BACKGROUND:Profound stressors such as the COVID-19 pandemic have highlighted the importance of understanding resilience mechanisms and approaches for quantifying them in longitudinal studies. METHODS:We used Bayesian mixed models to analyze resilience dynamics with ordinal dependent variables: subjective physical and mental health, and fear, sadness, and anger. The models included fixed effects for individual stressors and random intercepts for participants, applied to the Gutenberg-COVID-19 cohort study. RESULTS:There were 206,912 responses from 7386 participants (mean age 55.09 years, 51.52% women) over one year (Oct 29, 2020 - Oct 25, 2021). Social stressors, such as loss of social contacts, had stronger negative associations with health and negative affects than work-related stress. Subjective health and emotions declined during lockdowns but quickly recovered afterward. CONCLUSION:Our longitudinal study design and mixed-model analysis highlight the role of social stress and encourage further research into protective factors like social support and positive reappraisal.

OBJECTIVE:Frailty, nutritional deficiencies, and anemia frequently coexist in gynecologic cancer and may adversely influence clinical outcomes. This study aimed to evaluate the prognostic value of the G8 geriatric screening tool (G8) for survival outcomes in patients undergoing gynecologic oncology surgery, with postoperative complications and selected modifiable preoperative conditions assessed as secondary outcomes. METHODS:Patients ≥60 years undergoing gynecologic oncology surgery were prospectively screened for frailty between May 2020 - June 2025. Survival was evaluated with Kaplan-Meier curves and Cox regression. Propensity score matching included demographics, comorbidities, and tumor characteristics; matched samples were analyzed using weighted Cox models. RESULTS:Of 257 screened patients, 180 were included (endometrial n = 72, ovarian n = 71, vulvar n = 26, cervical n = 6, vaginal cancer n = 5; mean age 69.6 ± 7.9 years; follow-up 25.1 ± 16.3 months). G8 positive patients (≤14 points) had more comorbidities and were more likely to present with preoperative anemia, hypoalbuminemia, and vitamin D or B12 deficiency. FIGO stages, surgical approach and postoperative complications were comparable. G8 positive patients were less likely to receive standard adjuvant therapy (p = 0.003). In matched analyses, G8 positivity remained significantly associated with reduced progression-free survival (HR: 1.87, 95% CI: 1.01-3.49, p = 0.047) and showed a trend toward worse overall survival (HR: 2.25, 95% CI: 0.98-5.16, p = 0.055). Surgical resection status was the strongest predictor of oncological outcome. CONCLUSIONS:A low preoperative G8 score was associated with reduced progression-free and potentially worse overall survival in older women with gynecologic tumors. The G8 may help identify modifiable factors such as anemia or vitamin D deficiency, while complete tumor resection remained the strongest prognostic factor.

We develop blinded sample size re-estimation strategies for McNemar's test based on paired binary primary and secondary short-term surrogate endpoints. The development is motivated by a prospective randomized clinical trial on childhood glaucoma. A conditional power expression for McNemar's test given the primary endpoint at an interim analysis is derived and complemented by a sample size re-estimation rule. We show that this procedure preserves the type I error rate while allowing the second-stage sample size to be chosen to attain a prespecified target power. In the case where for some patients only a short-term surrogate endpoint is available at interim, we introduce a surrogate-based re-estimation approach that conditions on all possible numbers of primary-endpoint discordant pairs using transition rates from the surrogate to the primary outcome. We show how these transition rates can be estimated from data on a subsample for which both surrogate and primary endpoint are available. We derive the resulting surrogate endpoint-based conditional power and sample size rule and illustrate their use with the example of the motivating trial.

