Continuous symmetry breaking in a two-dimensional Rydberg array.

Spontaneous symmetry breaking underlies much of our classification of phases of matter and their associated transitions1-3. The nature of the underlying symmetry being broken determines many of the qualitative properties of the phase; this is illustrated by the case of discrete versus continuous symmetry breaking. Indeed, in contrast to the discrete case, the breaking of a continuous symmetry leads to the emergence of gapless Goldstone modes controlling, for instance, the thermodynamic stability of the ordered phase4,5. Here, we realize a two-dimensional dipolar XY model that shows a continuous spin-rotational symmetry using a programmable Rydberg quantum simulator. We demonstrate the adiabatic preparation of correlated low-temperature states of both the XY ferromagnet and the XY antiferromagnet. In the ferromagnetic case, we characterize the presence of a long-range XY order, a feature prohibited in the absence of long-range dipolar interaction. Our exploration of the many-body physics of XY interactions complements recent works using the Rydberg-blockade mechanism to realize Ising-type interactions showing discrete spin rotation symmetry6-9.

High-resolution transcriptomic and epigenetic profiling identifies novel regulators of COPD.

Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. Considering its environmental cause, we hypothesized that COPD will be associated with altered epigenetic signaling in lung cells. We generated genome-wide DNA methylation maps at single CpG resolution of primary human lung fibroblasts (HLFs) across COPD stages. We show that the epigenetic landscape is changed early in COPD, with DNA methylation changes occurring predominantly in regulatory regions. RNA sequencing of matched fibroblasts demonstrated dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization. Data integration identified 110 candidate regulators of disease phenotypes that were linked to fibroblast repair processes using phenotypic screens. Our study provides high-resolution multi-omic maps of HLFs across COPD stages. We reveal novel transcriptomic and epigenetic signatures associated with COPD onset and progression and identify new candidate regulators involved in the pathogenesis of chronic lung diseases. The presence of various epigenetic factors among the candidates demonstrates that epigenetic regulation in COPD is an exciting research field that holds promise for novel therapeutic avenues for patients.

Quantum simulation of 2D antiferromagnets with hundreds of Rydberg atoms.

Quantum simulation using synthetic systems is a promising route to solve outstanding quantum many-body problems in regimes where other approaches, including numerical ones, fail1. Many platforms are being developed towards this goal, in particular based on trapped ions2-4, superconducting circuits5-7, neutral atoms8-11 or molecules12,13. All of these platforms face two key challenges: scaling up the ensemble size while retaining high-quality control over the parameters, and validating the outputs for these large systems. Here we use programmable arrays of individual atoms trapped in optical tweezers, with interactions controlled by laser excitation to Rydberg states11, to implement an iconic many-body problem-the antiferromagnetic two-dimensional transverse-field Ising model. We push this platform to a regime with up to 196 atoms manipulated with high fidelity and probe the antiferromagnetic order by dynamically tuning the parameters of the Hamiltonian. We illustrate the versatility of our platform by exploring various system sizes on two qualitatively different geometries-square and triangular arrays. We obtain good agreement with numerical calculations up to a computationally feasible size (approximately 100 particles). This work demonstrates that our platform can be readily used to address open questions in many-body physics.

[Effects of pulmonary rehabilitation on dysfunctional respiratory patterns in patients with uncontrolled asthma]. / Effekte der pneumologischen Rehabilitation auf dysfunktionale Atemmuster bei Patienten mit unkontrolliertem Asthma.

