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The demand for rare and precious metals (RPMs), e.g. gold, is increasing, as these are used in the ever-increasing amount of electronics needed for technological development and digitalization. Due to their rarity, virgin mining of RPMs is becoming more difficult and expensive. At the same time, over 62 Mt of e-waste is created globally each year. The high concentration of gold and other RPMs in e-waste makes it an excellent source for recycling. Unfortunately, current recycling methods need to separate the different metals and the current pyrometallurgical and hydrometallurgical processes also create toxic pollutants, large amounts of wastewater and require highly corrosive substances. Here we present a new method for gold removal for the purpose of recycling, using only water and high-intensity focused ultrasound to induce material erosion through cavitation. An 11.8 MHz ultrasonic transducer is used to first image the sample to locate gold-coated pads on discarded printed circuit boards (PCBs) and subsequently to remove only the gold layer. We demonstrate that the gold removal can be controlled by the number of transmitted ultrasonic bursts and that the energy efficiency is optimal when only minute amounts of the nickel layer beneath are also removed. Removing solely the gold layer also decreases the need for further processing steps. This greener gold removal method for e-waste is therefore well aligned with, and contributing to, the United Nations Sustainable Development Goal 12: Ensure sustainable consumption and production patterns.

Objective: Prospective cohort study to test the real-life feasibility of longitudinal patient-reported outcome measurement PROM (Integrated Palliative Outcome Scale IPOS, and NCCN Distress Thermometer DT) required for outpatients with non-curable lung or prostate cancer in comprehensive cancer centers. Methods: Assessment with paper-based IPOS and DT was observed for 15 months. We analyzed response to patients' distress (requests for supportive and palliative services) following PROM. Focus groups to comprehensively explore the user experience of patients, informal caregivers and health care professionals (HCP) supplemented the analysis. Results: Ninety-seven percent (125/129) of the patients received a questionnaire once, but quarterly assessment as recommended by certification committees was achieved only in 50% and 31% of prostate and lung cancer patients. Although both instruments were well accepted, only IPOS showed a high content validity, because some patients had difficulties in understanding the DT. Patients felt comfortable with completing the PROM, and HCP found PROM helped to structure the patient encounter. Due to organizational deficiencies in the handling of the instruments and operationalization of reactions to identified distress, the referrals to supportive and palliative services were rare. Conclusion: To facilitate consequences from PROM it should be a standardized intervention rather than assessment alone. Innovation: The patient perspective improves the implementation of PROM under real-life clinical conditions.

Objectives: This prospective study tested the diagnostic accuracy, and absolute agreement with MRI of a low-dose CT protocol for left ventricular ejection fraction (LVEF) measurement. Furthermore we assessed its potential for combining it with Chest-Abdomen-Pelvis CT (CAP-CT) for a one-stop examination. Materials & methods: Eighty-two patients underwent helical low-dose CT. Cardiac magnetic resonance imaging (MRI) was the reference standard. In fifty patients, CAP-CT was performed concurrently, using a modified injection protocol. In these, LVEF was measured with radioisotope cardiography (MUGA). Patients >18 years, without contrast media or MRI contraindications, were included. Bias was measured with Bland-Altman analysis, classification accuracy with Receiver Operating Characteristics, and inter-reader agreement with Intra-Class Correlation Coefficient (ICC). Correlation was examined using Pearson's correlation coefficients. CAP image quality was compared to previous scans with visual grading characteristics. Results: The mean CT dose-length-product (DLP) was 51.8 mGycm, for an estimated effective dose of 1.4 mSv, compared to 5.7 mSv for MUGA. CT LVEF bias was between 2 % and 10 %, overestimating end-diastolic volume. When corrected for bias, sensitivity and specificity of 100 and 98.5 % for classifying reduced LVEF (50 % MRI value) was achieved. ICC for MUGA was significantly lower than MRI and CT. Distinction of renal medulla and cortex was reduced in the CAP scan, but proportion of diagnostic scans was not significantly different from standard protocol. Conclusion: When corrected for inter-modality bias, CT classifies patients with reduced LVEF with high accuracy at a quarter of MUGA dose and can be combined with CAP-CT without loss of diagnostic quality.

Abstract We present a novel internet of things (IoT) sensing platform that uses helical propagation paths of ultrasonic guided waves (UGWs) for structural health monitoring. This wireless sensor network comprises multiple identical sensor units that communicate with a host PC. The units have dedicated hardware to both generate and receive ultrasonic signals, as well as RF signals for use in triggering the sensors. The system was developed for monitoring and sensing pipelines and similar structures in real-time to facilitate interactive sensing. For accurate sensing with a limited number of arbitrarily scattered sensors, we obtain information from all sensor pairs and analyze helical propagation paths in addition to the commonly used shortest paths. UGWs can propagate long distances along the walls of pipelines, and their propagation velocity depends directly on the thickness of the waveguide, and is affected by energy leakage and mass loading. In this paper, we evaluated the network by utilizing it to detect fouling. The network could be adapted for further ultrasonic measurement tasks, e.g., measuring wall thicknesses or monitoring defects with pulse-echo methods.

The efficiency of bevel and hypoid gears is, alongside load capacity, one of their most important design criteria. To consider the efficiency of bevel and hypoid gears during the development and design process, validated calculation methods based on experimental investigations are necessary. However, the isolated experimental investigation of the load-dependent power losses of bevel and hypoid gears has not been adequately investigated, as most of the experimental investigations consider the complete gearbox. This paper presents a test rig that allows for the experimental investigation of the efficiency of bevel and hypoid gears with a measurement uncertainty of the efficiency of ∆η≤±0.08% according to the Guide to the Expression of Uncertainty in Measurement (GUM). Using the developed test rig, experimental investigations on the efficiency behavior of bevel and hypoid gears regarding the influence of the axial offset, driving direction, and microgeometry are carried out for different operating points varying in circumferential speed and load. This paper discusses the methodology and the first experimental results of a study on the efficiency of bevel and hypoid gears in detail.

