Cancer-related fatigue: Towards a more targeted approach based on classification by biomarkers and psychological factors.

Cancer-related fatigue is a frequent, burdensome and often insufficiently treated symptom. A more targeted treatment of fatigue is urgently needed. Therefore, we examined biomarkers and clinical factors to identify fatigue subtypes with potentially different pathophysiologies. The study population comprised disease-free breast cancer survivors of a German population-based case-control study who were re-assessed on average 6 (FU1, n = 1871) and 11 years (FU2, n = 1295) after diagnosis. At FU1 and FU2, we assessed fatigue with the 20-item multidimensional Fatigue Assessment Questionnaire and further factors by structured telephone-interviews. Serum samples collected at FU1 were analyzed for IL-1ß, IL-2, IL-4, IL-6, IL-10, TNF-a, GM-CSF, IL-5, VEGF-A, SAA, CRP, VCAM-1, ICAM-1, leptin, adiponectin and resistin. Exploratory cluster analyses among survivors with fatigue at FU1 and no history of depression yielded three clusters (CL1, CL2 and CL3). CL1 (n = 195) on average had high levels of TNF-α, IL1-ß, IL-6, resistin, VEGF-A and GM-CSF, and showed high BMI and pain levels. Fatigue in CL1 manifested rather in physical dimensions. Contrarily, CL2 (n = 78) was characterized by high leptin level and had highest cognitive fatigue. CL3 (n = 318) did not show any prominent characteristics. Fatigued survivors with a history of depression (n = 214) had significantly higher physical, emotional and cognitive fatigue and showed significantly less amelioration of fatigue from FU1 to FU2 than survivors without depression. In conclusion, from the broad phenotype "cancer-related fatigue" we were able to delineate subgroups characterized by biomarkers or history of depression. Future investigations may take these subtypes into account, ultimately enabling a better targeted therapy of fatigue.

Patterns and influencing factors of exercise attendance of breast cancer patients during neoadjuvant chemotherapy.

BACKGROUND: Performing 2-3 exercise sessions/week may relieve therapy-related side effects of breast cancer patients (BRCA) and improve their quality of life. However, attendance to the exercise sessions is often impaired. Thus, we investigated patterns and possible influencing factors of attendance to an aerobic (AT) or resistance training (RT) intervention in BRCA during neoadjuvant chemotherapy. METHODS: BRCA (N = 122) were randomly allocated to supervised AT or RT twice weekly during neoadjuvant chemotherapy (18 ± 4 weeks). Attendance was calculated individually and group-wise per training week as the percentage of the performed sessions out of the prescribed sessions. Possible influencing factors were investigated using multiple regression analyses. RESULTS: Mean individual attendance was 44.1% ± 29.3% with no significant differences between the groups. Group-wise attendance was highest in the first 6 weeks of training with ≥ 60% for AT and ≥ 50% for RT, but decreased over the course of the intervention accompanying chemotherapy. Significantly higher attendance was associated with not having vs. having nausea (ß = - 14.57; p = 0.007) and not having vs. having pain (ß = - 12.07; p = 0.12), whereas fatigue did not show any association (ß = - 0.006; p = 0.96). Having been randomized into a preferred intervention group (48.8%) showed no association with attendance. Yet, patients' rating of the exercise intervention as "good"/ "very good" (58.7%) was significantly associated with higher attendance (p = 0.01). CONCLUSION: For both exercise interventions, group-wise attendance/training week decreased during chemotherapy despite good intervention ratings. While some patients never started, others trained almost constantly twice weekly. The study revealed that patients who are nauseous or experience pain may need more support to attend more exercise sessions. Trial Registration Clinicaltrials.gov: NCT02999074 from May 6, 2016.

Dropout from exercise trials among cancer survivors-An individual patient data meta-analysis from the POLARIS study.

INTRODUCTION: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. METHODS: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. RESULTS: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m2 , performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. CONCLUSIONS: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects.

Longitudinal associations of bioelectrical phase angle and fatigue in breast cancer patients.