PURPOSE: Dysfunctional breathing patterns (DAM) are deviations from physiologic breathing patterns. DAM seem to be associated with lower asthma control. To date, it is unclear what effect inpatient rehabilitation can have on this problem. The aim of this work is to investigate the effect of pulmonary rehabilitation (PR) on DAM. METHODS: The data are based on a randomized controlled trial with a waiting control group. The intervention group (IG) received PR 4 weeks after application approval and the control group (KG) after 5 months. Dysfunctional breathing was assessed by Nijmegen-Questionnaire (NQ). Values ≥ 23 points indicate an existing DAM. Values at the end of rehabilitation (T2) and after three months (T3) were compared (analysis of covariance). Supplemental moderator analysis was performed to examine whether the effect of PR was related to baseline NQ scores. RESULTS: Significant differences in NQ score are found between IG (n=202) and KG (n=210) at T2 (AMD=10.5; 95%CI [9; 12]; d=1.4; p<0.001) and at T3 (AMD=5.8; 95%CI [4.3; 7.3]; d=0.8; p<0.001). There is an interaction effect between the difference in NQ score between the groups at T2 and baseline at T0 (b=5.6; 95%CI [2.2; 11.9]; p<0.001). At T3, this interaction effect was no longer detectable (b=4.5; 95%CI [-3.1; 14.1]; p=807). CONCLUSION: Inpatient, multimodality, and interdisciplinary PR is associated with significant and clinically relevant improvement in DAM both at discharge and 3 months later. In the short term, patients with existing DAM benefit more from PR than patients without DAM.

[The Blaufeuer measure for employees with mental stress and simultaneous workplace problems-Is the target group being reached?] / Die Maßnahme Blaufeuer für Erwerbstätige mit psychischer Belastung und gleichzeitiger Arbeitsplatzproblematik ­ Wird die Zielgruppe erreicht?

BACKGROUND: Employees with mental burden and simultaneous workplace problems have an increased risk of chronification and disability pension. To support this group of people, the German Pension Insurance (Deutsche Rentenversicherung Bund) developed the Systemic Integration Management for People with Mental Impairments (SEMpsych) project as part of the rehapro federal program. The Blaufeuer counselling service was implemented in three model regions (Berlin, Cologne, and Nuremberg). The measure usually comprises up to 12 counselling sessions in 12 months. This article describes the characteristics of the participants and examines whether they belong to the intended target group. METHOD: During September 2020 and June 2022, the participants completed a questionnaire between the first and second counselling sessions. Socio-demographic-, clinical- and work-related variables were assessed. The data were analysed using descriptive statistics and 95% confidence intervals. RESULTS: Data from n = 482 participants (66.4% female; MAge = 45.2 years (±10.2 years); 64.1% working full-time; 49.8% currently on sick leave) were included. The participants have high psychological impairments (e.g. PHQ-9: M = 14.6 (±5.4)) and low subjective work ability (e.g. WAS: M = 3.2 (±2.6)). Most participants report overload at work and problems with superiors. DISCUSSION: Participants exhibit mental burden values that correspond to those of patients at the beginning of outpatient psychotherapy or the first contact in an inpatient psychiatric clinic. Blaufeuer addresses a highly stressed group of people who have not yet received adequate treatment. Further studies on process and outcome evaluation will follow.

Quantum Optics Measurement Scheme for Quantum Geometry and Topological Invariants.

We show how a quantum optical measurement scheme based on heterodyne detection can be used to explore geometrical and topological properties of condensed matter systems. Considering a 2D material placed in a cavity with a coupling to the environment, we compute correlation functions of the photons exiting the cavity and relate them to the hybrid light-matter state within the cavity. Different polarizations of the intracavity field give access to all components of the quantum geometric tensor on contours in the Brillouin zone defined by the transition energy. Combining recent results based on the metric-curvature correspondence with the measured quantum metric allows us to characterize the topological phase of the material. Moreover, in systems where S_{z} is a good quantum number, the procedure also allows us to extract the spin Chern number. As an interesting application, we consider a minimal model for twisted bilayer graphene at the magic angle, and discuss the feasibility of extracting the Euler number.

[Patient-Reported Outcomes (PROs) 3 and 6 Months After Pulmonary Rehabilitation Following COVID-19]. / Patient-Reported Outcomes (PROs) 3 und 6 Monate nach pneumologischer Post-COVID-Rehabilitation.