Background: Measuring left ventricular ejection fraction (LVEF) is important for detecting heart failure, e.g., in treatment with potentially cardiotoxic chemotherapy. MRI is considered the reference standard for LVEF, but availability may be limited and claustrophobia or metal implants still present challenges. CT has been shown to be accurate and would be advantageous, as LVEF could be measured in conjunction with routine chest–abdomen–pelvis oncology CT. However, the use of CT is not recommended due to the excessive radiation dose. This study aimed to explore the potential for dose reduction using simulation. Using an anthropomorphic heart phantom scanned at 13 dose levels, a noise simulation algorithm was developed to introduce controlled Poisson noise. Filtered backprojection parameters were iteratively tested to minimise differences in myocardium-to-ventricle contrast/noise ratio, as well as structural similarity index (SSIM) differences between real and simulated images at all dose levels. Fifty-one clinical CT coronary angiographies, scanned with full dose through end-systolic and -diastolic phases, were located retrospectively. Using the developed algorithm, noise was introduced corresponding to 25, 10, 5 and 2% of the original dose level. LVEF was measured using clinical software (Syngo.via VB50) with papillary muscles in and excluded from the LV volume. At each dose level, LVEF was compared to the 100% dose level, using Bland–Altman analysis. The effective dose was calculated from DLP using a conversion factor of 0.026 mSv/mGycm. Results: In the clinical images, mean CTDIvol and DLP were 47.1 mGy and 771.9 mGycm, respectively (effective dose 20.0 mSv). Measurements with papillary muscles excluded did not exhibit statistically significant LVEF bias to full-dose images at 25, 10 and 5% simulated dose. At 2% dose, a significant bias of 4.4% was found. With papillary muscles included, small but significant biases were found at all simulated dose levels. Conclusion: Provided that measurements are performed with papillary muscles excluded from the LV volume, the dose can be reduced by a factor of 20 without significantly affecting LVEF measurements. This corresponds to an effective dose of 1 mSv. CT can potentially be used for LVEF measurement with minimal excessive radiation.

Abstract Microglial reactivity is a pathological hallmark in many neurodegenerative diseases. During stimulation, microglia undergo complex morphological changes, including loss of their characteristic ramified morphology, which is routinely used to detect and quantify inflammation in the brain. However, the underlying molecular mechanisms and the relation between microglial morphology and their pathophysiological function are unknown. Here, proteomic profiling of lipopolysaccharide (LPS)-reactive microglia identifies microtubule remodeling pathways as an early factor that drives the morphological change and subsequently controls cytokine responses. We find that LPS-reactive microglia reorganize their microtubules to form a stable and centrosomally-anchored array to facilitate efficient cytokine trafficking and release. We identify cyclin-dependent kinase 1 (Cdk-1) as a critical upstream regulator of microtubule remodeling and morphological change in-vitro and in-situ. Cdk-1 inhibition also rescues tau and amyloid fibril-induced morphology changes. These results demonstrate a critical role for microtubule dynamics and reorganization in microglial reactivity and modulating cytokine-mediated inflammatory responses.

Background: Patients with non-specific symptoms or signs of cancer (NSSC) present a challenge as they are a heterogeneous population who are not candidates for fast-track work-up in an organ-specific cancer pre-planned pathway (CPP). Denmark has a cancer pre-planned pathway for this population (NSSC-CPP), but several issues remain unclarified, for example, distribution and significance of symptoms and findings, and choice of imaging. Aim: To investigate symptoms, cancer diagnoses, and diagnostic yield of computed tomography (CT) and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in patients on NSSC-CPP to improve the overall diagnostic process. Design & setting: A retrospective medical chart review in a 1-year consecutive cohort (2020). Method: A total of 802 referrals were reviewed for diagnostic imaging in patients with NSSP from general practices, specialist practices, or the local hospital diagnostic centre responsible for NSSC-CPP. Results: The study included 248 patients; 21% had cancer, most frequently gastrointestinal cancer (27%). The most frequent symptom was weight loss (56%). CT had a sensitivity of 85%, specificity of 87%, positive predictive value (PPV) of 65%, and negative predictive value (NPV) of 96%. For 18F-FDG-PET/CT, the numbers were sensitivity 82%, specificity 62%, PPV 33%, and NPV 94%. Patients frequently underwent subsequent examinations following initial imaging. Conclusion: The findings were in accordance with the literature. Patients with NSSC had a cancer prevalence of 21%, most frequently gastrointestinal. The most frequent symptom was weight loss and, even as the only symptom, it is a potential marker for cancer. CT and 18F-FDG-PET/CT were sensitive with high NPV, whereas PPV was superior in CT. Better stratification by symptoms or findings is an obvious focus point for future studies to further optimise the NSSC-CPP work-up strategy.

The separate, advanced treatment of hospital wastewater might be a promising approach to prevent the dissemination of residual compounds of high environmental concern, like pharmaceuticals, viruses and pathogenic microorganisms. This study investigates the performance of a full-scale, on-site treatment plant, consisting of a membrane bioreactor and a subsequent ozonation, at a German hospital. We analysed the elimination of pharmaceutical residues, microbiological parameters and SARS-CoV-2 RNA fragments. Additionally, we conducted an orienting study on the practicability of implementing targeted wastewater monitoring at a hospital. Our results demonstrate that after 10 years of stable operation, the treatment plant works highly efficiently regarding the elimination of pharmaceuticals and bacterial indicators. Elimination rates for pharmaceutical substances were above 90%, and log reductions of up to 6 log10 units for microbiological parameters were achieved. SARS-CoV-2 RNA could be detected and quantified in the influent but not in the effluent. The RNA load in the raw wastewater showed good correspondence with COVID-19 case numbers in the hospital. We showed that the full-scale on-site treatment of hospital wastewater is technically feasible and contributes to sustainable hospital effluent management and that monitoring biological markers on the building level might be a useful complementary tool for disease surveillance. HIGHLIGHTS Separate on-site treatment of hospital wastewater with a membrane bioreactor and subsequent ozonation is a promising treatment technology to cope with future challenges in wastewater management like micropollutants and microbial hazards.; Elimination rates of over 90% for pharmaceutical residues and removals of up to 6 log10 units for bacterial indicators were achieved by a full-scale hospital wastewater treatment plant (WWTP).;

Noncommunicable diseases (NCDs) and maternal newborn and child health (MNCH) are two deeply intertwined health areas that have been artificially separated by global health policies, resource allocations and programming. Optimal MNCH care can provide a unique opportunity to screen for, prevent and manage early signs of NCDs developing in both the woman and the neonate. This paper considers how NCDs, NCD modifiable risk factors, and NCD metabolic risk factors impact MNCH. We argue that integrated management is essential, but this faces challenges that manifest across all levels of domestic health systems. Progress toward Sustainable Development targets requires joined-up action.