Cancer-related fatigue is commonly treated in an undifferentiated manner, because its pathophysiology is still not well understood. Therefore, we investigated if bioelectrical phase angle (PhA), a non-invasive marker of cell integrity, could help to single out specific fatigue subtypes. In a randomized controlled strength training intervention trial, PhA was measured by bioelectrical impedance analysis in 158 breast cancer patients. Fatigue was assessed with the multidimensional 20-item Fatigue Assessment Questionnaire. Multiple regression analyses considering changes in PhA and fatigue from baseline to post-intervention and ANCOVA models investigating the strength training effect on PhA were conducted. Further, explorative mediation and moderation analyses were performed. Decrease (=worsening) in PhA was significantly associated with increase in physical (P = .010) and emotional (P = .019) fatigue. These associations were markedly stronger in patients with normal BMI (interaction P = .059 and .097) and with low pre-diagnosis exercise level (interaction P = .058 and .19). Among patients with normal BMI strength training was associated with an increase in PhA (ANCOVA P = .059), but not among overweight/obese patients (interaction P = .035). Chemotherapy was a major determinant for low PhA, but PhA did not mediate the effect of chemotherapy on fatigue. In conclusion, PhA has a significant inverse association with physical and emotional fatigue. This association is moderated by BMI and previous exercise. Significant relationships of PhA were also observed with chemotherapy and strength training. Thus, PhA might be a marker that could help in the classification of subtypes of fatigue with different pathophysiology, which may require specifically tailored treatment. Further research on this is warranted.

Long-term effects of exercise interventions on physical activity in breast cancer patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Benefits of exercise interventions for cancer patients are well established. This systematic review aimed to investigate the sustainability of exercise interventions with respect to physical activity behaviour of breast cancer patients in the longer term. METHODS: The databases Pubmed, Cochrane, Embase, and Web of Science were systematically searched for randomized controlled trials (RCTs) investigating aerobic exercise, resistance exercise, or combined exercise interventions in breast cancer patients and assessing physical activity at least 2 months after the intervention. Random-effect models were used to calculate standardized mean differences (SMD). RESULTS: A total of 27 RCTs with 4120 participants were included in the review, of which 11 RCTs with 1545 participants had appropriate data for the meta-analyses. Physical activity was mainly self-reported, and most exercise interventions were supervised. Exercise interventions tended to show a moderate significant effect up to 6 months for moderate to vigorous physical activity (SMD [95% CI] = 0.39 [0.07, 0.70]) and small, non-significant effects on total physical activity at 6 months (SMD [95% CI] = 0.14 [- 0.00, 0.28]) and up to 60 months after the intervention (SMD = 0.29 [-0.31, 0.90]). Differences between intervention characteristics, such as supervised versus unsupervised, were inconclusive due to the small number of RCTs. CONCLUSIONS: The physical activity behaviour in breast cancer patients remained improved for several months beyond the end of exercise interventions, but effects were small to moderate and diminished over time. Future studies should clarify how to maintain a healthy level of physical activity after completion of an exercise intervention.

Psycho-oncologists' knowledge of cancer-related fatigue and the targets for improving education and training: results from a cross-sectional survey study.

PURPOSE: To explore psycho-oncologists' knowledge of cancer-related fatigue and their self-efficacy to intervene for fatigue. We further aimed to examine the role of fatigue in psycho-oncological training and derive specific suggestions for improvements. METHODS: For this cross-sectional survey study, psycho-oncologists working in Germany were systematically recruited via an address directory or invited by training institutes or colleagues. The online survey encompassed questions on knowledge of fatigue guidelines and interventions, self-efficacy, counseling, and fatigue in professional training. Data were analyzed descriptively and using Mann-Whitney U tests. A logistic regression analysis was performed to identify variables linked to fatigue guideline knowledge. RESULTS: Seventy two percent of the 144 surveyed psycho-oncologists stated not knowing any fatigue-specific guidelines. Those unaware of guidelines reported a lower self-efficacy to intervene for fatigue. However, despite low knowledge of the guidelines, more than 80% of the participants felt well informed about fatigue and reported high self-efficacy. Most participants were aware of the empirical evidence for psychotherapeutic interventions (95%); everyday physical activity, e.g., taking a walk (98%); yoga (82%); and mindfulness-based interventions (82%). Knowledge gaps existed concerning the evidence of resistance/endurance training for treating fatigue. Knowing that resistance/endurance training is an effective treatment was related to an increased frequency to recommend it to patients. Suggestions to improve training for psycho-oncologists included raising awareness earlier in the career path and offering multidisciplinary trainings for fatigue. CONCLUSION: To improve fatigue-related guideline knowledge among psycho-oncologists and enhance implementation into clinical practice multidisciplinary trainings are needed. Psycho-oncologists should play an important role in fatigue management. TRIAL REGISTRATION: Clinicaltrials.gov , identifier: NCT04921644. Registered in June 2021.