PURPOSE: If COVID-19 disease sequelae also (co-)affect the respiratory organs, national and international guidelines recommend pulmonary rehabilitation (PR). So far, however, no studies are available from Germany on the course after PR, nor on possible course differences between the two Long COVID subgroups "Ongoing symptomatic COVID-19" and "Post-COVID-19 syndrome" (PCS). METHODS: In a prospective observational study, patient-reported outcomes (PROs) regarding exertional dyspnea, quality of life, pain, fatigue, depression, and anxiety were assessed at the beginning of PR (T1), end of PR (T2), and after 3 (T3) and 6 months (T4). Statistical analyses were performed using latent difference models. RESULTS: There were 224 rehabilitation patients (MAge=54.4; SDAge=10.4; 42.0% female) included in the study. During PR, all PROs improved significantly. After PR, improvements either persisted with large pre-post effect sizes (exertional dyspnea, quality of life), decreased slightly to small pre-post effect sizes (depression, fatigue), or decreased to baseline levels (anxiety, pain). PCS patients had greater burdens in depression, fatigue, and pain at baseline, but did not differ in trajectories. Indicators of the severity of the preceding acute phase (oxygen therapy, ICU treatment, ventilation) were associated with higher burdens at T0 in depression, fatigue, and pain, but not with the courses during and after PR. In contrast, female patients showed higher burdens in both depression and fatigue at T1 and higher pre-post effects than male patients. CONCLUSION: The fact that improvements in PROs occurred in both subgroups only during PR, but not during the follow-up period suggests that the changes are not due to the natural healing process but at least partly due to PR. Moreover, the results suggest that both patient groups may benefit from PR. Persisting improvements in exertional dyspnea and quality of life and, to a reduced extent, in depression and fatigue until 6 months after PR, but not in pain and anxiety warrant study of additional multimodal interventions that may be needed to maintain these effects.

Decreased mental health, quality of life, and utilization of professional help in cancer patients with unexpressed needs: A longitudinal analysis.

BACKGROUND: Cancer patients' mental health and quality of life can be improved through professional support according to their needs. In previous analyses of the UNSAID study, we showed that a relevant proportion of cancer patients did not express their needs during the admission interview of inpatient rehabilitation. We now examine trajectories of mental health, quality of life, and utilization of professional help in cancer patients with unexpressed needs. METHODS: We enrolled 449 patients with breast, prostate, and colon cancer at beginning (T0) and end (T1) of a 3-week inpatient rehabilitation and 3 (T2) and 9 (T3) months after discharge. We explored depression (PHQ-2), anxiety (GAD-2), emotional functioning (EORTC QLQ-C30), fear of progression (FoP-Q-SF), and global quality of life (EORTC QLQ-C30) using structuring equation models. Furthermore, we evaluated self-reports about expressing needs and utilization of professional help at follow-up. RESULTS: Patients with unexpressed needs (24.3%, n = 107) showed decreased mental health compared to other patients (e.g., depression: d T0 = 0.32, d T1-T3 = 0.39). They showed a significant decline in global quality of life at discharge and follow-up (d = 0.28). Furthermore, they had a higher need for support (Cramer's V T2 = 0.10, T3 = 0.15), talked less about their needs (Cramer's V T2 = 0.18), and made less use of different health care services at follow-up. CONCLUSION: Unexpressed needs in cancer patients may be a risk factor for decreased mental health, quality of life, and non-utilization of professional help in the long term. Further research should clarify causal relationships and focus on this specific group of patients to improve cancer care.

Experiences of family caregivers 3-months after stroke: results of the prospective trans-regional network for stroke intervention with telemedicine registry (TRANSIT-Stroke).

