Evaluating palliative care case conferences in primary care for patients with advanced non-malignant chronic conditions: a cluster-randomised controlled trial (KOPAL).

BACKGROUND: Patients with congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) and dementia are underrepresented in specialist palliative home care (SPHC). However, the complexity of their conditions requires collaboration between general practitioners (GPs) and SPHC teams and timely integration into SPHC to effectively meet their needs. OBJECTIVE: To facilitate joint palliative care planning and the timely transfer of patients with advanced chronic non-malignant conditions to SPHC. METHODS: A two-arm, unblinded, cluster-randomised controlled trial. 49 GP practices in northern Germany were randomised using web-based block randomisation. We included patients with advanced CHF, COPD and/or dementia. The KOPAL intervention consisted of a SPHC nurse-patient consultation followed by an interprofessional telephone case conference between SPHC team and GP. The primary outcome was the number of hospital admissions 48 weeks after baseline. Secondary analyses examined the effects on health-related quality of life and self-rated health status, as measured by the EuroQol 5D scale. RESULTS: A total of 172 patients were included in the analyses. 80.4% of GP practices had worked with SHPC before, most of them exclusively for cancer patients. At baseline, patients reported a mean EQ-VAS of 48.4, a mean quality of life index (EQ-5D-5L) of 0.63 and an average of 0.80 hospital admissions in the previous year. The intervention did not significantly reduce hospital admissions (incidence rate ratio = 0.79, 95%CI: [0.49, 1.26], P = 0.31) or the number of days spent in hospital (incidence rate ratio = 0.65, 95%CI: [0.28, 1.49], P = 0.29). There was also no significant effect on quality of life (∆ = -0.02, 95%CI: [-0.09, 0.05], P = 0.53) or self-rated health (∆ = -2.48, 95%CI: [-9.95, 4.99], P = 0.51). CONCLUSIONS: The study did not show the hypothesised effect on hospitalisations and health-related quality of life. Future research should focus on refining this approach, with particular emphasis on optimising the timing of case conferences and implementing discussed changes to treatment plans, to improve collaboration between GPs and SPHC teams.

Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis.

OBJECTIVE: Early disease prediction is challenging in acute pancreatitis (AP). Here, we prospectively investigate whether the microbiome predicts severity of AP (Pancreatitis-Microbiome As Predictor of Severity; P-MAPS) early at hospital admission. DESIGN: Buccal and rectal microbial swabs were collected from 424 patients with AP within 72 hours of hospital admission in 15 European centres. All samples were sequenced by full-length 16S rRNA and metagenomic sequencing using Oxford Nanopore Technologies. Primary endpoint was the association of the orointestinal microbiome with the revised Atlanta classification (RAC). Secondary endpoints were mortality, length of hospital stay and severity (organ failure >48 hours and/or occurrence of pancreatic collections requiring intervention) as post hoc analysis. Multivariate analysis was conducted from normalised microbial and corresponding clinical data to build classifiers for predicting severity. For functional profiling, gene set enrichment analysis (GSEA) was performed and normalised enrichment scores calculated. RESULTS: After data processing, 411 buccal and 391 rectal samples were analysed. The intestinal microbiome significantly differed for the RAC (Bray-Curtis, p value=0.009), mortality (Bray-Curtis, p value 0.006), length of hospital stay (Bray-Curtis, p=0.009) and severity (Bray-Curtis, p value=0.008). A classifier for severity with 16 different species and systemic inflammatory response syndrome achieved an area under the receiving operating characteristic (AUROC) of 85%, a positive predictive value of 67% and a negative predictive value of 94% outperforming established severity scores. GSEA revealed functional pathway units suggesting elevated short-chain fatty acid (SCFA) production in severe AP. CONCLUSIONS: The orointestinal microbiome predicts clinical hallmark features of AP, and SCFAs may be used for future diagnostic and therapeutic concepts. TRIAL REGISTRATION NUMBER: NCT04777812.

Association of health behaviour and clinical manifestation in early multiple sclerosis in Germany - Baseline characteristics of the POWER@MS1 randomised controlled trial.