The emergence of post-COVID sequelae (PCS) represents a global challenge. However, understanding of biological mechanisms and the definition of quantifiable risk factors remains limited. This study harnessed the power of predictive machine learning models to explore the potential of proteomics in predicting individual post-COVID symptoms and their collective manifestation as PCS. The analysis utilized a panel of approximately 2900 proteins measured in 495 COVID-19 patients. The study identified 235 unique proteins associated with 21 distinct post-COVID symptoms. Symptoms more closely linked by similar protein patterns tended to co-occur more frequently in patients. Six symptom clusters with distinct molecular pathway signatures were uncovered, with metabolic and inflammatory pathways prominently involved across several clusters. The relevance of the specific protein signatures for post-COVID symptoms could be demonstrated and explored by objective, quantifiable clinical tests, including cognitive and somatic assessments, and underlined their relevance. Data from various modalities, including pre-existing conditions, disease risk factors and genetic susceptibility, revealed relevant relations that may contribute to PCS heterogeneity. This work underscores the complex and multifaceted nature of post-COVID symptoms. It emphasizes the need for systematic and more specific approaches to facilitate the development of targeted therapies and treatment strategies.

OBJECTIVE:Psychological distress is associated with a higher risk of cardiovascular disease (CVD) and mortality, whereas psychological resilience may confer a protective effect. However, evidence on these relationships remains limited. This study aimed to examine the associations between psychological resilience, CVD, and all-cause mortality within a large general population cohort. METHODS:Data from 12,675 participants in the German Gutenberg Health Study were analyzed. Psychological resilience was assessed using the Brief Resilient Coping Scale (BRCS). CVD prevalence and mortality data were obtained from medical records and registry updates. Logistic and Cox regression analyses examined the associations between resilience, CVD, and mortality, with adjustments for socio-demographics, lifestyle, and clinical factors. RESULTS:Cross-sectionally, lower resilience was linked to higher odds of any CVD (odds ratio (OR) 1.030, 95 % confidence interval [CI] 1.009-1.051). Participants with low resilience had 38 % higher odds of CVD and 61 % higher odds of peripheral artery disease compared to those with high resilience. Longitudinally, low resilience was associated with the highest all-cause mortality risk (log-rank test, p < 0.0001). This association remained significant in Cox models after adjusting for confounders (hazard ratio (HR) 1.362, 95 % CI 1.002-1.852). CONCLUSIONS:Lower psychological resilience is associated with increased CVD prevalence and all-cause mortality. These findings highlight resilience as a potential target for cardiovascular risk assessment and intervention. Incorporating resilience measures in clinical practice may help identify vulnerable individuals who could benefit from strategies to enhance adaptive coping, improving cardiovascular and overall health outcomes.

PURPOSE:Is plasma cell (PC)-diagnosed chronic endometritis a common phenomenon in patients with recurrent implantation failure, and what can be learned from it? METHODS:In this retrospective case-control study at Wiesbaden Fertility Centre, 147 patients with recurrent implantation failure (RIF) underwent endometrial biopsy (EB) between January 2017 and December 2021 to rule out chronic endometritis (CE). For diagnosis, samples were labelled immunohistochemically with anti-CD138 and anti-MUM1 antibodies for the detection of PCs. The cut-off for the diagnosis of CE was at least five PCs per 10 evaluated high-power fields (HPFs). Patients with four PCs or fewer in the endometrial stroma (ES) formed Group A. Patients with at least five PCs in the ES were subsequently treated with doxycycline for 14 days and formed Group B. Those patients in Group B with persistent findings in a control biopsy received a combination of ciprofloxacin and metronidazole for 7 days. The EB time was documented, and the outcomes of assisted reproductive technology (ART), pregnancy and birth within 9 months of diagnosis were evaluated, as well as patient characteristics for both groups. RESULTS:Following the calculation of a threshold value using receiver operating characteristic curve analysis to determine the optimal time for EB (between cycle days 8 and 9 in this study), 65 patients were excluded from further evaluation due to an inadequate EB time point. Of the remaining 82 patients, 49 (59.8%) were assigned to Group A and 33 (40.2%) were assigned to Group B. In four patients in Group B, the control biopsy revelated that they still had at least five PCs per 10 HPFs, and these patients were treated following the previously described protocol. A comparison of the two groups revealed no significant differences in terms of medical history, characteristics, ART used, and pregnancy and live birth rates. However, the timing of EB is crucial for a correct diagnosis of CE. CONCLUSION:In this retrospective case-control study, patients with RIF frequently (40%) exhibited histological signs (at least five PCs per 10 HPFs in ES) of CE. These findings indicate that EB for the detection of CE should be performed in the late follicular phase or after day 8 of an ovulatory cycle if a cut-off value of at least five PCs is used. Antibiotic treatment with doxycycline led to a reduction in PCs in over 80% of cases. Persistent findings can be treated successfully with ciprofloxacin and metronidazole. After treatment of CE, the outcomes of patients were found to be comparable with those without CE. Therefore, an investigation to exclude CE using PCs in patients with RIF seems advisable before performing further ART.

