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Persistent symptoms and clinical findings in adults with post-acute sequelae of COVID-19/post-COVID-19 syndrome in the second year after acute infection: a population-based, nested case-control study
No full textBackgroundSelf-reported health problems following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are common and often include relatively non-specific complaints such as fatigue, exertional dyspnoea, concentration or memory disturbance and sleep problems. The long-term prognosis of such post-acute sequelae of COVID-19/post-COVID-19 syndrome (PCS) is unknown, and data finding and correlating organ dysfunction and pathology with self-reported symptoms in patients with non-recovery from PCS is scarce. We wanted to describe clinical characteristics and diagnostic findings among patients with PCS persisting for >1 year and assessed risk factors for PCS persistence versus improvement.Methods and findingsThis nested population-based case-control study included subjects with PCS aged 18–65 years with (n = 982) and age- and sex-matched control subjects without PCS (n = 576) according to an earlier population-based questionnaire study (6–12 months after acute infection, phase 1) consenting to provide follow-up information and to undergo comprehensive outpatient assessment, including neurocognitive, cardiopulmonary exercise, and laboratory testing in four university health centres in southwestern Germany (phase 2, another 8.5 months [median, range 3–14 months] after phase 1). The mean age of the participants was 48 years, and 65% were female. At phase 2, 67.6% of the patients with PCS at phase 1 developed persistent PCS, whereas 78.5% of the recovered participants remained free of health problems related to PCS. Improvement among patients with earlier PCS was associated with mild acute index infection, previous full-time employment, educational status, and no specialist consultation and not attending a rehabilitation programme. The development of new symptoms related to PCS among participants initially recovered was associated with an intercurrent secondary SARS-CoV-2 infection and educational status. Patients with persistent PCS were less frequently never smokers (61.2% versus 75.7%), more often obese (30.2% versus 12.4%) with higher mean values for body mass index (BMI) and body fat, and had lower educational status (university entrance qualification 38.7% versus 61.5%) than participants with continued recovery. Fatigue/exhaustion, neurocognitive disturbance, chest symptoms/breathlessness and anxiety/depression/sleep problems remained the predominant symptom clusters. Exercise intolerance with post-exertional malaise (PEM) for >14 h and symptoms compatible with myalgic encephalomyelitis/chronic fatigue syndrome were reported by 35.6% and 11.6% of participants with persistent PCS patients, respectively. In analyses adjusted for sex-age class combinations, study centre and university entrance qualification, significant differences between participants with persistent PCS versus those with continued recovery were observed for performance in three different neurocognitive tests, scores for perceived stress, subjective cognitive disturbances, dysautonomia, depression and anxiety, sleep quality, fatigue and quality of life. In persistent PCS, handgrip strength (40.2 [95% confidence interval (CI) [39.4, 41.1]] versus 42.5 [95% CI [41.5, 43.6]] kg), maximal oxygen consumption (27.9 [95% CI [27.3, 28.4]] versus 31.0 [95% CI [30.3, 31.6]] ml/min/kg body weight) and ventilatory efficiency (minute ventilation/carbon dioxide production slope, 28.8 [95% CI [28.3, 29.2]] versus 27.1 [95% CI [26.6, 27.7]]) were significantly reduced relative to the control group of participants with continued recovery after adjustment for sex-age class combinations, study centre, education, BMI, smoking status and use of beta blocking agents. There were no differences in measures of systolic and diastolic cardiac function at rest, in the level of N-terminal brain natriuretic peptide blood levels or other laboratory measurements (including complement activity, markers of Epstein–Barr virus [EBV] reactivation, inflammatory and coagulation markers, serum levels of cortisol, adrenocorticotropic hormone and dehydroepiandrosterone sulfate). Screening for viral persistence (PCR in stool samples and SARS-CoV-2 spike antigen levels in plasma) in a subgroup of the patients with persistent PCS was negative. Sensitivity analyses (pre-existing illness/comorbidity, obesity, medical care of the index acute infection) revealed similar findings. Patients with persistent PCS and PEM reported more pain symptoms and had worse results in almost all tests. A limitation was that we had no objective information on exercise capacity and cognition before acute infection. In addition, we did not include patients unable to attend the outpatient