BACKGROUND: Receiving a multiple sclerosis (MS) diagnosis is a significant stressor. Therefore, highly individualised counselling is needed, especially in early MS. Modifiable risk factors (e.g. smoking and obesity) are gaining relevance in MS. Despite evidence for worse MS-related health outcomes, prevalence of adverse health behaviours, such as smoking and physical inactivity, is high across all MS stages. However, knowledge regarding health behaviours as well as their association with MS-related health outcomes among newly diagnosed PwMS in Germany is scarce. Currently, the efficacy of an interactive digital lifestyle management application intended to be used as an add-on to standard care among newly diagnosed PwMS in Germany is evaluated in an ongoing multicentre randomised controlled trial (RCT) ('POWER@MS1'). OBJECTIVES: To describe baseline disease characteristics and health behaviours of the POWER@MS1 cohort and investigate associations between MS characteristics, quality of life (QOL), health behaviours and intention to optimise health behaviour habits. METHODS: This study included 234 persons with early MS from 20 study centres located across Germany who participate in the POWER@MS1 RCT. Participants were recruited by treating neurologists from different regions and health-care settings in Germany. Baseline data was obtained using paper-based questionnaires and a web-based healthy diet screener between July 2019 and end of March 2022 and analysed descriptively. RESULTS: In this early MS cohort (mean disease duration 4 months), a screening tool showed severe symptoms of anxiety in 15 % of the participants. Better means for stress management appeared to be particularly relevant for the whole cohort. Moreover, 19 % were current smokers, 15 % were obese and 36 % were insufficiently physically active. On average, participants only moderately adhered to dietary guidelines for recommended intake of key food groups (e.g. vegetables, fruits and fatty marine fish). Higher EDSS scores were associated with approximately 20 % higher T2-lesion burden (rate ratio RR=1.2, p<0.001) and 13 % higher relapse rate (RR=1.13,p=0.02) per EDSS disability level. Moreover, a higher T2-lesion burden was associated with current smoking (RR=0.76, p=0.033), resulting in approximately 24 % less T2-lesions at disease onset among non-smokers. In addition, smoking was associated with unhealthier dietary habits according to lower diet scores (linear regression coefficient ß=-1.27, p<0.001). Higher EDSS scores (ß=0.19,p<0.001) and higher BMI (ß=0.013,p=0.03) were associated with higher HAQUAMS (lower QOL). Further, lower diet scores (ß=-0.044,p=0.039) were associated with lower QOL. Moreover, higher HAQUAMS (lower QOL) indicated a higher intention to optimise stress management (ß=0.98,p<0.001), physical activity (ß=0.74,p=0.046) and sleep behaviour (ß=1.82,p<0.001). Further, higher intention to optimise stress management was accounted for by higher EDSS scores (ß=0.39,p=0.004) and a higher number of T2-lesions (ß=0.029,p=0.015) in this newly diagnosed MS cohort. CONCLUSION: Results indicate a clear need for modifications of health behaviours among newly diagnosed PwMS participating in POWER@MS1. Individualised psychological and health behaviour counselling appears to be an important factor in treatment, also for similar early MS cohorts and particularly in those who demonstrate a more severe disease in clinical and MRI metrics.

Cost-effectiveness of a specialist palliative care nurse-patient consultation followed by an interprofessional case conference for patients with non-oncological palliative care needs: results of the KOPAL trial.