Objectives To revise the 37-item Advanced Cancer Patients’ Distress Scale (ACPDS) regarding its content, comprehensibility, applicability, and relevance by healthcare professionals (HCPs) and patients in order to enhance an existing instrument that is appropriate for the needs of patients with advanced cancer admitted to palliative care.Design A preliminary revision of items regarding psychometric indices and relevance to initially shorten the scale, complemented by cognitive interviews with patients combining think-aloud and verbal-probe techniques and an HCP focus group on the detected remaining items. Interviews and the focus group were audio-recorded, transcribed verbatim and analysed using MAXQDA.Setting The study took place at a German palliative care unit.Participants 10 patients were interviewed (50% female) and 6 HCPs (3 physicians, 2 nurses and 1 psychologist) participated in the focus group.Outcome Measures Comprehensibility, applicability, and relevance of the ACPDS were evaluated.Results Based on the psychometric revision, a reduced number of 17 items was discussed by the HCP focus group and within cognitive interviews with patients. For the rest of the analysis of the HCP focus group and the patient interview data, the introduction of the ACPDS was simplified and adapted to everyday language. As recommended by HCPs and patients, the example question was replaced. Nine items were reworded to boost clarity, openness, redundancy and mitigation. Three items were eliminated, and another three items were added.Conclusion With this revised 17-item version of the ACPDS, we constructed an instrument that seems to be appropriate for the needs of patients with advanced cancer in a palliative care setting. In the next step, the shortened scale will be tested on psychometric data and validated by a large sample of inpatients on palliative care suffering from advanced cancer.Trial registration number DRKS ID: DRKS00022425.

Abstract Mutations in the GBA1 gene encoding glucocerebrosidase (GCase) are linked to Gaucher (GD) and Parkinson’s Disease (PD). Since some GD and PD patients develop ocular phenotypes, we determined whether ocular phenotypes might result from impaired GCase activity and the corresponding accumulation of glucosylceramide (GluCer) and glucosylsphingosine (GluSph) in the Gba1 D409V/D409V knock-in (Gba KI/KI; “KI”) mouse. Gba KI mice developed age-dependent pupil dilation deficits to an anti-muscarinic agent; histologically, the iris covered the anterior part of the lens with adhesions between the iris and the anterior surface of the lens (posterior synechia). This may prevent pupil dilation in general, beyond an un-responsiveness of the iris to anti-muscarinics. Gba KI mice displayed atrophy and pigment dispersion of the iris, and occlusion of the iridocorneal angle by pigment-laden cells, reminiscent of secondary open angle glaucoma. Gba KI mice showed progressive thinning of the retina consistent with retinal degeneration. GluSph levels were increased in the anterior and posterior segments of the eye, suggesting that accumulation of lipids in the eye may contribute to degeneration in this compartment. We conclude that the Gba KI model provides robust and reproducible eye phenotypes which may be used to test for efficacy and establish biomarkers for GBA1-related therapies.

Abstract Background New-generation cell-based assays have demonstrated a robust association of serum autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis, and brainstem encephalitis, as well as with neuromyelitis optica (NMO)-like or acute-disseminated encephalomyelitis (ADEM)-like presentations. However, only limited data are yet available on cerebrospinal fluid (CSF) findings in MOG-IgG-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD). Objective To describe systematically the CSF profile in MOG-EM. Material and methods Cytological and biochemical findings (including white cell counts and differentiation; frequency and patterns of oligoclonal bands; IgG/IgM/IgA and albumin concentrations and CSF/serum ratios; intrathecal IgG/IgA/IgM fractions; locally produced IgG/IgM/IgA concentrations; immunoglobulin class patterns; IgG/IgA/IgM reibergrams; Link index; measles/rubella/zoster (MRZ) reaction; other anti-viral and anti-bacterial antibody indices; CSF total protein; CSF l-lactate) from 163 lumbar punctures in 100 adult patients of mainly Caucasian descent with MOG-EM were analyzed retrospectively. Results Most strikingly, CSF-restricted oligoclonal IgG bands, a hallmark of multiple sclerosis (MS), were absent in almost 90% of samples (N = 151), and the MRZ reaction, the most specific laboratory marker of MS known so far, in 100% (N = 62). If present, intrathecal IgG (and, more rarely, IgM) synthesis was low, often transient and mostly restricted to acute attacks. CSF WCC was elevated in > 50% of samples (median 31 cells/μl; mostly lymphocytes and monocytes; > 100/μl in 12%). Neutrophils were present in > 40% of samples; activated lymphocytes were found less frequently and eosinophils and/or plasma cells only very rarely (< 4%). Blood–CSF barrier dysfunction (as indicated by an elevated albumin CSF/serum ratio) was present in 48% of all samples and at least once in 55% of all patients (N = 88) tested. The frequency and degree of CSF alterations were significantly higher in patients with acute myelitis than in patients with acute ON and varied strongly depending on attack severity. CSF l-lactate levels correlated significantly with the spinal cord lesion load in patients with acute myelitis (p < 0.0001). Like pleocytosis, blood–CSF barrier dysfunction was present also during remission in a substantial number of patients. Conclusion MOG-IgG-positive EM is characterized by CSF features that are distinct from those in MS. Our findings are important for the differential diagnosis of MS and MOG-EM and add to the understanding of the immunopathogenesis of this newly described autoimmune disease.

Abstract Background International studies indicate deficits in end-of-life care that can lead to distress for patients and their next-of-kin. The aim of the study was to translate and validate the “Care of the Dying Evaluation” (CODE) into German (CODE-GER). Methods Translation according to EORTC (European Organisation for Research and Treatment of Cancer) guidelines was followed by data collection to evaluate psychometric properties of CODE-GER. Participants were next-of-kin of patients who had died an expected death in two hospitals. They were invited to participate at least eight, but not later than 16 weeks after the patient’s death. To calculate construct validity, the Palliative care Outcome Scale (POS) was assessed. Difficulty and perceived strain of answering the questionnaire were assessed by a numeric scale (0–10). Results Out of 1137 next-of-kin eligible, 317 completed the questionnaire (response rate: 27.9%). Data from 237 main sample participants, 38 interraters and 55 next-of-kin who participated for repeated measurement were analysed. Overall internal consistency, α = 0.86, interrater reliability, ICC (1) = 0.79, and retest-reliability, ICC (1, 2) = 0.85, were good. Convergent validity between POS and CODE-GER, r = −.46, was satisfactory. A principal component analysis with varimax rotation showed a 7-factor solution. Difficulty, M = 2.2; SD ± 2.4, and perceived strain, M = 4.1; SD ± 3.0, of completing the questionnaire were rather low. Conclusion The results from the present study confirm CODE-GER as a reliable and valid instrument to assess the quality of care of the dying person. More over our study adds value to the original questionnaire by proposing a deepened analysis of obtained data. The development of seven subscales increases its potential for further surveys and research. Trial registration This study was registered retrospectively on the 25th of January 2018 at the German Clinical Trials Register ( DRKS00013916 ).