clinic for whatever reason including severe illness, immobility or social deprivation or exclusion.ConclusionsIn this study, we observed that the majority of working age patients with PCS did not recover in the second year of their illness. Patterns of reported symptoms remained essentially similar, non-specific and dominated by fatigue, exercise intolerance and cognitive complaints. Despite objective signs of cognitive deficits and reduced exercise capacity, there was no major pathology in laboratory investigations, and our findings do not support viral persistence, EBV reactivation, adrenal insufficiency or increased complement turnover as pathophysiologically relevant for persistent PCS. A history of PEM was associated with more severe symptoms and more objective signs of disease and might help stratify cases for disease severity
Spatially resolved transcriptomics and graph-based deep learning improve accuracy of routine CNS tumor diagnostics
No full textThe diagnostic landscape of brain tumors integrates comprehensive molecular markers alongside traditional histopathological evaluation. DNA methylation and next-generation sequencing (NGS) have become a cornerstone in central nervous system (CNS) tumor classification. A limiting requirement for NGS and methylation profiling is sufficient DNA quality and quantity, which restrict its feasibility. Here we demonstrate NePSTA (neuropathology spatial transcriptomic analysis) for comprehensive morphological and molecular neuropathological diagnostics from single 5-µm tissue sections. NePSTA uses spatial transcriptomics with graph neural networks for automated histological and molecular evaluations. Trained and evaluated across 130 participants with CNS malignancies and healthy donors across four medical centers, NePSTA predicts tissue histology and methylation-based subclasses with high accuracy. We demonstrate the ability to reconstruct immunohistochemistry and genotype profiling on tissue with minimal requirements, inadequate for conventional molecular diagnostics, demonstrating the potential to enhance tumor subtype identification with implications for fast and precise diagnostic workup
Diurnal timing of physical activity in relation to obesity and diabetes in the German National Cohort (NAKO)
No full textBackgroundPhysical activity supports weight regulation and metabolic health, but its timing in relation to obesity and diabetes remains unclear. We aimed to assess the diurnal timing of physical activity and its association with obesity and diabetes.MethodsWe cross-sectionally analyzed hip-worn accelerometry data from 61,116 participants aged 20–75 in the German National Cohort between 2015 and 2019. We divided physical activity into sex- and age-standardized quartiles of total morning (06:00–11:59), afternoon (12:00–17:59), evening (18:00–23:59), and nighttime (00:00–06:00) physical activity. Using multivariable logistic regression, we estimated associations of physical activity timing with obesity (BMI ≥ 30.0 kg/m2) and diabetes (self-reported or HbA1c ≥ 6.5%). We accounted for sex, age, study region, education, employment, risky alcohol use, smoking, night shift work, and sleep duration.ResultsHigh afternoon (top vs. bottom quartile, OR: 0.36, 95% CI: 0.33–0.38) and evening physical activity (OR: 0.45, 95% CI: 0.42–0.48) showed lower obesity odds than high morning activity (OR: 0.71, 95% CI: 0.66–0.76), whereas nighttime activity increased obesity odds (OR: 1.58, 95% CI: 1.48–1.68). Associations were similar for diabetes, with the lowest odds for afternoon (OR: 0.47, 95% CI: 0.42–0.53), followed by evening (OR: 0.56, 95% CI: 0.50–0.62) and morning activity (OR: 0.80, 95% CI: 0.71–0.89), and higher odds for nighttime activity (OR: 1.43, 95% CI: 1.29–1.58). Findings were not modified by employment status, night shift work, and sleep duration.ConclusionsOur cross-sectional findings require longitudinal corroboration but suggest afternoon and evening activity provide greater metabolic health benefits than morning activity, while nighttime activity is discouraged
Proof of concept of personalized modular psychotherapy in depressive adults : efficacy and therapists′ perspective