BACKGROUND: Long-term support of stroke patients living at home is often delivered by family caregivers (FC). We identified characteristics of stroke patients being associated with receiving care by a FC 3-months (3 M) after stroke, assessed positive and negative experiences and individual burden of FC caring for stroke patients and determined factors associated with caregiving experiences and burden of FC 3 M after stroke. METHODS: Data were collected within TRANSIT-Stroke, a regional telemedical stroke-network comprising 12 hospitals in Germany. Patients with stroke/TIA providing informed consent were followed up 3 M after the index event. The postal patient-questionnaire was accompanied by an anonymous questionnaire for FC comprising information on positive and negative experiences of FC as well as on burden of caregiving operationalized by the Caregiver Reaction Assessment and a self-rated burden-scale, respectively. Multivariable logistic and linear regression analyses were performed. RESULTS: Between 01/2016 and 06/2019, 3532 patients provided baseline and 3 M-follow-up- data and 1044 FC responded to questionnaires regarding positive and negative caregiving experiences and caregiving burden. 74.4% of FC were older than 55 years, 70.1% were women and 67.5% were spouses. Older age, diabetes and lower Barthel-Index in patients were significantly associated with a higher probability of receiving care by a FC at 3 M. Positive experiences of FC comprised the importance (81.5%) and the privilege (70.0%) of caring for their relative; negative experiences of FC included financial difficulties associated with caregiving (20.4%). Median overall self-rated burden was 30 (IQR: 0-50; range 0-100). Older age of stroke patients was associated with a lower caregiver burden, whereas younger age of FC led to higher burden. More than half of the stroke patients in whom a FC questionnaire was completed did self-report that they are not being cared by a FC. This stroke patient group tended to be younger, more often male with less severe stroke and less comorbidities who lived more often with a partner. CONCLUSIONS: The majority of caregivers wanted to care for their relatives but experienced burden at the same time. Elderly patients, patients with a lower Barthel Index at discharge and diabetes are at higher risk of needing care by a family caregiver. TRIAL REGISTRATION: The study was registered at "German Clinical Trial Register": DRKS00011696. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011696.

Dynamically Induced Exceptional Phases in Quenched Interacting Semimetals.

We report on the dynamical formation of exceptional degeneracies in basic correlation functions of nonintegrable one- and two-dimensional systems quenched to the vicinity of a critical point. Remarkably, fine-tuned semimetallic points in the phase diagram of the considered systems are thereby promoted to topologically robust non-Hermitian (NH) nodal phases emerging in the coherent time evolution of a dynamically equilibrating system. Using nonequilibrium Green's function methods within the conserving second Born approximation, we predict observable signatures of these NH nodal phases both in equilibrated spectral functions and in the nonequilibrium dynamics of momentum distribution functions.

Recapitulating idiopathic pulmonary fibrosis related alveolar epithelial dysfunction in a human iPSC-derived air-liquid interface model.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown cause that is characterized by progressive fibrotic lung remodeling. An abnormal emergence of airway epithelial-like cells within the alveolar compartments of the lung, herein termed bronchiolization, is often observed in IPF. However, the origin of this dysfunctional distal lung epithelium remains unknown due to a lack of suitable human model systems. In this study, we established a human induced pluripotent stem cell (iPSC)-derived air-liquid interface (ALI) model of alveolar epithelial type II (ATII)-like cell differentiation that allows us to investigate alveolar epithelial progenitor cell differentiation in vitro. We treated this system with an IPF-relevant cocktail (IPF-RC) to mimic the pro-fibrotic cytokine milieu present in IPF lungs. Stimulation with IPF-RC during differentiation increases secretion of IPF biomarkers and RNA sequencing (RNA-seq) of these cultures reveals significant overlap with human IPF patient data. IPF-RC treatment further impairs ATII differentiation by driving a shift toward an airway epithelial-like expression signature, providing evidence that a pro-fibrotic cytokine environment can influence the proximo-distal differentiation pattern of human lung epithelial cells. In conclusion, we show for the first time, the establishment of a human model system that recapitulates aspects of IPF-associated bronchiolization of the lung epithelium in vitro.

Cross-sectional study on patients' understanding and views of the informed consent procedure of a secondary stroke prevention trial.

