reactive protein was negatively associated (respectively, P = 0.015 and P = 0.008). Conclusions: Indices of both sympathetic and parasympathetic sinoatrial reinnervation increased with time after HTx. A pretransplant diagnosis of nonischemic cardiomyopathy and higher index visit handgrip strength predicted higher indices of mainly sympathetic reinnervation, whereas age, rejection episodes, and duration of extracorporeal circulation had no association. HTx recipients with higher indices of reinnervation had higher average handgrip strength, suggesting a link between reinnervation and improved frailty. The more reinnervated participants had lower average C-reactive protein, suggesting an inhibitory effect of reinnervation on inflammation, possibly through enhanced function of the inflammatory reflex. These potential effects of reinnervation may affect long-term morbidity in HTx patients and should be scrutinized in future research.

Predictors of Hypertension Development 1 Year After Heart Transplantation.

BACKGROUND: Hypertension after heart transplantation (HTx) is common. We investigated predictors of and mechanisms for hypertension development during the first year after HTx, with particular attention toward immunosuppressive agents, reinnervation processes, and donor/recipient sex. METHODS: Heart transplant recipients (HTxRs) were consecutively enrolled 7 to 12 wk after surgery and followed prospectively for 12 mo. Ambulatory blood pressure recordings and autonomic cardiovascular control assessments were performed at baseline and follow-up. Possible predictors of posttransplant hypertension development were investigated in bivariate linear regression analyses followed by multiple regression modeling. RESULTS: A total of 50 HTxRs were included; 47 attended the follow-up appointment at 12 mo. Mean systolic and diastolic blood pressure increased significantly during the observational period (systolic blood pressure from 133 to 139 mm Hg, P = 0.007; diastolic blood pressure from 81 to 84 mm Hg, P = 0.005). The blood pressure increment was almost exclusively confined to HTxRs with a female donor heart, doubling the cases of systolic hypertension (from 6 to 13/14; 46% to 93%, P = 0.031) and diastolic hypertension (from 7 to 14/14; 54% to 100%, P = 0.031) in this subgroup. Autonomic cardiovascular control assessments suggested tonically constricted resistance and capacitance vessels in recipients with female donor hearts. Immunosuppressive agents and reinnervation markers were not associated with hypertension development. CONCLUSIONS: Blood pressures increase during the first year after HTx, with female donor sex as a strong predictor of recipient hypertension development. The underlying mechanism seems to be enhanced peripheral vasoconstriction caused by attenuated cardiovascular homeostasis capabilities. Further studies are needed to confirm the results.

Strong evidence for parasympathetic sinoatrial reinnervation after heart transplantation.

BACKGROUND: Heart transplantation (HTx) surgically denervates the heart. We examined indices of sinoatrial reinnervation, with emphasis on (1) the occurrence and timing of parasympathetic reinnervation, and (2) the consequences of reinnervation for heart rate (HR) responsiveness and arterial baroreceptor sensitivity. METHODS: Fifty HTx recipients were prospectively followed for 36 months after surgery. Hemodynamic variables and heart rate variability were continuously recorded at supine rest, 60 degrees head-up-tilt, during the Valsalva maneuver and during handgrip isometric exercise. RESULTS: Suggesting parasympathetic reinnervation: at baseline rest, root of the mean squared differences of successive RR intervals increased from median 3.9(5.9) to 7.1(5.1) ms (p < 0.001); high-frequency power increased from 4.0(12) to 5.7(18.9) ms2 (p = 0.018); and baroreceptor sensitivity increased from 0.04(0.36) to 1.3(2.4) ms/mmHg (p < 0.001). Suggesting sympathetic reinnervation: at baseline rest low-frequency power increased from 0.49(2.5) to 7.5(18.1) ms2 (p < 0.001); and HR responses to sympathetic stimulation during (1) head-up tilt increased from 1.9(4.2) to 9.1(8.2) bpm (p < 0.001), (2) Valsalva increased from 1.6(1.4) to 8.3(10.8) bpm (p < 0.001) and (3) handgrip increased from 0.3(0.6) to 1.9(5.1) bpm (p < 0.001). Signs of sympathetic reinnervation emerged within 6 months, while signs of parasympathetic reinnervation emerged by 24 months. CONCLUSIONS: Root of the mean squared differences of successive RR intervals, high-frequency and low-frequency variability, HR responsiveness and arterial baroreflex sensitivity all increased after HTx, suggesting functional parasympathetic and sympathetic sinoatrial reinnervation. Accordingly, the pathological regulatory state present in heart transplant recipients, which is responsible for a host of functional and clinical abnormalities, is being partially offset over time by restored autonomic control of the heart in many heart transplant recipients.

Early Signs of Sinoatrial Reinnervation in the Transplanted Heart.

BACKGROUND: Heart transplantation (HTx) surgically transects all connections to the heart, including the autonomic nerves. We prospectively examined signs, timing and consequences of early sympathetic and parasympathetic sinoatrial reinnervation, as well as explored indirect evidence of afferent cardiopulmonary reinnervation. METHODS: Fifty HTx recipients were assessed at 2.5, 6, and 12 mo after HTx. For comparison, 50 healthy controls were examined once. Continuous, noninvasive recordings of hemodynamic variables and heart rate variability indices were performed at supine rest, 0.2 Hz controlled breathing, 60° head-up-tilt, during the Valsalva maneuver and during handgrip isometric exercise. RESULTS: In HTx recipients, supine low-frequency heart rate variability gradually increased; supine high-frequency variability did not change; heart rate variability indices during controlled breathing remained unaltered; heart rate responses during tilt and isometric exercise gradually increased; the tachycardia response during Valsalva maneuver increased, while the bradycardia response remained unchanged; and indices of baroreflex sensitivity improved. Responses remained low compared to healthy controls. A negative correlation between indices of preload and heart rate response during head-up tilt emerged at 12 mo. CONCLUSIONS: Results suggest that sympathetic reinnervation of the sinoatrial node starts within 6 mo after HTx and strengthens during the first year. No evidence of early parasympathetic reinnervation was found. Indirect signs of afferent reinnervation of cardiopulmonary low-pressure baroreceptors emerged at 12 mo. Better sympathetic sinoatrial control improved heart rate responsiveness to orthostatic challenge and isometric exercise, as well as heart rate buffering of blood pressure fluctuations.