No full textDas Prinzip der Modularität ist ein vielversprechender Ansatz, um Psychotherapie zu personalisieren. Bislang gibt es jedoch keine Evidenz, wie modulare Psychotherapie („modular-based psychotherapy“, MoBa) anhand eines systematischen Behandlungsalgorithmus für erwachsene Patient:innen umgesetzt werden kann. Deshalb wurden in dieser Proof-of-Concept-Studie 70 Patient:innen mit Depression, komorbiden psychischen Störungen und einer Vorgeschichte von Kindesmisshandlung randomisiert einer MoBa oder einer herkömmlichen Kognitiven Verhaltenstherapie (KVT) zugeordnet. In die MoBa-Intervention wurden neben KVT-Elementen anhand eines systematischen Behandlungsalgorithmus zusätzlich ein bis 3 weitere Therapiemodule integriert. Diese adressieren transdiagnostische dysfunktionale Mechanismen, die psychischen Störungen nach Kindesmisshandlungen häufig zugrunde liegen und für deren Aufrechterhaltung essenziell sind, und bestehen aus Elementen des Cognitive Behavioral Analysis System of Psychotherapy (CBASP), der Mentalisierungsbasierten Therapie (MBT) oder der Achtsamkeitsbasierten Kognitiven Therapie (MBCT). Im Folgenden werden die Ergebnisse hinsichtlich Durchführbarkeit, Akzeptanz und initialer Wirksamkeit nach 20 Sitzungen ambulanter Psychotherapie dargestellt sowie die Implikationen für Forschung und Praxis diskutiert.The principle of modularity is a promising approach to personalize psychotherapy; however, to date there is no evidence on how modular-based psychotherapy (MoBa) can be implemented using a systematic treatment algorithm for adult patients. Therefore, in this proof of concept study 70 patients with depression, comorbid mental disorders and a history of child maltreatment were randomly assigned to MoBa or conventional cognitive behavioral therapy (CBT). In the MoBa intervention, 1–3 further therapy modules were integrated in addition to CBT elements using a systematic treatment algorithm. These address transdiagnostic dysfunctional mechanisms that often underlie mental disorders after child maltreatment and are essential for their maintenance and consist of elements from the cognitive behavioral analysis system of psychotherapy (CBASP), mentalization-based therapy (MBT) or mindfulness-based cognitive therapy (MBCT). In this article the results regarding feasibility, acceptance and initial efficacy after 20 sessions of outpatient psychotherapy are presented and the implications for research and practice are discussed
How sustainable are hospital menus in the United Kingdom? Identifying untapped potential based on a novel scoring system for plant-based provisions
No full textBackgroundAdopting plant-forward diets is essential for achieving climate targets. As the second-largest provider of public sector meals in the UK, the National Health Service (NHS) can significantly reduce its environmental impact by transitioning to plant-forward menus, contributing to its goal of being a net-zero healthcare service by 2045. This study evaluates the extent to which NHS hospitals currently align with sustainable practices by assessing the plant-forward nature of in-patient menus.MethodsGreen Plans from 40 hospital trusts were analysed to assess commitment to plant-forward, lower-emission menus. Freedom of Information requests were sent to 50 NHS trusts, and 36 menus from the spring/summer season of 2024 were analysed. A novel scoring system was developed to assess the hospital menus, with subscores reflecting the availability of plant-based meals, ruminant-meat meals, and menu strategies to encourage plant-forward choices.ResultsGreen Plans showed limited commitment to increasing plant-based food options. Hospital menus scored poorly overall (average score of 20/100, range: 9–38). The lowest subscores were observed in the provision of fully plant-based meals and nudging techniques. The provision of ruminant meat varied (subscore range: 0–100) and all hospitals included processed meat on their menu. Hospitals with outsourced catering scored higher than those with in-house catering.ConclusionDespite national recommendations to shift towards plant-forward diets, NHS hospitals currently show little commitment and provide limited offerings in this regard. The novel scoring system offers a practical framework for monitoring progress and guiding hospitals towards environmentally sustainable, plant-forward menus
Bakry-Émery curvature sharpness and curvature flow in finite weighted graphs: theory
No full textIn this sequence of two papers, we introduce a curvature flow on (mixed) weighted graphs which is based on the Bakry-Émery calculus. The flow is described via a time-continuous evolution through the weighting schemes. By adapting this flow to preserve the Markovian property, its limits turn out to be curvature sharp. Our aim is to present the flow in the most general case of not necessarily reversible random walks allowing laziness, including vanishing transition probabilities along some edges (“degenerate” edges). This approach requires to extend all concepts (in particular, the Bakry-Émery curvature related notions) to this general case and it leads to a distinction between the underlying topology (a mixed combinatorial graph) and the weighting scheme (given by transition rates). We present various results about curvature sharp vertices and weighted graphs as well as some fundamental properties of this new curvature flow. This paper is accompanied by another paper discussing the curvature flow implementation in Python for practical use, where we present various examples and exhibit further properties of the flow, like stability properties of curvature flow equilibria