BACKGROUND AND PURPOSE: Improving understanding of study contents and procedures might enhance recruitment into studies and retention during follow-up. However, data in stroke patients on understanding of the informed consent (IC) procedure are sparse. METHODS: We conducted a cross-sectional study among ischemic stroke patients taking part in the IC procedure of an ongoing cluster-randomized secondary prevention trial. All aspects of the IC procedure were assessed in an interview using a standardized 20-item questionnaire. Responses were collected within 72 h after the IC procedure and analyzed quantitatively and qualitatively. Participants were also asked their main reasons for participation. RESULTS: A total of 146 stroke patients (65 ± 12 years old, 38% female) were enrolled. On average, patients recalled 66.4% (95% confidence interval = 65.2%-67.5%) of the content of the IC procedure. Most patients understood that participation was voluntary (99.3%) and that they had the right to withdraw consent (97.1%); 79.1% of the patients recalled the study duration and 56.1% the goal. Only 40.3% could clearly state a benefit of participation, and 28.8% knew their group allocation. Younger age, higher graduation, and allocation to the intervention group were associated with better understanding. Of all patients, 53% exclusively stated a personal and 22% an altruistic reason for participation. CONCLUSIONS: Whereas understanding of patient rights was high, many patients were unable to recall other important aspects of study content and procedures. Increased attention to older and less educated patients may help to enhance understanding in this patient population. Actual recruitment and retention benefit of an improved IC procedure remains to be tested in a randomized trial.

Cost-Effectiveness of Pulmonary Rehabilitation in Patients With Bronchial Asthma: An Analysis of the EPRA Randomized Controlled Trial.

OBJECTIVES: At 3 months after the intervention, this study evaluates the cost-effectiveness of a 3-week inpatient pulmonary rehabilitation (PR) in patients with asthma compared with usual care alongside the single-center randomized controlled trial-Effectiveness of Pulmonary Rehabilitation in Patients With Asthma. METHODS: Adopting a societal perspective, direct medical costs and productivity loss were assessed using the Questionnaire for Health-Related Resource Use-Lung, a modification of the FIM in an Elderly Population. The effect side was operationalized as minimal important differences (MIDs) of the Asthma Control Test (ACT) and the Asthma Quality of Life Questionnaire (AQLQ) and through quality-adjusted life-years (QALYs) gained. Adjusted mean differences in costs (gamma-distributed model) and each effect parameter (Gaussian-distributed model) were simultaneously calculated within 1000 bootstrap replications to determine incremental cost-effectiveness ratios (ICERs) and to subsequently delineate cost-effectiveness acceptability curves. RESULTS: PR caused mean costs per capita of €3544. Three months after PR, we observed higher mean costs (Δ€3673; 95% confidence interval (CI) €2854-€4783) and improved mean effects (ACT Δ1.59 MIDs, 95% CI 1.37-1.81; AQLQ Δ1.76 MIDs, 95% CI 1.46-2.08; QALYs gained Δ0.01, 95% CI 0.01-0.02) in the intervention group. The ICER was €2278 (95% CI €1653-€3181) per ACT-MID, €1983 (95% CI €1430-€2830) per AQLQ-MID, and €312 401 (95% CI €209 206-€504 562) per QALY gained. CONCLUSIONS: Contrasting of PR expenditures with ICERs suggests that the intervention, which achieves clinically relevant changes in asthma-relevant parameters, has a high probability to be already cost-effective in the short term. However, in terms of QALYs, extended follow-up periods are likely required to comprehensively judge the added value of a one-time initial investment in PR.

Unexpressed psychosocial needs in cancer patients at the beginning of inpatient rehabilitation: a qualitative analysis.

OBJECTIVE: Cancer patients often need professional help to alleviate their psychosocial distress. However, not all patients express their needs. In this study, we explored possible barriers to patients' expressing needs, contents of needs difficult to express, and conditions facilitating expressing needs. METHODS: We conducted semi-structured interviews with 29 oncological inpatient rehabilitation patients, 7 members of self-help groups, and 10 health professionals. We analyzed data with structuring content analysis. RESULTS: Fear of stigmatization and difficulties in the physician-patient-relationship were the most critical expression barriers reported. Sexuality deemed to be one of the most challenging themes for patients. Changes in the physician's behavior and sufficient resources were mentioned as the main facilitating conditions. Our results indicate a wide diversity within the barriers and topics, but a general consistency between patients and health professionals. CONCLUSION: This study provides evidence for the existence of a variety of barriers to cancer patients' expressing their needs. PRACTICE IMPLICATIONS: Health professionals should be aware of the different possible expression barriers to facilitate patient communication.