BACKGROUND: Worldwide, progressive chronic, non-malignant diseases are highly prevalent. Especially with increasing age, they are characterised by high hospitalisation rates and high healthcare costs. Improved interprofessional collaboration between general practitioners (GPs) and specialist palliative home care (SPHC) teams might reduce hospitalisation while improving symptoms and quality of life, or preventing them from deterioration. The aim of this study was to examine the cost-effectiveness of a newly developed intervention in patients with advanced chronic, non-malignant diseases consisting of a structured palliative care nurse-patient consultation followed by an interprofessional telephone case conference. METHODS: The analysis was based on data from 172 participants of the KOPAL multi-centre, cluster randomised controlled trial. Patients with advanced congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), or dementia were randomised into intervention group (IG) and control group (CG, usual care). Cost-effectiveness was examined over 48 weeks from a societal and healthcare payer's perspective. Effects were quantified as quality-adjusted life years (QALYs, EQ-5D-5L). Incremental cost-effectiveness ratios were calculated and cost-effectiveness acceptability curves were constructed. RESULTS: Baseline imbalances in costs and effects could be observed between IG and CG. After adjusting for these imbalances and compared to the CG, mean costs in the IG were non-significantly higher from a societal and lower from a payer's perspective. On the effect side, the IG had marginally lower mean QALYs. The results were characterized by high statistical uncertainty, indicated by large confidence intervals for the cost and effect differences between groups and probabilities of cost-effectiveness between 18% and 65%, depending on the perspective and willingness-to-pay. CONCLUSIONS: Based on the results of this study, the cost-effectiveness of the KOPAL intervention was uncertain. The results highlighted (methodological) challenges of economic evaluations in patients with chronic, non-malignant diseases related to sample size, heterogeneity of participants, and the way the intervention effectiveness is typically captured in economic evaluations.

Adherence to interdisciplinary tumor board recommendations as an expression of quality-assured patient care: results of a bicentric German analysis.

PURPOSE: Interdisciplinary tumor boards (ITBs) represent a central part of standard cancer care defining a guidelines-guided treatment plan adapted to the patient's capabilities, comorbidities and wishes in a multi-professional team. The implementation rate of ITB recommendations can be monitored by structured adherence analyses. But (inter)national definitions how to measure the level of implementation are missing. Here, we present results of 4 years of ITB adherence analyses in a bicentric German Comprehensive Cancer Center (CCC). METHODS: Between 2018 and 2021, for at least 1 month, the implementation rate of recommendations of 8 different ITBs of 2 CCC sites was evaluated manually according to harmonized criteria between both sites regarding the degree of implementation of ITB's recommendations. RESULTS: In total, 1104 cases were analyzed (65% male, 35% female). Mean distance from patient's home to the CCC was 57 km (range 0.8-560.6 km). For 949 cases (86%) with known follow-up, the adherence rate was 91.9% (95% CI 0.9; 0.935). In 8.1%, ITB decisions were not implemented due to medical reasons (45.4%), patient's wish (35.1%) and unknown reasons (19.5%). Logistic regression revealed neither age (OR = 0.998, p = 0.90), nor gender (OR = 0.98, p = 0.92) or the distance from patient's home to the CCC (OR = 1.001, p = 0.54) were significantly associated with ITB adherence. CONCLUSION: ITB adherences analyses can serve as a quality management tool to monitor the implementation rate of ITB recommendations and to stay in contact with practitioners, other hospitals and state cancer registries to share data and resources in accordance with data protection requirements for continuously improvement of quality management and patient care.

Prehabilitation in older patients prior to elective cardiac procedures (PRECOVERY): study protocol of a multicenter randomized controlled trial.

BACKGROUND: Previous studies have demonstrated the efficacy of rehabilitation after a cardiovascular procedure. Especially older and multimorbid patients benefit from rehabilitation after a cardiac procedure. Prehabilitation prior to cardiac procedures may also have positive effects on patients' pre- and postoperative outcomes. Results of a current meta-analysis show that prehabilitation prior to cardiac procedures can improve perioperative outcomes and alleviate adverse effects. Germany currently lacks a structured cardiac prehabilitation program for older patients, which is coordinated across healthcare sectors. METHODS: In a randomized, controlled, two-arm parallel group, assessor-blinded multicenter intervention trial (PRECOVERY), we will randomize 422 patients aged 75 years or older scheduled for an elective cardiac procedure (e.g., coronary artery bypass graft surgery or transcatheter aortic valve replacement). In PRECOVERY, patients randomized to the intervention group participate in a 2-week multimodal prehabilitation intervention conducted in selected cardiac-specific rehabilitation facilities. The multimodal prehabilitation includes seven modules: exercise therapy, occupational therapy, cognitive training, psychosocial intervention, disease-specific education, education with relatives, and nutritional intervention. Participants in the control group receive standard medical care. The co-primary outcomes are quality of life (QoL) and mortality after 12 months. QoL will be measured by the EuroQol 5-dimensional questionnaire (EQ-5D-5L). A health economic evaluation using health insurance data will measure cost-effectiveness. A mixed-methods process evaluation will accompany the randomized, controlled trial to evaluate dose, reach, fidelity and adaptions of the intervention. DISCUSSION: In this study, we investigate whether a tailored prehabilitation program can improve long-term survival, QoL and functional capacity. Additionally, we will analyze whether the intervention is cost-effective. This is the largest cardiac prehabilitation trial targeting the wide implementation of a new form of care for geriatric cardiac patients. TRIAL REGISTRATION: German Clinical Trials Register (DRKS; http://www.drks.de ; DRKS00030526). Registered on 30 January 2023.