"Being prevented from providing good care: a conceptual analysis of moral stress among health care workers during the COVID-19 pandemic".

BACKGROUND: Health care workers (HCWs) are susceptible to moral stress and distress when they are faced with morally challenging situations where it is difficult to act in line with their moral standards. In times of crisis, such as disasters and pandemics, morally challenging situations are more frequent, due to the increased imbalance between patient needs and resources. However, the concepts of moral stress and distress vary and there is unclarity regarding the definitions used in the literature. This study aims to map and analyze the descriptions used by HCWs regarding morally challenging situations (moral stress) and refine a definition through conceptual analysis. METHODS: Qualitative data were collected in a survey of 16,044 Swedish HCWs who attended a COVID-19 online course in autumn 2020. In total, 643 free-text answers with descriptions of moral stress were analyzed through content analysis. RESULTS: Three themes emerged from the content analysis (1) "Seeing, but being prevented to act; feeling insufficient/inadequate and constrained in the profession," (2) "Someone or something hindered me; organizational structures as an obstacle," and (3) "The pandemic hindered us; pandemic-related obstacles." The three themes correspond to the main theme, "Being prevented from providing good care." DISCUSSION: The main theme describes moral stress as various obstacles to providing good care to patients in need and acting upon empathic ability within the professional role. The themes are discussed in relation to established definitions of moral stress and are assessed through conceptual analysis. A definition of moral stress was refined, based on one of the established definitions. CONCLUSIONS: On the basis of the study results and conceptual analysis, it is argued that the presented definition fulfils certain conditions of adequacy. It is essential to frame the concept of moral stress, which has been defined in different ways in different disciplines, in order to know what we are talking about and move forward in developing prevention measures for the negative outcomes of this phenomenon.

Systemic Evidence for Mitochondrial Dysfunction in Age-Related Macular Degeneration as Revealed by mtDNA Copy Number Measurements in Peripheral Blood.

Mitochondrial dysfunction is a common occurrence in the aging process and is observed in diseases such as age-related macular degeneration (AMD). Increased levels of reactive oxygen species lead to damaged mitochondrial DNA (mtDNA), resulting in dysfunctional mitochondria, and, consequently, mtDNA causes further harm in the retinal tissue. However, it is unclear whether the effects are locally restricted to the high-energy-demanding retinal pigment epithelium or are also systematically present. Therefore, we measured mtDNA copy number (mtDNA-CN) in peripheral blood using a qPCR approach with plasmid normalization in elderly participants with and without AMD from the AugUR study (n = 2262). We found significantly lower mtDNA-CN in the blood of participants with early (n = 453) and late (n = 170) AMD compared to AMD-free participants (n = 1630). In regression analyses, we found lower mtDNA-CN to be associated with late AMD when compared with AMD-free participants. Each reduction of mtDNA-CN by one standard deviation increased the risk for late AMD by 24%. This association was most pronounced in geographic atrophy (OR = 1.76, 95% CI 1.19-2.60, p = 0.004), which has limited treatment options. These findings provide new insights into the relationship between mtDNA-CN in blood and AMD, suggesting that it may serve as a more accessible biomarker than mtDNA-CN in the retina.

Late effects, long-term problems and unmet needs of cancer survivors.