[The Impact of Health literacy on Health Outcomes in Cancer Patients Attending Inpatient Rehabilitation]. / Health literacy bei onkologischen Rehabilitanden und deren Relevanz für den subjektiven Rehabilitationsverlauf.

PURPOSE: Health literacy (HL) entails people's knowledge, motivation, and competences to access, understand, appraise, and apply health information. Lower HL is associated with poorer psychosocial health. However, there are no studies so far evaluating the impact of HL within oncological rehabilitation in Germany. Therefore, we explored HL in cancer patients in inpatient rehabilitation and its association with rehabilitation outcome. METHODS: We conducted a secondary data analysis of a questionnaire survey with 449 cancer patients (breast, prostate, and colon cancer) at 3 measurement occasions (end of rehabilitation, 3- and 9 months follow-up). We assessed HL with the European Health Literacy Survey (HLS-EU-Q6). We evaluated rehabilitation outcomes by measuring fear of progression (FoP-Q-SF), need for psychosocial support, physical functioning and global quality of life (EORTC-QLQ-C30), and the work ability index (WAI). To explore the impact of HL on rehabilitation outcome, we used multiple regression analyses controlling for other factors. RESULTS: At the end of rehabilitation, up to 56% of the patients reported difficulties in HL dimensions. Better HL was significantly associated with lower fear of progression (ß=- 0,33) and need for psychosocial support (OR=0,28), higher physical functioning (ß=0,22), higher global health status (ß=0,23), and higher work ability (ß=0,21). Longitudinal analyses showed that improvement in HL was significantly accompanied by improvements in all rehabilitation outcomes (0,18 ≤ ß ≤ 0,24). CONCLUSION: HL is a relevant factor within cancer rehabilitation. More than half of the patients showed problematic HL at discharge. Furthermore, HL is a predictor of psychosocial, somatic, and work-related rehabilitation outcomes up to 9 months. Effective strategies to support patients in dealing with health information are essential and should be promoted within rehabilitation.

Towards a better understanding of physical activity in people with COPD: predicting physical activity after pulmonary rehabilitation using an integrative competence model.

The integrative Physical Activity-related Health Competence (PAHCO) model specifies competences (movement competence, control competence, and self-regulation competence) that enable people to lead a physically active lifestyle. This longitudinal study analyses the predictive quality of a multidimensional PAHCO assessment for levels of physical activity (PA) and their relevance for quality of life in COPD patients after pulmonary rehabilitation. At the end of an inpatient pulmonary rehabilitation (T2), 350 COPD patients participating in the Stay Active after Rehabilitation (STAR) study underwent assessments, including a six-factor measurement of PAHCO. PA (triaxial accelerometry) and quality of life (Saint George's Respiratory Questionnaire) were recorded 6 weeks (T3) and 6 months (T4) after rehabilitation. Structural equation modelling (SEM) was used to regress the PAHCO assessment on PA, which should, in turn, influence quality of life. In univariable analysis, five and six factors of the PAHCO model were related to PA and quality of life, respectively. Multivariate modelling showed that the predictive analyses for the PA level were dominated by the 6-minute walking test representing movement competence (0.562 ≤ |ß| ≤ 0.599). Affect regulation as an indicator of control competence co-predicted quality of life at T3 and levels of PA at T4. The PA level was, in turn, significantly associated with patients' quality of life (0.306 ≤ |ß| ≤ 0.388). The integrative PAHCO model may be used as a theoretical framework for predicting PA in COPD patients following pulmonary rehabilitation. The results improve our understanding of PA behaviour in COPD patients and bear implications for person-oriented PA promotion.