Long COVID and Post-infective Fatigue Syndrome: A Review.

Fatigue is a dominant feature of both acute and convalescent coronavirus disease 2019 (COVID-19) (sometimes termed "long-COVID"), with up to 46% of patients reporting fatigue that lasts from weeks to months. The investigators of the international Collaborative on Fatigue Following Infection (COFFI) conducted a systematic review of post-COVID fatigue and a narrative review on fatigue after other infections, and made recommendations for clinical and research approaches to assessing fatigue after COVID-19. In the majority of COVID-19 cohort studies, persistent fatigue was reported by a significant minority of patients, ranging from 13% to 33% at 16-20 weeks post-symptom onset. Data from the prospective cohort studies in COFFI and others indicate that fatigue is also a prevalent outcome from many acute systemic infections, notably infectious mononucleosis, with a case rate for clinically significant Post-infective fatigue after exclusion of recognized medical and psychiatric causes, ranging from 10%-35% at 6 months. To better characterize post-COVID fatigue, the COFFI investigators recommend the following: application of validated screening questionnaires for case detection; standardized interviews encompassing fatigue, mood, and other symptoms; and investigative approaches to identify end-organ damage and mental health conditions.

Can sustained arousal explain the Chronic Fatigue Syndrome?

We present an integrative model of disease mechanisms in the Chronic Fatigue Syndrome (CFS), unifying empirical findings from different research traditions. Based upon the Cognitive activation theory of stress (CATS), we argue that new data on cardiovascular and thermoregulatory regulation indicate a state of permanent arousal responses - sustained arousal - in this condition. We suggest that sustained arousal can originate from different precipitating factors (infections, psychosocial challenges) interacting with predisposing factors (genetic traits, personality) and learned expectancies (classical and operant conditioning). Furthermore, sustained arousal may explain documented alterations by establishing vicious circles within immunology (Th2 (humoral) vs Th1 (cellular) predominance), endocrinology (attenuated HPA axis), skeletal muscle function (attenuated cortical activation, increased oxidative stress) and cognition (impaired memory and information processing). Finally, we propose a causal link between sustained arousal and the experience of fatigue. The model of sustained arousal embraces all main findings concerning CFS disease mechanisms within one theoretical framework.

Sympathetic predominance of cardiovascular regulation during mild orthostatic stress in adolescents with chronic fatigue.

Haemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular control. This study was designed to explore the pathophysiology in adolescent CFS-patients by analysing RR-interval (RRI) variability and diastolic blood pressure (DBP) variability during mild orthostatic stress, using an algorithm which accounts for non-stationary biosignals. A total of 27 adolescents with CFS and 33 healthy control subjects having equal age- and sex distribution underwent 15 min of 20 degrees head-up tilt (HUT). The spectral power densities of RRI and DBP were computed in the low-frequency (LF) band (0.04-0.15 Hz) and the high-frequency (HF) band (0.15-0.4 Hz) using an adaptive autoregressive algorithm to obtain a time-varying spectrum. RMSSD, a time domain index of RRI variability, was also computed. At rest, all indices of variability were similar in the two groups. During tilt, CFS patients had a larger increase in the LF/HF ratio (P

Relationship between autonomic cardiovascular control, case definition, clinical symptoms, and functional disability in adolescent chronic fatigue syndrome: an exploratory study.

Chronic Fatigue Syndrome (CFS) is characterized by severe impairment and multiple symptoms. Autonomic dysregulation has been demonstrated in several studies. We aimed at exploring the relationship between indices of autonomic cardiovascular control, the case definition from Centers for Disease Control and Prevention (CDC criteria), important clinical symptoms, and disability in adolescent chronic fatigue syndrome. 38 CFS patients aged 12-18 years were recruited according to a wide case definition (ie. not requiring accompanying symptoms) and subjected to head-up tilt test (HUT) and a questionnaire. The relationships between variables were explored with multiple linear regression analyses. In the final models, disability was positively associated with symptoms of cognitive impairments (p<0.001), hypersensitivity (p<0.001), fatigue (p=0.003) and age (p=0.007). Symptoms of cognitive impairments were associated with age (p=0.002), heart rate (HR) at baseline (p=0.01), and HR response during HUT (p=0.02). Hypersensitivity was associated with HR response during HUT (p=0.001), high-frequency variability of heart rate (HF-RRI) at baseline (p=0.05), and adherence to the CDC criteria (p=0.005). Fatigue was associated with gender (p=0.007) and adherence to the CDC criteria (p=0.04). In conclusion, a) The disability of CFS patients is not only related to fatigue but to other symptoms as well; b) Altered cardiovascular autonomic control is associated with certain symptoms; c) The CDC criteria are poorly associated with disability, symptoms, and indices of altered autonomic nervous activity.