Abstract Background Patients with multiple myeloma report more problems with quality of life (QoL) than other haematological malignancies over the course of their incurable illness. The patient-centred Myeloma Patient Outcome Scale (MyPOS) was developed to assess and monitor symptoms and supportive care factors in routine care. Our aim was to translate and culturally adapt the outcome measure to the German context, and to explore its face and content validity. Methods Translation and cultural adaptation following established guidelines used an exploratory, sequential mixed method study design. Steps included: (1) forward translation to German; (2) backward translation to English; (3) expert review; (4) focus groups with the target population (patients, family members, healthcare professionals) to achieve conceptual equivalence; (5) cognitive interviews using Tourangeau’s model with think-aloud technique to evaluate comprehension and acceptability; (6) final review. Results were analysed using thematic analysis. Results Cultural and linguistic differences were noted between the German and English original version. The focus groups (n = 11) and cognitive interviews (n = 9) both highlighted the need for adapting individual items and their answer options to the German healthcare context. Greater individuality regarding need for information with the right to not be informed was elaborated by patients. While the comprehensive nature of the tool was appreciated, item wording regarding satisfaction with healthcare was deemed not appropriate in the German context. Before implementation into routine care, patients’ concerns about keeping their MyPOS data confidential need to be addressed as a barrier, whereas the MyPOS itself was perceived as a facilitator/prompt for a patient-centred discussion of QoL issues. Conclusion With adaptations to answer options and certain items, the German version of the MyPOS can help monitor symptoms and problems afflicting myeloma patients over the course of the disease trajectory. It can help promote a model of comprehensive supportive and patient-centred care for these patients.

A common issue with X-ray examinations (XE) is the erroneous quality classification of the XE, implying that the process needs to be repeated, thus delaying the diagnostic assessment of the XE and increasing the amount of radiation the patient receives. The authors propose a system for automatic quality classification of XE based on convolutional neural networks (CNN) that would simplify this process and significantly decrease erroneous quality classification. The data used for CNN training consist of 4000 knee images obtained via radiography procedure (KXE) in total, with 2000 KXE labeled as acceptable and 2000 as unacceptable. Additionally, half of the KXE belonging to each label are right knees and left knees. Due to the sensitivity to image orientation of some CNNs, three approaches are discussed: (1) Left-right-knee (LRK) classifies XE based just on their label, without taking into consideration their orientation; (2) Orientation discriminator (OD) for the left knee (LK) and right knee (RK) analyses images based on their orientation and inserts them into two separate models regarding orientation; (3) Orientation discriminator combined with knee XRs flipped to the left or right (OD-LFK)/OD-RFK trains the models with all images being horizontally flipped to the same orientation and uses the aforementioned OD to determine whether the image needs to be flipped or not. All the approaches are tested with five CNNs (AlexNet, ResNet50, ResNet101, ResNet152, and Xception), with grid search and k-fold cross-validation. The best results are achieved using the OD-RFK hybrid approach with the Xception network architecture as the classifier and ResNet152 as the OD, with an average AUC of 0.97 (±0.01).

Hyperuricemia is a risk factor for heart disease. Cardiomyocytes produce uric acid via xanthine oxidase. The enzymatic reaction leads to oxidative stress in uric-acid-producing cells. However, extracellular uric acid is the largest scavenger of reactive oxygen species, specifically to nitrosative stress, which can directly affect cells. Here, the effect of plasma-relevant concentrations of uric acid on adult rat ventricular cardiomyocytes is analyzed. A concentration- and time-dependent reduction of load-free cell shortening is found. This is accompanied by an increased protein expression of ornithine decarboxylase, the rate-limiting enzyme of the polyamine metabolism, suggesting a higher arginine turnover. Subsequently, the effect of uric acid was attenuated if other arginine consumers, such as nitric oxide synthase, are blocked or arginine is added. In the presence of uric acid, calcium transients are increased in cardiomyocytes irrespective of the reduced cell shortening, indicating calcium desensitization. Supplementation of extracellular calcium or stimulation of intracellular calcium release by β-adrenergic receptor stimulation attenuates the uric-acid-dependent effect. The effects of uric acid are attenuated in the presence of a protein kinase C inhibitor, suggesting that the PKC-dependent phosphorylation of troponin triggers the desensitizing effect. In conclusion, high levels of uric acid stress cardiomyocytes by accelerating the arginine metabolism via the upregulation of ornithine decarboxylase.

Poor communication contributes to morbidity and mortality, not only in general medical care but also at the end oflife. This leads to issues relating to symptom control and quality of care. As part of an international project focused on bereaved relatives’ perceptions about quality of end-of-life care, we undertook a quality improvement (QI) project in a general hospital in Córdoba city, Argentina.By using two iterative QI cycles, we launched an educational process and introduced a clinical mnemonic tool, I-PASS, during ward handovers. The introduction of the handover tool was intended to improve out-of-hours care.Our clinical outcome measure was ensuring comfort in at least 60% of dying patients, as perceived by family carers, during night shifts in an oncology ward during the project period (March–May 2019). As process-based measures, we selected the proportion of staff completing the I-PASS course (target 60%) and using I-PASS in at least 60% of handovers. Participatory action research was the chosen method.During the study period, 13/16 dying patients were included. We received 23 reports from family carers about the level of patient comfort during the previous night.Sixty-five per cent of healthcare professionals completed the I-PASS training. The percentage of completed handovers increased from 60% in the first Plan-Do-Study-Act (PDSA) cycle to 68% in the second one.The proportion of positive reports about patient comfort increased from 63% (end of the first PDSA cycle) to 87% (last iterative analysis after 3 months). Moreover, positive responses to ‘Did doctors and nurses do enough for the patient to be comfortable during the night?’ increased from 75% to 100% between the first and the second QI cycle.In conclusion, we achieved the successful introduction and staff training for use of the I-PASS tool. This led to improved perceptions by family carers, about comfort for dying patients.