The impact of orthodontic-surgical treatment on facial expressions-a four-dimensional clinical trial.

OBJECTIVE: The objective of this clinical trial was to compare facial expressions (magnitude, shape change, time, and symmetry) before (T0) and after (T1) orthognathic surgery by implementing a novel method of four-dimensional (4D) motion capture analysis, known as videostereophotogrammetry, in orthodontics. METHODS: This prospective, single-centre, single-arm trial included a total of 26 adult patients (mean age 28.4 years; skeletal class II: n = 13, skeletal class III: n = 13) with indication for orthodontic-surgical treatment. Two reproducible facial expressions (maximum smile, lip purse) were captured at T0 and T1 by videostereophotogrammetry as 4D face scan. The magnitude, shape change, symmetry, and time of the facial movements were analysed. The motion changes were analysed in dependence of skeletal class and surgical movements. RESULTS: 4D motion capture analysis was feasible in all cases. The magnitude of the expression maximum smile increased from 15.24 to 17.27 mm (p = 0.002), while that of the expression lip purse decreased from 9.34 to 8.31 mm (p = 0.01). Shape change, symmetry, and time of the facial movements did not differ significantly pre- and postsurgical. The changes in facial movements following orthodontic-surgical treatment were observed independently of skeletal class and surgical movements. CONCLUSIONS: Orthodontic-surgical treatment not only affects static soft tissue but also soft tissue dynamics while smiling or lip pursing. CLINICAL RELEVANCE: To achieve comprehensive orthodontic treatment plans, the integration of facial dynamics via videostereophotogrammetry provides a promising approach in diagnostics. TRIAL REGISTRATION NUMBER: DRKS00017206.

Optimizing the structure of interdisciplinary tumor boards for effective cancer care.

Introduction: Multi-professional interdisciplinary tumor boards (ITB) are essential institutions to discuss all newly diagnosed, relapsed or complex cancer patients in a team of specialists to find an optimal cancer care plan for each individual patient with regard to national and international clinical practice guidelines, patient´s preference and comorbidities. In a high-volume cancer center, entity-specific ITBs take place at least once a week discussing a large number of patients. To a high level of expertise and dedication, this also requires an enormous amount of time for physicians, cancer specialists and administrative support colleagues, especially for radiologists, pathologists, medical oncologists and radiation oncologists, who must attend all cancer-specific boards according to certification requirements. Methods: In this 15-month prospective German single-center analysis, we examined the established structures of 12 different cancer-specific ITBs at the certified Oncology Center and demonstrate tools helping to optimize processes before, during and after the boards for optimal, time-saving procedures. Results: By changing pathways, introducing revised registration protocols and new digital supports we could show that the workload of preparation by radiologists and pathologists could be reduced significantly by 22.9% (p=<0.0001) and 52.7% (p=<0.0001), respectively. Furthermore, two questions were added to all registration forms about the patient´s need for specialized palliative care support that should lead to more awareness and early integration of specialized help. Discussion: There are several ways to reduce the workload of all ITB team members while maintaining high quality recommendations and adherence to national and international guidelines.

Semi-quantitative assessment of environmental tobacco smoke exposure and its association with the development of oral squamous cell carcinoma: A pilot study.