Great efforts are being made in cancer treatment, with impressive improvement in survival. The situation concerning research and care for long-term problems and late effects in the growing population of cancer survivors, however, is unsatisfactory. Therefore, in the FiX survey 1348 disease-free survivors about 4 years after diagnosis of different cancer types were asked to rate existing burdens and support received for them along a list of 36 potential problems. Health-related quality of life (HRQoL) was assessed with the EORTC QLQ-C30. Determinants of burdens were explored using logistic regression analysis. While cancer survivors' global HRQoL, physical and role function ratings were comparable or better than age- and sex-matched reference values of the general population, emotional and cognitive function was worse, especially among women (P < .01). Most frequently reported problems with at least moderate burden were loss of physical performance (36.3%), fatigue (35.1%), sexual problems (34.7%), sleep problems (34.1%), arthralgia (33.8%), anxiety (28.0%), neuropathy (25.6%), memory problems (23.0%) and concentration problems (21.9%). Burdened survivors often rated received support as poor, especially regarding support for problems that physicians might consider medically nonthreatening, or for which no effective pharmacologic or medical treatment is known. Determinants for burden included higher age, female gender, having ever received chemotherapy and overweight/obesity. In conclusion, a significant number of cancer survivors suffer from long-term or late effects and have unmet care needs. Awareness of health care professionals should be increased for these issues. The results of our study can contribute to the development of targeted survivorship plans.

Estimation of Relative Vaccine Effectiveness in Influenza: A Systematic Review of Methodology.

BACKGROUND: When new vaccine components or platforms are developed, they will typically need to demonstrate noninferiority or superiority over existing products, resulting in the assessment of relative vaccine effectiveness (rVE). This review aims to identify how rVE evaluation is being performed in studies of influenza to inform a more standardized approach. METHODS: We conducted a systematic search on PubMed, Google Scholar, and Web of Science for studies reporting rVE comparing vaccine components, dose, or vaccination schedules. We screened titles, abstracts, full texts, and references to identify relevant articles. We extracted information on the study design, relative comparison made, and the definition and statistical approach used to estimate rVE in each study. RESULTS: We identified 63 articles assessing rVE in influenza virus. Studies compared multiple vaccine components (n = 38), two or more doses of the same vaccine (n = 17), or vaccination timing or history (n = 9). One study compared a range of vaccine components and doses. Nearly two-thirds of all studies controlled for age, and nearly half for comorbidities, region, and sex. Assessment of 12 studies presenting both absolute and relative effect estimates suggested proportionality in the effects, resulting in implications for the interpretation of rVE effects. CONCLUSIONS: Approaches to rVE evaluation in practice is highly varied, with improvements in reporting required in many cases. Extensive consideration of methodologic issues relating to rVE is needed, including the stability of estimates and the impact of confounding structure on the validity of rVE estimates.

Sorting nexin 24 is required for α-granule biogenesis and cargo delivery in megakaryocytes.

Germline defects affecting the DNA-binding domain of the transcription factor FLI1 are associated with a bleeding disorder that is characterized by the presence of large, fused α-granules in platelets. We investigated whether the genes showing abnormal expression in FLI1-deficient platelets could be involved in platelet α-granule biogenesis by undertaking transcriptome analysis of control platelets and platelets harboring a DNA-binding variant of FLI1. Our analysis identified 2,276 transcripts that were differentially expressed in FLI1-deficient platelets. Functional annotation clustering of the coding transcripts revealed significant enrichment for gene annotations relating to protein transport, and identified Sorting nexin 24 (SNX24) as a candidate for further investigation. Using an induced pluripotent stem cell-derived megakaryocyte model, SNX24 expression was found to be increased during the early stages of megakaryocyte differentiation and downregulated during proplatelet formation, indicating tight regulatory control during megakaryopoiesis. CRISPR-Cas9 mediated knockout (KO) of SNX24 led to decreased expression of immature megakaryocyte markers, CD41 and CD61, and increased expression of the mature megakaryocyte marker CD42b (P=0.0001), without affecting megakaryocyte polyploidisation, or proplatelet formation. Electron microscopic analysis revealed an increase in empty membrane-bound organelles in SNX24 KO megakaryocytes, a reduction in α-granules and an absence of immature and mature multivesicular bodies, consistent with a defect in the intermediate stage of α-granule maturation. Co-localization studies showed that SNX24 associates with each compartment of α-granule maturation. Reduced expression of CD62P and VWF was observed in SNX24 KO megakaryocytes. We conclude that SNX24 is required for α-granule biogenesis and intracellular trafficking of α-granule cargo within megakaryocytes.