Abstract Background Although patients in palliative care commonly report high emotional and spiritual needs, effective psychosocial treatments based on high quality studies are rare. First research provides evidence for benefits of psychosocial interventions in advanced cancer care. To specifically address end-of-life care requirements, life review techniques and creative-arts based therapies offer a promising potential. Therefore, the present study protocol presents a randomized controlled trial on the effectiveness of a newly developed music therapy technique that is based on a biographically meaningful song (“Song of Life”; SOL). Methods In a design with two parallel arms, 104 patients at two palliative care units will be randomly assigned to three sessions of either SOL (experimental group) or relaxation exercises (control group). Improvements in the psychological domain of quality of life will be the primary endpoint, while secondary outcomes encompass spiritual well-being, ego-integrity, overall quality of life, and distress. Additionally, caregivers will be asked to provide feedback about the treatment. Assessment of biopsychological stress markers and qualitative analysis of perceived strengths and weaknesses will complement data collection. Discussion Based on the results of a previous pilot study, we dedicated considerable efforts to optimizing the intervention and selecting appropriate outcomes for the present trial. We are confident to have designed a methodologically rigorous study that will contribute to the evidence-base and help to develop the potential of psychosocial interventions in palliative care. Trial registration German Clinical Trials Register (DRKS) – DRKS00015308 (date of registration: September 07th 2018).

Abstract Background Dignity Therapy (DT) is a short-term intervention to reduce psychological suffering in end-of-life care. Its strength lies in evidenced-based development and investigation. The aim of the present study is to investigate the feasibility of DT at German palliative care units (PCU), as well as the acceptability and adaption of a German version of the DT question protocol (DTQP). Method A clinical multicentre mixed methods study, whereby patients and relatives provided quantitative (feedback questionnaires) and qualitative (cognitive interviews) data on the DT intervention. Before using the DTQP on patients, healthcare professionals (HCP) were invited to participate in cognitive interviews to provide input on DT. Therefore 360° feedback was achieved. Finally, the conducted DT interviews were examined. The study took place at two German PCUs (Mainz and Würzburg). Participating HCPs were physicians, psychologists, nurses and chaplains. Patients admitted to the PCUs were eligible to participate if they had a terminal illness and a life expectancy ranging from 2 weeks to 12 months. Results: Out of 410 admitted patients, 72 were eligible and 30 (7.3% of all patients and 41.7% of eligible patients) participated. On average, 9 questions from the DTQP were used per DT interview. Subsequent cognitive interviews with patients produced four main categories of feedback (on the title, the question protocol, wording, and the questions actually asked). Finally, of the 30 participants, 19 completed the feedback questionnaire, as did 26 relatives. Of those, 18 patients and 24 relatives evaluated DT as helpful. Conclusions DT is feasible for German PCUs. Our research yielded a validated German translation of the DTQP following EORTC guidelines and findings were reported according to the COREQ checklist for qualitative design. Trial registration. The study was registered retrospectively on the 22nd of December 2017 at the German Clinical Trials Register (DRKS00013627).

Abstract Background Bereavement support is part of palliative care. Sending out bereavement anniversary cards is one intervention of follow-up support for the bereaved. This study evaluated the suitability of bereavement anniversary cards as an appropriate method in bereavement care. Methods A questionnaire was sent to each card recipient since the starting point of this practice (October 2014-June 2015). Data was analyzed descriptively. Results 24 of 68 deliverable questionnaires were returned (response rate 35%). 22 out of 24 recipients felt pleased receiving the card. No participant felt annoyed on receiving the bereavement anniversary card; every participant agreed to at least one positive reaction (i.e. pleased, grateful or consoled). Conclusions The participants’ reactions and opinions about receiving the anniversary card were decidedly positive and indicate the continuation of this practice. Those few less pleased reactions may be related to timing and the first anniversary of the patients’ death and therefore an expression of grief rather than a dissatisfaction with bereavement anniversary cards, as such.

Summary: NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via allosteric modulation are largely unknown. We examine the in vivo effects of GNE-0723, a positive allosteric modulator of GluN2A-subunit-containing NMDARs, on brain network and cognitive functions in mouse models of Dravet syndrome (DS) and Alzheimer’s disease (AD). GNE-0723 use dependently potentiates synaptic NMDA receptor currents and reduces brain oscillation power with a predominant effect on low-frequency (12–20 Hz) oscillations. Interestingly, DS and AD mouse models display aberrant low-frequency oscillatory power that is tightly correlated with network hypersynchrony. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in DS and AD mouse models. GluN2A-subunit-containing NMDAR enhancers may have therapeutic benefits in brain disorders with network hypersynchrony and cognitive impairments. : Hanson et al. examine the therapeutic effects of enhancing GluN2A-subunit-containing NMDAR function in Dravet syndrome and Alzheimer’s disease mice. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in both disease models. GluN2A NMDAR enhancers may benefit brain disorders with network hypersynchrony and cognitive impairments. Keywords: J20, epilepsy, learning, memory, APP, Nav1.1, SCN1A, interneuron, EEG, MK-801

Category: Sports Introduction/Purpose: There is a controversy if non-operative or operative treatment for acute Achilles tendon rupture is superior. It is unknown, if young and active patients with acute Achilles tendon rupture, return to previous sports activity level after treatment with standardized non-operative immediate full weight-bearing protocol. The purpose of this was to assess (1) the return-to-sport rate and subjective satisfaction in patients with different activity levels before the rupture, at 1-year, and at 5-year follow-up, (2) the clinical outcome at 1-year follow-up, and (3) re-ruptures and complications. Methods: Out of 171 consecutive patients that were treated nonoperatively, 114 patients were available for 1-year follow-up. Eighty-nine patients responded to questionnaires for sports activity. Non-operative treatment consisted of a combination of an equinus cast and rehabilitation boot, that enables immediate full weight-bearing and early functional rehabilitation. Clinical 1-year follow-up and follow-up with questionnaires at 1-year and 5-year follow-up were evaluated to calculate Tegner Activity Scale (TAS), and Activity Rating Scale (ARS) and were compared to the status before the rupture. Based on the TAS before the rupture, patients were divided into a low-level activity (5) group and the return-to-sport rate was compared between those two groups.Clinical assessment at minimum 1-year follow-up included testing of plantarflexion strength and endurance, calf circumference, and subjective parameters to calculate a modified Thermann score. Mean clinical follow-up was 34 ± 23 months (range 12-88 months). Results: (1) A significantly higher proportion (91%) of the patients in the low-level activity group returned to their previous TA at 5-year follow-up compared to patients (67%) in the high-level activity group (p=0.029). A higher proportion (91%) of the patients in the low-level activity group returned to their previous ARS Score at 5-year follow-up compared to patients (82%) in the high- level activity group (p=0,115). (2) The mean Thermann score was not significantly different between the two activity groups at minimum 1-year follow-up: 84 ±12 (range, 41-100) and 82 ±12 (range, 44 -100). (3) There were a total of 17 complications. There were 9,6% reruptures (8 with and 3 without an adequate trauma), 5 deep venous thromboses, 1 complex regional pain syndrome at 1 year follow-up. Conclusion: After 17 years of prospective evaluation, our non-operative treatment protocol for acute rupture of the Achilles tendon leads to good functional outcome, high patient satisfaction and high return-to-sport rate. Most patients return to their previous sports activity level after a standardized nonoperative early full-weightbearing treatment protocol for acute Achilles tendon rupture. Even for patients with a high activity level return to pre-rupture sports level activity was possible in two third of the patients. The re-rupture rate with immediate weight bearing is low and comparable to other non-operative treatment methods.