INTRODUCTION: Two known major risk factors for oral squamous cell carcinoma are smoking and alcohol consumption. Environmental tobacco smoke (also known as secondhand smoke) has been proven to be associated with the occurrence of lung and breast carcinoma. This study aimed to assess exposure to environmental tobacco smoke and its association with the development of oral squamous cell carcinomas. METHODS: Using a standardized questionnaire, 165 cases and 167 controls were asked about their demographic data and risk behaviors, including environmental tobacco smoke exposure. An environmental tobacco smoke score (ETS-score) was developed to semi-quantitatively record the previous exposure to ETS. Statistical analyses were performed with χ2 test or Fishers exact test, and with ANOVA or Welch's t-test as appropriate. An analysis was done using multiple logistic regression. RESULTS: Cases had a significantly increased previous exposure to environmental tobacco smoke compared to the controls (ETS-score: 36.69 ± 26.34 vs 13.92 ± 12.44; p<0.0001). Comparing only the groups without additional active risk factors, exposure to environmental tobacco smoke was associated with a more than threefold higher likelihood of oral squamous cell carcinoma (OR=3.47; 95% CI: 1.31-10.55). Statistically significant differences in ETS-score were found for different tumor locations (p=0.0012) and different histopathological gradings (p=0.0399). A multiple logistic regression analysis confirmed exposure to environmental tobacco smoke as an independent risk factor for the development of oral squamous cell carcinomas (p<0.0001). CONCLUSIONS: Environmental tobacco smoke is an important but yet underestimated risk factor for the development of oral squamous cell carcinomas. Further studies are needed to confirm the results, including the usefulness of the developed environmental tobacco smoke score for exposure.

Integrated care for older multimorbid heart failure patients: protocol for the ESCAPE randomized trial and cohort study.

ESCAPE: Evaluation of a patient-centred biopsychosocial blended collaborative care pathway for the treatment of multimorbid elderly patients. THERAPEUTIC AREA: Healthcare interventions for the management of older patients with multiple morbidities. AIMS: Multi-morbidity treatment is an increasing challenge for healthcare systems in ageing societies. This comprehensive cohort study with embedded randomized controlled trial tests an integrated biopsychosocial care model for multimorbid elderly patients. HYPOTHESIS: A holistic, patient-centred pro-active 9-month intervention based on the blended collaborative care (BCC) approach and enhanced by information and communication technologies can improve health-related quality of life (HRQoL) and disease outcomes as compared with usual care at 9 months. METHODS: Across six European countries, ESCAPE is recruiting patients with heart failure, mental distress/disorder plus ≥2 medical co-morbidities into an observational cohort study. Within the cohort study, 300 patients will be included in a randomized controlled assessor-blinded two-arm parallel group interventional clinical trial (RCT). In the intervention, trained care managers (CMs) regularly support patients and informal carers in managing their multiple health problems. Supervised by a clinical specialist team, CMs remotely support patients in implementing the treatment plan-customized to the patients' individual needs and preferences-into their daily lives and liaise with patients' healthcare providers. An eHealth platform with an integrated patient registry guides the intervention and helps to empower patients and informal carers. HRQoL measured with the EQ-5D-5L as primary endpoint, and secondary outcomes, that is, medical and patient-reported outcomes, healthcare costs, cost-effectiveness, and informal carer burden, will be assessed at 9 and ≥18 months. CONCLUSIONS: If proven effective, the ESCAPE BCC intervention can be implemented in routine care for older patients with multiple morbidities across the participating countries and beyond.

[Clinical trials as a central part of patient-centered clinical research]. / Klinische Studien als zentraler Bestandteil patientenorientierter Forschung.

As the continuation and implementation of findings from basic (pre­)clinical research, clinical trials make a significant contribution to medical research. They form the central building block of translational medicine and thus make a decisive contribution to bringing medical knowledge into general care. This helps to make possible a healthcare system that is aligned to the needs of patients and functions efficiently in the long term. Based on the specific objective, clinical trials must comply with national, but increasingly also with European and international regulatory requirements. In academia in particular, expertise in a variety of fields is required in order to make investigator-driven clinical trials a success. This expertise can be provided by a clinical trial center based within the institution conducting the trial.

Screening versus multidimensional assessment of symptoms and psychosocial distress in cancer patients from the time of incurability.