Patients with vulvar (VC) and vaginal (VaC) cancer are often frail and should be prescreened before a time-consuming comprehensive geriatric assessment (CGA). This study assessed the impact of the preoperatively determined frailty status with the G8 geriatric screening tool (G8) and comorbidity assessment on the outcome of patients with VC/VaC. We conducted an observational study with prospective data collection of patients aged ≥ 60 undergoing surgery for VC and VAC from 05/2020 to 01/2025. Patients were assessed with the G8 tool, age-adjusted Charlson-Comorbidity Index and the Lee-index. Positive G8 results led to CGA-based testing and, if indicated, geriatric consultation. Cox regression, Kaplan–Meier curves and propensity score matching (PSM) were used to analyze the predictive validity of the G8. 41 patients were screened. 26 patients were included with a mean follow-up of 23 months. 10 patients were considered G8 positive (G8 ≤ 14 points). Median age was 74.5 (interquartile range: 66–81.3) years. The G8 positive cohort was older, had more comorbidities and had higher ECOG and ASA performance status than the G8 negative cohort. 20

BACKGROUND:Psychological resilience is known as a protective factor against mental health disorders for which valid measures are indispensable. The present work aims to evaluate the Resilience Scale-5 (RS-5) psychometrically, and provide norm values. METHODS:Data from the Gutenberg Health Study (GHS), encompassing 7,496 participants aged 25 to 86, spanning the years 2017 to 2022, was used. Selectivity, item difficulty, internal consistency, construct and factor validity, as well as factorial invariance were tested. Additionally, correlations and associations with depression, anxiety, and sociodemographic factors were determined. Furthermore, norm values were provided. RESULTS:The RS-5 displayed robust psychometric properties. Participants reported an average resilience score of 28.94 (SD = 5.53, median = 30, IQR = 6, range = 5-35), with those aged ≥75 exhibiting the highest resilience levels (M = 30.21, SD = 5.75, median = 32, IQR = 7). The RS-5 displayed a very good model fit, affirming measurement invariance across sex and age decades. Construct validity found support through anticipated intercorrelations with related psychological constructs. Significant correlations (p < .001) linked higher resilience with female gender, advanced age, higher education, elevated household income, and diminished psychological distress. CONCLUSION:The RS-5 emerged as a reliable and economic instrument for assessing psychological resilience in individuals aged 25 to 86. The study unraveled distinct sociodemographic characteristics significantly tied to resilience levels within this cohort. In contributing recent norm values tailored to the German population, this research enhances the practical applicability of the RS-5 across diverse contexts and enriches our comprehension of the demographic nuances associated with psychological resilience.

We study random walks on the giant component of Hyperbolic Random Graphs (HRGs), in the regime when the degree distribution obeys a power law with exponent in the range (2,3)$$ \left(2,3\right) $$. In particular, we first focus on the expected time for a random walk to hit a given vertex or visit, that is, cover, all vertices. We show that, a.a.s. (with respect to the HRG), and up to multiplicative constants: the cover time is n(logn)2$$ n{\left(\log n\right)}<^>2 $$, the maximum hitting time is nlogn$$ n\log n $$, and the average hitting time is n$$ n $$. We then determine the expected time to commute between two given vertices a.a.s., up to a small factor polylogarithmic in n$$ n $$, and under some mild hypothesis on the pair of vertices involved. Our results are proved by controlling effective resistances using the energy dissipated by carefully designed network flows associated to a tiling of the hyperbolic plane, on which we overlay a forest-like structure.