By reacting [{Cp‴Fe(CO)2}2(µ,η1:1-P4)] (1) with in situ generated phosphenium ions [Ph2P][A] ([A]− = [OTf]− = [O3SCF3]−, [PF6]−), a mixture of two main products of the composition [{Cp‴Fe(CO)2}2(µ,η1:1-P5(C6H5)2)][PF6] (2a and 3a) could be identified by extensive 31P NMR spectroscopic studies at 193 K. Compound 3a was also characterized by X-ray diffraction analysis, showing the rarely observed bicyclo[2.1.0]pentaphosphapentane unit. At room temperature, the novel compound [{Cp‴Fe}(µ,η4:1-P5Ph2){Cp‴(CO)2Fe}][PF6] (4) is formed by decarbonylation. Reacting 1 with in situ generated diphenyl arsenium ions gives short-lived intermediates at 193 K which disproportionate at room temperature into tetraphenyldiarsine and [{Cp‴Fe(CO)2}4(µ4,η1:1:1:1-P8)][OTf]2 (5) containing a tetracyclo[3.3.0.02,7.03,6]octaphosphaoctane ligand.

In this study, a triblock copolymer was used as additive to fabricate new dual layer hollow fiber membranes with a hydrophilic active inner surface in order to improve their fouling resistance. The polymeric components of the solutions for membrane fabrication were poly(ether sulfone), poly(N-vinyl pyrrolidone), and the triblock copolymer. The additive consists of three blocks: a middle hydrophobic poly(ether sulfone) block and two outer hydrophilic alkyl poly(ethylene glycol) blocks. By varying the additive concentration in the solutions, it was possible to fabricate dual layer hollow fiber membranes that are characterized by a hydrophilic inner layer, a pure water permeance of over 1800 L/(m2 bar h) and a molecular weight cut-off of 100 kDa similar to commercial membranes. Contact angle and composition determination by XPS measurements revealed the hydrophilic character of the membranes, which improved with increasing additive concentration. Rheological, dynamic light scattering, transmission, and cloud point experiments elucidated the molecular interaction, precipitation, and spinning behavior of the solutions. The low-molecular weight additive reduces the solution viscosity and thus the average relaxation time. On the contrary, slow processes appear with increasing additive concentration in the scattering data. Furthermore, phase separation occurred at a lower non-solvent concentration and the precipitation time increased with increasing additive content. These effects revealed a coupling mechanism of the triblock copolymer with poly(N-vinyl pyrrolidone) in solution. The chosen process parameters as well as the additive solutions provide an easy and inexpensive way to create an antifouling protection layer in situ with established recipes of poly(ether sulfone) hollow fiber membranes. Therefore, the membranes are promising candidates for fast integration in the membrane industry.

A repository of cultural history, a landscape documents past civilizations and can be viewed as a specific type of heritage. UNESCO distinguishes three types of cultural landscape, of which a clearly defined landscape designed and created by man is the most easily identifiable. Such a landscape embraces gardens and parklands constructed for aesthetic reasons with monumental buildings and ensembles. Old maps, aerial photographs, and GIS technology enabled us to study historic land cover and to trace its changes up to the present. Designed landscapes are highly valuable, and their identification and protection is an important aspect of cultural monument protection. Detailed archival research and knowledge of historical development form the basis of the analyses. Historical cultural artifacts, designed landscape composition, and dendrological history were defined using ArcGIS software. We present a case study on Červený Hrádek, which is located near the towns of Jirkov and Chomutov and adjacent to lignite mines in the Most basin. This location represents a high risk of endangerment to valuable cultural history. Therefore, the identification of Červený Hrádek’s significant historical artifacts and their careful management are highly recommended.

BackgroundIschemic preconditioning (IPC) and ischemic postconditioning (IPoC) are currently among the most efficient strategies protecting the heart against ischemia/reperfusion injury. However, the effect of IPC and IPoC on functional recovery following ischemia/reperfusion is less clear, particularly with regard to the specific receptor‐mediated signaling of the postischemic heart. The current article examines the effect of IPC or IPoC on the regulation and coupling of β‐adrenergic receptors and their effects on postischemic left ventricular function. Methods and ResultsThe β‐adrenergic signal transduction was analyzed in 3‐month‐old Wistar rats for each of the intervention strategies (Sham, ischemia/reperfusion, IPC, IPoC) immediately and 7 days after myocardial infarction. Directly after the infarction a cardioprotective potential was demonstrated for both IPC and IPoC: the infarct size was reduced, apoptosis and production of reactive oxygen species were lowered, and the myocardial tissue was preserved. Seven days after myocardial ischemia, only IPC hearts showed significant functional improvement. Along with a deterioration in fractional shortening, IPoC hearts no longer responded adequately to β‐adrenergic stimulation. The stabilization of β‐adrenergic receptor kinase‐2 via increased phosphorylation of Mdm2 (an E3‐ubiquitin ligase) was responsible for desensitization of β‐adrenergic receptors and identified as a characteristic specific to IPoC hearts. ConclusionsImmediately after myocardial infarction, rapid and transient activation of β‐adrenergic receptor kinase‐2 may be an appropriate means to protect the injured heart from excessive stress. In the long term, however, induction and stabilization of β‐adrenergic receptor kinase‐2, with the resultant loss of positive inotropic function, leads to the functional picture of heart failure.