Objective: Previous symptom prevalence studies show a diverse spectrum of symptoms and a large diversity in symptom intensities in patients being just diagnosed as having incurable cancer. It is unclear, how physical symptoms and psychosocial burden should be recorded in order to determine the variable need for palliative care and further support. Therefore, we compared two different strategies for detecting physical symptoms and psychosocial burden of patients with newly diagnosed incurable cancer and their effects on the further course of the disease. Methods: SCREBEL is a controlled, randomized, non-blinded, longitudinal study of the research network of the Palliative Medicine Working Group (APM) of the German Cancer Society (DKG). We compared: a less complex repeated brief screening for symptoms and burden in patients using the NCCN Distress Thermometer and IPOS questionnaire versus a multidimensional comprehensive assessment using the FACT-G and their entity-specific questionnaires, the PHQ4 scales, SCNS-34-SF, IPOS and NCCN Distress Thermometer. The primary study endpoint was quality of life (QoL), measured using FACT-G, after six months. Secondary study endpoints were QoL by using evaluation of secondary scores (NCCN DT, IPOS, PHQ4, SCNS-SF-34G) at time 6 months, the number of hospital days, the utilization of palliative care, emergency services, and psychosocial care structures. To assess effects and differences, multiple linear regression models were fitted and survival analyses were conducted. Results: 504 patients were included in the study. 262 patients were lost to follow-up, including 155 fatalities. There were no significant differences between the low-threshold screening approach and a comprehensive assessment with respect to symptoms and other aspects of QoL. Using the IPOS, we were able to measure an improvement in the quality of life in the low-threshold screening arm by a decrease of 0.67 points (95%-CI: 0.34 to 0.99) every 30 days. (p<0.001). Data on the involvement of emergency facilities and on supportive services were insufficient for analysis. Conclusion: A comprehensive, multidimensional assessment did not significantly differ from brief screening in preserving several dimensions of quality of life. These findings may positively influence the implementation of structured low-threshold screening programs for supportive and palliative needs in DKG certified cancer centers.DRKS -No. DRKS00017774 https://drks.de/search/de/trial/DRKS00017774.

Evaluation of the non-invasive Temple Touch Pro temperature monitoring system compared with oesophageal temperature in paediatric anaesthesia (PETER PAN): A prospective observational study.

BACKGROUND: Monitoring peri-operative body temperature in children is currently mainly achieved through invasive devices. The Temple Touch Pro Temperature Monitoring System estimates core temperature noninvasively based on heat flux thermometry. OBJECTIVE: To investigate the agreement of this noninvasive sensor against standard oesophageal core temperature. DESIGN: A prospective observational study. SETTING: University hospital recruiting between April and July 2021. PATIENTS: One hundred children (32 girls) aged 6 years or younger scheduled for noncardiac surgery, resulting in 6766 data pairs. Exclusion criteria were contraindication for the insertion of an oesophageal temperature probe, and procedures in which one of the measurement methods would interfere with the surgical field. MAIN OUTCOME MEASURES: Primary outcome was the agreement analysis by a Bland-Altman comparison with multiple measurements. Posthoc, we performed another agreement analysis after exclusion of a statistically determined equilibration time. Secondary outcomes were the temperature differences over time and subgroup analysis of hypothermic, normothermic and hyperthermic temperature ranges, age, sex and sensor's side by type III analysis of variance. Further, we correlated the sonographically determined depth of the artery with trueness. RESULTS: The mean difference was -0.07°C (95% CI -0.15 to +0.05) with limits of agreement of -1.00 and +0.85°C. After adjusting for an equilibration time of 13 min, the mean difference improved to -0.04°C (95% CI -0.08 to +0.01) with limits of agreement of -0.68 and +0.60°C. Concordance correlation coefficient was 0.83 (95% CI 0.82 to 0.84). Differences between the skin sensor and oesophageal reference increased over time by -0.05°C per hour. Subgroup analysis showed no clinically relevant differences. Depth of artery negatively correlated with trueness by 0.03°C per millimetre. CONCLUSIONS: Although the Temple Touch Pro sensor showed acceptable accuracy after allowing for an equilibration time, it still needs further investigation for routine use in children. This particularly affects accuracy in hypothermic ranges, imprecise positioning and applicability in children with immature or vulnerable skin. TRIAL REGISTRATION: German Clinical Trials Register, identifier: DRKS00024703.