Cancer-related fatigue: Identification of hallmarks to enable refined treatment approaches.

OBJECTIVE: Recommendations for fatigue management are commonly given in an undifferentiated manner without further evaluation of patient's specific symptomatology. Thus, we aimed to identify hallmarks of potential fatigue subgroups which might guide more refined treatment. METHODS: The FiX study assessed fatigue with the EORTC QLQ-FA12 in patients around 2 years after cancer diagnosis (T0) including 15 different entities. After 2 years, a follow-up survey (T1) was conducted. The analyses comprised all patients with prevalent fatigue at T0 (N = 1023). Hierarchical cluster analysis was performed using the Ward method and including the dichotomized factors emotional distress, pain, insomnia, and obesity. Emotional distress, that is, depressive symptoms and anxiety, was assessed by the PHQ-4. Pain and insomnia were based on the according symptom scores of the EORTC QLQ-C30. Analysis of covariance was conducted to investigate the association of the fatigue clusters at T0 with subsequent fatigue at T1. RESULTS: Four hierarchical clusters were identified. The first cluster comprised patients with moderate-to-severe distress. The remaining fatigue cases were differentiated by obesity and then by pain. Fatigue cases without any of these three symptoms formed the last cluster. Physical, emotional and cognitive fatigue were highest in the distress cluster. Additionally, this cluster was associated with higher physical, emotional and cognitive fatigue at T1 compared to the other clusters. CONCLUSIONS: Fatigue in conjunction with emotional distress had worse impact, persisted longer, and may require other treatment approaches than fatigue in patients without emotional distress. Obesity and pain may be further distinguishing hallmarks for refined fatigue management.

Sample size estimation using a latent variable model for mixed outcome co-primary, multiple primary and composite endpoints.

Mixed outcome endpoints that combine multiple continuous and discrete components are often employed as primary outcome measures in clinical trials. These may be in the form of co-primary endpoints, which conclude effectiveness overall if an effect occurs in all of the components, or multiple primary endpoints, which require an effect in at least one of the components. Alternatively, they may be combined to form composite endpoints, which reduce the outcomes to a one-dimensional endpoint. There are many advantages to joint modeling the individual outcomes, however in order to do this in practice we require techniques for sample size estimation. In this article we show how the latent variable model can be used to estimate the joint endpoints and propose hypotheses, power calculations and sample size estimation methods for each. We illustrate the techniques using a numerical example based on a four-dimensional endpoint and find that the sample size required for the co-primary endpoint is larger than that required for the individual endpoint with the smallest effect size. Conversely, the sample size required in the multiple primary case is similar to that needed for the outcome with the largest effect size. We show that the empirical power is achieved for each endpoint and that the FWER can be sufficiently controlled using a Bonferroni correction if the correlations between endpoints are less than 0.5. Otherwise, less conservative adjustments may be needed. We further illustrate empirically the efficiency gains that may be achieved in the composite endpoint setting.

The cancer patients' perspective on feasibility of using a fatigue diary and the benefits on self-management: results from a longitudinal study.

PURPOSE: To evaluate the patients' perspective on feasibility of using a fatigue diary and its benefits on self-management. METHODS: This longitudinal study enrolled 50 cancer patients in routine care. Following baseline (t0) assessment, patients were asked to complete a 7-day fatigue diary and subsequently obtained written diary evaluation. Feasibility, benefits, and fatigue-related attitudes were assessed via self-report 1 (t1) and 4 months (t2) after distributing the diary. Data were analyzed descriptively and using Wilcoxon signed-rank tests. RESULTS: Most patients (94%) completed the diary for 7 days and rated feasibility as high. After diary completion and receiving the evaluation, fewer patients felt helpless in the face of fatigue (t1: 21% vs. t0: 53%). Additionally, more patients addressed fatigue with their general practitioner (t2: 49% vs. t0: 36%) and pro-actively searched for information and help (t2: 59% vs. t0: 38%). The diary enabled a majority of patients to be aware of their fatigue patterns, to plan daily routines accordingly and to take adequate actions against fatigue. CONCLUSION: The study showed that symptom monitoring via a fatigue diary was considered feasible and enhanced self-management in cancer patients. Thus, fatigue diaries might be a useful measure contributing to an improved fatigue management. The results reinforce guideline recommendations for routine application of fatigue diaries in clinical care. Healthcare professionals should encourage patients to fatigue diary use and provide individually tailored counseling based on diary entries.