Prevalence and predictors of cancer patients' unexpressed needs in the admission interview of inpatient rehabilitation.

OBJECTIVE: The admission interview in oncological inpatient rehabilitation might be a good opportunity to identify cancer patients' needs present after acute treatment. However, a relevant number of patients may not express their needs. In this study, we examined (a) the proportion of cancer patients with unexpressed needs, (b) topics of unexpressed needs and reasons for not expressing needs, (c) correlations of not expressing needs with several patient characteristics, and (d) predictors of not expressing needs. METHODS: We enrolled 449 patients with breast, prostate, and colon cancer at beginning and end of inpatient rehabilitation. We obtained self-reports about unexpressed needs and health-related variables (quality of life, depression, anxiety, adjustment disorder, and health literacy). We estimated frequencies and conducted correlation and ordinal logistic regression analyses. RESULTS: A quarter of patients stated they had "rather not" or "not at all" expressed all relevant needs. Patients mostly omitted fear of cancer recurrence. Most frequent reasons for not expressing needs were being focused on physical consequences of cancer, concerns emerging only later, and not knowing about the possibility of talking about distress. Not expressing needs was associated with several health-related outcomes, for example, emotional functioning, adjustment disorder, fear of progression, and health literacy. Depression measured at the beginning of rehabilitation showed only small correlations and is therefore not sufficient to identify patients with unexpressed needs. CONCLUSIONS: A relevant proportion of cancer patients reported unexpressed needs in the admission interview. This was associated with decreased mental health. Therefore, it seems necessary to support patients in expressing needs.

How does the EQ-5D-5L perform in asthma patients compared with an asthma-specific quality of life questionnaire?

BACKGROUND: Asthma patients experience impairments in health-related quality of life (HRQL). Interventions are available to improve HRQL. EQ-5D-5L is a common generic tool used to evaluate health interventions. However, there is debate over whether the use of this measure is adequate in asthma patients. METHODS: We used data from 371 asthma patients participating in a pulmonary rehabilitation (PR) program from the EPRA randomized controlled trial. We used four time points: T0 randomization, T1 start PR, T2 end PR, T3 3 months follow-up. We calculated floor and ceiling effects, intra-class correlation (ICC), Cohen's d, and regression analysis to measure the sensitivity to changes of EQ-5D-5 L (EQ-5D index and Visual Analog Scale (VAS)) and the disease-specific Asthma Quality of Life Questionnaire (AQLQ). Furthermore, we estimated the minimally important difference (MID). Based on the Asthma Control Test (ACT) scores, we defined three groups: 1. ACT-A (ACT> 19) controlled asthma, 2. ACT-B (14 < ACT≤19) not well-controlled asthma, and 3. ACT-C (ACT≤14) very poorly controlled asthma. RESULTS: Only the EQ-5D index showed ceiling effects at T2 and T3 (32%). ICC (between T0 and T1) was moderate or good for all measures. Cohen's d at T2 and T3 was better at differentiating between ACT-A and ACT-B than between ACT-B and ACT-C. The EQ-5D index showed moderate effect sizes (0.63-0.75), while AQLQ showed large effect sizes (0.74-1,48). VAS was responsive to pronounced positive and negative ACT changes in every period, and AQLQ mostly to the positive changes, whereas the EQ-5D index was less responsive. We estimated a MID of 0.08 for the EQ-5D index, 12.3 for VAS, and 0.65 for AQLQ. CONCLUSION: All presented HRQL tools had good discriminatory power and good reliability. However, EQ-5D-5 L did not react very sensitively to small changes in asthma control. Therefore, we would suggest using supplementary measures in addition to EQ-5D-5 L to evaluate asthma-specific interventions more comprehensively. TRIAL REGISTRATION: German Clinical Trial Register, DRKS00007740 (date of registration: 05/15/2015), https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00007740. The registration took place prospectively.

[Postoperative mobilization after total hip arthroplasty : Measured by Fitbit activity trackers]. / Die postoperative Mobilisation nach Hüfttotalendoprothesenimplantation : Messung mittels Fitbit-Tracker.