Renal disease in sarcoidosis patients in a German multicentric retrospective cohort study.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease potentially affecting every organ system. Renal involvement is reportedly rare, and the evidence consists of case reports and cohort studies. Systematic investigations are scarce and show a varying prevalence ranging from <1% to 30-50%. METHODS: We retrospectively analyzed data from patients with a recent diagnosis of sarcoidosis from five tertiary care centers focusing on renal sarcoidosis. RESULTS: We analyzed data from 327 patients with sarcoidosis between 2001 and 2021. Of 327 patients, 109 (33.3%) had probable or definite renal sarcoidosis. 90 (27.5%) had histopathologic confirmation. 57 (64%) had an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. The most prominent associated finding was an elevated soluble interleukin-2 receptor. Patients with renal sarcoidosis more frequently received glucocorticoids than other non-renal sarcoidosis patients (92% vs. 78%, p < 0.01). Also, azathioprine (38% vs. 16%, p < 0.001) and mycophenolate mofetil (5% vs. 1%, p < 0.05) were more frequently used in renal sarcoidosis compared to non-renal sarcoidosis, whereas methotrexate was used less frequently (7% vs. 17%, p < 0.05). CONCLUSIONS: Our data of the largest cohort with biopsy-confirmed renal sarcoidosis demonstrate a higher prevalence (27.5% of all patients) than previously published with a relevant disease burden. The urinary findings in most cases were only mildly abnormal, and some patients did not have renal biopsy despite abnormal urinary results. A renal workup should be performed in all patients with a new diagnosis of sarcoidosis.

Guedel oropharyngeal airway: The validation of facial landmark-distances to estimate sizing in children - Visualisation by magnetic resonance imaging (GUEDEL-I): A prospective observational study.

OBJECTIVE: To validate the ERC-recommended facial landmark-distance for oropharyngeal airway sizing in children. METHODS: We conducted a prospective observational study in anaesthetised, spontaneously breathing children ≤12 years undergoing cranial MRI. Oropharyngeal airways were inserted following the distance from the maxillary incisors to the mandibular angle. Primary outcome was the rate of properly sized oropharyngeal airways on MRI, defined as the distal end positioned within 10 mm from the epiglottis without contacting it. Secondary outcomes were the occurrence of tongue protrusion, oropharyngeal airways clinical efficacy, and related adverse events. Furthermore, we calculated probabilities for the estimation of proper size when considering five facial landmark-distances and optimal rules based on biometric parameters. RESULTS: In 94 children with a mean (SD) age of 4.7 (±3) years, 47.9% [95%-CI 38%-57.9%] oropharyngeal airways were properly sized, while 23.4% [95%-CI 15.9%-33%] were undersized, and 28.7% [95%-CI 20.5%-38.7%] oversized. Tongue protrusion occurred in 59.1% [95%-CI 38.2%-77.2%] of undersized and 15.6% [95%-CI 7.6%-29.2%] of properly sized oropharyngeal airways. No oropharyngeal airway required replacement. Comparing probabilities for five landmark-distances, "maxillary incisors to the angle of the mandible" proved superior for proper sizing at 41.2% [95%-CI 32%-51.7%]. The best-fit formula was "22.43 + 17.54 × log(weight[kg])" with a probability of 61.7% [95%-CI 51.5%-70.9%]. CONCLUSION: Although the facial landmark-distance "maxillary incisors to the angle of the mandible" does not reliably predict oropharyngeal airway size, no clinical problems have been encountered. Since it can be considered the least inaccurate facial landmark-distance, it can serve as an approximation, but the efficacy of oropharyngeal airways should be evaluated clinically. REGISTERED CLINICAL TRIAL: German Clinical Trials Register; DRKS00025918.

[Clinical trials as a central part of patient-centered clinical research]. / Klinische Studien als zentraler Bestandteil patientenorientierter Forschung.

As the continuation and implementation of findings from basic (pre-)clinical research, clinical trials make a significant contribution to medical research. They form the central building block of translational medicine and thus make a decisive contribution to bringing medical knowledge into general care. This helps to make possible a healthcare system that is aligned to the needs of patients and functions efficiently in the long term. Based on the specific objective, clinical trials must comply with national, but increasingly also with European and international regulatory requirements. In academia in particular, expertise in a variety of fields is required in order to make investigator-driven clinical trials a success. This expertise can be provided by a clinical trial center based within the institution conducting the trial.