Objective:: Pelvic organ prolapse is a common condition with an increasing prevalence among elderly women. Currently, an efficient surgery to treat such a condition requires both cost-efficiency and time efficiency, since operating rooms also serve as the financial center of modern hospitals. This study is aimed at comparing different approaches to treating an apical prolapse based on perioperative variables, including operating room times and their efficiency. Materials and Methods: We reviewed and compared the perioperative data of postmenopausal women over 60 who had undergone POP surgery for an apical prolapse via laparoscopic approach between 2012 and 2022 with women who underwent surgery via vaginal approach between 2018 and 2022. The groups were divided into subdivisions based on concomitant hysterectomy. The operating room time, perioperative complications, blood loss, and the time of hospital stay were compared under different groups. Results:: A total of 199 patients were included in this study, out of which 66 underwent laparoscopic surgery and 133 underwent vaginal surgery for apical pelvic organ prolapse (POP). The vaginal approach showed significantly shorter operating room times when it came to the duration of anesthesia induction, case preparation, and the surgery. The blood loss did not significantly differ between the groups. The length of hospital stay was significantly longer in the groups with a laparoscopic approach. Conclusion:: The advantage of traditional vaginal surgery is the significant time efficiency with better perioperative variables compared to the laparoscopic approach.

Background/Objectives: Anal incontinence is linked to pelvic floor dysfunction. Diagnosis involves assessing both the function and structure of the anorectal unit. Although transperineal ultrasound has gained attention as a less invasive option, its effectiveness as a diagnostic tool for evaluating the relationship between structure and function is still debated. This study aimed to explore the relationship between quantitative measurements of anal sphincter and pelvic floor structures as well as the subjective symptoms and objective assessments of sphincter function regarding anal incontinence. Methods: 50 women with pelvic floor dysfunction were recruited for the study. The severity of anal incontinence was assessed using the CACP score. Ultrasound imaging was employed to measure anal sphincter area, while sphincter pressures were evaluated through manometry. The relationships between variables were analyzed using Pearson’s and Spearman’s correlation tests. Results: The mean anal sphincter area was 5.51 cm2 at rest and 4.06 cm2 during maximal contraction. Resting anal sphincter pressure had an average of 46.29 mmHg, and contraction pressure averaged 103.25 mmHg. No significant correlation was found between the anal sphincter area and pressure at rest (r = 0.018) or during contraction (r = −0.210). However, a moderate correlation was observed between the change in sphincter pressure and area during contraction (r = 0.312). The CACP score showed no significant correlation with the sphincter area at rest (r = −0.084) but was weakly correlated during contraction (r = −0.270). Conclusions: Conventional diagnostic tools for evaluating anal incontinence can be uncomfortable and are not always readily available. Perineal sonography presents a promising, less invasive alternative for dynamic assessment of the anal sphincter.

Background The Brief Resilience Coping Scale (BRCS) is a brief instrument suitable for epidemiological studies. The aims of this paper were to analyze changes in BRCS depending on time, sex, age group, relationship status, as well as risk of poverty, to test the psychometric properties including test-retest reliability and measurement invariance, and to determine associations with psychosocial stress, depressiveness, anxiety, social support, as well as subjective mental and physical health. As the data from this study was collected during the pandemic, an additional sensitivity analysis was performed with pre-pandemic data. Methods A longitudinal study of resilience and distress in a large-sized community sample was performed at one pre-pandemic (T0) and three pandemic time points (T1-3). Resilient coping was assessed by the 4-Item short form of the BRCS, distress by the PHQ-9 and GAD-2. Results BRCS decreased between the first and the second and increased at the third pandemic time point. The scale had a good internal consistency. Test-retest correlation coefficients ranged from 0.527 to 0.589. Higher resilient coping was found in younger participants, participants not at-risk-of-poverty and in males. Stability was higher in those with a partner, and at-risk-of-poverty. Significant negative associations with psychosocial stress, loneliness, depressiveness, anxiety, social support, as well as subjective and physical health and SES underscored the construct validity. Conclusion Overall, findings underscore that resilient coping is a dynamic construct with considerable stability. The scale showed good psychometric properties including test-retest reliability over four months to two years. We found that it is not only important to describe the level of resilient coping, but also its stability.