The cardiac expression of the mitochondrial uncoupling protein (UCP)-2 is increased in patients with heart failure. However, the underlying causes as well as the possible consequences of these alterations during the transition from hypertrophy to heart failure are still unclear. To investigate the role of UCP-2 mechanistically, expression of UCP-2 was silenced by small interfering RNA in adult rat ventricular cardiomyocytes. We demonstrate that a downregulation of UCP-2 by siRNA in cardiomyocytes preserves contractile function in the presence of angiotensin II. Furthermore, silencing of UCP-2 was associated with an upregulation of glucose transporter type (Glut)-4, increased glucose uptake, and reduced intracellular lactate levels, indicating improvement of the oxidative glucose metabolism. To study this adaptation in vivo, spontaneously hypertensive rats served as a model for cardiac hypertrophy due to pressure overload. During compensatory hypertrophy, we found low UCP-2 levels with an upregulation of Glut-4, while the decompensatory state with impaired function was associated with an increase of UCP-2 and reduced Glut-4 expression. By blocking the aldosterone receptor with spironolactone, both cardiac function as well as UCP-2 and Glut-4 expression levels of the compensated phase could be preserved. Furthermore, we were able to confirm this by left ventricular (LV) biopsies of patients with end-stage heart failure. The results of this study show that UCP-2 seems to impact the cardiac glucose metabolism during the transition from hypertrophy to failure by affecting glucose uptake through Glut-4. We suggest that the failing heart could benefit from low UCP-2 levels by improving the efficiency of glucose oxidation. For this reason, UCP-2 inhibition might be a promising therapeutic strategy to prevent the development of heart failure.

Die Statistischen Zählsprengel stellen die kleinsten räumlichen Einheiten der amtlichen Statistik dar, über die Großzählungsdaten verfügbar sind. Bei den Statistischen Zählsprengeln tritt das Problem der räumlichen Vergleichbarkeit eines Sachverhaltes auf, da die räumlichen Bezugsflächen in ihrer Größe stark differieren. Eine Möglichkeit der Gebietsgliederung in möglichst gleich große Bezugsflächen ist die Verwendung von Quadratgitternetzen. Dabei werden die Siedlungsschwerpunkte der Zählsprengel möglichst kleinen Gitternetzmaschen zugeordnet und die Daten aggregiert.

OBJECTIVE: To compare the cost-effectiveness of interventions to reduce pneumonia mortality through risk reduction, immunization and case management. METHODS: Country-specific pneumonia burden estimates and intervention costs from WHO were used to review estimates of pneumonia risk in children under 5 years of age and the efficacy of interventions (case management, pneumonia-related vaccines, improved nutrition and reduced indoor air pollution from household solid fuels). We calculated health benefits (disability-adjusted life years, DALYs, averted) and intervention costs over a period of 10 years for 40 countries, accounting for 90% of pneumonia child deaths. FINDINGS: Solid fuel use contributes 30% (90% confidence interval: 18-44) to the burden of childhood pneumonia. Efficacious community-based treatment, promotion of exclusive breastfeeding, zinc supplementation and Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae immunization through existing programmes showed cost-effectiveness ratios of 10-60 International dollars (I$) per DALY in low-income countries and less than I$ 120 per DALY in middle-income countries. Low-emission biomass stoves and cleaner fuels may be cost-effective in low-income regions. Facility-based treatment is potentially cost-effective, with ratios of I$ 60-120 per DALY. The cost-effectiveness of community case management depends on home visit cost. CONCLUSION: Vaccines against Hib and S. pneumoniae, efficacious case management, breastfeeding promotion and zinc supplementation are cost-effective in reducing pneumonia mortality. Environmental and nutritional interventions reduce pneumonia and provide other benefits. These strategies combined may reduce total child mortality by 17%.

Recent findings suggest that adult terminally differentiated cardiomyocytes adapt to stress by cellular de- and redifferentiation. In the present study we tested the hypothesis that swiprosin-1 is a key player in this process. Furthermore, the relationship between swiprosin-1 and β-adrenoceptor coupling was analyzed.In order to study the function of swiprosin-1 in adult rat ventricular cardiomyocytes (ARVC) they were isolated and cultured in a medium containing 20% fetal calf serum (FCS). Changes in cell morphology of ARVC during cultivation were quantified by light and confocal laser scan microscopy. Small interfering RNA (siRNA) was used to reduce the expression of swiprosin-1. The impact of calcium on swiprosin-1 dependent processes was investigated with Bapta-AM. Immunoblot techniques and qRT-PCR were performed to measure mRNA and protein expression.In culture, ARVC first lost their contractile elements, which was followed by a formation of pseudopodia-like structures (spreading). Swiprosin-1 was detected in ARVC at all time points. However, swiprosin-1 expression was increased when ARVC started to spread. Reduction of swiprosin-1 expression with siRNA delayed ARVC spreading. Similarly, Bapta-AM attenuated swiprosin-1 expression and spreading of ARVC. Furthermore, swiprosin-1 expression correlated with the expression of G protein-coupled receptor kinase 2 (GRK2). Moreover, silencing of swiprosin-1 was associated with a down regulation of GRK2 and caused a sensitization of β-adrenergic receptors.Swiprosin-1 is required for ARVC to adapt to culture conditions. Additionally, it seems to be involved in the desensitization of β-adrenergic receptors. Assuming that ARVC adapt to cardiac stress in a similar way, swiprosin-1 may play a key role in cardiac remodeling.

OBJECTIVE: Trials of environmental risk factors and acute lower respiratory infections (ALRI) face a double challenge: implementing sufficiently sensitive and specific outcome assessments, and blinding. We evaluate methods used in the first randomized exposure study of pollution indoors and respiratory effects (RESPIRE): a controlled trial testing the impact of reduced indoor air pollution on ALRI, conducted among children < 18 months in rural Guatemala. METHODS: Case-finding used weekly home visits by fieldworkers trained in integrated management of childhood illness methods to detect ALRI signs such as fast breathing. Blindness was maintained by referring cases to study physicians working from community centres. Investigations included oxygen saturation (SaO2), respiratory syncytial virus (RSV) antigen test and chest X-ray (CXR). FINDINGS: Fieldworkers referred > 90% of children meeting ALRI criteria, of whom about 70% attended a physician. Referrals for cough without respiratory signs and self-referrals contributed 19.0% and 17.9% of physician-diagnosed ALRI cases respectively. Intervention group attendance following ALRI referral was 7% higher than controls, a trend also seen in compliance with RSV tests and CXR. There was no evidence of bias by intervention status in fieldworker classification or physician diagnosis. Incidence of fieldworker ALRI (1.12 episodes/child/year) is consistent with high sensitivity and low specificity; incidence of physician-diagnosed ALRI (0.44 episodes/child/year) is consistent with comparable studies. CONCLUSION: The combination of case-finding methods achieved good sensitivity and specificity, but intervention cases had greater likelihood of reaching the physician and being investigated. There was no evidence of bias in fieldworkers’ classifications despite lack of concealment at home visits. Pulse oximetry offers practical, objective severity assessment for field studies of ALRI.