BACKGROUND: Patients are becoming increasingly more independent and self-determined, in addition to having shorter post-operative hospitalization. This is why it is more important than ever to actively involve patients in the follow-up treatment. The question arises as to whether post-operative rehabilitation can be improved with modern devices. METHODS: As part of a prospective study, the post-operative mobilization was recorded and analyzed by Fitbit®-activity-trackers between 05/2016 and 08/2017 in 100 patients who received a THA. 50 men (Ø 70.6y) and 50 women (Ø 71.1y) were included. Furthermore, the patients were interviewed about their acceptance of the Fitbit®-wristband. RESULTS: The average hospital stay was 7.98 days (SD ± 1.76). The number of steps on the first post-operative day was 712 (SD ± 617). On average (during total hospitalization), 1528 (SD ± 1076) steps were completed daily. One day before discharge, the average number of steps was 2165 (SD ± 1570) on that particular day. There were no gender differences in age and pre-operative Harris hip scores (♂55.3 vs. ♀53.9). Also, there were no statistically significant differences in the number of steps on the first postoperative day (♂745 vs. ♀678). A statistically significant result can be found in the number of steps prior to discharge: on this day, the men took 2483 and the women 1846 steps (p = 0.04). 42% of our patients own a modern smartphone and are able to operate software applications. 52% of the patients found the activity tracker to be motivating, 65% were open to new technologies (e.g. activity trackers) in the hospital. 14% did not check at all or only queried their wristband data once a day, 65% queried 2-4 times/day, and 21% retrieved the data >5 times/day. DISCUSSION: On average, 1528 steps were completed daily. In a comparison of the men and women, the men were only able to demonstrate significantly more steps than the women on the day prior to discharge. The men had significantly shorter hospital stays than the women. The younger the patients, the more mobile they were. A majority of patients are familiar with and/or interested in new technologies. This interest and curiosity should be consciously used for integration in the post-operative treatment.

Human lung fibroblast-to-myofibroblast transformation is not driven by an LDH5-dependent metabolic shift towards aerobic glycolysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by aberrant fibroblast activation and progressive fibrotic remodelling of the lungs. Though the exact pathophysiological mechanisms of IPF remain unknown, TGF-ß1 is thought to act as a main driver of the disease by mediating fibroblast-to-myofibroblast transformation (FMT). Recent reports have indicated that a metabolic shift towards aerobic glycolysis takes place during FMT and that metabolic shifts can directly influence aberrant cell function. This has led to the hypothesis that inhibition of lactate dehydrogenase 5 (LDH5), an enzyme responsible for converting pyruvate into lactate, could constitute a therapeutic concept for IPF. METHODS: In this study, we investigated the potential link between aerobic glycolysis and FMT using a potent LDH5 inhibitor (Compound 408, Genentech). Seahorse analysis was performed to determine the effect of Compound 408 on TGF-ß1-driven glycolysis in WI-38 fibroblasts. TGF-ß1-mediated FMT was measured by quantifying α-smooth muscle actin (α-SMA) and fibronectin in primary human lung fibroblasts following treatment with Compound 408. Lactate and pyruvate levels in the cell culture supernatant were assessed by LC-MS/MS. In addition to pharmacological LDH5 inhibition, the effect of siRNA-mediated knockdown of LDHA and LDHB on FMT was examined. RESULTS: We show that treatment of lung fibroblasts with Compound 408 efficiently inhibits LDH5 and attenuates the TGF-ß1-mediated metabolic shift towards aerobic glycolysis. Additionally, we demonstrate that LDH5 inhibition has no significant effect on TGF-ß1-mediated FMT in primary human lung fibroblasts by analysing α-SMA fibre formation and fibronectin expression. CONCLUSIONS: Our data strongly suggest that while LDH5 inhibition can prevent metabolic shifts in fibroblasts, it has no influence on FMT and therefore glycolytic dysregulation is unlikely to be the sole driver of FMT.