OBJECTIVES:Loss of muscle quantity and function is associated with frailty and reduced quality of life. Sonography is a simple option to quantify muscle mass, which could be included into routine diagnostic workup. This study was designed to prospectively evaluate sonographic measurement and to compare it with established measurements of muscle quantity and function. METHODS:Between March 2020 and May 2022, 723 patients were enrolled in the study. Psoas muscle area index (PMAI) and psoas muscle thickness height index (PMTI) were quantified. Thigh muscle thickness indices (TMTI) were either measured without compression (fTMTI) or under compression (cTMTI). Variation coefficient (VC) as well as intra- and inter-observer reliability were analyzed. The reliability and reproducibility of the sonographic morphometry were assessed using two examiners. Sonographic morphometry was compared with established measurements of muscle using computed tomography and hand grip strength, respectively. RESULTS:In 156 patients, sonographic indices were compared with corresponding CT indices. Of the 723 patients included, sonographic indices were compared with hand strength in 429 patients. Interobserver and intraobserver variability showed better results for the femur indices than for the psoas indices (correlation coefficient: 0.8697/0.9118 vs 0.7502/0.7319). Psoas muscle indices correlated best with the reference standard of the SMI. The optimal cut-off for each muscle index for determining muscle loss according to the SMI and hand grip strength was calculated. CONCLUSION:Sonography can simplify muscle measurement and should be used in the future. Sonographic muscle indices have the potential to simplify evaluation, especially in risk groups such as patients with liver cirrhosis or other wasting disorders.

BACKGROUND:One provision of the Care Provision Strengthening Act in Germany was that psychotherapeutic appointments (psychotherapeutic consultation, acute care, and probatory sessions) are now arranged through the Association of Statutory Health Insurance Physicians organizations. We examined how many appointments were requested and given in 2019, differentiated by appointment type and by city state versus areal state organizations. METHODS:The frequency of requests and appointments made in 2019 were collected from the Association of Statutory Health Insurance Physicians organizations in Germany using a questionnaire. Statistical analysis comprised descriptive evaluations and a Kruskal-Wallis test. RESULTS:Data for appointments were available from 17 and information on requests from 16 Association of Statutory Health Insurance Physicians organizations. A total of 134,578 appointments were given. The number of granted appointments ranged from 193 to 21,810, revealing substantial differences between the individual organizations. The share of psychotherapeutic consultations among all psychotherapeutic appointments granted amounted to a median of 92%. Per organization, appointments were given for a median of 87% of requests for a psychotherapeutic consultation (range 56-100%), 96% for acute care requests (range 29-100%), and 97% for probatory session requests (range 27-100%) (n = 16, respectively). There were minor differences between city states and areal states in granting acute care and probatory sessions. DISCUSSION:There are deficits both in city state and areal state Association of Statutory Health Insurance Physicians organizations in terms of granting acute care and probatory sessions. Our results do not allow conclusions about distance to the practices or waiting times.

Previous evidence suggested that non-COVID-19-related medical care was reduced during the first wave of the COVID-19 pandemic, but it remained unclear whether or to which extent this effect lasted beyond the first wave, or existed in a longer time frame. Here, we consider questionnaire data of the Gutenberg-COVID-19 study together with pre-pandemic baseline data of the Gutenberg Health Study concerning the region around Mainz, Germany, to study the effects of the pandemic on the provision of medical care until April 2021. We observed that the proportion of cancelled medical appointments was low and that the fraction of participants with a medical appointment as an indicator for the number of appointments being made was in line with pre-pandemic levels. Appointments were more likely cancelled by the patient (rather than the provider), and more likely cancelled by medical specialists such as dentists or ophthalmologists (rather than GPs). In conclusion, we found some evidence that, at least with regard to realized appointments, the medical system and the provision of medical care were not harmed by the COVID-19 pandemic on a longer time scale.