Abstract Background Symptoms associated with pes planovalgus or flatfeet occur frequently, even though some people with a flatfoot deformity remain asymptomatic. Pes planovalgus is proposed to be associated with foot/ankle pain and poor function. Concurrently, the multifactorial weakness of the tibialis posterior muscle and its tendon can lead to a flattening of the longitudinal arch of the foot. Those affected can experience functional impairment and pain. Less severe cases at an early stage are eligible for non‐surgical treatment and foot orthoses are considered to be the first line approach. Furthermore, strengthening of arch and ankle stabilising muscles are thought to contribute to active compensation of the deformity leading to stress relief of soft tissue structures. There is only limited evidence concerning the numerous therapy approaches, and so far, no data are available showing functional benefits that accompany these interventions. Methods After clinical diagnosis and clarification of inclusion criteria (e.g., age 40–70, current complaint of foot and ankle pain more than three months, posterior tibial tendon dysfunction stage I & II, longitudinal arch flattening verified by radiography), sixty participants with posterior tibial tendon dysfunction associated complaints will be included in the study and will be randomly assigned to one of three different intervention groups: (i) foot orthoses only (FOO), (ii) foot orthoses and eccentric exercise (FOE), or (iii) sham foot orthoses only (FOS). Participants in the FOO and FOE groups will be allocated individualised foot orthoses, the latter combined with eccentric exercise for ankle stabilisation and strengthening of the tibialis posterior muscle. Participants in the FOS group will be allocated sham foot orthoses only. During the intervention period of 12 weeks, all participants will be encouraged to follow an educational program for dosed foot load management (e.g., to stop activity if they experience increasing pain). Functional impairment will be evaluated pre‐ and post‐intervention by the Foot Function Index. Further outcome measures include the Pain Disability Index, Visual Analogue Scale for pain, SF‐12, kinematic data from 3D‐movement analysis and neuromuscular activity during level and downstairs walking. Measuring outcomes pre‐ and post‐intervention will allow the calculation of intervention effects by 3×3 Analysis of Variance (ANOVA) with repeated measures. Discussion The purpose of this randomised trial is to evaluate the therapeutic benefit of three different non‐surgical treatment regimens in participants with posterior tibial tendon dysfunction and accompanying pes planovalgus. Furthermore, the analysis of changes in gait mechanics and neuromuscular control will contribute to an enhanced understanding of functional changes and eventually optimise conservative management strategies for these patients. Trial registration ClinicalTrials.gov Protocol Registration System: ClinicalTrials.gov ID NCT01839669

Reduction of indoor air pollution (IAP) exposure from solid fuel use is a potentially important intervention for childhood pneumonia prevention. This review updates a prior meta-analysis and investigates whether risk varies by etiological agent and pneumonia severity among children aged less than 5 years who are exposed to unprocessed solid fuels. Searches were made of electronic databases (including Africa, China and Latin America) without language restriction. Search terms covered all sources of IAP and wide-ranging descriptions of acute lower respiratory infections, including viral and bacterial agents. From 5317 studies in the main electronic databases (plus 307 African and Latin American, and 588 Chinese studies, in separate databases), 25 were included in the review and 24 were suitable for meta-analysis. Due to substantial statistical heterogeneity, random effects models were used. The overall pooled odds ratio was 1.78 (95% confidence interval, CI: 1.45-2.18), almost unchanged at 1.79 (95% CI: 1.26-2.21) after exclusion of studies with low exposure prevalence (< 15%) and one high outlier. There was evidence of publication bias, and the implications for the results are explored. Sensitivity subanalyses assessed the impact of control selection, adjustment for confounding, exposure and outcome assessment, and age, but no strong effects were identified. Evidence on respiratory syncytial virus was conflicting, while risk for severe or fatal pneumonia was similar to or higher than that for all pneumonia. Despite heterogeneity, this analysis demonstrated sufficient consistency to conclude that risk of pneumonia in young children is increased by exposure to unprocessed solid fuels by a factor of 1.8. Greater efforts are now required to implement effective interventions.

Background: Patients with non-specific symptoms or signs of cancer (NSSC) present a challenge as they are a heterogeneous population who are not candidates for fast-track work-up in an organ-specific cancer pre-planned pathway (CPP). Denmark has a cancer pre-planned pathway for this population (NSSC-CPP), but several issues remain unclarified, for example, distribution and significance of symptoms and findings, and choice of imaging. Aim: To investigate symptoms, cancer diagnoses, and diagnostic yield of computed tomography (CT) and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in patients on NSSC-CPP to improve the overall diagnostic process. Design & setting: A retrospective medical chart review in a 1-year consecutive cohort (2020). Method: A total of 802 referrals were reviewed for diagnostic imaging in patients with NSSP from general practices, specialist practices, or the local hospital diagnostic centre responsible for NSSC-CPP. Results: The study included 248 patients; 21% had cancer, most frequently gastrointestinal cancer (27%). The most frequent symptom was weight loss (56%). CT had a sensitivity of 85%, specificity of 87%, positive predictive value (PPV) of 65%, and negative predictive value (NPV) of 96%. For 18F-FDG-PET/CT, the numbers were sensitivity 82%, specificity 62%, PPV 33%, and NPV 94%. Patients frequently underwent subsequent examinations following initial imaging. Conclusion: The findings were in accordance with the literature. Patients with NSSC had a cancer prevalence of 21%, most frequently gastrointestinal. The most frequent symptom was weight loss and, even as the only symptom, it is a potential marker for cancer. CT and 18F-FDG-PET/CT were sensitive with high NPV, whereas PPV was superior in CT. Better stratification by symptoms or findings is an obvious focus point for future studies to further optimise the NSSC-CPP work-up strategy. [ABSTRACT FROM AUTHOR]