Cancer-related fatigue: benefits of information booklets to improve patients' knowledge and empowerment.

PURPOSE: To investigate cancer patients' knowledge and attitudes regarding fatigue and the potential benefits and acceptability of a brief information booklet. METHODS: The CARPE DIEM study assessed knowledge and attitudes regarding fatigue in a diverse group of 50 cancer patients before (T0) and about one (T1) and four months (T2) after reading the booklet. At T1, participants additionally rated its usefulness. RESULTS: At baseline, 37.5% of respondents did not know the term "fatigue" or what it meant. Those who already knew something about fatigue mainly had obtained their information from booklets, books, or articles (63.3%) and/or the internet (46.7%). Overall, knowledge gaps existed, particularly about potential fatigue treatment options and whether fatigue is an indicator of cancer progression. Furthermore, 56.4% felt poorly informed, and 46.1% reported feeling helpless in the face of fatigue. Lower knowledge at baseline was significantly associated with lower education and older age. At T1 and T2, there were significant improvements in several knowledge questions and attitudes. Patient-reported benefits included getting new information about fatigue (91.1%), awareness of not being alone with their problems (89.7%), taking appropriate actions (72.9%), and encouragement to talk about their fatigue with family/friends (55.3%) or with a health professional (52.7%). CONCLUSIONS: Specific gaps were identified in the provision of information and education for cancer patients about fatigue. A low-cost intervention asking to read a brief information booklet was associated with improved knowledge. This could be considered as a first step offered as part of a bundle of further efforts to improve knowledge and care of fatigue.

Changes in healthcare seeking and lifestyle in old aged individuals during COVID-19 lockdown in Germany: the population-based AugUR study.

BACKGROUND: Containment measures in the COVID-19 pandemic protected individuals at high risk, particularly individuals at old age, but little is known about how these measures affected health-related behavior of old aged individuals. We aimed to investigate the impact of the spring 2020 lockdown in Germany on healthcare-seeking and health-related lifestyle in the old aged and to identify susceptible subgroups. METHODS: We conducted a follow-up survey among the pre-pandemically well-characterized participants of our AugUR cohort study, residents in/around Regensburg aged 70+ years and relatively mobile. A self-completion questionnaire on current behavior, perceived changes, and SARS-Cov-2 infection was mailed in May 2020, shortly before contact restrictions ended. Pre-pandemic lifestyle and medical conditions were derived from previous study center visits. RESULTS: Among 1850 survey participants (73-98 years; net-response 89%), 74% were at increased risk for severe COVID-19 according to medical conditions; four participants reported SARS-CoV-2 infection (0.2%). Participants reported changes in behavior: 29% refrained from medical appointments, 14% increased TV consumption, 26% reported less physical activity, but no systematic increase of smoking or alcohol consumption. When comparing during- and pre-lockdown reports of lifestyle within participant, we found the same pattern as for the reported perceived changes. Women and the more educated were more susceptible to changes. Worse QOL was perceived by 38%. CONCLUSIONS: Our data suggest that the spring 2020 lockdown did not affect the lifestyle of a majority of the mobile old aged individuals, but the substantial proportions with decreased physical activity and healthcare-seeking are markers of collateral damage.

Society for Endocrinology UK Guidance on the initial evaluation of a suspected difference or disorder of sex development (Revised 2021).

It is paramount that any child or adolescent with a suspected difference or disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD and is discussed with the regional DSD service. In most cases, the paediatric endocrinologist within this service acts as the first point of contact but involvement of the regional multidisciplinary service will also ensure prompt access to specialist psychology and nursing care. The underlying pathophysiology of DSD and the process of delineating this should be discussed with the parents and affected young person with all diagnostic tests undertaken in a timely fashion. Finally, for rare conditions such as these, it is imperative that clinical experience is shared through national and international clinical and research collaborations.