Zusammenfassung Hintergrund Eine Maßnahme des Versorgungsstärkungsgesetzes war die Vermittlung psychotherapeutischer Leistungen (psychotherapeutische Sprechstunde, Akutbehandlung und probatorische Sitzungen) durch die Terminservicestellen der Kassenärztlichen Vereinigungen (KVen). Wir untersuchten diese Vermittlung differenziert nach Vermittlungsanliegen sowie nach Stadtstaat versus Flächenland. Methoden Die Anzahl der Anfragen und Terminvereinbarungen im Jahr 2019 wurde bei den KVen Deutschlands mittels Fragebogen erfragt. Die statistische Analyse bestand aus einer deskriptiven Auswertung und einem Kruskal-Wallis-Test. Ergebnisse Daten zu Terminvereinbarungen lagen von 17 KVen und Informationen zu Anfragen von 16 KVen vor. Insgesamt wurden 134.578 Termine vereinbart. Die Spannweite von 193 bis 21.810 Terminvereinbarungen offenbarte deutliche Unterschiede zwischen den einzelnen KVen. Der Anteil der psychotherapeutischen Sprechstunde an allen psychotherapeutischen Terminvereinbarungen lag im Median bei 92 %. Pro KV konnten im Median 87 % der Anfragen nach psychotherapeutischen Sprechstunden (Spannweite 56–100 %), 96 % nach Akutbehandlungen (29–100 %) und 97 % nach probatorischen Sitzungen (27–100 %) vermittelt werden (je n = 16). Es zeigten sich geringe Unterschiede zwischen Stadtstaaten und Flächenländern bei der Vermittlung von Akutbehandlungen und probatorischen Sitzungen. Diskussion Bei KVen sowohl in Stadtstaaten als auch in Flächenländern bestehen Defizite insbesondere bei der Vermittlung von Akutbehandlungen und probatorischen Sitzungen. Unsere Ergebnisse lassen keine Rückschlüsse auf den Vermittlungsradius oder die Wartezeit auf Termine zu.

The use of extracorporeal life support (ECLS) as part of cardio-circulatory support has increased rapidly in recent years. Severe hyperlactatemia is not uncommon in this group of patients. Lactate peak concentrations and lactate clearance have already been identified as independent marker for mortality in critical ill patients without mechanical device support. The aim of this study was to determine a supposed correlation between the variables lactate peak concentration and clearance in the blood and mortality in the ECLS context. Therefore, a total of 51 cardiac surgery ICU patients with ECLS therapy were included in this retrospective, clinical observational study (survivors n = 23; non-survivors n = 28). Lactate measurement was performed before, during and after ECLS therapy. Further, common ICU scores (SAPSII, SOFA, TISS28), the rates of transfusion and the different vasopressor therapies will be compared. Significant elevated peak lactate levels and poor lactate clearance were associated with higher mortality during ECLS therapy (p < 0.001). Deceased patients had higher SAPSII scores (p < 0.001), received more transfusions (p < 0.001) and presented with higher rates of epinephrine (p < 0.001). In conclusion, hyperlactatemia during ECLS therapy is a time sensitive emergency. Lactate cannot be cleared in all patients. Reversible causes should be explored and treated. In cases where the cause is irreversible, the prognosis of elevated lactate concentrations and reduced clearance is very poor.

Background: Although the private household setting is considered a major driver of viral spread, only little is known about the contextual details of SARS-CoV-2 household transmission, thus hampering political decision-making. Materials and methods: We analyzed individual case and cluster data from statutory notifications from August to November 2020 in Rhineland-Palatinate - the period preceding the second SARS-CoV-2 wave. We also conducted an into-depth survey on contextual details of household transmission in a representative sample of 149 private household clusters that had occurred during this period. Results: During the study period, 18,695 PCR-confirmed SARS-CoV-2 cases were notified, 3,642 of which occurred in 911 clusters (private households (67.3%), the workplace (7.8%), elderly homes (1.8%), others (23.2%). Demographically, clustered cases were representative of all notified cases. Two-thirds (77/113, 68%) of sample response clusters involved more than one private household. These caused on average more close contact persons (mean 13.5, +/- SD 15.8) and secondary cases (3.9, +/- SD 0.4) than clusters involving one household only (5.1 +/- 13.8 and 2.9 +/- 0.2). About one in six multi-household clusters in the private setting (13/77) followed a social gathering (e.g. birthday party). Breaches of one or more of the three major barrier concepts (mask, ventilation, and distance) were identified in most (10/13) of these social gatherings. SARS-CoV-2 clusters following social gatherings were overrepresented during the second half of the study period. Conclusion: In times of increasing infectious pressure in a given population, multi-household social gatherings appear to be an important target for reducing SARS-CoV-2 transmission. (C) 2022 The British Infection Association. Published by Elsevier Ltd. All rights reserved.