Preoperative Delirium Risk Screening in Patients Undergoing a Cardiac Surgery: Results from the Prospective Observational FINDERI Study.

OBJECTIVE: Postoperative delirium (POD) is a common complication of cardiac surgery that is associated with higher morbidity, longer hospital stay, cognitive decline, and mortality. Preoperative assessments may help to identify patients´ POD risk. However, a standardized screening assessment for POD risk has not been established. DESIGN: Prospective observational FINd DElirium RIsk factors (FINDERI) study. PARTICIPANTS: Patients aged ≥50 years undergoing cardiac surgery. MEASUREMENTS: The primary aim was to analyze the predictive value of the Delirium Risk Screening Questionnaire (DRSQ) prior to cardiac surgery. Secondary aims are to investigate cognitive, frailty, and geriatric assessments, and to use data-driven machine learning (ML) in predicting POD. Predictive properties were assessed using receiver operating characteristics analysis and multivariate approaches (regularized LASSO regression and decision trees). RESULTS: We analyzed a data set of 504 patients (68.3 ± 8.2 years, 21.4% women) who underwent cardiac surgery. The incidence of POD was 21%. The preoperatively administered DRSQ showed an area under the curve (AUC) of 0.68 (95% CI 0.62, 0.73), and the predictive OR was 1.25 (95% CI 1.15, 1.35, p <0.001). Using a ML approach, a three-rule decision tree prediction model including DRSQ (score>7), Trail Making Test B (time>118), and Montreal Cognitive Assessment (score ≤ 22) was identified. The AUC of the three-rule decision tree on the training set was 0.69 (95% CI 0.63, 0.75) and 0.62 (95% CI 0.51, 0.73) on the validation set. CONCLUSION: Both the DRSQ and the three-rule decision tree might be helpful in predicting POD risk before cardiac surgery.

"SpezPat"- common advance directives versus disease-centred advance directives: a randomised controlled pilot study on the impact on physicians' understanding of non-small cell lung cancer patients' end-of-life decisions.

BACKGROUND: The advance directive represents patients' health care choices and fosters patients' autonomy. Nevertheless, understanding patients' wishes based on the information provided in advance directives remains a challenge for health care providers. Based on the ethical premises of positive obligation to autonomy, an advanced directive that is disease-centred and details potential problems and complications of the disease should help health care providers correctly understand patients' wishes. To test this hypothesis, a pilot-study was conducted to investigate whether physicians could make the correct end-of-life decision for their patients when patients used a disease-centred advance directive compared to a common advance directive.  MATERIAL AND METHODS: A randomised, controlled, prospective pilot study was designed that included patients with non-small cell lung cancer (NSCLC) stage VI from the Department of Haematology and Medical Oncology, University Medical Centre, Goettingen. Patients were randomised into intervention and control groups. The control group received a common advance directive, and the intervention group received a disease-centred advance directive. Both groups filled out their advance directives and returned them. Subsequently, patients were asked to complete nine medical scenarios with different treatment decisions. For each scenario the patients had to decide whether they wanted to receive treatment on a 5-point Likert scale. Four physicians were given the same scenarios and asked to decide on the treatment according to the patients' wishes as stated in their advance directives. The answers by patients and physicians were then compared to establish whether physicians had made the correct assumptions. RESULTS: Recruitment was stopped prior to reaching anticipated sample target. 15 patients with stage IV NSCLC completed the study, 9 patients were randomised into the control group and 6 patients in the intervention group. A total of 135 decisions were evaluated. The concordance between physicians' and patients' answers, was 0.83 (95%-CI 0.71-0.91) in the intervention group, compared to 0.60 (95%-CI 0.48-0.70) in the control group, and the difference between the two groups was statistically significant (p = 0.005). CONCLUSION: This pilot study shows that disease-centred advance directives help physicians understand their NSCLC patients' wishes more precisely and make treatment choices according to these wishes. TRIAL REGISTRATION: The study is registered at the German Clinical Trial Register (no. DRKS00017580, registration date 27/08/2019).