Comparison of subjectively and objectively assessed sleep problems in breast cancer patients starting neoadjuvant chemotherapy.

PURPOSE: To characterize sleep problems and to compare subjective and objective assessments in breast cancer patients starting neoadjuvant chemotherapy. METHODS: Sleep characteristics of 54 breast cancer patients starting neoadjuvant chemotherapy were analyzed. Subjective sleep characteristics were assessed with the Pittsburgh Sleep Quality Index (PSQI) and objective sleep measurements with an accelerometer (ActiGraph wGT3X-BT) worn on the wrist for 7 consecutive days. RESULTS: According to the common PSQI cut-off of 8, 10 (18.87%) of the patients were poor sleepers. ActiGraph measures did not mirror this classification as values for poor, and good sleepers did not differ significantly. Overall, Bland-Altman plots illustrated higher ActiGraph values for sleep efficiency and effective sleep time and lower values for sleep latency, compared with PSQI. For total sleep time, less disagreement between both measures was observed. Actigraphy was limited in precise identification of sleep begin and sleep latency but provided supplementary information about number and minutes of awakenings during the night. CONCLUSION: Subjective and objective measurement methods differed substantially in various parameters, with limitations in both methods. A combination of both methods might be most promising. TRIAL REGISTRATION: Clinicaltrials.gov : NCT02999074.

Knowledge, perceptions, and management of cancer-related fatigue: the patients' perspective.

PURPOSE: This study aimed to assess cancer patients' knowledge and perceptions regarding fatigue and to provide up-to-date information on the current fatigue management from the patients' perspective. METHODS: The FiX study recruited 2508 cancer patients approximately 2 years after diagnosis via a cancer registry in Germany. Participants completed a questionnaire on their knowledge and perceptions of fatigue and the management received. RESULTS: More than half of respondents (58%), especially among the elderly patients, did not feel well informed about fatigue. Overall, 41% reported having never been asked about being exhausted by their treating physician. Even fewer patients stated that general practitioners or nurses have asked if they felt exhausted. Only 13% of patients who had experienced severe fatigue had received a fatigue assessment by means of a rating scale or questionnaire-although this is recommended by existing guidelines for fatigue screening. Health care professionals seemed less likely to address fatigue with elderly as well as female patients. The most commonly reported measure against fatigue was exercise or regular physical activity (68%). However, this was mostly done on patients' own initiative. Psychological support was rarely used (13%) and only in approximately half of the cases upon the advice of a physician. Yoga, another promising intervention against fatigue, was performed by only 9% of patients. CONCLUSIONS: Our study indicates deficits in terms of knowledge, education, screening, counseling, and treatment for fatigue and highlights starting points for targeted improvements in fatigue management based on patients' needs.

Frequency of hand eczema in the elderly: Cross-sectional findings from the German AugUR study.

BACKGROUND: Hand eczema (HE) is a chronic inflammatory skin disease caused by a genetic predisposition and environmental exposures. There is a lack of population-based studies on skin diseases in the elderly. OBJECTIVES: Our aim was to estimate the frequency of HE in the elderly to determine its burden of disease in this particular population. METHODS: We analyzed data from the research platform AugUR, a study on chronic diseases in the elderly (n = 1133, ages 70-95 years, mean age 77.6, 45.1% women). Raw frequencies were estimated using self-reports on physician-diagnosed HE from a standardized personal interview. Frequencies were standardized to the Bavarian population weighted by gender and 5-year age-groups. RESULTS: In our sample 2.7% (95% confidence interval [CI] 1.6-4.3) of the paticipants reported to ever have been diagnosed with HE. Among those 57% were male. After standardization, the frequency was estimated at 2.8% (95% CI 1.9-3.9). There were no differences between male and female participants. CONCLUSIONS: Compared to other studies on lifetime frequency of HE, our estimates seem to be remarkably lower. More in-depth studies with validated diagnoses are warranted to precisely estimate the burden of HE in the elderly.